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Sample records for accurate treatment delivery

  1. Fast and Accurate Packet Delivery Estimation based on DSSS Chip Errors Pirmin Heinzer

    E-print Network

    Lenders, Vincent

    , or (iii) a combination of both. RSSI-based models tend to be fast but researchers have found accurate representation of the channel conditions and have shown to be more accurate than the RSSI basedFast and Accurate Packet Delivery Estimation based on DSSS Chip Errors Pirmin Heinzer ETH Zurich

  2. 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.

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

    SciTech Connect

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

    2013-03-01

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

  4. 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.

  5. 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

  6. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  8. Drug delivery strategies for the treatment of malignant gliomas.

    PubMed

    Allhenn, Daniela; Boushehri, Maryam Alsadat Shetab; Lamprecht, Alf

    2012-10-15

    As primary brain tumors, malignant gliomas are known to be one of the most insidious types of brain cancer afflicting the humans. The current standard strategy for the treatment of malignant gliomas includes the surgical resection of the tumor when possible, followed by a combination of radiotherapy and/or a certain chemotherapeutic protocol. However, due to the short mean survival, frequent recurrences, and poor prognosis associated with the tumors, new therapeutic strategies are investigated consecutively. These novel drug delivery approaches can be subdivided as systemic and local drug administration. This review focuses on localized drug delivery strategies for the treatment of malignant gliomas, including the injections, infusions, trans-nasal delivery systems, convection enhanced delivery (CED) systems, and various types of polymeric implants. Furthermore, systemic strategies to increase the drug penetration into the brain, such as temporary disruption of the blood brain barrier (BBB), chemical modification of the available therapeutic substances, and utilization of endogenous transport systems will be briefly discussed. PMID:22721856

  9. Can glucose be monitored accurately at the site of subcutaneous insulin delivery?

    PubMed

    Ward, W Kenneth; Castle, Jessica R; Jacobs, Peter G; Cargill, Robert S

    2014-05-01

    Because insulin promotes glucose uptake into adipocytes, it has been assumed that during measurement of glucose at the site of insulin delivery, the local glucose level would be much lower than systemic glucose. However, recent investigations challenge this notion. What explanations could account for a reduced local effect of insulin in the subcutaneous space? One explanation is that, in humans, the effect of insulin on adipocytes appears to be small. Another is that insulin monomers and dimers (from hexamer disassociation) might be absorbed into the circulation before they can increase glucose uptake locally. In addition, negative cooperativity of insulin action (a lower than expected effect of very high insulin concentrations)may play a contributing role. Other factors to be considered include dilution of interstitial fluid by the insulin vehicle and the possibility that some of the local decline in glucose might be due to the systemic effect of insulin. With regard to future research, redundant sensing units might be able to quantify the effects of proximity, leading to a compensatory algorithm. In summary, when measured at the site of insulin delivery, the decline in subcutaneous glucose level appears to be minimal, though the literature base is not large. Findings thus far support (1) the development of integrated devices that monitor glucose and deliver insulin and (2) the use of such devices to investigate the relationship between subcutaneous delivery of insulin and its local effects on glucose. A reduction in the number of percutaneous devices needed to manage diabetes would be welcome. PMID:24876621

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

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

    PubMed

    Areia, A; Fonseca, E; Moura, P

    2013-10-01

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

  19. Sustained-release delivery systems for treatment of dental diseases.

    PubMed

    Friedman, M; Steinberg, D

    1990-04-01

    Sustained-release delivery systems allow the effective targeting of drugs for treating dental and periodontal diseases. Since dental diseases are chronic, the therapeutic agents used should persist in the oral cavity for as long as possible. Implanting fluoride, chlorhexidine, and other antiseptic agents embedded into sustained-release polymeric matrices into the oral cavity prevents cariogenic plaque accumulation. Both fibers and slab-like sustained-delivery devices bearing chemotherapeutic agents reduced periopathogenic bacteria levels associated with clinical improvement. This review provides useful background information for researchers seeking to develop controlled-release delivery systems for dental applications. PMID:2194197

  20. 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, th

  1. Microcapsule drug delivery device for treatment of glioblastoma multiforme

    E-print Network

    Scott, Alexander Wesley

    2010-01-01

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

  2. 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

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

    PubMed

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

    2014-01-01

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

  4. 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 ? <1 for the plans. For planar dosimetry image comparisons, we defined an acceptable pass rate of >90% of percentage pixels with ? <1. We found that over 90% of control points in the plans passed this criterion. In general, our results indicate that the simulation tool is suitable for accurately calculating both patient/phantom doses and planar doses for VMAT dose delivery. The tool will be valuable to check performance and advance the development of in vivo planar detectors for use in measurement-based VMAT dose verification. In addition, the tool can be useful as an independent research tool for VMAT commissioning of the TPS and delivery system. PMID:23640066

  5. 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 ? <1 for the plans. For planar dosimetry image comparisons, we defined an acceptable pass rate of >90% of percentage pixels with ? <1. We found that over 90% of control points in the plans passed this criterion. In general, our results indicate that the simulation tool is suitable for accurately calculating both patient/phantom doses and planar doses for VMAT dose delivery. The tool will be valuable to check performance and advance the development of in vivo planar detectors for use in measurement-based VMAT dose verification. In addition, the tool can be useful as an independent research tool for VMAT commissioning of the TPS and delivery system.

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

    PubMed

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

    2012-11-10

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

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

    PubMed

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

    2015-04-01

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

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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

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

    SciTech Connect

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

    2012-07-01

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

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

    SciTech Connect

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

    2007-08-01

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

  15. 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.

  16. 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

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

    PubMed Central

    Uskokovi?, 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

  18. 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

  19. 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

  20. Opioid delivery in the treatment of cancer breakthrough pain: a review of routes of administration.

    PubMed

    Nicholson, Bruce; Agarwala, Sanjiv S

    2011-01-01

    Analgesics delivered via the oral route of administration (capsules, tablets, or solutions) are most commonly used to treat cancer breakthrough pain (BTP); however, the effectiveness of oral opioids may be limited by slow gastrointestinal absorption and first-pass metabolic effects. Although the limitations presented by oral opioid delivery are acknowledged and formulations and delivery systems that mirror the temporal characteristics of the majority of cancer BTP episodes are available, short-acting oral opioids are the accepted standard of care. The purpose of this review is to provide an overview of the different routes of opioid administration used in the treatment of cancer BTP and briefly discuss the characteristics of different delivery systems. PMID:21434586

  1. 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

  2. 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

  3. 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

  4. A computational model of drug delivery through microcirculation to compare different tumor treatments.

    PubMed

    Cattaneo, L; Zunino, P

    2014-11-01

    Starting from the fundamental laws of filtration and transport in biological tissues, we develop a computational model to capture the interplay between blood perfusion, fluid exchange with the interstitial volume, mass transport in the capillary bed, through the capillary walls and into the surrounding tissue. These phenomena are accounted at the microscale level, where capillaries and interstitial volume are viewed as two separate regions. The capillaries are described as a network of vessels carrying blood flow. We apply the model to study drug delivery to tumors. The model can be adapted to compare various treatment options. In particular, we consider delivery using drug bolus injection and nanoparticle injection into the blood stream. The computational approach is suitable for a systematic quantification of the treatment performance, enabling the analysis of interstitial drug concentration levels, metabolization rates and cell surviving fractions. Our study suggests that for the treatment based on bolus injection, the drug dose is not optimally delivered to the tumor interstitial volume. Using nanoparticles as intermediate drug carriers overrides the shortcomings of the previous delivery approach. This work shows that the proposed theoretical and computational framework represents a promising tool to compare the efficacy of different cancer treatments. PMID:25044965

  5. 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

  6. 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

  7. The case for intraocular delivery of PPAR agonists in the treatment of diabetic retinopathy

    PubMed Central

    2012-01-01

    Background Systemic therapeutics targeting the peroxisome proliferator-activated receptors have been found to be beneficial in the treatment of diabetic retinopathy. In this paper, we provide a rationale for the use of these therapeutics as intraocular agents. In addition, we introduce the peroxisome proliferator-activated receptors and describe their functions in response to the drugs. Discussion Based on the evidence of large-scale clinical studies investigating the systemic administration of fenofibrate, this ligand for peroxisome proliferator-activated receptor-? is potentially a good candidate for intraocular delivery. Here, we describe the mechanisms by which it might be acting to improve diabetic retinopathy, its relative safety and we speculate on how it could be developed for intraocular delivery. Summary In this paper, we provide a rationale for the further investigation of peroxisome proliferator-activated receptor-? agonists as intraocular agents for the treatment of diabetic retinopathy. PMID:22937835

  8. Nucleic acid delivery into skin for the treatment of skin disease: Proofs-of-concept, potential impact, and remaining challenges.

    PubMed

    Zakrewsky, Michael; Kumar, Sunny; Mitragotri, Samir

    2015-12-10

    Nucleic acids (NAs) hold significant potential for the treatment of several diseases. Topical delivery of NAs for the treatment of skin diseases is especially advantageous since it bypasses the challenges associated with systemic administration which suffers from enzymatic degradation, systemic toxicity and lack of targeting to skin. However, the skin's protective barrier function limits the delivery of NAs into skin after topical application. Here, we highlight strategies for enhancing delivery of NAs into skin, and provide evidence that translation of topical NA therapies could have a transformative impact on the treatment of skin diseases. PMID:26385169

  9. 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.

  10. 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

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

    PubMed Central

    Aslan, Fatih; Cekiç, 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

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

    PubMed

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

    2009-11-01

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

  13. 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

  14. Localized Co-delivery of Doxorubicin, Cisplatin, and Methotrexate by Thermosensitive Hydrogels for Enhanced Osteosarcoma Treatment.

    PubMed

    Ma, Hecheng; He, Chaoliang; Cheng, Yilong; Yang, Zhiming; Zang, Junting; Liu, Jianguo; Chen, Xuesi

    2015-12-16

    Localized cancer treatments with combination drugs have recently emerged as crucial approaches for effective inhibition of tumor growth and reoccurrence. In this study, we present a new strategy for the osteosarcoma treatment by localized co-delivery of multiple drugs, including doxorubicin (DOX), cisplatin (CDDP) and methotraxate (MTX), using thermosensitive PLGA-PEG-PLGA hydrogels. The release profiles of the drugs from the hydrogels were investigated in vitro. It was found that the multidrug coloaded hydrogels exhibited synergistic effects on cytotoxicity against osteosarcoma Saos-2 and MG-63 cells in vitro. After a single peritumoral injection of the drug-loaded hydrogels into nude mice bearing human osteosarcoma Saos-2 xenografts, the hydrogels coloaded with DOX, CDDP, and MTX displayed the highest tumor suppression efficacy in vivo for up to 16 days, as well as led to enhanced tumor apoptosis and increased regulation of the expressions of apoptosis-related genes. Moreover, the monitoring on the mice body change and the ex vivo histological analysis of the key organs indicated that the localized treatments caused less systemic toxicity and no obvious damage to the normal organs. Therefore, the approach of localized co-delivery of DOX, CDDP, and MTX by the thermosensitive hydrogels may be a promising approach for enhanced osteosarcoma treatment. PMID:26575336

  15. 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

  16. On the accuracy of a moving average algorithm for target tracking during radiation therapy treatment delivery

    PubMed Central

    George, Rohini; Suh, Yelin; Murphy, Martin; Williamson, Jeffrey; Weiss, Elizabeth; Keall, Paul

    2008-01-01

    Real-time tumor targeting involves the continuous realignment of the radiation beam with the tumor. Real-time tumor targeting offers several advantages such as improved accuracy of tumor treatment and reduced dose to surrounding tissue. Current limitations to this technique include mechanical motion constraints. The purpose of this study was to investigate an alternative treatment scenario using a moving average algorithm. The algorithm, using a suitable averaging period, accounts for variations in the average tumor position, but respiratory induced target position variations about this average are ignored during delivery and can be treated as a random error during planning. In order to test the method a comparison between five different treatment techniques was performed: (1) moving average algorithm, (2) real-time motion tracking, (3) respiration motion gating (at both inhale and exhale), (4) moving average gating (at both inhale and exhale) and (5) static beam delivery. Two data sets were used for the purpose of this analysis: (a) external respiratory-motion traces using different coaching techniques included 331 respiration motion traces from 24 lung-cancer patients acquired using three different breathing types [free breathing (FB), audio coaching (A) and audio-visual biofeedback (AV)]; (b) 3D tumor motion included implanted fiducial motion data for over 160 treatment fractions for 46 thoracic and abdominal cancer patients obtained from the Cyberknife Synchrony. The metrics used for comparison were the group systematic error (M), the standard deviation (SD) of the systematic error (?) and the root mean square of the random error (?). Margins were calculated using the formula by Stroom et al. [Int. J. Radiat. Oncol., Biol., Phys. 43(4), 905–919 (1999)]: 2?+0.7?. The resultant calculations for implanted fiducial motion traces (all values in cm) show that M and ? are negligible for moving average algorithm, moving average gating, and real-time tracking (i.e., M and ?=0 cm) compared to static beam (M=0.02 cm and ?=0.16 cm) or gated beam delivery (M=?0.05 and 0.16 cm at both exhale and inhale, respectively, and ?=0.17 and 0.26 cm at both exhale and inhale, respectively). Moving average algorithm ?=0.22 cm has a slightly lower random error than static beam delivery ?=0.24 cm, though gating, moving average gating, and real-time tracking have much lower random error values for implanted fiducial motion. Similar trends were also observed for the results using the external respiratory motion data. Moving average algorithm delivery significantly reduces M and ? compared with static beam delivery. The moving average algorithm removes the nonstationary part of the respiration motion which is also achieved by AV, and thus the addition of the moving average algorithm shows little improvement with AV. Overall, a moving average algorithm shows margin reduction compared with gating and static beam delivery, and may have some mechanical advantages over real-time tracking when the beam is aligned with the target and patient compliance advantages over real-time tracking when the target is aligned to the beam. PMID:18649469

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

    PubMed

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

    2014-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2009-04-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2013-05-01

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

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

    PubMed

    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

    2010-10-01

    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

  2. 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.

  3. 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)

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

    SciTech Connect

    Westerly, David C. Soisson, Emilie; Chen Quan; Woch, Katherine; Schubert, Leah; Olivera, Gustavo; Mackie, Thomas R.

    2009-07-15

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

  5. 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

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

    PubMed

    Takedatsu, Hidetoshi; Mitsuyama, Keiichi; Torimura, Takuji

    2015-10-28

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

  7. Feasibility of two modes of treatment delivery for child anxiety in primary care.

    PubMed

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

    2014-09-01

    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. (clinicaltrials.gov unique identifier: NCT00769925). PMID:25075802

  8. 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

  9. 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.

  10. 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

  11. Organizational context, systems change, and adopting treatment delivery systems in the criminal justice system.

    PubMed

    Taxman, Faye S; Henderson, Craig E; Belenko, Steven

    2009-08-01

    The correctional system does not include service provision as a primary goal, even though individuals in prison, jail, and on probation/parole have large unmet substance abuse treatment needs. In response to mandates in the U.S. Constitution for basic health care, services are provided for incarcerated offenders, but generally do not include substance abuse treatment. The system does little to extend any type of health care service to individuals in community settings. This leaves the majority of offenders (6 million under community supervision in the U.S.) basically unattended, even with substance abuse disorders that are four times greater than the general public. The challenge of adapting the correctional system to be part of an integrated service provision system - working in conjunction with the public and private community-based service delivery sector - has intrigued researchers and policy makers over the last two decades. A series of articles using data from the National Criminal Justice Treatment Practices survey have examined factors that influence the adoption of a myriad of substance abuse treatment services for offender populations in various settings. These articles explore the factors that affect adoption and implementation, and provide guidance on issues relevant to organizational change and a dual mission of correctional agencies to advance public safety and public health. This special issue of Drug and Alcohol Dependence is devoted to understanding organizational constructs and factors to improve health outcomes for offenders. PMID:19423241

  12. 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

  13. 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

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

    PubMed

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

    2006-06-01

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

  15. 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

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

    PubMed

    Kanzaki, Sho

    2014-01-01

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

  18. Thermal treatment of galactose-branched polyelectrolyte microcapsules to improve drug delivery with reserved targetability.

    PubMed

    Zhang, Fu; Wu, Qi; Liu, Li-Jun; Chen, Zhi-Chun; Lin, Xian-Fu

    2008-06-01

    A novel multilayered drug delivery system by LbL assembly of galactosylated polyelectrolyte, which is possible to have the potential in hepatic targeting by the presence of galactose residues at the microcapsule's surface, is designed. Thermal treatment was performed on the capsules and a dramatic thermal shrinkage up to 60% decrease of capsule diameter above 50 degrees C was observed. This thermal behavior was then used to manipulate drug loading capacity and release rate. Heating after drug loading could seal the capsule shell, enhancing the loading capacity and reducing the release rate significantly. Excellent affinity between galactose-binding lectin and heated galactose-containing microcapsules were observed, indicating a stable targeting potential even after high temperature elevating up to 90 degrees C. PMID:18304765

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

    PubMed

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

    2014-11-01

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

  20. 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…

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

    PubMed Central

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

    2008-01-01

    Background Previous publications indicate that acupuncture is efficient for the treatment of pelvic girdle pain, PGP, in pregnant women. However, the use of acupuncture for PGP is rare due to insufficient documentation of adverse effects of this treatment in this specific condition. The aim of the present work was to assess adverse effects of acupuncture on the pregnancy, mother, delivery and the fetus/neonate in comparison with women that received stabilising exercises as adjunct to standard treatment or standard treatment alone. Methods In all, 386 women with PGP entered this controlled, single-blind trial. They were randomly assigned to standard treatment plus acupuncture (n = 125), standard treatment plus specific stabilising exercises (n = 131) or to standard treatment alone (n = 130) for 6 weeks. Acupuncture that may be considered strong was used and treatment was started as early as in the second trimester of pregnancy. Adverse effects were recorded during treatment and throughout the pregnancy. Influence on the fetus was measured with cardiotocography (CTG) before-during and after 43 acupuncture sessions in 43 women. A standardised computerized method to analyze the CTG reading numerically (Oxford 8000, Oxford, England) was used. After treatment, the women rated their overall experience of the treatment and listed adverse events if any in a questionnaire. Data of analgesia and oxytocin augmentation during labour, duration of labour, frequency of preterm birth, operative delivery, Apgar score, cord-blood gas/acid base balance and birth weight were also recorded. Results There were no serious adverse events after any of the treatments. Minor adverse events were common in the acupuncture group but women rated acupuncture favourably even despite this. The computerized or visually assessed CTG analyses of antenatal recordings in connection with acupuncture were all normal. Conclusion This study shows that acupuncture administered with a stimulation that may be considered strong led to minor adverse complaints from the mothers but had no observable severe adverse influences on the pregnancy, mother, delivery or the fetus/neonate. PMID:18582370

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

    PubMed

    Dwivedi, Priyanka; Nayak, Vijayashree; Kowshik, Meenal

    2015-09-01

    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. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:1416-1422, 2015. PMID:26193993

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

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

    PubMed

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

    2014-07-01

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

  12. 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 (660nm). 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

  13. 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.

  14. 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.

  15. Depot delivery of dexamethasone and cediranib for the treatment of brain tumor associated edema in an intracranial rat glioma model.

    PubMed

    Ong, Qunya; Hochberg, Fred H; Cima, Michael J

    2015-11-10

    Treatments of brain tumor associated edema with systemically delivered dexamethasone, the standard of care, and cediranib, a novel anti-edema agent, are associated with systemic toxicities in brain tumor patients. A tunable, reservoir-based drug delivery device was developed to investigate the effects of delivering dexamethasone and cediranib locally in the brain in an intracranial 9L gliosarcoma rat model. Reproducible, sustained releases of both dexamethasone and solid dispersion of cediranib in polyvinylpyrrolidone (AZD/PVP) from these devices were achieved. The water-soluble AZD/PVP, which exhibited similar bioactivity as cediranib, was developed to enhance the release of cediranib from the device. Local and systemic administration of both dexamethasone and cediranib was equally efficacious in alleviating edema but had no effect on tumor growth. Edema reduction led to modest but significant improvement in survival. Local delivery of dexamethasone prevented dexamethasone-induced weight loss, an adverse effect seen in animals treated with systemic dexamethasone. Local deliveries of dexamethasone and cediranib via these devices used only 2.36% and 0.21% of the systemic doses respectively, but achieved similar efficacy as systemic drug deliveries without the side effects associated with systemic administration. Other therapeutic agents targeting brain tumor can be delivered locally in the brain to provide similar improved treatment outcomes. PMID:26285064

  16. 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

  17. Strategies of targeting oral drug delivery systems to the colon and their potential use for the treatment of colorectal cancer.

    PubMed

    Krishnaiah, Yellela S R; Khan, Mansoor A

    2012-01-01

    Colorectal cancer (CRC) is the third most common cause of cancer-related death in both men and women. Often, surgical intervention remains the choice in treating CRC. Traditional dosage forms used for treating CRC deliver drug to wanted as well as unwanted sites of drug action resulting in several adverse side effects. Targeted oral drug delivery systems are being investigated to target and deliver chemotherapeutic and chemopreventive agents directly to colon and rectum. Site-specific delivery of a drug to colon increases its concentration at the target site, and thus requires a lower dose with reduced incidence of side effects. The major obstacle to be overcome for successful targeting of drug to colon through oral route is that drug absorption/degradation must be avoided in stomach and small intestine before the dosage form reaches colon. The review includes discussion of physiological factors that must be considered when targeting drugs directly to colorectal region, an outline on drugs used for treatment and prevention of CRC, and a brief description of various types of colon-targeted oral drug delivery systems. The focus is on the assessment of various formulation approaches being investigated for oral colon-specific delivery of drugs used in the treatment and prevention of CRC. PMID:22681390

  18. 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 ?-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 ?-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

  19. Integrin-mediated active tumor targeting and tumor microenvironment response dendrimer-gelatin nanoparticles for drug delivery and tumor treatment.

    PubMed

    Hu, Guanlian; Zhang, Huiqing; Zhang, Li; Ruan, Shaobo; He, Qin; Gao, Huile

    2015-12-30

    Due to the high morbidity and mortality of cancer, it has become an urgent matter to develop an effective and a safe treatment strategy. Nanoparticles (NP) based drug delivery systems have gained much attention nowadays but they faced a paradoxical issue in delivering drugs into tumors: NP with large size were characterized with weak tumor penetration, meanwhile NP with small size resulted in poor tumor retention. To solve this problem, we proposed a multistage drug delivery system which could intelligently shrink its size from large size to small size in the presence of matrix metalloproteinase-2 (MMP-2) which were highly expressed in tumor tissues, therefore the multistage system could benefit from its large size for better retention effect in tumor and then shrunk to small size to contribute to better penetration efficiency. The multistage drug delivery system, RGD-DOX-DGL-GNP, was constructed by 155.4nm gelatin NP core (the substrate of MMP-2) and surface decorated with doxorubicin (DOX) and RGD peptide conjugated dendritic poly-l-lysine (DGL, 34.3nm in diameter). In vitro, the size of multistage NP could effectively shrink in the presence of MMP-2. Thus, the RGD-DOX-DGL-GNP could penetrate deep into tumor spheroids. In vivo, this multistage drug delivery system showed higher tumor retention and deeper penetration than both DOX-DGL and DOX-GNP. Consequently, RGD-DOX-DGL-GNP successfully combined the advantages of dendrimers and GNP in vivo, resulting in an outstanding anti-tumor effect. In conclusion, the multistage drug delivery system could intelligently shrink from large size to small size in the tumor microenvironment and displayed better retention and penetration efficiency, making it an impressing system for cancer treatment. PMID:26598487

  20. 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

  1. 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

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

    E-print Network

    Upadhyay, Urvashi M.

    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 ...

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

    PubMed

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

    2008-05-01

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

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

    PubMed Central

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

    2014-01-01

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

  5. 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

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

    PubMed Central

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

    2014-01-01

    Purpose: To compare real-time dynamic multileaf collimator (MLC) tracking, respiratory amplitude and phase gating, and no compensation for intrafraction motion management during intensity modulated arc therapy (IMAT). Methods: Motion management with MLC tracking and gating was evaluated for four lung cancer patients. The IMAT plans were delivered to a dosimetric phantom mounted onto a 3D motion phantom performing patient-specific lung tumor motion. The MLC tracking system was guided by an optical system that used stereoscopic infrared (IR) cameras and five spherical reflecting markers attached to the dosimetric phantom. The gated delivery used a duty cycle of 35% and collected position data using an IR camera and two reflecting markers attached to a marker block. Results: The average gamma index failure rate (2% and 2 mm criteria) was <0.01% with amplitude gating for all patients, and <0.1% with phase gating and <3.7% with MLC tracking for three of the four patients. One of the patients had an average failure rate of 15.1% with phase gating and 18.3% with MLC tracking. With no motion compensation, the average gamma index failure rate ranged from 7.1% to 46.9% for the different patients. Evaluation of the dosimetric error contributions showed that the gated delivery mainly had errors in target localization, while MLC tracking also had contributions from MLC leaf fitting and leaf adjustment. The average treatment time was about three times longer with gating compared to delivery with MLC tracking (that did not prolong the treatment time) or no motion compensation. For two of the patients, the different motion compensation techniques allowed for approximately the same margin reduction but for two of the patients, gating enabled a larger reduction of the margins than MLC tracking. Conclusions: Both gating and MLC tracking reduced the effects of the target movements, although the gated delivery showed a better dosimetric accuracy and enabled a larger reduction of the margins in some cases. MLC tracking did not prolong the treatment time compared to delivery with no motion compensation while gating had a considerably longer delivery time. In a clinical setting, the optical monitoring of the patients breathing would have to be correlated to the internal movements of the tumor. PMID:25281946

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

    SciTech Connect

    Hua Chiaho Gray, Jonathan M.; Merchant, Thomas E.; Kun, Larry E.; Krasin, Matthew J.

    2008-04-01

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

  8. 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.

  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. Addressing challenges of heterogeneous tumor treatment through bispecific protein-mediated pretargeted drug delivery.

    PubMed

    Yang, Qi; Parker, Christina L; McCallen, Justin D; Lai, Samuel K

    2015-12-28

    Tumors are frequently characterized by genomically and phenotypically distinct cancer cell subpopulations within the same tumor or between tumor lesions, a phenomenon termed tumor heterogeneity. These diverse cancer cell populations pose a major challenge to targeted delivery of diagnostic and/or therapeutic agents, as the conventional approach of conjugating individual ligands to nanoparticles is often unable to facilitate intracellular delivery to the full spectrum of cancer cells present in a given tumor lesion or patient. As a result, many cancers are only partially suppressed, leading to eventual tumor regrowth and/or the development of drug-resistant tumors. Pretargeting (multistep targeting) approaches involving the administration of 1) a cocktail of bispecific proteins that can collectively bind to the entirety of a mixed tumor population followed by 2) nanoparticles containing therapeutic and/or diagnostic agents that can bind to the bispecific proteins accumulated on the surface of target cells offer the potential to overcome many of the challenges associated with drug delivery to heterogeneous tumors. Despite its considerable success in improving the efficacy of radioimmunotherapy, the pretargeting strategy remains underexplored for a majority of nanoparticle therapeutic applications, especially for targeted delivery to heterogeneous tumors. In this review, we will present concepts in tumor heterogeneity, the shortcomings of conventional targeted systems, lessons learned from pretargeted radioimmunotherapy, and important considerations for harnessing the pretargeting strategy to improve nanoparticle delivery to heterogeneous tumors. PMID:26407672

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

    PubMed

    Aghazadeh-Habashi, Ali; Yang, Yang; Tang, Kathy; L?benberg, Raimar; Doschak, Michael R

    2015-12-01

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

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

    PubMed

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

    2015-03-10

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

  13. 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.

  14. 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.

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

    PubMed

    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

  16. 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

  17. 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…

  18. How Accurate is Psychiatry?

    ERIC Educational Resources Information Center

    Greenburg, Joel

    1977-01-01

    The problems that plague psychiatry; such as poor diagnoses, inappropriate treatment, and outdated resources are detailed. A new, more accurate, Diagnostic and Statistical Manual of Mental Disorders (DSM III) to be adopted in 1978 may alleviate many improper diagnoses and treatments. (BT)

  19. 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

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

    PubMed Central

    Adamson, Justus; Wu, Qiuwen

    2008-01-01

    Margin reduction for prostate radiotherapy is limited by uncertainty in prostate localization during treatment. We investigated the feasibility and accuracy of measuring prostate intrafraction motion using kV fluoroscopy performed simultaneously with radiotherapy. Three gold coils used for target localization were implanted into the patient’s prostate gland before undergoing hypofractionated online image-guided step-and-shoot intensity modulated radiation therapy (IMRT) on an Elekta Synergy linear accelerator. At each fraction, the patient was aligned using a cone-beam computed tomography (CBCT), after which the IMRT treatment delivery and fluoroscopy were performed simultaneously. In addition, a post-treatment CBCT was acquired with the patient still on the table. To measure the intrafraction motion, we developed an algorithm to register the fluoroscopy images to a reference image derived from the post-treatment CBCT, and we estimated coil motion in three-dimensional (3D) space by combining information from registrations at different gantry angles. We also detected the MV beam turning on and off using MV scatter incident in the same fluoroscopy images, and used this information to synchronize our intrafraction evaluation with the treatment delivery. In addition, we assessed the following: the method to synchronize with treatment delivery, the dose from kV imaging, the accuracy of the localization, and the error propagated into the 3D localization from motion between fluoroscopy acquisitions. With 0.16 mAs?frame and a bowtie filter implemented, the coils could be localized with the gantry at both 0° and 270° with the MV beam off, and at 270° with the MV beam on when multiple fluoroscopy frames were averaged. The localization in two-dimensions for phantom and patient measurements was performed with submillimeter accuracy. After backprojection into 3D the patient localization error was (?0.04±0.30) mm, (0.09±0.36) mm, and (0.03±0.68) mm in the right-left (RL), anterior-posterior (AP), and superior-inferior (SI) axes, respectively. Simulations showed that while oscillating (stationary) motion cannot be effectively represented in 3D, linearly drifting (nonstationary) motion is detectable with good accuracy. These results show that measuring prostate intrafraction motion using a single kV imager during radiotherapy is feasible and can be performed with acceptable accuracy. PMID:18561654

  1. 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

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

    PubMed

    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

    2011-01-01

    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

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

    NASA Astrophysics Data System (ADS)

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

    2010-03-01

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

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

    PubMed

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

    2010-09-01

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

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

    PubMed

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

    2015-05-28

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

  6. Paclitaxel in cancer treatment: perspectives and prospects of its delivery challenges.

    PubMed

    Singh, Somnath; Dash, Alekha K

    2009-01-01

    Paclitaxel (PTX) is a potent anticancer agent whose clinical usefulness is marred by a delivery problem that is caused by its unfavorable pharmacokinetic and physical properties. Paclitaxel is currently formulated in a mixture of Cremophor EL and ethanol, which is diluted 5-20 times with normal saline or 5% dextrose prior to administration via slow infusion to avoid precipitation in plasma. Many adverse reactions to the PTX formulation have been reported because of the presence of Cremophor EL, including hypersensitivity reactions, nephrotoxicity, and neurotoxicity. Cremophor EL also causes vasodilation, labored breathing, lethargy, hypotension, and leaching of plasticizers, such as diethylhexylpthalate, from the polyvinylchloride infusion bags/sets. Significant research efforts have been conducted to develop an alternative formulation approach to increase the aqueous solubility of PTX without using Cremophor, thereby decreasing its toxicity. This article reviews the various investigated formulation approaches including pastes; liposomes; conjugates with antibodies, peptides, and fatty acids; nanospheres and microspheres; cyclodextrin complexes; emulsions; mucoadhesive gel; prodrugs; and nanoparticulate systems. The pros and cons of each approach are also discussed. Finally, this review concludes with a discussion of nanoparticulate delivery, which is the most promising PTX delivery system of the future because it incorporates the benefits of other approaches such as conjugation, complexation, and prodrugs. PMID:20001890

  7. Fentanyl pectin nasal spray: a novel intranasal delivery method for the treatment of breakthrough cancer pain.

    PubMed

    Bulloch, Marilyn N; Hutchison, Amber M

    2013-01-01

    Fentanyl pectin nasal spray is a novel intranasal formulation for the management of breakthrough cancer pain in patients taking and tolerant to opioids for persistent cancer pain. The pectin-based delivery modulates the product's transmucosal absorption. Nasal delivery allows fentanyl pectin nasal spray to achieve a greater maximum plasma concentration than oral transmucosal fentanyl products and at a much faster rate. Compared with intranasal fentanyl compounded with aqueous solutions, the pectin-based system decreases the maximum plasma concentration and prolongs exposure to more closely match the time course of a typical breakthrough cancer pain episode. Throughout all phases of clinical studies, it was shown to be safe and effective in doses between 100 and 800 µg per breakthrough pain episode. Fentanyl pectin nasal spray is the only proprietary intranasal fentanyl formulation in the USA and one of two in Europe. Owing to the medication's delivery system, the pharmacokinetics and subsequent dosing are unique to this product and should not be interchanged with any other proprietary or compounded fentanyl product. PMID:23272789

  8. 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

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

    PubMed

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

    2015-01-01

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

  10. 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.

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

    E-print Network

    Elleri, Daniela; Dunger, David B.; Hovorka, Roman

    2011-11-09

    , 23:1-12. 10. Steil GM, Rebrin K: Closed-loop insulin delivery - what lies between where we are and where we are going? Expert Opin Drug Deliv 2005, 2:353-362. 11. Renard E, Costalat G, Chevassus H, Bringer J: Artificial beta-cell: clinical experience... , Bequette BW: A closed-loop artificial pancreas using model predictive control and a sliding meal size estimator. J Diabetes Sci Technol 2009, 3:1082-1090. 21. Wang Y, Dassau E, Doyle FJ III: Closed-loop control of artificial pancreatic Beta -cell in type 1...

  12. 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

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

    PubMed

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

    2015-01-01

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

  14. 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

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

    PubMed Central

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

    2013-01-01

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

  16. A passive MEMS drug delivery pump for treatment of ocular diseases.

    PubMed

    Lo, Ronalee; Li, Po-Ying; Saati, Saloomeh; Agrawal, Rajat N; Humayun, Mark S; Meng, Ellis

    2009-10-01

    An implantable manually-actuated drug delivery device, consisting of a refillable drug reservoir, flexible cannula, check valve, and suture tabs, was investigated as a new approach for delivering pharmaceuticals to treat chronic ocular diseases. Devices are fabricated by molding and bonding three structured layers of polydimethylsiloxane. A 30 gauge non-coring needle was used to refill the reservoir; this size maximized the number of repeated refills while minimizing damage to the reservoir. The check valve cracking pressure was 76 +/- 8.5 mmHg (mean +/- SE, n = 4); the valve sustained > 2000 mmHg of reverse pressure without leakage. Constant delivery at 1.57 +/- 0.2 microL/sec and 0.61 +/- 0.2 microL/sec (mean +/- SE, n = 4) under 500 mmHg and 250 mmHg of applied pressure, respectively, was obtained in benchtop experiments. The valve closing time constant was 10.2 s for 500 mmHg and 14.2 s for 250 mmHg. Assembled devices were successfully demonstrated in benchtop, ex vivo, and in vivo experiments. PMID:19396548

  17. 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.

  18. 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…

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

    PubMed

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

    2010-09-01

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

  20. Drug delivery optimization through Bayesian networks.

    PubMed Central

    Bellazzi, R.

    1992-01-01

    This paper describes how Bayesian Networks can be used in combination with compartmental models to plan Recombinant Human Erythropoietin (r-HuEPO) delivery in the treatment of anemia of chronic uremic patients. Past measurements of hematocrit or hemoglobin concentration in a patient during the therapy can be exploited to adjust the parameters of a compartmental model of the erythropoiesis. This adaptive process allows more accurate patient-specific predictions, and hence a more rational dosage planning. We describe a drug delivery optimization protocol, based on our approach. Some results obtained on real data are presented. PMID:1482938

  1. Polymeric micelle nanocarriers for the cutaneous delivery of tacrolimus: a targeted approach for the treatment of psoriasis.

    PubMed

    Lapteva, Maria; Mondon, Karine; Möller, Michael; Gurny, Robert; Kalia, Yogeshvar N

    2014-09-01

    Tacrolimus (TAC) suffers from poor cutaneous bioavailability when administered topically using conventional vehicles with the consequence that although it is indicated for the treatment of atopic dermatitis, it has poor efficacy against psoriasis. The aim of this work was to formulate TAC loaded polymeric micelles using the biodegradable and biocompatible methoxy-poly(ethylene glycol)-dihexyl substituted polylactide (MPEG-dihexPLA) diblock copolymer and to investigate their potential for targeted delivery of TAC into the epidermis and upper dermis. Micelle formulations were characterized with respect to drug content, stability, and size. An optimal 0.1% micelle formulation was developed and shown to be stable over a period of 7 months at 4 °C; micelle diameters ranged from 10 to 50 nm. Delivery experiments using human skin and involving quantification by UHPLC-MS/MS demonstrated that this formulation resulted in significantly greater TAC deposition in skin than that with Protopic (0.1% w/w; TAC ointment), (1.50 ± 0.59 and 0.47 ± 0.20 ?g/cm(2), respectively). The cutaneous biodistribution profile of TAC in the upper 400 ?m of tissue (at a resolution of 20 ?m) demonstrated that the increase in cutaneous drug levels was due to improved TAC deposition in the stratum corneum, viable epidermis, and upper dermis. Given that there was no increase in the amount of TAC in deeper skin layers or any transdermal permeation, the results suggested that it would be possible to increase TAC levels selectively in the target tissue without increasing systemic absorption and the risk of side effects in vivo. Micelle distribution and molecular penetration pathways were subsequently visualized with confocal laser scanning microscopy (CLSM) using a fluorescently labeled copolymer and fluorescent dyes. The CLSM study indicated that the copolymer was unable to cross the stratum corneum and that release of the micelle "payload" was dependent on the molecular properties of the "cargo" as evidenced by the different behaviors of DiO and fluorescein. A preferential deposition of micelles into the hair follicle was also confirmed by CLSM. Overall, the results indicate that MPEG-dihexPLA micelles are highly efficient nanocarriers for the selective cutaneous delivery of tacrolimus, superior to the marketed formulation (Protopic). Furthermore, they may also have significant potential for targeted delivery to the hair follicle. PMID:25057896

  2. 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

  3. CD44-targeting for antitumor drug delivery: a new SN-38-hyaluronan bioconjugate for locoregional treatment of peritoneal carcinomatosis.

    PubMed

    Serafino, Annalucia; Zonfrillo, Manuela; Andreola, Federica; Psaila, Rossana; Mercuri, Luana; Moroni, Noemi; Renier, Davide; Campisi, Monica; Secchieri, Cynthia; Pierimarchi, Pasquale

    2011-06-01

    An innovative approach for cancer therapy implies the use of drugs covalently conjugated to macromolecular carriers that specifically target molecules over-expressed on tumor cells. This drug delivery strategy may allow a controlled release of the drug and a high targeting selectivity on tumor cells, increasing drug cytotoxicity and decreasing its undesirable side effects. We provide in vitro and in vivo preclinical data on the antitumor efficacy of ONCOFID™-S, a new bioconjugate of hyaluronic acid (HA) with SN-38 (the CPT11 active metabolite), that support the validity of the drug delivery strategy implying the use of HA as macromolecular carrier of antineoplastic drugs, an approach based on the over-expression of its target CD44 (the receptor for HA-mediated motility) in a wide variety of cancers. We show that ONCOFID™-S exerts a strong in vitro anti-proliferative activity on CD44 over-expressing rat DHD/K12/trb colon adenocarcinoma cells, as well as on gastric, breast, oesophageal, ovarian and lung human cancer cells, higher than that exerted by unconjugated SN-38. We also demonstrated the in vivo anti-tumor efficacy of locoregional treatment with ONCOFID™-S on two pre-clinical models of colorectal cancer (CRC) in BDIX rats: a) syngeneic model of subcutaneous tumor; b) syngeneic model of metastatic tumor induced by injection of cells into the peritoneal cavity, mimicking the clinical situation of peritoneal carcinomatosis. Specifically, in the latter model ONCOFID™-S is able to dramatically reduce all parameters indicative of a poor prognosis in peritoneal metastatization of CRC without any myelotoxicity or mesothelial inflammation. We propose this CD44-targeted therapeutic strategy for locoregional treatment of peritoneal carcinomatosis from CRC, against which systemic chemotherapy results almost inefficient. PMID:21486216

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

    E-print Network

    Ye, Hongye

    2014-01-01

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

  5. Development of polysaccharide-based colon targeted drug delivery systems for the treatment of amoebiasis.

    PubMed

    Mundargi, Raghavendra C; Patil, Sangamesh A; Agnihotri, Sunil A; Aminabhavi, Tejraj M

    2007-03-01

    The main focus of this study is to develop colon targeted drug delivery systems for metronidazole (MTZ). Tablets were prepared using various polysaccharides or indigenously developed graft copolymer of methacrylic acid with guar gum (GG) as a carrier. Various polysaccharides such as GG, xanthan gum, pectin, carrageenan, beta-cyclodextrin (CD) or methacrylic acid-g-guar (MAA-g-GG) gum have been selected and evaluated. The prepared tablets were tested in vitro for their suitability as colon-specific drug delivery systems. To further improve the colon specificity, some selected tablet formulations were enteric coated with Eudragit-L 100 to give protection in an acidic environment. Drug release studies were performed in simulated gastric fluid (SGF) for 2 hr followed by simulated intestinal fluid (SIF) at pH 7.4. The dissolution data demonstrate that the rate of drug release is dependent upon the nature and concentration of polysaccharide/polymer used in the formulations. Uncoated tablets containing xanthan gum or mixture of xanthan gum with graft copolymer showed 30-40% drug release during the initial 4-5 hr, whereas for tablets containing GG with the graft copolymer, it was 70%. After enteric coating, the release was drastically reduced to 18-24%. The other polysaccharides were unable to protect drug release under similar conditions. Preparations with xanthan gum as a matrix showed the time-dependent release behavior. Further, in vitro release was performed in the dissolution media with rat caecal contents. Results indicated an enhanced release when compared to formulations studied in dissolution media without rat caecal contents, because of microbial degradation or polymer solubilization. The nature of drug transport was found to be non-Fickian in case of uncoated formulations, whereas for the coated formulations, it was found to be super-Case-II. Statistical analyses of release data indicated that MTZ release is significantly affected by the nature of the polysaccharide used and enteric coating of the tablet. Differential scanning calorimetry indicated the presence of crystalline nature of drug in the formulations. PMID:17454058

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

    PubMed

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

    2015-04-28

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

  7. 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

  8. 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…

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

  10. 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±14.8nm 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±9.8nm 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

  11. 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 ?L cross-linker TEGDMA leads to an adequate meloxicam release for therapeutic application. The ocular irritation studies showed that BSA-MX-NA loaded p-HEMA gels are significantly less irritating to the ocular tissues as compared to marketed MX solutions. The developed contact lenses loaded with BSA-MX-NA could be very useful for extended delivery in postcataract endophthalmitis treatment. PMID:25158220

  12. The use of a hydrogel matrix for controlled delivery of niacin to the gastrointestinal tract for treatment of hyperlipidemia.

    PubMed

    Sirc, J; Hrib, J; Vetrik, M; Hobzova, R; Zak, A; Stankova, B; Slanar, O; Hromadka, R; Sandrikova, V; Michalek, J

    2015-10-01

    Hyperlipidemia treatment based on niacin requires gastrointestinal administration of relatively high doses. The recommended dietary allowance of niacin as vitamin B3 is 14 to 16 mg daily in adults, while the doses of niacin used in the treatment of hyperlipidemia are generally in the range of 1 to 3 g. Administration of such large doses requires a high concentration of the active compound in the tablet and proper control of the drug release. In this study, a hydrogel matrix based on poly(2-hydroxyethyl methacrylate) and polyvinylpyrrolidone was investigated as delivery vehicle for controlled NA release into the gastrointestinal environment. The prepared hydrogel matrices varied in used monomer and crosslinker types and concentrations. The content of NA in tablets was between 65-80 %. The release profiles of NA from tablets were examined under three different pH values (1, 4.5 and 6.8) over the time period of 30 h. The effects of the monomer ratio, the crosslinking of the polymer network, and the solubility of niacin during drug release under various pH are discussed. The results showed that the release time period can be achieved in a relatively wide range of time and can be adjusted according to the medical requirements. PMID:26447595

  13. 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

  14. 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.

  15. A prediction study on radiation-induced second malignancies for IMRT treatment delivery.

    PubMed

    Stathakis, Sotirios; Roland, Teboh; Papanikolaou, Niko; Li, Jinseng; Ma, Charlie

    2009-04-01

    Low-level peripheral organ dose and its effect on second malignancies for patients undergoing radiation therapy have been reported in the literature. However, a comprehensive database outlining the treatment modalities, the tumor location, and a quantification of the overall relative risk of second malignancies is rather limited. In this work, we quantify the relative risks or percent likelihood of second malignancies for patients undergoing IMRT and conventional radiotherapy for four different tumor sites: breast, head and neck, lung, and prostate. We utilize Monte Carlo methods based on actual patient plans to compute the whole body effective dose equivalent for each plan and then deduce the percent likelihood of the occurrence of second malignancy. Based on an evaluation of over 30 actual patient plans and Monte Carlo simulations using 6, 10, and 18MV photon beam energies, we observed that the IMRT patients treated for head and neck cancer showed a 40% increase in risk for developing a second malignancy compared to those treated with conventional radiotherapy. The increase in risk for prostrate patients was 30% while the IMRT lung patients gave the highest relative risk almost tripling that observed in their conventionally treated counterparts. There was negligible difference in risk between breast patients undergoing IMRT treatment versus conventional therapy. The overall relative risk of radiation induced malignancy observed was below 6% in all treatment plans considered. PMID:19334795

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

    PubMed

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

    2014-04-01

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

  17. 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

  18. 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)

  19. 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.

  20. 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.

  1. 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

  2. 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

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

    PubMed

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

    2014-07-01

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

  4. 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

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

    PubMed

    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

  6. 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

  7. 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 ?g BCNU could be immobilized on 1 mg of MNP-3 (bound-BCNU-3). Bound-BCNU-3 was more stable than free-BCNU when stored at 4 °C, 25 °C or 37 °C. Bound-BCNU-3 could be concentrated at targeted sites in vitro and in vivo using an externally applied magnet. When applied to brain tumors, magnetic targeting increased the concentration and retention of bound-BCNU-3. This drug delivery system promises to provide more effective tumor treatment using lower therapeutic doses and potentially reducing the side effects of chemotherapy. PMID:21030073

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

  9. 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.

  10. 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

  11. 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

  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. 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.

  15. 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)

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

  17. 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

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

    PubMed

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

    2012-03-01

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

  19. 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(?-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 (~48nm), 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

  20. 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 ?g) significantly suppressed immunoglobulin formation against GAA in Pompe mice injected with 500 ?g 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 ?g 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

  1. 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

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

    PubMed

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

    2013-06-25

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

  3. 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.

  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. Contrast ultrasound targeted treatment of gliomas in mice via drug-bearing nanoparticle delivery and microvascular ablation.

    PubMed

    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

  6. 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.

  7. 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)

    Kneževi?, 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.

  8. Comparing Different Short-Term Service Delivery Methods of Visual-Motor Treatment for First Grade Students in Mainstream Schools

    ERIC Educational Resources Information Center

    Ratzon, Navah Z.; Lahav, Orit; Cohen-Hamsi, Shifra; Metzger, Yehiela; Efraim, Daniela; Bart, Orit

    2009-01-01

    To compare the efficacy of three different short-term service delivery methods on first grade children with soft neurological signs who suffer from visual-motor difficulties. One hundred and forty seven first grade students who scored below the 21st percentile on the Visual-Motor Integration Test (VMI) were recruited from schools and randomly…

  9. Phospholipase A2-responsive antibiotic delivery via nanoparticle-stabilized liposomes for the treatment of bacterial infection

    PubMed Central

    Thamphiwatana, Soracha; Gao, Weiwei; Pornpattananangkul, Dissaya; Zhang, Qiangzhe; Fu, Victoria; Li, Jiayang; Li, Jieming; Obonyo, Marygorret; Zhang, Liangfang

    2014-01-01

    Adsorbing small charged nanoparticles onto liposome surfaces to stabilize them against fusion and payload leakage has resulted in a new class of liposomes capable of environment-responsive drug delivery. Herein, we engineered a liposome formulation with a lipid composition sensitive to bacterium-secreted phospholipase A2 (PLA2) and adsorbed chitosan-modified gold nanoparticles (AuChi) onto the liposome surface. The resulting AuChi-stabilized liposomes (AuChi-liposomes) showed prohibited fusion activity and negligible drug leakage. However, upon exposure to either purified PLA2 enzyme or PLA2 secreted by Helicobacter pylori (H. pylori) bacteria in culture, AuChi-liposomes rapidly released the encapsulated payloads and such responsive release was retarded by adding quinacrine dihydrochloride, a PLA2 inhibitor. When loaded with doxycycline, AuChi-liposomes effectively inhibited H. pylori growth. Overall, the AuChi-liposomes allowed for smart “on-demand” antibitoic delivery: the more enzymes or bacteria present at the infection site, the more drug will be released to treat the infection. Given the strong association of PLA2 with a diverse range of diseases, the present liposomal delivery technique holds broad application potential for tissue microenvironment-responsive drug delivery. PMID:25544886

  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. 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

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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 180–200 g (n = 54), received doxorubicin in cumulative dose of 12.0 mg/kg to model advance heart failure, registered by ultrasonography. We formed six groups: the first three groups of animals received, respectively, 0.06 ml Simdax, AuNPs, and conjugate (AuNPs-Simdax), intrapleurally, and the second three received them intravenously. The seventh group was control (saline). We performed dynamic assessment of heart failure regression in vivo measuring hydrothorax. Sonoporation of gold nanoparticles to cardiomyocytes was tested. Results We designed and constructed colloidal, spherical gold nanoparticles, AuNPs-Simdax conjugate, both founded biosafety (in cytotoxicity, genotoxicity, and immunoreactivity). In all animals of the six groups after the third day post-medication injection, no ascites and liver enlargement were registered (P < 0.001 vs controls). Conjugate injection showed significantly higher hydrothorax reduction than Simdax injection only (P < 0.01); gold nanoparticle injection showed significantly higher results than Simdax injection (P < 0.05). AuNPs and conjugate showed no significant difference for rat recovery. Difference in rat life continuity was significant between Simdax vs AuNPs (P < 0.05) and Simdax vs conjugate (P < 0.05). Sonoporation enhances AuNP transfer into the cell and mitochondria that were highly localized, superior to controls (P < 0.01 for both). Conclusions Gold nanoparticles of 30 nm and its AuNPs-Simdax conjugate gave positive results in biosafety and biocompatibility in vitro and in vivo. AuNPs-Simdax and AuNPs have similar significant cardioprotective effects in rats with doxorubicin-induced heart failure, higher than that of Simdax. Intrapleural (local) delivery is preferred over intravenous (systemic) delivery according to all tested parameters. Sonoporation is able to enhance gold nanoparticle delivery to myocardial cells in vivo. PMID:23889805

  17. 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

  18. 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.

  19. 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 ?-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

  20. 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

  1. 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

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

    PubMed Central

    2014-01-01

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

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

    PubMed

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

    2015-12-21

    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. PMID:26568525

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

    PubMed Central

    Costa, Pedro M; Cardoso, Ana L; Mendonça, Liliana S; Serani, Angelo; Custódia, Carlos; Conceição, Mariana; Simões, Sérgio; Moreira, João N; Pereira de Almeida, Luís; Pedroso de Lima, Maria C

    2013-01-01

    The present work aimed at the development and application of a lipid-based nanocarrier for targeted delivery of nucleic acids to glioblastoma (GBM). For this purpose, chlorotoxin (CTX), a peptide reported to bind selectively to glioma cells while showing no affinity for non-neoplastic cells, was covalently coupled to liposomes encapsulating antisense oligonucleotides (asOs) or small interfering RNAs (siRNAs). The resulting targeted nanoparticles, designated CTX-coupled stable nucleic acid lipid particles (SNALPs), exhibited excellent features for in vivo application, namely small size (<180?nm) and neutral surface charge. Cellular association and internalization studies revealed that attachment of CTX onto the liposomal surface enhanced particle internalization into glioma cells, whereas no significant internalization was observed in noncancer cells. Moreover, nanoparticle-mediated miR-21 silencing in U87 human GBM and GL261 mouse glioma cells resulted in increased levels of the tumor suppressors PTEN and PDCD4, caspase 3/7 activation and decreased tumor cell proliferation. Preliminary in vivo studies revealed that CTX enhances particle internalization into established intracranial tumors. Overall, our results indicate that the developed targeted nanoparticles represent a valuable tool for targeted nucleic acid delivery to cancer cells. Combined with a drug-based therapy, nanoparticle-mediated miR-21 silencing constitutes a promising multimodal therapeutic approach towards GBM. PMID:23778499

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

    PubMed

    Costa, Pedro M; Cardoso, Ana L; Mendonça, Liliana S; Serani, Angelo; Custódia, Carlos; Conceição, Mariana; Simões, Sérgio; Moreira, João N; Pereira de Almeida, Luís; Pedroso de Lima, Maria C

    2013-01-01

    The present work aimed at the development and application of a lipid-based nanocarrier for targeted delivery of nucleic acids to glioblastoma (GBM). For this purpose, chlorotoxin (CTX), a peptide reported to bind selectively to glioma cells while showing no affinity for non-neoplastic cells, was covalently coupled to liposomes encapsulating antisense oligonucleotides (asOs) or small interfering RNAs (siRNAs). The resulting targeted nanoparticles, designated CTX-coupled stable nucleic acid lipid particles (SNALPs), exhibited excellent features for in vivo application, namely small size (<180?nm) and neutral surface charge. Cellular association and internalization studies revealed that attachment of CTX onto the liposomal surface enhanced particle internalization into glioma cells, whereas no significant internalization was observed in noncancer cells. Moreover, nanoparticle-mediated miR-21 silencing in U87 human GBM and GL261 mouse glioma cells resulted in increased levels of the tumor suppressors PTEN and PDCD4, caspase 3/7 activation and decreased tumor cell proliferation. Preliminary in vivo studies revealed that CTX enhances particle internalization into established intracranial tumors. Overall, our results indicate that the developed targeted nanoparticles represent a valuable tool for targeted nucleic acid delivery to cancer cells. Combined with a drug-based therapy, nanoparticle-mediated miR-21 silencing constitutes a promising multimodal therapeutic approach towards GBM.Molecular Therapy-Nucleic Acids (2013) 2, e100; doi:10.1038/mtna.2013.30; published online 18 June 2013. PMID:23778499

  6. Reversal of multidrug resistance by co-delivery of paclitaxel and lonidamine using a TPGS and hyaluronic acid dual-functionalized liposome for cancer treatment.

    PubMed

    Assanhou, Assogba G; Li, Wenyuan; Zhang, Lei; Xue, Lingjing; Kong, Lingyi; Sun, Hongbin; Mo, Ran; Zhang, Can

    2015-12-01

    Multidrug resistance (MDR) remains the primary issue in cancer therapy, which is characterized by the overexpressed P-glycoprotein (P-gp)-included efflux pump or the upregulated anti-apoptotic proteins. In this study, a D-alpha-tocopheryl poly (ethylene glycol 1000) succinate (TPGS) and hyaluronic acid (HA) dual-functionalized cationic liposome containing a synthetic cationic lipid, 1,5-dioctadecyl-N-histidyl-l-glutamate (HG2C18) was developed for co-delivery of a small-molecule chemotherapeutic drug, paclitaxel (PTX) with a chemosensitizing agent, lonidamine (LND) to treat the MDR cancer. It was demonstrated that the HG2C18 lipid contributes to the endo-lysosomal escape of the liposome following internalization for efficient intracellular delivery. The TPGS component was confirmed able to elevate the intracellular accumulation of PTX by inhibiting the P-gp efflux, and to facilitate the mitochondrial-targeting of the liposome. The intracellularly released LND suppressed the intracellular ATP production by interfering with the mitochondrial function for enhanced P-gp inhibition, and additionally, sensitized the MDR breast cancer (MCF-7/MDR) cells to PTX for promoted induction of apoptosis through a synergistic effect. Functionalized with the outer HA shell, the liposome preferentially accumulated at the tumor site and showed a superior antitumor efficacy in the xenograft MCF-7/MDR tumor mice models. These findings suggest that this dual-functional liposome for co-delivery of a cytotoxic drug and an MDR modulator provides a promising strategy for reversal of MDR in cancer treatment. PMID:26426537

  7. 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-?-tocopheryl polyethylene glycol 1000-poly(?-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-?-tocopheryl polyethylene glycol 1000-poly(?-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

  8. 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

  9. 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

  10. 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.

  11. 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?treatment vs placebo device (70% vs 45%, P?treatment with AVP-825 at 1 hour (19% vs 9%; P?=?.04). There were no serious adverse events (AEs), and no systemic AEs occurred in more than one patient. Chest pain or pressure was not reported, and only one patient taking AVP-825 reported mild paresthesia. No other triptan sensations were reported. Conclusions Targeted delivery of a low-dose of sumatriptan powder via a novel, closed-palate, Breath Powered, intranasal device (AVP-825) provided fast relief of moderate or severe migraine headache in adults that reached statistical significance over placebo by 30 minutes. The treatment was well tolerated with a low incidence of systemic AEs. PMID:25355310

  12. Optimal control of hepatitis C antiviral treatment programme delivery for prevention amongst a population of injecting drug users.

    PubMed

    Martin, Natasha K; Pitcher, Ashley B; Vickerman, Peter; Vassall, Anna; Hickman, Matthew

    2011-01-01

    In most developed countries, HCV is primarily transmitted by injecting drug users (IDUs). HCV antiviral treatment is effective, and deemed cost-effective for those with no re-infection risk. However, few active IDUs are currently treated. Previous modelling studies have shown antiviral treatment for active IDUs could reduce HCV prevalence, and there is emerging interest in developing targeted IDU treatment programmes. However, the optimal timing and scale-up of treatment is unknown, given the real-world constraints commonly existing for health programmes. We explore how the optimal programme is affected by a variety of policy objectives, budget constraints, and prevalence settings. We develop a model of HCV transmission and treatment amongst active IDUs, determine the optimal treatment programme strategy over 10 years for two baseline chronic HCV prevalence scenarios (30% and 45%), a range of maximum annual budgets (£50,000-300,000 per 1,000 IDUs), and a variety of objectives: minimising health service costs and health utility losses; minimising prevalence at 10 years; minimising health service costs and health utility losses with a final time prevalence target; minimising health service costs with a final time prevalence target but neglecting health utility losses. The largest programme allowed for a given budget is the programme which minimises both prevalence at 10 years, and HCV health utility loss and heath service costs, with higher budgets resulting in greater cost-effectiveness (measured by cost per QALY gained compared to no treatment). However, if the objective is to achieve a 20% relative prevalence reduction at 10 years, while minimising both health service costs and losses in health utility, the optimal treatment strategy is an immediate expansion of coverage over 5-8 years, and is less cost-effective. By contrast, if the objective is only to minimise costs to the health service while attaining the 20% prevalence reduction, the programme is deferred until the final years of the decade, and is the least cost-effective of the scenarios. PMID:21853030

  13. 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…

  14. 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 ?g/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

  15. 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

  16. 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.

  17. 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

  18. 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 (8–10 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

  19. 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.

  20. Efficacy of Intracerebral Delivery of Carboplatin in Combination With Photon Irradiation for Treatment of F98 Glioma-Bearing Rats

    SciTech Connect

    Rousseau, Julia; Barth, Rolf F.; Moeschberger, Melvin L.; Elleaume, Helene

    2009-02-01

    Purpose: To evaluate the efficacy of prolonged intracerebral (i.c.) administration of carboplatin by means of ALZET osmotic pumps, in combination with radiotherapy for the treatment of intracranial F98 glioma in rats. Methods and Materials: Seven days after stereotactic implantation of F98 glioma cells into the brains of Fischer rats, carboplatin was administrated i.c. by means of ALZET pumps over 6 days. Rats were treated at the European Synchrotron Radiation Facility with a single 15-Gy X-ray dose, either given alone or 24 h after administration of carboplatin. Results: Untreated rats had a mean survival time (MST) {+-} SE of 23 {+-} 1 days, compared with 44 {+-} 3 days for X-irradiated animals and 69 {+-} 20 days for rats that received carboplatin alone, with 3 of 13 of these surviving >195 days. Rats that received carboplatin followed by X-irradiation had a MST of >142 {+-} 21 days and a median survival time of >195 days, with 6 of 11 rats (55%) still alive at the end of the study. The corresponding percentage increases in lifespan, based on median survival times, were 25%, 85%, and 713%, respectively, for carboplatin alone, radiotherapy alone, or the combination. Conclusions: Our data demonstrate that i.c. infusion of carboplatin by means of ALZET pumps in combination with X-irradiation is highly effective for the treatment of the F98 glioma. They provide strong support for the approach of concomitantly administering chemo- and radiotherapy for the treatment of brain tumors.

  1. 4D analysis of influence of patient movement and anatomy alteration on the quality of 3D U/S-based prostate HDR brachytherapy treatment delivery

    SciTech Connect

    Milickovic, Natasa; Mavroidis, Panayiotis; Tselis, Nikolaos; Nikolova, Iliyana; Katsilieri, Zaira; Kefala, Vasiliki; Zamboglou, Nikolaos; Baltas, Dimos

    2011-09-15

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

  2. 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

  3. 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

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

    PubMed

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

    2014-07-20

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

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

    PubMed Central

    2014-01-01

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

  6. 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

  7. 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

  8. 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

  9. 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

  10. Starch-based coatings for colon-specific drug delivery. Part I: the influence of heat treatment on the physico-chemical properties of high amylose maize starches.

    PubMed

    Cristina Freire, A; Fertig, Christiane C; Podczeck, Fridrun; Veiga, Francisco; Sousa, João

    2009-08-01

    In this study, the changes in the physico-chemical properties of different high amylose maize starches, i.e., Hylon VII, Hylon V and IM-DS acetate starch, were studied prior and after heat treatment used in the preparation of film coatings (WO 2008/012573 A1). Characterisation of the unprocessed maize starches was carried out with regard to the outer particle morphology, particle size distribution, specific surface area, moisture content, apparent particle density, swelling, polarised light microscopy, Fourier Transform Infrared (FT-IR), X-ray powder diffraction and modulated Differential Scanning Calorimetry (mDSC). Pure amylopectin and low amylopectin samples (LAPS) were also used to aid the interpretation of the results. The effect of heat processing was evaluated in terms of degree of crystallinity, FT-IR and mDSC. Enzymatic digestibility of both processed and unprocessed maize starches was estimated qualitatively using various alpha-amylases resembling those present under in vivo conditions. A significant decrease in the degree of crystallinity of the dried samples after processing was observed, in particular for amylopectin. Only LAPS and Hylon VII samples showed differences in their thermal behaviour upon heat treatment, thus suggesting that a minimum amount of amylose is required for an effect to be detectable. High amylose starches maintained a well-ordered arrangement of their macromolecular chains, as was seen by X-ray and FT-IR studies. This effect could be explained by a formation of retrograded forms of the starches. The retrograded starches were found to be less digestible by various types of amylase, in particular those found in the upper intestines, indicating that the formation of a butanol complex as claimed elsewhere is not essential in the preparation of colon delivery devices. PMID:19233267

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

    PubMed

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

    2013-02-01

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

  12. 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 dr

  13. 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.

  14. Delivery presentations

    MedlinePLUS

    ... your baby is positioned during delivery. The best position for the baby to be in to pass ... the body facing towards the mother's back. This position is called occiput anterior (OA). In breech position, ...

  15. 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

  16. Caesarean delivery: conflicting interests.

    PubMed

    Osuna, Eduardo; Pérez Cárceles, Maria Dolores; Sánchez Ferrer, Maria Luisa; Machado, Francisco

    2015-12-01

    Within the maternal-fetal relationship, interests may sometimes diverge. In this paper, a pregnant woman's refusal to undergo a caesarean delivery, which was recommended both to save the life of the fetus and to minimize risks to her, is described. The legal aspects involved in the conflict between maternal autonomy and fetal well-being are analysed. The patient requested an abortion because of the poor condition of the fetus; however, according to Spanish legislation, the possibility of abortion was rejected as the pregnancy was in its 27th week. The woman still persisted in her refusal to accept a caesarian delivery. After the medical team sought guidance on the course to follow, the Duty Court authorized a caesarean delivery against the wishes of the patient. From a legal point of view, at stake were the freedom of the woman - expressed by the decision to reject a caesarean delivery - and the life of the unborn child. In clinical treatment, the interests of the fetus are generally aligned with those of the pregnant woman. When they are not, it is the pregnant woman's autonomy that should be respected, and coercion should form no part of treatment, contrary to the decision of this court. PMID:26371711

  17. 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…

  18. Development of Polyphosphoester-Based Polymeric Nanoparticles as Delivery Carriers for Silver-Based Antimicrobial Agents for Treatment of Infectious Diseases 

    E-print Network

    Lim, Young

    2015-07-16

    The development of well-defined polymeric nanoparticles (NPs) as delivery carriers for antimicrobials targeting human infectious diseases requires rational design of the polymer template, an efficient synthetic approach and fundamental understanding...

  19. 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.

  20. Microspheres and Nanotechnology for Drug Delivery.

    PubMed

    Jóhannesson, Gauti; Stefánsson, Einar; Loftsson, Thorsteinn

    2016-01-01

    Ocular drug delivery to the posterior segment of the eye can be accomplished by invasive drug injections into different tissues of the eye and noninvasive topical treatment. Invasive treatment involves the risks of surgical trauma and infection, and conventional topical treatments are ineffective in delivering drugs to the posterior segment of the eye. In recent years, nanotechnology has become an ever-increasing part of ocular drug delivery. In the following, we briefly review microspheres and nanotechnology for drug delivery to the eye, including different forms of nanotechnology such as nanoparticles, microparticles, liposomes, microemulsions and micromachines. The permeation barriers and anatomical considerations linked to ocular drug delivery are discussed and a theoretical overview on drug delivery through biological membranes is given. Finally, in vitro, in vivo and human studies of x03B3;-cyclodextrin nanoparticle eyedrop suspensions are discussed as an example of nanotechnology used for drug delivery to the eye. PMID:26501994

  1. Radiation delivery system and method

    DOEpatents

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

    2002-01-01

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

  2. Preterm Delivery

    EPA Science Inventory

    This indicator describes the proportion of preterm infants—which are infants born prior to 37 weeks of gestation—born in the United States from 1995 to 2008. Preterm delivery is a leading cause of infant death. Scientists continue to explore possible links between ...

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

    E-print Network

    Das, Suman

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

  4. GENE DELIVERY TO BONE

    PubMed Central

    Evans, C. H.

    2012-01-01

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

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

    SciTech Connect

    Rana, Suresh; Zeidan, Omar; Ramirez, Eric; Rains, Michael; Gao, Junfang; Zheng, Yuanshui

    2013-09-15

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

  6. 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.

  7. Noninvasive ocular drug delivery: potential transcorneal and other alternative delivery routes for therapeutic molecules in glaucoma.

    PubMed

    Foldvari, Marianna

    2014-01-01

    Drug delivery to the eye is made difficult by multiple barriers (such as the tear film, cornea, and vitreous) between the surface of the eye and the treatment site. These barriers are difficult to surmount for the purposes of drug delivery without causing toxicity. Using nanotechnology tools to control, manipulate, and study delivery systems, new approaches to delivering drugs, genes, and antigens that are effective and safe can be developed. Topical administration to the ocular surface would be the safest method for delivery, as it is noninvasive and painless compared with other delivery methods. However, there is only limited success using topical delivery methods, especially for gene therapy. Current thinking on treatments of the future enabled by nanodelivery systems and the identification of target specificity parameters that require deeper understanding to develop successful topical delivery systems for glaucoma is highlighted. PMID:25275915

  8. Image-Guided Drug Delivery with Single-Photon Emission Computed Tomography: A Review of Literature

    PubMed Central

    Chakravarty, Rubel; Hong, Hao; Cai, Weibo

    2014-01-01

    Tremendous resources are being invested all over the world for prevention, diagnosis, and treatment of various types of cancer. Successful cancer management depends on accurate diagnosis of the disease along with precise therapeutic protocol. The conventional systemic drug delivery approaches generally cannot completely remove the competent cancer cells without surpassing the toxicity limits to normal tissues. Therefore, development of efficient drug delivery systems holds prime importance in medicine and healthcare. Also, molecular imaging can play an increasingly important and revolutionizing role in disease management. Synergistic use of molecular imaging and targeted drug delivery approaches provides unique opportunities in a relatively new area called `image-guided drug delivery' (IGDD). Single-photon emission computed tomography (SPECT) is the most widely used nuclear imaging modality in clinical context and is increasingly being used to guide targeted therapeutics. The innovations in material science have fueled the development of efficient drug carriers based on, polymers, liposomes, micelles, dendrimers, microparticles, nanoparticles, etc. Efficient utilization of these drug carriers along with SPECT imaging technology have the potential to transform patient care by personalizing therapy to the individual patient, lessening the invasiveness of conventional treatment procedures and rapidly monitoring the therapeutic efficacy. SPECT-IGDD is not only effective for treatment of cancer but might also find utility in management of several other diseases. Herein, we provide a concise overview of the latest advances in SPECT-IGDD procedures and discuss the challenges and opportunities for advancement of the field. PMID:25182469

  9. An implantable MEMS drug delivery device for rapid delivery in ambulatory emergency care.

    PubMed

    Elman, N M; Ho Duc, H L; Cima, M J

    2009-06-01

    We introduce the first implantable drug delivery system based on MEMS (Micro-Electro-Mechanical-Systems) technology specifically designed as a platform for treatment in ambulatory emergency care. The device is named IRD(3) (implantable rapid drug delivery device) and allows rapid delivery of drugs. Vasopressin was used as a model drug for in vitro tests as it is a commonly used drug for cardiac resuscitation. Experimental results reveal that the IRD(3) provides an effective method for rapid delivery without significant drug degradation. Several medical uses and delivery modalities for IRD(3) are proposed. PMID:19169826

  10. Treatment

    MedlinePLUS

    ... States, smallpox vaccine, antivirals, and vaccinia immune globulin (VIG) can be used. Learn more about smallpox vaccine, antivirals, and VIG treatments . Resource CDC's Smallpox Vaccine Information for the ...

  11. Anemia and Oxygen Delivery.

    PubMed

    Bliss, Stuart

    2015-09-01

    Clinical assessment of tissue oxygenation is challenging. Anemia reflects a decreased oxygen carrying capacity of the blood and its significance in the perioperative setting relates largely to the associated risk of insufficient oxygen delivery and cellular hypoxia. Until meaningful clinical measures of tissue oxygenation are available in veterinary practice, clinicians must rely on evaluation of a patient's hemodynamic and ventilatory performance, along with biochemical and hemogasometric measurements. Blood transfusion is used commonly for treatment of perioperative anemia, and may improve tissue oxygenation by normalizing the rheologic properties of blood and enhancing perfusion, independent of increases in oxygen carrying capacity. PMID:26033442

  12. Magnetic Resonance-Guided Drug Delivery.

    PubMed

    Mikhail, Andrew S; Partanen, Ari; Yarmolenko, Pavel; Venkatesan, Aradhana M; Wood, Bradford J

    2015-11-01

    The use of clinical imaging modalities for the guidance of targeted drug delivery systems, known as image-guided drug delivery (IGDD), has emerged as a promising strategy for enhancing antitumor efficacy. MR imaging is particularly well suited for IGDD applications because of its ability to acquire images and quantitative measurements with high spatiotemporal resolution. The goal of IGDD strategies is to improve treatment outcomes by facilitating planning, real-time guidance, and personalization of pharmacologic interventions. This article reviews basic principles of targeted drug delivery and highlights the current status, emerging applications, and future paradigms of MR-guided drug delivery. PMID:26499281

  13. Dendrimers as Nanovectors for Nucleic Acid Delivery

    NASA Astrophysics Data System (ADS)

    Liu, Xiaoxuan; Wang, Qi; Peng, Ling

    2013-09-01

    Nucleic acid based gene therapy holds great promise in the treatment of various diseases. However, the success of both DNA- and siRNAbased gene therapies depends critically on safe and efficient nucleic acid delivery systems. Owing to their well-defined structure and multivalent cooperativity, dendrimers have attracted particular attention as ideal nanocarriers for nucleic acid delivery. The present chapter highlights the current status of dendrimers as non-viral nanovectors for both DNA and siRNA delivery, focusing on the different dendrimers investigated for their delivery efficiency with respect to structural alterations in the view to developing safe and efficient nanovectors for gene therapy application.

  14. Pure Insulin Nanoparticle Agglomerates for Pulmonary Delivery

    E-print Network

    Bailey, Mark Michael

    2008-04-29

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

  15. Fabrication of drug delivery MEMS devices

    E-print Network

    Lei, Wang S

    2007-01-01

    There is considerable amount of interest in the immediate treatment of personnel involved in high risk situations on the battlefield. A novel approach to drug delivery on the battlefield based on MEMS technology is discussed. ...

  16. Drug delivery systems: An updated review

    PubMed Central

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

    2012-01-01

    Drug delivery is the method or process of administering a pharmaceutical compound to achieve a therapeutic effect in humans or animals. For the treatment of human diseases, nasal and pulmonary routes of drug delivery are gaining increasing importance. These routes provide promising alternatives to parenteral drug delivery particularly for peptide and protein therapeutics. For this purpose, several drug delivery systems have been formulated and are being investigated for nasal and pulmonary delivery. These include liposomes, proliposomes, microspheres, gels, prodrugs, cyclodextrins, among others. Nanoparticles composed of biodegradable polymers show assurance in fulfilling the stringent requirements placed on these delivery systems, such as ability to be transferred into an aerosol, stability against forces generated during aerosolization, biocompatibility, targeting of specific sites or cell populations in the lung, release of the drug in a predetermined manner, and degradation within an acceptable period of time. PMID:23071954

  17. Microneedles: an innovative platform for gene delivery.

    PubMed

    McCaffrey, Joanne; Donnelly, Ryan F; McCarthy, Helen O

    2015-08-01

    The advent of microneedle (MN) technology has provided a revolutionary platform for the delivery of therapeutic agents, particularly in the field of gene therapy. For over 20 years, the area of gene therapy has undergone intense innovation and progression which has seen advancement of the technology from an experimental concept to a widely acknowledged strategy for the treatment and prevention of numerous disease states. However, the true potential of gene therapy has yet to be achieved due to limitations in formulation and delivery technologies beyond parenteral injection of the DNA. Microneedle-mediated delivery provides a unique platform for the delivery of DNA therapeutics clinically. It provides a means to overcome the skin barriers to gene delivery and deposit the DNA directly into the dermal layers, a key site for delivery of therapeutics to treat a wide range of skin and cutaneous diseases. Additionally, the skin is a tissue rich in immune sentinels, an ideal target for the delivery of a DNA vaccine directly to the desired target cell populations. This review details the advancement of MN-mediated DNA delivery from proof-of-concept to the delivery of DNA encoding clinically relevant proteins and antigens and examines the key considerations for the improvement of the technology and progress into a clinically applicable delivery system. PMID:26122168

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-03-01

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

  20. Ultrasonic drug delivery in Oncology.

    PubMed

    Udroiu, Ion

    2015-01-01

    Ultrasound-assisted drug delivery is an emerging technique that has the advantage of being non-invasive, efficiently and specifically targeted and controllable. While systemic drugs often show detrimental side effects, their ultrasound-triggered local release at the selected tissue may improve safety and specifity of therapy. An increasing amount of animal and preclinical studies demonstrates how ultrasound can also be used for increasing the efficacy of chemotherapeutic drug release to solid tumors. In particular, this technique may be functional to reach uniform delivery of chemotherapeutic agents throughout tumors, which is naturally restricted by their abnormal vascularization and interstitial pressure. This review deals with the physical mechanisms of ultrasound, the different kinds of drug carriers (microbubbles, liposomes and micelles) and the biological phenomena useful for cancer treatment (hyperthermia, sonoporation, enhanced extravasation, sonophoresis and blood-brain barrier disruption), showing how much ultrasonic drug delivery is a promising method in the oncological field. PMID:26011326

  1. A novel platform for minimally invasive delivery of cellular therapy as a thin layer across the subretina for treatment of retinal degeneration

    NASA Astrophysics Data System (ADS)

    Rotenstreich, Ygal; Tzameret, Adi; Kalish, Sapir E.; Belkin, Michael; Meir, Amilia; Treves, Avraham J.; Nagler, Arnon; Sher, Ifat

    2015-03-01

    Incurable retinal degenerations affect millions worldwide. Stem cell transplantation rescued visual functions in animal models of retinal degeneration. In those studies cells were transplanted in subretinal "blebs", limited number of cells could be injected and photoreceptor rescue was restricted to areas in proximity to the injection sites. We developed a minimally-invasive surgical platform for drug and cell delivery in a thin layer across the subretina and extravascular spaces of the choroid. The novel system is comprised of a syringe with a blunt-tipped needle and an adjustable separator. Human bone marrow mesenchymal stem cells (hBM-MSCs) were transplanted in eyes of RCS rats and NZW rabbits through a longitudinal triangular scleral incision. No immunosuppressants were used. Retinal function was determined by electroretinogram analysis and retinal structure was determined by histological analysis and OCT. Transplanted cells were identified as a thin layer across the subretina and extravascular spaces of the choroid. In RCS rats, cell transplantation delayed photoreceptor degeneration across the entire retina and significantly enhanced retinal functions. No retinal detachment or choroidal hemorrhages were observed in rabbits following transplantation. This novel platform opens a new avenue for drug and cell delivery, placing the transplanted cells in close proximity to the damaged RPE and retina as a thin layer, across the subretina and thereby slowing down cell death and photoreceptor degeneration, without retinal detachment or choroidal hemorrhage. This new transplantation system may increase the therapeutic effect of other cell-based therapies and therapeutic agents. This study is expected to directly lead to phase I/II clinical trials for autologous hBM-MSCs transplantation in retinal degeneration patients.

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

    PubMed

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

    2015-01-01

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

  3. Defined polymeric materials for gene delivery.

    PubMed

    He, Dongsheng; Wagner, Ernst

    2015-05-01

    For successful gene therapy, the delivery of the curative genetic information into target cells is the main hurdle and the development of efficient and safe gene delivery carriers the crucial challenge. Polymeric materials have been widely investigated as gene delivery agents, generating first promising results. However, the heterogeneity and polydispersity of polymers and lack of site specific modifications make it difficult to achieve accurate structure-activity relationship studies. Moreover it will hamper manufacturing of highly defined materials which could be used in clinical development. Therefore, polymers with precise chemical structure are required. In this review, we focus on the current design of defined polymeric materials for gene transfer. We first discuss the barriers for gene delivery, and then provide examples which illustrate defined polymeric vectors, including dendrimers, peptide carriers, and sequence-defined oligoaminoamides. PMID:25655078

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

    E-print Network

    Elman, Noel

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

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

    SciTech Connect

    Ma Lijun; Chuang, Cynthia; Descovich, Martina; Petti, Paula; Smith, Vernon; Verhey, Lynn

    2008-11-15

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

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

    PubMed Central

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

    2012-01-01

    Robust data measurement systems assess health care performance and monitor population-level treatment trends. A key challenge in the assessment of substance abuse treatment is the development of systems to accurately monitor service delivery indicators. Wait time to treatment, as defined by the days between first request for service and first treatment, is an important measure of organizational process and delivery of care. The Network for the Improvement of Addiction Treatment emphasizes wait time as a primary outcome in their study of 201 addiction treatment agencies in the USA. This article describes the changes made in five state data systems to monitor wait times and outlines lessons learned that could be applied to other health data tracking systems. PMID:22193826

  7. Drug delivery systems from nose to brain.

    PubMed

    Misra, Ambikanandan; Kher, Gitanjali

    2012-09-01

    The treatment of brain disorders is particularly challenging due to the presence of a variety of formidable obstacles to deliver drugs selectively and effectively to the brain. Blood-brain-barrier (BBB) constitutes the major obstacle to the uptake of drugs into the brain following systemic administration. Intranasal delivery offers a non-invasive and convenient method to bypass the BBB and delivery of therapeutics directly to the brain. The review discusses the potential of intranasal route to deliver drugs to the brain, the mechanisms and pathways of direct nose to brain drug transport, the various factors influencing transnasal drug absorption, the conventional and novel intranasal drug delivery systems, the various intranasal drug delivery techniques and devices, and examples of brain drug transport that have been feasible in treating various brain disorders. Moreover, products on the market, investigational drugs, and the author's perceptions about the prospect of intranasal delivery for treating brain disorders are also been discussed. PMID:23016642

  8. Controlled delivery of antibodies from injectable hydrogels.

    PubMed

    Fletcher, Nathan A; Babcock, Lyndsey R; Murray, Ellen A; Krebs, Melissa D

    2016-02-01

    Therapeutic antibodies are currently used for the treatment of various diseases, but large doses delivered systemically are typically required. Localized controlled delivery techniques would afford major benefits such as decreasing side effects and required doses. Injectable biopolymer systems are an attractive solution due to their minimally invasive potential for controlled release in a localized area. Here, alginate-chitosan hydrogels are demonstrated to provide controlled delivery of IgG model antibodies and also of Fab antibody fragments. Also, an alternate delivery system comprised of poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with antibodies and encapsulated in alginate was shown to successfully provide another level of control over release. These biopolymer systems that offer controlled delivery for antibodies and antibody fragments will be promising for many applications in drug delivery and regenerative medicine. PMID:26652435

  9. Precise Delivery Into Chronic Spinal Cord Injury Syringomyelic Cysts with Magnetic Nanoparticles MRI Visualization

    PubMed Central

    Zhang, Chao; Morozova, Anna Y.; Abakumov, Maxim A.; Gubsky, Ilya L.; Douglas, Patricia; Feng, Shiqing; Bryukhovetskiy, Andrey S.; Chekhonin, Vladimir P.

    2015-01-01

    Background Traumatic spinal cord injury (SCI) often results in the deficiency of glia and neurons in cystic cavities. These syringomyelic cysts can prevent axonal regeneration and sprouting. Details of the mechanism of syringomyelic cyst formation are unknown and an effective treatment for overcoming syringomyelic cysts is not available. Material/Methods Ten adult female Wistar rats underwent contusion SCI modeling resulting in syringomyelic cyst formation. A novel method for locating the cysts was developed and employed. MRI safe silver needles were inserted through the erector spinae of anesthetized rats to create a stable reference point. MRI images of the rodent spine were taken with the needles in situ. This information was used to accurately locate the cyst and determine the 3-dimensional entry point coordinates for nanoparticle delivery. Nanoparticles were injected into the cyst during a primary injection of 8 ul and a secondary injection of 8 ul, to prove the procedure can be accurately repeated. Results None of the rats died intra- or post-operatively. The syringomyelic cysts were accurately located with the 3-dimensional entry point coordinates. After nanoparticle delivery twice into each rat, the visualized syringomyelic cyst volume significantly decreased from 5.71±0.21 mm3 to 3.23±0.364 mm3 and to 1.48±0.722 mm3. Conclusions The present study describes a novel strategy for precise nanoparticle delivery into a syringomyelic cyst, using measurements obtained from MRI images. This strategy may aid in developing a new method for studying chronic spinal cord injury and a novel treatment for syringomyelic cysts. PMID:26486048

  10. Transdermal drug delivery

    PubMed Central

    Prausnitz, Mark R.; Langer, Robert

    2009-01-01

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

  11. Verification of helical tomotherapy delivery using autoassociative kernel regression

    SciTech Connect

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

    2007-08-15

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

  12. Spectroscopic analysis of aluminum chloride phthalocyanine in binary water/ethanol systems for the design of a new drug delivery system for photodynamic therapy cancer treatment

    NASA Astrophysics Data System (ADS)

    Jayme, Cristiano Ceron; Calori, Italo Rodrigo; Tedesco, Antonio Claudio

    2016-01-01

    This study evaluated the behavior of aluminum chloride phthalocyanine in a binary water/ethanol mixture using electronic absorption spectroscopy and static and time-resolved fluorescence spectroscopy. The electronic absorption spectra, resonance light scattering and fluorescence quenching of aluminum chloride phthalocyanine in water/ethanol mixtures were studied at several concentrations. The electronic absorption spectra and fluorescence quenching changed significantly at approximately 50% water (v/v). Below 50% water, the dimerization constant values were negative (- 2609.2 M- 1 and - 506.5 M- 1 at 30% and 40% of water, respectively), indicating that the formation of aggregates under these conditions is not favored. However, at 50% water, the dimerization constant value was estimated to be 559.7 M- 1, which indicates the presence of dimers. Above 60% water, the aggregation process was responsible for the balance between large complexes (such as trimers, tetramers or oligomers) formed in the medium under these conditions. The appearance of new absorption bands at 387 nm and 802 nm and their bathochromic shift relative to the monomer bands suggested that some J-type aggregates form. These results are relevant to understanding the behavior and use of aluminum chloride phthalocyanine in the design of new drug delivery systems for clinical application in photodynamic therapy as a new approach to treat skin cancer.

  13. Spectroscopic analysis of aluminum chloride phthalocyanine in binary water/ethanol systems for the design of a new drug delivery system for photodynamic therapy cancer treatment.

    PubMed

    Jayme, Cristiano Ceron; Calori, Italo Rodrigo; Tedesco, Antonio Claudio

    2016-01-15

    This study evaluated the behavior of aluminum chloride phthalocyanine in a binary water/ethanol mixture using electronic absorption spectroscopy and static and time-resolved fluorescence spectroscopy. The electronic absorption spectra, resonance light scattering and fluorescence quenching of aluminum chloride phthalocyanine in water/ethanol mixtures were studied at several concentrations. The electronic absorption spectra and fluorescence quenching changed significantly at approximately 50% water (v/v). Below 50% water, the dimerization constant values were negative (-2609.2M(-1) and -506.5M(-1) at 30% and 40% of water, respectively), indicating that the formation of aggregates under these conditions is not favored. However, at 50% water, the dimerization constant value was estimated to be 559.7M(-1), which indicates the presence of dimers. Above 60% water, the aggregation process was responsible for the balance between large complexes (such as trimers, tetramers or oligomers) formed in the medium under these conditions. The appearance of new absorption bands at 387nm and 802nm and their bathochromic shift relative to the monomer bands suggested that some J-type aggregates form. These results are relevant to understanding the behavior and use of aluminum chloride phthalocyanine in the design of new drug delivery systems for clinical application in photodynamic therapy as a new approach to treat skin cancer. PMID:26311478

  14. AVP-825 Breath-Powered Intranasal Delivery System Containing 22?mg Sumatriptan Powder vs 100?mg Oral Sumatriptan in the Acute Treatment of Migraines (The COMPASS Study): A Comparative Randomized Clinical Trial Across Multiple Attacks

    PubMed Central

    Tepper, Stewart J; Cady, Roger K; Silberstein, Stephen; Messina, John; Mahmoud, Ramy A; Djupesland, Per G; Shin, Paul; Siffert, Joao

    2015-01-01

    Objective The objective of this study was to compare the efficacy, tolerability, and safety of AVP-825, an investigational bi-directional breath-powered intranasal delivery system containing low-dose (22?mg) sumatriptan powder, vs 100?mg oral sumatriptan for acute treatment of migraine in a double-dummy, randomized comparative efficacy clinical trial allowing treatment across multiple migraine attacks. Background In phases 2 and 3, randomized, placebo-controlled trials, AVP-825 provided early and sustained relief of moderate or severe migraine headache in adults, with a low incidence of triptan-related adverse effects. Methods This was a randomized, active-comparator, double-dummy, cross-over, multi-attack study (COMPASS; NCT01667679) with two ?12-week double-blind periods. Subjects experiencing 2-8 migraines/month in the past year were randomized 1:1 using computer-generated sequences to AVP-825 plus oral placebo tablet or an identical placebo delivery system plus 100?mg oral sumatriptan tablet for the first period; patients switched treatment for the second period in this controlled comparative design. Subjects treated ?5 qualifying migraines per period within 1 hour of onset, even if pain was mild. The primary end-point was the mean value of the summed pain intensity differences through 30 minutes post-dose (SPID-30) using Headache Severity scores. Secondary outcomes included pain relief, pain freedom, pain reduction, consistency of response across multiple migraines, migraine-associated symptoms, and atypical sensations. Safety was also assessed. Results A total of 275 adults were randomized, 174 (63.3%) completed the study (ie, completed the second treatment period), and 185 (67.3%) treated at least one migraine in both periods (1531 migraines assessed). There was significantly greater reduction in migraine pain intensity with AVP-825 vs oral sumatriptan in the first 30 minutes post-dose (least squares mean SPID-30?=?10.80 vs 7.41, adjusted mean difference 3.39 [95% confidence interval 1.76, 5.01]; P?treatment compared with oral sumatriptan. At 2 hours, rates of pain relief and pain freedom became comparable; rates of sustained pain relief and sustained pain freedom from 2 to 48 hours remained comparable. Nasal discomfort and abnormal taste were more common with AVP-825 vs oral sumatriptan (16% vs 1% and 26% vs 4%, respectively), but ?90% were mild, leading to only one discontinuation. Atypical sensation rates were significantly lower with AVP-825 than with conventional higher dose 100?mg oral sumatriptan. Conclusions AVP-825 (containing 22?mg sumatriptan nasal powder) provided statistically significantly greater reduction of migraine pain intensity over the first 30 minutes following treatment, and greater rates of pain relief and pain freedom within 15 minutes, compared with 100?mg oral sumatriptan. Sustained pain relief and pain freedom through 24 and 48 hours was achieved in a similar percentage of attacks for both treatments, despite substantially lower total systemic drug exposure with AVP-825. Treatment was well tolerated, with statistically significantly fewer atypical sensations with AVP-825. PMID:25941016

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

    PubMed Central

    Glide-Hurst, Carri K.

    2014-01-01

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

  16. Kidney–targeted drug delivery systems

    PubMed Central

    Zhou, Peng; Sun, Xun; Zhang, Zhirong

    2014-01-01

    Kidney-targeted drug delivery systems represent a promising technology to improve drug efficacy and safety in the treatment of renal diseases. In this review, we summarize the strategies that have been employed to develop kidney-targeted drug delivery systems. We also describe how macromolecular carriers and prodrugs play crucial roles in targeting drugs to particular target cells in the kidney. New technologies render it possible to create renal targeting conjugates and other delivery systems including nanoparticles and liposomes present promising strategies to achieve the goal of targeting drugs to the kidney.

  17. Application of nanoparticles for oral delivery of acid-labile lansoprazole in the treatment of gastric ulcer: in vitro and in vivo evaluations

    PubMed Central

    Alai, Milind; Lin, Wen Jen

    2015-01-01

    The aim of this study was to develop nanoparticles for oral delivery of an acid-labile drug, lansoprazole (LPZ), for gastric ulcer therapy. LPZ-loaded positively charged Eudragit® RS100 nanoparticles (ERSNPs-LPZ) and negatively charged poly(lactic-co-glycolic acid) nanoparticles (PLGANPs-LPZ) were prepared. The effect of charge on nanoparticle deposition in ulcerated and non-ulcerated regions of the stomach was investigated. The cellular uptake of nanoparticles in the intestine was evaluated in a Caco-2 cell model. The pharmacokinetic performance and ulcer healing response of LPZ-loaded nanoparticles following oral administration were evaluated in Wistar rats with induced ulcers. The prepared drug-loaded ERSNPs-LPZ and PLGANPs-LPZ possessed opposite surface charge (+38.5±0.3 mV versus ?27.3±0.3 mV, respectively) and the particle size was around 200 nm with a narrow size distribution. The negatively charged PLGANPs adhered more readily to the ulcerated region (7.22%±1.21% per cm2), whereas the positively charged ERSNPs preferentially distributed in the non-ulcerated region (8.29%±0.35% per cm2). Both ERSNPs and PLGANPs were prominent uptake in Caco-2 cells, too. The nanoparticles sustained and prolonged LPZ concentrations up to 24 hours, and the half-life and mean residence time of LPZ were prolonged by 3.5-fold and 4.5-fold, respectively, as compared with LPZ solution. Oral administration of LPZ-loaded nanoparticles healed 92.6%–95.7% of gastric ulcers in Wistar rats within 7 days. PMID:26124659

  18. Nanoparticles as Smart Treatment-delivery Systems in Plants: Assessment of Different Techniques of Microscopy for their Visualization in Plant Tissues

    PubMed Central

    González-Melendi, P.; Fernández-Pacheco, R.; Coronado, M. J.; Corredor, E.; Testillano, P. S.; Risueño, M. C.; Marquina, C.; Ibarra, M. R.; Rubiales, D.; Pérez-de-Luque, A.

    2008-01-01

    Background and Aims The great potential of using nanodevices as delivery systems to specific targets in living organisms was first explored for medical uses. In plants, the same principles can be applied for a broad range of uses, in particular to tackle infections. Nanoparticles tagged to agrochemicals or other substances could reduce the damage to other plant tissues and the amount of chemicals released into the environment. To explore the benefits of applying nanotechnology to agriculture, the first stage is to work out the correct penetration and transport of the nanoparticles into plants. This research is aimed (a) to put forward a number of tools for the detection and analysis of core-shell magnetic nanoparticles introduced into plants and (b) to assess the use of such magnetic nanoparticles for their concentration in selected plant tissues by magnetic field gradients. Methods Cucurbita pepo plants were cultivated in vitro and treated with carbon-coated Fe nanoparticles. Different microscopy techniques were used for the detection and analysis of these magnetic nanoparticles, ranging from conventional light microscopy to confocal and electron microscopy. Key Results Penetration and translocation of magnetic nanoparticles in whole living plants and into plant cells were determined. The magnetic character allowed nanoparticles to be positioned in the desired plant tissue by applying a magnetic field gradient there; also the graphitic shell made good visualization possible using different microscopy techniques. Conclusions The results open a wide range of possibilities for using magnetic nanoparticles in general plant research and agronomy. The nanoparticles can be charged with different substances, introduced within the plants and, if necessary, concentrated into localized areas by using magnets. Also simple or more complex microscopical techniques can be used in localization studies. PMID:17998213

  19. Novel pH sensitive ferrogels as new approach in cancer treatment: Effect of the magnetic field on swelling and drug delivery.

    PubMed

    Muzzalupo, Rita; Tavano, Lorena; Rossi, Cesare Oliviero; Picci, Nevio; Ranieri, Giuseppe Antonio

    2015-10-01

    Ferrogels (or magnetic hydrogels) are cross-linked polymer networks containing magnetic nanoparticles: they are mechanically soft and highly elastic and at the same time they exhibit a strong magnetic response. Our work focuses on an combinatorial strategy to improve the efficacy of 5-Fluorouracil (5-FU) assisted chemotherapy, by developing novel multifunctional pH-sensitive ferrogels. We designed gels based on N,N'-dimethylacrylamide monomers polymerized in presence of methacrylic acid or 2-aminoethyl methacrylate hydrochloride, containing ferro-nanoparticles. The influence of polymeric matrix composition and exposition to magnetic field (MF) on swelling behavior and drugs release were investigated at pH 7.4 and 5. In particular, the magnetic field was obtained by using permanent magnetic bar (0.25T) or electromagnet (0.5 and 1.2T), with the aim to analyze quantitatively the magnetic effects. A strong influence of the magnetic field on ferrogels properties have been observed. Swelling analysis indicated a dependence on both pH and network composition, reaching a maximum at pH 7.4, for formulations containing methacrylic acid, while the application of MF appeared to decrease the swelling percentages. Release profiles of 5-FU showed effective modulation in release by application of MF: drug release is always higher in the presence of a magnetic field and generally increases with its intensity. The combining effect of pH sensitive properties and application of MF improved the performance of the systems. Results showed that our ferrogels may be technologically applicable as devices for delivery of 5-FU in a controllable manner. PMID:26209777

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

    PubMed

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

    2014-06-01

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

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

    PubMed Central

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

    2015-01-01

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

  2. Impact of intermittent preventive treatment in pregnancy with azithromycin-containing regimens on maternal nasopharyngeal carriage and antibiotic sensitivity of Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus: a cross-sectional survey at delivery.

    PubMed

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

    2015-04-01

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

  3. Comparison of Borate Bioactive Glass and Calcium Sulfate as Implants for the Local Delivery of Teicoplanin in the Treatment of Methicillin-Resistant Staphylococcus aureus-Induced Osteomyelitis in a Rabbit Model.

    PubMed

    Jia, Wei-Tao; Fu, Qiang; Huang, Wen-Hai; Zhang, Chang-Qing; Rahaman, Mohamed N

    2015-12-01

    There is growing interest in biomaterials that can cure bone infection and also regenerate bone. In this study, two groups of implants composed of 10% (wt/wt) teicoplanin (TEC)-loaded borate bioactive glass (designated TBG) or calcium sulfate (TCS) were created and evaluated for their ability to release TEC in vitro and to cure methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis in a rabbit model. When immersed in phosphate-buffered saline (PBS), both groups of implants provided a sustained release of TEC at a therapeutic level for up to 3 to 4 weeks while they were gradually degraded and converted to hydroxyapatite. The TBG implants showed a longer duration of TEC release and better retention of strength as a function of immersion time in PBS. Infected rabbit tibiae were treated by debridement, followed by implantation of TBG or TCS pellets or intravenous injection with TEC, or were left untreated. Evaluation at 6 weeks postimplantation showed that the animals implanted with TBG or TCS pellets had significantly lower radiological and histological scores, lower rates of MRSA-positive cultures, and lower bacterial loads than those preoperatively and those of animals treated intravenously. The level of bone regeneration was also higher in the defects treated with the TBG pellets. The results showed that local TEC delivery was more effective than intravenous administration for the treatment of MRSA-induced osteomyelitis. Borate glass has the advantages of better mechanical strength, more desirable kinetics of release of TEC, and a higher osteogenic capacity and thus could be an effective alternative to calcium sulfate for local delivery of TEC. PMID:26416858

  4. Healthcare Delivery Research Blog

    Cancer.gov

    Skip to main content at the National Institutes of Health | www.cancer.gov Search form Search Search Healthcare Delivery Research Blog Toggle navigation Healthcare Delivery Research Blog Home Blog Purpose and Policies About HDRP Contact Us Subscribe

  5. Gantries and dose delivery systems

    NASA Astrophysics Data System (ADS)

    Meer, David; Psoroulas, Serena

    2015-04-01

    Particle therapy is a field in remarkable development, with the goal of increasing the number of indications which could benefit from such treatments and the access to the therapy. The therapeutic usage of a particle beam defines the technical requirements of all the elements of the therapy chain: we summarize the main characteristics of accelerators, the beam line, the treatment room, the integrated therapy and imaging systems used in particle therapy. Aiming at a higher flexibility in the choice of treatments, an increasing number of centers around the world have chosen to equip their treatment rooms with gantries, rotating beam line structures that allow a complete flexibility in the choice of the treatment angle. We review the current designs. A particle therapy gantry though is a quite expensive structure, and future development will increasingly consider reducing the cost and the footprint. Increasing the number of indications also means development in the delivery techniques and solving some of the issues which traditionally affected particle therapy, for example the precision of the delivery in presence of motion and the large penumbras for low depths. We show the current strategies in these fields, focusing on pencil beam scanning (PBS), and give some hints about future developments.

  6. Strategy Guideline: Accurate Heating and

    E-print Network

    (HVAC) Mechanical Contractors · HVAC System Designers · Builders · House Remodelers. This guide can, as the first step of HVAC system design. Accurate load calculations have a direct impact on energy efficiency of the iterative HVAC design procedure, as a full HVAC design involves much more than just the load calculation

  7. SYSTEMS BIOLOGY Accurate information transmission

    E-print Network

    Tsimring, Lev S.

    SYSTEMS BIOLOGY Accurate information transmission through dynamic biochemical signaling networks) and variability in cellular states (extrinsic noise) degrade information transmitted through signaling networks-induced information loss. In the extracellular signal­regulated kinase (ERK), calcium (Ca2+ ), and nuclear factor

  8. Clinical and microbiological efficacy of 3% satranidazole gel as a local drug delivery system in the treatment of chronic periodontitis: A randomized, controlled clinical trial

    PubMed Central

    Priyanka, N; Kalra, Nitish; Saquib, Shahab; Kudyar, Nitin; Malgaonkar, Nikhil; Jain, Hunny; Pradeep, A. R.

    2015-01-01

    Aim: The present clinical trial was designed to investigate the effectiveness of subgingivally delivered satranidazole (SZ) gel as an adjunct to scaling and root planing (SRP) in the treatment of chronic periodontitis. Materials and Methods: Seventy subjects with probing depth (PD) ?5 mm were selected. Thirty-five subjects each were randomly assigned to SRP + placebo (Group 1) and SRP + SZ (Group 2). The clinical outcomes evaluated were plaque index, gingival index, clinical attachment level (CAL), and PD at baseline; 1 month, 3 months, and 6 months interval. Furthermore, microbial analysis using polymerase chain reaction was done to estimate the number of sites harboring periodontopathogens. Results: Sixty four subjects were evaluated up to 6 months. At 6 months, the Group 2 resulted in greater mean reduction (4.10 mm) in PD as compared to Group 1 (1.49 mm), and also a greater mean CAL gain (4.20 mm) in Group 2 as compared to Group 1 (1.13 mm). These subjects also showed a significant reduction in the number of sites harboring periodontopathogens. Conclusion: The use of 3% SZ gel, when used as an adjunct to nonsurgical periodontal therapy in subjects with periodontitis, achieved better results than initial periodontal treatment alone. PMID:26321836

  9. A global health delivery framework approach to epilepsy care in resource-limited settings.

    PubMed

    Cochran, Maggie F; Berkowitz, Aaron L

    2015-11-15

    The Global Health Delivery (GHD) framework (Farmer, Kim, and Porter, Lancet 2013;382:1060-69) allows for the analysis of health care delivery systems along four axes: a care delivery value chain that incorporates prevention, diagnosis, and treatment of a medical condition; shared delivery infrastructure that integrates care within existing healthcare delivery systems; alignment of care delivery with local context; and generation of economic growth and social development through the health care delivery system. Here, we apply the GHD framework to epilepsy care in rural regions of low- and middle-income countries (LMIC) where there are few or no neurologists. PMID:26371698

  10. Novel delivery approaches for cancer therapeutics.

    PubMed

    Mitra, Ashim K; Agrahari, Vibhuti; Mandal, Abhirup; Cholkar, Kishore; Natarajan, Chandramouli; Shah, Sujay; Joseph, Mary; Trinh, Hoang M; Vaishya, Ravi; Yang, Xiaoyan; Hao, Yi; Khurana, Varun; Pal, Dhananjay

    2015-12-10

    Currently, a majority of cancer treatment strategies are based on the removal of tumor mass mainly by surgery. Chemical and physical treatments such as chemo- and radiotherapies have also made a major contribution in inhibiting rapid growth of malignant cells. Furthermore, these approaches are often combined to enhance therapeutic indices. It is widely known that surgery, chemo- and radiotherapy also inhibit normal cells growth. In addition, these treatment modalities are associated with severe side effects and high toxicity which in turn lead to low quality of life. This review encompasses novel strategies for more effective chemotherapeutic delivery aiming to generate better prognosis. Currently, cancer treatment is a highly dynamic field and significant advances are being made in the development of novel cancer treatment strategies. In contrast to conventional cancer therapeutics, novel approaches such as ligand or receptor based targeting, triggered release, intracellular drug targeting, gene delivery, cancer stem cell therapy, magnetic drug targeting and ultrasound-mediated drug delivery, have added new modalities for cancer treatment. These approaches have led to selective detection of malignant cells leading to their eradication with minimal side effects. Lowering multi-drug resistance and involving influx transportation in targeted drug delivery to cancer cells can also contribute significantly in the therapeutic interventions in cancer. PMID:26456750

  11. Evaluation of the Melody transcatheter pulmonary valve and Ensemble delivery system for the treatment of dysfunctional right ventricle to pulmonary artery conduits.

    PubMed

    Asnes, Jeremy; Hellenbrand, William E

    2015-11-01

    Synthetic conduits and bioprosthetic valves are used in the treatment of patients with congenital heart disease involving the right ventricular outflow tract and pulmonary valve. In-situ time-dependent degradation uniformly results in conduit and valve dysfunction. The abnormal hemodynamics imposed by valve and conduit dysfunction have been linked to exercise intolerance, arrhythmia, right heart failure, and sudden death. Starting in childhood, affected patients are subjected to repeated open-heart surgeries to restore valve function and potentially reduce morbidity and mortality. Percutaneous transcatheter pulmonary valve replacement with the Melody(®) Transcatheter Pulmonary Valve (Medtronic, Inc., Minneapolis, MN) has been performed in ?8000 patients worldwide. The valve and implant procedure provide a far less invasive means of restoring valve and conduit function and allow patients to forego multiple operations. Recent clinical trials have shown excellent and durable results in terms of valve function, relief of obstruction, and improvement in functional class up to 7 years from implant. PMID:26513599

  12. Low-dose RUTF protocol and improved service delivery lead to good programme outcomes in the treatment of uncomplicated SAM: a programme report from Myanmar.

    PubMed

    James, Philip T; Van den Briel, Natalie; Rozet, Aurélie; Israël, Anne-Dominique; Fenn, Bridget; Navarro-Colorado, Carlos

    2015-10-01

    The treatment of uncomplicated severe acute malnutrition (SAM) requires substantial amounts of ready-to-use therapeutic food (RUTF). In 2009, Action Contre la Faim anticipated a shortfall of RUTF for their nutrition programme in Myanmar. A low-dose RUTF protocol to treat children with uncomplicated SAM was adopted. In this protocol, RUTF was dosed according to beneficiary's body weight, until the child reached a Weight-for-Height z-score of ?-3 and mid-upper arm circumference ?110?mm. From this point, the child received a fixed quantity of RUTF per day, independent of body weight until discharge. Specific measures were implemented as part of this low-dose RUTF protocol in order to improve service quality and beneficiary support. We analysed individual records of 3083 children treated from July 2009 to January 2010. Up to 90.2% of children recovered, 2.0% defaulted and 0.9% were classified as non-responders. No deaths were recorded. Among children who recovered, median [IQR] length of stay and weight gain were 42 days [28; 56] and 4.0?g?kg(-1) day(-1) [3.0; 5.7], respectively. Multivariable logistic regression showed that children older than 48 months had higher odds of non-response to treatment than younger children (adjusted odds ratio: 3.51, 95% CI: 1.67-7.42). Our results indicate that a low-dose RUTF protocol, combined with specific measures to ensure good service quality and beneficiary support, was successful in treating uncomplicated SAM in this setting. This programmatic experience should be validated by randomised studies aiming to test, quantify and attribute the effect of the protocol adaptation and programme improvements presented here. PMID:25850698

  13. Increasing the Efficiency of Parkinson's Disease Treatment Using a poly(lactic-co-glycolic acid) (PLGA) Based L-DOPA Delivery System

    PubMed Central

    Kondrasheva, I.G.; Severin, E.S.; Guseva, A.A.; Kamensky, A.A.

    2014-01-01

    To compare the efficacy of L-DOPA administered intranasally in the form of nanoparticles (nano-DOPA) and in standard drug forms using a rat Parkinson's Disease (PD) model. L-DOPA-containing nanoparticles (250±50 nm) were synthesized using the double emulsion method. The efficacy of nano-DOPA therapy was studied in Wistar rats with 6-OHDA-induced PD. Drugs were administered daily, 0.35 mg/kg (by L-DOPA). Animals' motor coordination and behavior were analyzed using the forelimb placing task and several other tests. Thirty minutes after the first administration, animals treated with L-DOPA, L-DOPA+benserazide, and nano-DOPA showed equally significant (p<0.05) improvements in coordination performance in comparison to the non-treated group. After 4 weeks of treatment, coordination performance in the nano-DOPA group (89±13% of the intact control level) was twice as high as in the L-DOPA and L-DOPA+benserazide groups, which did not differ from non-treated animals. The effect of nano-DOPA was significantly higher and more long-lasting (90±13% at 24 h after administration); moreover, it was still significant one week after the treatment was discontinued. Intranasal nano-DOPA was found to provide a lasting motor function recovery in the 6-OHDA-induced rat PD model with the effect sustained for one week after discontinuation, while the same doses of standard drugs provided significant effect only after the first administration. L-DOPA administered in the form of PLGA-based nanoparticles had a higher effective half-life, bioavailability, and efficacy; it was also efficiently delivered to the brain by intranasal administration. PMID:25258572

  14. Non-invasive, photonics-based diagnostic, imaging, monitoring, and light delivery techniques for the recognition, quantification and treatment of malignant and chronic inflammatory conditions

    NASA Astrophysics Data System (ADS)

    Davies, N.; Davies-Shaw, D.; Shaw, J. D.

    2007-02-01

    We report firsthand on innovative developments in non-invasive, biophotonic techniques for a wide range of diagnostic, imaging and treatment options, including the recognition and quantification of cancerous, pre-cancerous cells and chronic inflammatory conditions. These techniques have benefited from the ability to target the affected site by both monochromatic light and broad multiple wavelength spectra. The employment of such wavelength or color-specific properties embraces the fluorescence stimulation of various photosensitizing drugs, and the instigation and detection of identified fluorescence signatures attendant upon laser induced fluorescence (LIF) phenomena as transmitted and propagated by precancerous, cancerous and normal tissue. In terms of tumor imaging and therapeutic and treatment options, we have exploited the abilities of various wavelengths to penetrate to different depths, through different types of tissues, and have explored quantifiable absorption and reflection characteristics upon which diagnostic assumptions can be reliably based and formulated. These biophotonic-based diagnostic, sensing and imaging techniques have also benefited from, and have been further enhanced by, the integrated ability to provide various power levels to be employed at various stages in the procedure. Applications are myriad, including non-invasive, non destructive diagnosis of in vivo cell characteristics and functions; light-based tissue analysis; real-time monitoring and mapping of brain function and of tumor growth; real time monitoring of the surgical completeness of tumor removal during laser-imaged/guided brain resection; diagnostic procedures based on fluorescence life-time monitoring, the monitoring of chronic inflammatory conditions (including rheumatoid arthritis), and continuous blood glucose monitoring in the control of diabetes.

  15. Low–dose RUTF protocol and improved service delivery lead to good programme outcomes in the treatment of uncomplicated SAM: a programme report from Myanmar

    PubMed Central

    James, Philip T; Van den Briel, Natalie; Rozet, Aurélie; Israël, Anne-Dominique; Fenn, Bridget; Navarro-Colorado, Carlos

    2015-01-01

    The treatment of uncomplicated severe acute malnutrition (SAM) requires substantial amounts of ready-to-use therapeutic food (RUTF). In 2009, Action Contre la Faim anticipated a shortfall of RUTF for their nutrition programme in Myanmar. A low-dose RUTF protocol to treat children with uncomplicated SAM was adopted. In this protocol, RUTF was dosed according to beneficiary's body weight, until the child reached a Weight-for-Height z-score of ??3 and mid-upper arm circumference ?110?mm. From this point, the child received a fixed quantity of RUTF per day, independent of body weight until discharge. Specific measures were implemented as part of this low-dose RUTF protocol in order to improve service quality and beneficiary support. We analysed individual records of 3083 children treated from July 2009 to January 2010. Up to 90.2% of children recovered, 2.0% defaulted and 0.9% were classified as non-responders. No deaths were recorded. Among children who recovered, median [IQR] length of stay and weight gain were 42 days [28; 56] and 4.0?g?kg–1 day–1 [3.0; 5.7], respectively. Multivariable logistic regression showed that children older than 48 months had higher odds of non-response to treatment than younger children (adjusted odds ratio: 3.51, 95% CI: 1.67–7.42). Our results indicate that a low-dose RUTF protocol, combined with specific measures to ensure good service quality and beneficiary support, was successful in treating uncomplicated SAM in this setting. This programmatic experience should be validated by randomised studies aiming to test, quantify and attribute the effect of the protocol adaptation and programme improvements presented here. PMID:25850698

  16. Intravenous drug delivery in neonates: lessons learnt.

    PubMed

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

    2014-06-01

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

  17. Ultrasound-mediated gastrointestinal drug delivery.

    PubMed

    Schoellhammer, Carl M; Schroeder, Avi; Maa, Ruby; Lauwers, Gregory Yves; Swiston, Albert; Zervas, Michael; Barman, Ross; DiCiccio, Angela M; Brugge, William R; Anderson, Daniel G; Blankschtein, Daniel; Langer, Robert; Traverso, Giovanni

    2015-10-21

    There is a significant clinical need for rapid and efficient delivery of drugs directly to the site of diseased tissues for the treatment of gastrointestinal (GI) pathologies, in particular, Crohn's and ulcerative colitis. However, complex therapeutic molecules cannot easily be delivered through the GI tract because of physiologic and structural barriers. We report the use of ultrasound as a modality for enhanced drug delivery to the GI tract, with an emphasis on rectal delivery. Ultrasound increased the absorption of model therapeutics inulin, hydrocortisone, and mesalamine two- to tenfold in ex vivo tissue, depending on location in the GI tract. In pigs, ultrasound induced transient cavitation with negligible heating, leading to an order of magnitude enhancement in the delivery of mesalamine, as well as successful systemic delivery of a macromolecule, insulin, with the expected hypoglycemic response. In a rodent model of chemically induced acute colitis, the addition of ultrasound to a daily mesalamine enema (compared to enema alone) resulted in superior clinical and histological scores of disease activity. In both animal models, ultrasound treatment was well tolerated and resulted in minimal tissue disruption, and in mice, there was no significant effect on histology, fecal score, or tissue inflammatory cytokine levels. The use of ultrasound to enhance GI drug delivery is safe in animals and could augment the efficacy of GI therapies and broaden the scope of agents that could be delivered locally and systemically through the GI tract for chronic conditions such as inflammatory bowel disease. PMID:26491078

  18. Ungual and transungual drug delivery.

    PubMed

    Shivakumar, H N; Juluri, Abhishek; Desai, B G; Murthy, S Narasimha

    2012-08-01

    Topical therapy is desirable in treatment of nail diseases like onychomycosis (fungal infection of nail) and psoriasis. The topical treatment avoids the adverse effects associated with systemic therapy, thereby enhancing the patient compliance and reducing the treatment cost. However the effectiveness of the topical therapies has been limited due to the poor permeability of the nail plate to topically applied therapeutic agents. Research over the past one decade has been focused on improving the transungual permeability by means of chemical treatment, penetration enhancers, mechanical and physical methods. The present review is an attempt to discuss the different physical and chemical methods employed to increase the permeability of the nail plate. Minimally invasive electrically mediated techniques such as iontophoresis have gained success in facilitating the transungual delivery of actives. In addition drug transport across the nail plate has been improved by filing the dorsal surface of the nail plate prior to application of topical formulation. But attempts to improve the trans-nail permeation using transdermal chemical enhancers have failed so far. Attempts are on to search suitable physical enhancement techniques and chemical transungual enhancers in view to maximize the drug delivery across the nail plate. PMID:22149347

  19. Image-guided drug delivery: preclinical applications and clinical translation.

    PubMed

    Ojha, Tarun; Rizzo, Larissa; Storm, Gert; Kiessling, Fabian; Lammers, Twan

    2015-08-01

    Image-guided drug delivery refers to the combination of drug targeting and imaging. Preclinically, image-guided drug delivery can be used for several different purposes, including for monitoring biodistribution, target site accumulation, off-target localization, drug release and drug efficacy. Clinically, it holds significant potential for preselecting patients. In this editorial, we briefly summarize the main principles of image-guided drug delivery, and we describe its potential for facilitating, furthering and personalizing nanomedicine treatments. PMID:26083469

  20. Image-guided Drug Delivery : Preclinical Applications and Clinical Translation

    PubMed Central

    2015-01-01

    Image-guided drug delivery refers to the combination of drug targeting and imaging. Preclinically, image-guided drug delivery can be used for several different purposes, e.g. for monitoring biodistribution, target site accumulation, off-target localization, drug release and drug efficacy. Clinically, it holds significant potential for preselecting patients. In this perspective, we briefly summarize the main principles of image-guided drug delivery, and we describe its potential for facilitating, furthering and personalizing nanomedicine treatments. PMID:26083469

  1. Prophylaxis and treatment of Alzheimer's disease by delivery of an adeno-associated virus encoding a monoclonal antibody targeting the amyloid Beta protein.

    PubMed

    Shimada, Masaru; Abe, Shinya; Takahashi, Toru; Shiozaki, Kazumasa; Okuda, Mitsue; Mizukami, Hiroaki; Klinman, Dennis M; Ozawa, Keiya; Okuda, Kenji

    2013-01-01

    We previously reported on a monoclonal antibody (mAb) that targeted amyloid beta (Aß) protein. Repeated injection of that mAb reduced the accumulation of Aß protein in the brain of human Aß transgenic mice (Tg2576). In the present study, cDNA encoding the heavy and light chains of this mAb were subcloned into an adeno-associated virus type 1 (AAV) vector with a 2A/furin adapter. A single intramuscular injection of 3.0×10(10) viral genome of these AAV vectors into C57BL/6 mice generated serum anti-Aß Ab levels up to 0.3 mg/ml. Anti-Aß Ab levels in excess of 0.1 mg/ml were maintained for up to 64 weeks. The effect of AAV administration on Aß levels in vivo was examined. A significant decrease in Aß levels in the brain of Tg2576 mice treated at 5 months (prophylactic) or 10 months (therapeutic) of age was observed. These results support the use of AAV vector encoding anti-Aß Ab for the prevention and treatment of Alzheimer's disease. PMID:23555563

  2. Drug Delivery Strategies of Chemical CDK Inhibitors.

    PubMed

    Alvira, Daniel; Mondragón, Laura

    2016-01-01

    The pharmacological use of new therapeutics is often limited by a safe and effective drug-delivery system. In this sense, new chemical CDK inhibitors are not an exception. Nanotechnology may be able to solve some of the main problems limiting cancer treatments such as more specific delivery of therapeutics and reduction of toxic secondary effects. It provides new delivery systems able to specifically target cancer cells and release the active molecules in a controlled fashion. Specifically, silica mesoporous supports (SMPS) have emerged as an alternative for more classical drug delivery systems based on polymers. In this chapter, we describe the synthesis of a SMPS containing the CDK inhibitor roscovitine as cargo molecule and the protocols for confirmation of the proper cargo release of the nanoparticles in cell culture employing cell viability, cellular internalization, and cell death induction studies. PMID:26231714

  3. Brain tumor-targeted drug delivery strategies

    PubMed Central

    Wei, Xiaoli; Chen, Xishan; Ying, Man; Lu, Weiyue

    2014-01-01

    Despite the application of aggressive surgery, radiotherapy and chemotherapy in clinics, brain tumors are still a difficult health challenge due to their fast development and poor prognosis. Brain tumor-targeted drug delivery systems, which increase drug accumulation in the tumor region and reduce toxicity in normal brain and peripheral tissue, are a promising new approach to brain tumor treatments. Since brain tumors exhibit many distinctive characteristics relative to tumors growing in peripheral tissues, potential targets based on continuously changing vascular characteristics and the microenvironment can be utilized to facilitate effective brain tumor-targeted drug delivery. In this review, we briefly describe the physiological characteristics of brain tumors, including blood–brain/brain tumor barriers, the tumor microenvironment, and tumor stem cells. We also review targeted delivery strategies and introduce a systematic targeted drug delivery strategy to overcome the challenges.

  4. Local delivery of nitric oxide: targeted delivery of therapeutics to bone and connective tissues

    PubMed Central

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

    2012-01-01

    Non-invasive treatment of injuries and disorders affecting bones and connective tissue is a significant challenge facing the medical community. A treatment route that has recently been proposed is nitric oxide (NO) therapy. Nitric oxide plays several roles in physiology with many conditions lacking adequate levels of NO. As NO is a radical, localized delivery via NO donors is essential to promoting biological activity. Herein, we review current literature related to therapeutic NO delivery in the treatment of bone, skin and tendon repair. PMID:22433782

  5. Delivery system for molten salt oxidation of solid waste

    DOEpatents

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

    2002-01-01

    The present invention is a delivery system for safety injecting solid waste particles, including mixed wastes, into a molten salt bath for destruction by the process of molten salt oxidation. The delivery system includes a feeder system and an injector that allow the solid waste stream to be accurately metered, evenly dispersed in the oxidant gas, and maintained at a temperature below incineration temperature while entering the molten salt reactor.

  6. Total Body Irradiation, Toward Optimal Individual Delivery: Dose Evaluation With Metal Oxide Field Effect Transistors, Thermoluminescence Detectors, and a Treatment Planning System

    SciTech Connect

    Bloemen-van Gurp, Esther J. Mijnheer, Ben J.; Verschueren, Tom A.M.; Lambin, Philippe

    2007-11-15

    Purpose: To predict the three-dimensional dose distribution of our total body irradiation technique, using a commercial treatment planning system (TPS). In vivo dosimetry, using metal oxide field effect transistors (MOSFETs) and thermoluminescence detectors (TLDs), was used to verify the calculated dose distributions. Methods and Materials: A total body computed tomography scan was performed and loaded into our TPS, and a three-dimensional-dose distribution was generated. In vivo dosimetry was performed at five locations on the patient. Entrance and exit dose values were converted to midline doses using conversion factors, previously determined with phantom measurements. The TPS-predicted dose values were compared with the MOSFET and TLD in vivo dose values. Results: The MOSFET and TLD dose values agreed within 3.0% and the MOSFET and TPS data within 0.5%. The convolution algorithm of the TPS, which is routinely applied in the clinic, overestimated the dose in the lung region. Using a superposition algorithm reduced the calculated lung dose by approximately 3%. The dose inhomogeneity, as predicted by the TPS, can be reduced using a simple intensity-modulated radiotherapy technique. Conclusions: The use of a TPS to calculate the dose distributions in individual patients during total body irradiation is strongly recommended. Using a TPS gives good insight of the over- and underdosage in a patient and the influence of patient positioning on dose homogeneity. MOSFETs are suitable for in vivo dosimetry purposes during total body irradiation, when using appropriate conversion factors. The MOSFET, TLD, and TPS results agreed within acceptable margins.

  7. Accurate shear measurement with faint sources

    NASA Astrophysics Data System (ADS)

    Zhang, Jun; Luo, Wentao; Foucaud, Sebastien

    2015-01-01

    For cosmic shear to become an accurate cosmological probe, systematic errors in the shear measurement method must be unambiguously identified and corrected for. Previous work of this series has demonstrated that cosmic shears can be measured accurately in Fourier space in the presence of background noise and finite pixel size, without assumptions on the morphologies of galaxy and PSF. The remaining major source of error is source Poisson noise, due to the finiteness of source photon number. This problem is particularly important for faint galaxies in space-based weak lensing measurements, and for ground-based images of short exposure times. In this work, we propose a simple and rigorous way of removing the shear bias from the source Poisson noise. Our noise treatment can be generalized for images made of multiple exposures through MultiDrizzle. This is demonstrated with the SDSS and COSMOS/ACS data. With a large ensemble of mock galaxy images of unrestricted morphologies, we show that our shear measurement method can achieve sub-percent level accuracy even for images of signal-to-noise ratio less than 5 in general, making it the most promising technique for cosmic shear measurement in the ongoing and upcoming large scale galaxy surveys.

  8. Psychosocial, behavioural and health system barriers to delivery and uptake of intermittent preventive treatment of malaria in pregnancy in Tanzania – viewpoints of service providers in Mkuranga and Mufindi districts

    PubMed Central

    2014-01-01

    Background Intermittent preventive treatment of malaria in pregnancy (IPTp) using sulphurdoxine-pyrimethamine (SP) is one of key malaria control strategies in Africa. Yet, IPTp coverage rates across Africa are still low due to several demand and supply constraints. Many countries implement the IPTp-SP strategy at antenatal care (ANC) clinics. This paper reports from a study on the knowledge and experience of health workers (HWs) at ANC clinics regarding psychosocial, behavioural and health system barriers to IPTp-SP delivery and uptake in Tanzania. Methods Data were collected through questionnaire-based interviews with 78 HWs at 28 ANC clinics supplemented with informal discussions with current and recent ANC users in Mkuranga and Mufindi districts. Qualitative data were analysed using a qualitative content analysis approach. Quantitative data derived from interviews with HWs were analysed using non-parametric statistical analysis. Results The majority of interviewed HWs were aware of the IPTp-SP strategy’s existence and of the recommended one month spacing of administration of SP doses. Some HWs were unsure of that it is not recommended to administer IPTp-SP and ferrous/folic acid concurrently. Others were administering three doses of SP per client following instruction from a non-governmental agency while believing that this was in conflict with national guidelines. About half of HWs did not find it appropriate for the government to recommend private ANC providers to provide IPTp-SP free of charge since doing so forces private providers to recover the costs elsewhere. HWs noted that pregnant women often register at clinics late and some do not comply with the regularity of appointments for revisits, hence miss IPTp and other ANC services. HWs also noted some amplified rumours among clients regarding health risks and treatment failures of SP used during pregnancy, and together with clients’ disappointment with waiting times and the sharing of cups at ANC clinics for SP, limit the uptake of IPTp-doses. Conclusion HWs still question SP’s treatment advantages and are confused about policy ambiguity on the recommended number of IPTp-SP doses and other IPTp-SP related guidelines. IPTp-SP uptake is further constrained by pregnant women’s perceived health risks of taking SP and of poor service quality. PMID:24410770

  9. Bioavailability of phytochemicals and its enhancement by drug delivery systems

    PubMed Central

    Aqil, Farrukh; Munagala, Radha; Jeyabalan, Jeyaprakash; Vadhanam, Manicka V.

    2013-01-01

    Issues of poor oral bioavailability of cancer chemopreventives have hindered progress in cancer prevention. Novel delivery systems that modulate the pharmacokinetics of existing drugs, such as nanoparticles, cyclodextrins, niosomes, liposomes and implants, could be used to enhance the delivery of chemopreventive agents to target sites. The development of new approaches in prevention and treatment of cancer could encompass new delivery systems for approved and newly investigated compounds. In this review, we discuss some of the delivery approaches that have already made an impact by either delivering a drug to target tissue or increasing its bioavailability by many fold. PMID:23435377

  10. Therapeutic potential of CERE-110 (AAV2-NGF): Targeted, stable, and sustained NGF delivery and trophic activity on rodent basal forebrain cholinergic neurons

    PubMed Central

    Bishop, Kathie M.; Hofer, Eva K.; Mehta, Arpesh; Ramirez, Anthony; Sun, Liangwu; Tuszynski, Mark; Bartus, Raymond T.

    2009-01-01

    Treatment of degenerating basal forebrain cholinergic neurons with nerve growth factor (NGF) in Alzheimer’s disease has long been contemplated, but an effective and safe delivery method has been lacking. Towards achieving this goal, we are currently developing CERE-110, an adeno-associated virus-based gene delivery vector that encodes for human NGF, for stereotactic surgical delivery to the human nucleus basalis of Meynert. Results indicate that NGF transgene delivery to the targeted brain region via CERE-110 is reliable and accurate, that NGF transgene distribution can be controlled by altering CERE-110 dose, and that it is possible to achieve restricted NGF expression limited to but covering the target brain region. Results from animals examined at longer time periods of 3, 6, 9 and 12 months after CERE-110 delivery indicate that NGF transgene expression is stable and sustained at all time points, with no loss or build-up of protein over the long-term. In addition, results from a series of experiments indicate that CERE-110 is neuroprotective and neurorestorative to basal forebrain cholinergic neurons in the rat fimbria-fornix lesion and aged rat models, and has bioactive effects on young rat basal forebrain cholinergic neurons. These findings, as well as those from several additional non-clinical experiments conducted in both rats and monkeys, led to the initiation of a Phase I clinical study to evaluate the safety and efficacy of CERE-110 in Alzheimer’s disease subjects, which is currently ongoing. PMID:18439998

  11. Ultrasound mediated nanoparticle drug delivery

    NASA Astrophysics Data System (ADS)

    Mullin, Lee B.

    Ultrasound is not only a powerful diagnostic tool, but also a promising therapeutic technology that can be used to improve localized drug delivery. Microbubble contrast agents are micron sized encapsulated gas filled bubbles that are administered intravenously. Originally developed to enhance ultrasound images, microbubbles are highly echogenic due to the gas core that provides a detectable impedance difference from the surrounding medium. The core also allows for controlled response of the microbubbles to ultrasound pulses. Microbubbles can be pushed using acoustic radiation force and ruptured using high pressures. Destruction of microbubbles can increase permeability at the cellular and vascular level, which can be advantageous for drug delivery. Advances in drug delivery methods have been seen with the introduction of nanoparticles, nanometer sized objects often carrying a drug payload. In chemotherapy, nanoparticles can deliver drugs to tumors while limiting systemic exposure due to abnormalities in tumor vasculature such large gaps between endothelial cells that allow nanoparticles to enter into the interstitial space; this is referred to as the enhanced permeability and retention (EPR) effect. However, this effect may be overestimated in many tumors. Additionally, only a small percentage of the injected dose accumulates in the tumor, which most the nanoparticles accumulating in the liver and spleen. It is hypothesized that combining the acoustic activity of an ultrasound contrast agent with the high payload and extravasation ability of a nanoparticle, localized delivery to the tumor with reduced systemic toxicity can be achieved. This method can be accomplished by either loading nanoparticles onto the shell of the microbubble or through a coadministration method of both nanoparticles and microbubbles. The work presented in this dissertation utilizes novel and commercial nanoparticle formulations, combined with microbubbles and a variety of ultrasound systems. Ultrasound parameters are optimized to achieve maximum cell internalization of molecules and increased nanoparticle delivery to a cell layer on a coverslip. In-vivo studies demonstrate the possibility of using a lower dose of paclitaxel to slow tumor growth rates, increase doxorubicin concentration in tumor tissue, and enhance tumor delivery of fluorescent molecules through treatments that combine nanoparticles with ultrasound and microbubbles.

  12. Delivery quality assurance with ArcCHECK

    SciTech Connect

    Neilson, Christopher; Klein, Michael; Barnett, Rob; Yartsev, Slav

    2013-04-01

    Radiation therapy requires delivery quality assurance (DQA) to ensure that treatment is accurate and closely follows the plan. We report our experience with the ArcCHECK phantom and investigate its potential optimization for the DQA process. One-hundred seventy DQA plans from 84 patients were studied. Plans were classified into 2 groups: those with the target situated on the diodes of the ArcCHECK (D plans) and those with the target situated at the center (C plans). Gamma pass rates for 8 target sites were examined. The parameters used to analyze the data included 3%/3 mm with the Van Dyk percent difference criteria (VD) on, 3%/3 mm with the VD off, 2%/2 mm with the VD on, and x/3 mm with the VD on and the percentage dosimetric agreement “x” for diode plans adjusted. D plans typically displayed maximum planned dose (MPD) on the cylindrical surface containing ArcCHECK diodes than center plans, resulting in inflated gamma pass rates. When this was taken into account by adjusting the percentage dosimetric agreement, C plans outperformed D plans by an average of 3.5%. ArcCHECK can streamline the DQA process, consuming less time and resources than radiographic films. It is unnecessary to generate 2 DQA plans for each patient; a single center plan will suffice. Six of 8 target sites consistently displayed pass rates well within our acceptance criteria; the lesser performance of head and neck and spinal sites can be attributed to marginally lower doses and increased high gradient of plans.

  13. Coaxial electrohydrodynamic atomization: microparticles for drug delivery applications.

    PubMed

    Davoodi, Pooya; Feng, Fang; Xu, Qingxing; Yan, Wei-Cheng; Tong, Yen Wah; Srinivasan, M P; Sharma, Vijay Kumar; Wang, Chi-Hwa

    2015-05-10

    As cancer takes its toll on human health and well-being, standard treatment techniques such as chemotherapy and radiotherapy often fall short of ideal solutions. In particular, adverse side effects due to excess dosage and collateral damage to healthy cells as well as poor patient compliance due to multiple administrations continue to pose challenges in cancer treatment. Thus, the development of appropriately engineered drug delivery systems (DDS) for effective, controlled and sustained delivery of drugs is of interest for patient treatment. Moreover, the physiopathological characteristics of tumors play an essential role in the success of cancer treatment. Here, we present an overview of the application of double-walled microparticles for local drug delivery with particular focus on the electrohydrodynamic atomization (EHDA) technique and its fabrication challenges. The review highlights the importance of a combination of experimental data and computational simulations for the design of an optimal delivery system. PMID:25483422

  14. Nanoparticle-based drug delivery to the vagina: a review

    PubMed Central

    Ensign, Laura M.; Cone, Richard; Hanes, Justin

    2014-01-01

    Vaginal drug administration can improve prophylaxis and treatment of many conditions affecting the female reproductive tract, including sexually transmitted diseases, fungal and bacterial infections, and cancer. However, achieving sustained local drug concentrations in the vagina can be challenging, due to the high permeability of the vaginal epithelium and expulsion of conventional soluble drug dosage forms. Nanoparticle-based drug delivery platforms have received considerable attention for vaginal drug delivery, as nanoparticles can provide sustained release, cellular targeting, and even intrinsic antimicrobial or adjuvant properties that can improve the potency and/or efficacy of prophylactic and therapeutic modalities. Here, we review the use of polymeric nanoparticles, liposomes, dendrimers, and inorganic nanoparticles for vaginal drug delivery. Although most of the work toward nanoparticle-based drug delivery in the vagina has been focused on HIV prevention, strategies for treatment and prevention of other sexually transmitted infections, treatment for reproductive tract cancer, and treatment of fungal and bacterial infections are also highlighted. PMID:24830303

  15. A fully implantable intracochlear drug delivery device : development and characterization

    E-print Network

    Swan, Erin Eileen Leary, 1976-

    2009-01-01

    In a collaborative effort with the Massachusetts Eye and Ear Infirmary, Draper Laboratory is developing an implantable microfluidic drug delivery system for long-term treatment of inner ear disorders and prevention of ...

  16. Novel drug delivery systems for glaucoma

    PubMed Central

    Lavik, E; Kuehn, M H; Kwon, Y H

    2011-01-01

    Reduction of intraocular pressure (IOP) by pharmaceutical or surgical means has long been the standard treatment for glaucoma. A number of excellent drugs are available that are effective in reducing IOP. These drugs are typically applied as eye drops. However, patient adherence can be poor, thus reducing the clinical efficacy of the drugs. Several novel delivery systems designed to address the issue of adherence and to ensure consistent reduction of IOP are currently under development. These delivery systems include contact lenses-releasing glaucoma medications, injectables such as biodegradable micro- and nanoparticles, and surgically implanted systems. These new technologies are aimed at increasing clinical efficacy by offering multiple delivery options and are capable of managing IOP for several months. There is also a desire to have complementary neuroprotective approaches for those who continue to show progression, despite IOP reduction. Many potential neuroprotective agents are not suitable for traditional oral or drop formulations. Their potential is dependent on developing suitable delivery systems that can provide the drugs in a sustained, local manner to the retina and optic nerve. Drug delivery systems have the potential to improve patient adherence, reduce side effects, increase efficacy, and ultimately, preserve sight for glaucoma patients. In this review, we discuss benefits and limitations of the current systems of delivery and application, as well as those on the horizon. PMID:21475311

  17. Novel Aerosol Delivery Devices.

    PubMed

    Singh, Supriya; Kanbar-Agha, Faisal; Sharafkhaneh, Amir

    2015-08-01

    Delivery of medication to sites of action through airways has been used for centuries but has gained momentum in recent decades. Currently available modes of aerosol delivery offer advantages but still there are shortcomings. Delivery of active agents to sites of action is affected by many factors beyond the characteristics of the delivery devices, including the coordination between inhalation and actuation and dependence on the patient's inspiratory flow and breathing pattern. Recent advances in drug delivery focus around changes in the generation of particle size with better penetration to the targeted sites, easier activation of the device with inspiratory flow, ease of use including fewer steps in using the device, and better portability. Availability of computer chips allows for smart delivery devices to tailor delivery to the patient's breathing pattern and lung function. Further, smart devices can provide feedback to patients. Novel inhaler technologies, separately or in combination with new therapeutic agents, are in development not only for respiratory diseases but also for diseases of other systems. This article reviews some of the recent clinically relevant advances in aerosol delivery devices. PMID:26238640

  18. Elective Delivery Before 39 Weeks

    MedlinePLUS

    ... Delivery, and Postpartum Care Elective Delivery Before 39 Weeks • What is a “medically indicated” delivery? • What is ... the baby grow and develop during the last weeks of pregnancy? • What are the risks for babies ...

  19. Design and in vitro development of resorbable urologic drug delivery device

    E-print Network

    Tobias, Irene S. (Irene Sophie)

    2008-01-01

    Implantable, controlled release drug delivery devices offer several advantages over systemic oral administration routes and immediate drug release treatments including direct therapy to target organ, more continuous ...

  20. Hydrogen peroxide mediated transvaginal drug delivery.

    PubMed

    Fatakdawala, Hussain; Uhland, Scott A

    2011-05-16

    Simple, safe and effective permeability enhancers are crucial for successful non-invasive drug delivery methods. We seek local permeability augmentation mechanisms for integration into passive or active architectures in order to enable novel therapeutic delivery routes of the target drug while minimizing drug formulation challenges. This study explores the efficacy of hydrogen peroxide (HP) as a permeability enhancer for transmucosal delivery of macromolecules. HP at low concentrations (2–8 mM) is an effective permeability enhancer that is locally metabolized and safe. HP improves drug permeation through mucosa by altering tight junctions (TJ) between cells and oxidizing enzymes that function to degrade the foreign species. Results from trans-epithelial electrical resistance measurements and cell viability assay show reversible disassembly of TJ with minimal cell damage demonstrating the feasibility of HP as a safe permeability enhancer for drug delivery. Permeation studies show that HP treatment of cell cultured vaginal mucosa significantly enhances the permeability to insulin by more than an order of magnitude. This work lays foundation for the development of a drug delivery platform that administers drug doses by enhancing the permeability of local epithelial tissue via a separate HP treatment step. PMID:21498011

  1. FUNCTIONAL NANOPARTICLES FOR MOLECULAR IMAGING GUIDED GENE DELIVERY

    PubMed Central

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

    2010-01-01

    Gene therapy has great potential to bring tremendous changes in treatment of various diseases and disorders. However, one of the impediments to successful gene therapy is the inefficient delivery of genes to target tissues and the inability to monitor delivery of genes and therapeutic responses at the targeted site. The emergence of molecular imaging strategies has been pivotal in optimizing gene therapy; since it can allow us to evaluate the effectiveness of gene delivery noninvasively and spatiotemporally. Due to the unique physiochemical properties of nanomaterials, numerous functional nanoparticles show promise in accomplishing gene delivery with the necessary feature of visualizing the delivery. In this review, recent developments of nanoparticles for molecular imaging guided gene delivery are summarized. PMID:22473061

  2. NANOMATERIALS FOR PROTEIN MEDIATED THERAPY AND DELIVERY

    PubMed Central

    Barry, John N.; Vertegel, Alexey A.

    2014-01-01

    There has been a significant amount of research done on liposomes and nanoparticles as drug carriers for protein drugs. Proteins and enzymes have been used both as targeting moieties and for their therapeutic potential. High specificity and rapid reaction rates make proteins and enzymes excellent candidates for therapeutic treatment, but some limitations exist. Many of these limitations can be addressed by a well studied nanotechnology based delivery system. Such a system can provide a medium for delivery, stabilization of the drugs, and enable site specific accumulation of drugs. Nanomedicines such as these have great potential to revolutionize the pharmaceutical industry and improve healthcare worldwide. PMID:25414730

  3. Therapeutic gene delivery using bioreducible polymers.

    PubMed

    Ryu, Kitae; Kim, Tae-Il

    2014-01-01

    Bioreducible polymers, which can be degraded in reducing environment due to the cleavage of internal disulfide bonds, have been developed for gene delivery systems. They show high stability in extracellular physiological condition and cytoplasm-specific release of genetic materials, as well as decreased cytotoxicity because cytoplasm is a reducing environment containing high level of reducing molecules such as glutathione. Based on these advantages, recently, many bioreducible polymers have been further investigated with therapeutic genes for the treatment of diseases and demonstrated promising results. This review will focus on the therapeutic gene delivery using bioreducible polymers and the evaluation of therapeutic efficacy for cancer, myocardial infarction, diabetes and miscellaneous diseases. PMID:24178745

  4. Ultrahighly accurate 3D profilometer

    NASA Astrophysics Data System (ADS)

    Tsutsumi, Hideki; Yoshizumi, Keiichi; Takeuchi, Hiroyuki

    2005-02-01

    We have developed an Ultrahigh-Accurate 3-D Profilometer (UA3P), which, using a new, in-house-developed atomic force probe, has an accuracy of 10 nm. It is capable of measuring corners as small as 2 micro meter in radius and can cover an area up to 400 x 400 x 90 (mm), providing a powerful boost to nano-level processing. A commercial product was introduced in 1994. Examples of the key components made possible by this technology include aspherical lenses (used for a Blu-ray Disc device, a next-generation DVD, digital cameras, cellular phones, optical communications), free form lenses (used for frennel lens common to CD and DVD, laser printer lens, multi focus glass lens, cubic phase plate to extend depth of focus), gigabit semiconductor wafers, hard discs, air conditioner scroll vanes, DVC cylinders. The premiere ultra high-precision three-dimensional profilometer delivers superb performance using a variety of micro-measurements for a wide range of applications.

  5. Protein-Based Nanomedicine Platforms for Drug Delivery

    SciTech Connect

    Ma Ham, Aihui; Tang, Zhiwen; Wu, Hong; Wang, Jun; Lin, Yuehe

    2009-08-03

    Drug delivery systems have been developed for many years, however some limitations still hurdle the pace of going to clinical phase, for example, poor biodistribution, drug molecule cytotoxicity, tissue damage, quick clearance from the circulation system, solubility and stability of drug molecules. To overcome the limitations of drug delivery, biomaterials have to be developed and applied to drug delivery to protect the drug molecules and to enhance the drug’s efficacy. Protein-based nanomedicine platforms for drug delivery are platforms comprised of naturally self-assembled protein subunits of the same protein or a combination of proteins making up a complete system. They are ideal for drug delivery platforms due to their biocompatibility and biodegradability coupled with low toxicity. A variety of proteins have been used and characterized for drug delivery systems including the ferritin/apoferritin protein cage, plant derived viral capsids, the small Heat shock protein (sHsp) cage, albumin, soy and whey protein, collagen, and gelatin. There are many different types and shapes that have been prepared to deliver drug molecules using protein-based platforms including the various protein cages, microspheres, nanoparticles, hydrogels, films, minirods and minipellets. There are over 30 therapeutic compounds that have been investigated with protein-based drug delivery platforms for the potential treatment of various cancers, infectious diseases, chronic diseases, autoimmune diseases. In protein-based drug delivery platforms, protein cage is the most newly developed biomaterials for drug delivery and therapeutic applications. Their uniform sizes, multifunctions, and biodegradability push them to the frontier for drug delivery. In this review, the recent strategic development of drug delivery has been discussed with a special emphasis upon the polymer based, especially protein-based nanomedicine platforms for drug delivery. The advantages and disadvantages are also discussed for each type of protein based drug delivery system.

  6. SU-E-T-373: A Motorized Stage for Fast and Accurate QA of Machine Isocenter

    SciTech Connect

    Moore, J; Velarde, E; Wong, J

    2014-06-01

    Purpose: Precision delivery of radiation dose relies on accurate knowledge of the machine isocenter under a variety of machine motions. This is typically determined by performing a Winston-Lutz test consisting of imaging a known object at multiple gantry/collimator/table angles and ensuring that the maximum offset is within specified tolerance. The first step in the Winston-Lutz test is careful placement of a ball bearing at the machine isocenter as determined by repeated imaging and shifting until accurate placement has been determined. Conventionally this is performed by adjusting a stage manually using vernier scales which carry the limitation that each adjustment must be done inside the treatment room with the risks of inaccurate adjustment of the scale and physical bumping of the table. It is proposed to use a motorized system controlled outside of the room to improve the required time and accuracy of these tests. Methods: The three dimensional vernier scales are replaced by three motors with accuracy of 1 micron and a range of 25.4mm connected via USB to a computer in the control room. Software is designed which automatically detects the motors and assigns them to proper axes and allows for small shifts to be entered and performed. Input values match calculated offsets in magnitude and sign to reduce conversion errors. Speed of setup, number of iterations to setup, and accuracy of final placement are assessed. Results: Automatic BB placement required 2.25 iterations and 13 minutes on average while manual placement required 3.76 iterations and 37.5 minutes. The average final XYZ offsets is 0.02cm, 0.01cm, 0.04cm for automatic setup and 0.04cm, 0.02cm, 0.04cm for manual setup. Conclusion: Automatic placement decreased time and repeat iterations for setup while improving placement accuracy. Automatic placement greatly reduces the time required to perform QA.

  7. Dosimetric verification of IMAT delivery with a conventional EPID system and a commercial portal dose image prediction tool

    SciTech Connect

    Iori, Mauro; Cagni, Elisabetta; Paiusco, Marta; Munro, Peter; Nahum, Alan E.

    2010-01-15

    Purpose: The electronic portal imaging device (EPID) is a system for checking the patient setup; as a result of its integration with the linear accelerator and software customized for dosimetry, it is increasingly used for verification of the delivery of fixed-field intensity-modulated radiation therapy (IMRT). In order to extend such an approach to intensity-modulated arc therapy (IMAT), the combined use of an EPID system and a portal dose image prediction (PDIP) tool has been investigated. Methods: The dosimetric behavior of an EPID system, mechanically reinforced to maintain its positional stability during the accelerator gantry rotation, has been studied to assess its ability to measure portal dose distributions for IMAT treatment beams. In addition, the PDIP tool of a commercial treatment planning system, commonly used for static IMRT dosimetry, has been validated for simulating the PDIs of IMAT treatment fields. The method has been applied to the delivery verification of 23 treatment fields that were measured in their dual mode of IMRT and IMAT modalities. Results: The EPID system has proved to be appropriate for measuring the PDIs of IMAT fields; additionally the PDIP tool was able to simulate these accurately. The results are quite similar to those obtained for static IMRT treatment verification, although it was necessary to investigate the dependence of the EPID signal and of the accelerator monitor chamber response on variable dose rate. Conclusions: Our initial tests indicate that the EPID system, together with the PDIP tool, is a suitable device for the verification of IMAT plan delivery; however, additional tests are necessary to confirm these results.

  8. Optical delivery and monitoring of photodynamic therapy of prostate cancer

    NASA Astrophysics Data System (ADS)

    Weersink, Robert A.; Bogaards, Arjun; Gertner, Mark; Davidson, Sean; Zhang, Kai; Netchev, George; Giewercer, David J.; Trachtenberg, John; Wilson, Brian C.

    2004-10-01

    Photodynamic therapy of recurrent prostate cancer is currently undergoing Phase II clinical trials with the vascular targeting drug TOOKAD. Proper PDT dosage requires sound estimates of the light fluence and drug concentration throughout the organ. The treatment requires multiple diffusing light delivery fibers placed in position according to a light dose treatment plan under ultrasound guidance. Fluence rate is monitored by multiple sensor fibers placed throughout the organ and in sensitive organs near the prostate. The combination of multiple light delivery and fluence sensor fibers is used to estimate the optical properties of the tissue and to provide a general fluence map throughout the organ. This fluence map is then used to estimate extent of photodynamic dose. Optical spectroscopy is used to monitor drug pharmacokinetics in the organ and blood hemodynamics within the organ. Further development of these delivery and monitoring techniques will permit full online monitoring of the treatment that will enable real-time patient-specific delivery of photodynamic therapy.

  9. Recovering from Delivery

    MedlinePLUS

    ... Expect Emotionally Emotionally, you may be feeling: "Baby blues." Many new moms have irritability, sadness, crying, or ... the first several days after delivery. These baby blues are very common and may be related to ...

  10. Healthcare Delivery Research Blog

    Cancer.gov

    Over the course of my career I have often been frustrated with the gap between the research I was conducting and the clinical operations of the health care delivery systems with which I was affiliated.

  11. Transdermal delivery of heparin: Physical enhancement techniques.

    PubMed

    Ita, Kevin

    2015-12-30

    Thromboembolic complications are the most common preventable cause of mortality and morbidity in trauma patients. Thrombosis is also the common cause of ischemic heart disease (acute coronary syndrome), stroke, and venous thromboembolism. Heparin, as a potent anticoagulant, has been used in clinical practice for more than five decades and remains the major medicine for the prevention and treatment of venous thromboembolism. However it binds to the endothelium and has a high affinity for plasma proteins resulting in a short half-life and unpredictable bioavailability. Transdermal drug delivery can address the problems of short half-life and unpredictable bioavailability. Other advantages of transdermal drug delivery include convenience, improved patient compliance, prompt termination of dosing and avoidance of the first-pass effect. This review focuses on different approaches used for transdermal delivery of heparin. PMID:26611668

  12. Current perspectives on intrathecal drug delivery

    PubMed Central

    Bottros, Michael M; Christo, Paul J

    2014-01-01

    Advances in intrathecal analgesia and intrathecal drug delivery systems have allowed for a range of medications to be used in the control of pain and spasticity. This technique allows for reduced medication doses that can decrease the side effects typically associated with oral or parenteral drug delivery. Recent expert panel consensus guidelines have provided care paths in the treatment of nociceptive, neuropathic, and mixed pain syndromes. While the data for pain relief, adverse effect reduction, and cost-effectiveness with cancer pain control are compelling, the evidence is less clear for noncancer pain, other than spasticity. Physicians should be aware of mechanical, pharmacological, surgical, and patient-specific complications, including possible granuloma formation. Newer intrathecal drug delivery systems may allow for better safety and quality of life outcomes. PMID:25395870

  13. Gene Delivery to the Spinal Cord: Comparison Between Lentiviral, Adenoviral, and Retroviral Vector Delivery Systems

    PubMed Central

    Abdellatif, Ahmed A.; Pelt, Jennifer L.; Benton, Richard L.; Howard, Russell M.; Tsoulfas, Pantelis; Ping, Peipei; Xu, Xiao-Ming; Whittemore, Scott R.

    2010-01-01

    Viral gene delivery for spinal cord injury (SCI) is a promising approach for enhancing axonal regeneration and neuroprotection. An understanding of spatio-temporal transgene expression in the spinal cord is essential for future studies of SCI therapies. Commonly, intracellular marker proteins (e.g., EGFP) were used as indicators of transgene levels after viral delivery, which may not accurately reflect levels of secreted transgene. This study examined transgene expression using ELISA after viral delivery of D15A, a neurotrophin with BDNF and NT-3 activities, at 1, 2, and 4 weeks after in vivo and ex vivo delivery using lentiviral, adenoviral, and retroviral vectors. Further, the inflammatory responses and viral infection patterns after in vivo delivery were examined. Lentiviral vectors had the most stable pattern of gene expression, with D15A levels of 536 ± 38 and 363 ± 47 pg/mg protein seen at 4 weeks after the in vivo and ex vivo delivery, respectively. Our results show that protein levels downregulate disproportionately to levels of EGFP after adenoviral vectors both in vivo and ex vivo. D15A dropped from initial levels of 422 ± 87 to 153 ± 18 pg/mg protein at 4 weeks after in vivo administration. Similarly, ex vivo retrovirus-mediated transgene expression exhibited rapid downregulation by 2 weeks post-grafting. Compared to adenoviral infection, macrophage activation was attenuated after lentiviral infection. These results suggest that lentiviral vectors are most suitable in situations where stable long-term transgene expression is needed. Retroviral ex vivo delivery is optional when transient expression within targeted spinal tissue is desired, with adenoviral vectors in between. PMID:16786574

  14. Carbohydrate Polymers for Nonviral Nucleic Acid Delivery

    PubMed Central

    Sizovs, Antons; McLendon, Patrick M.; Srinivasachari, Sathya

    2014-01-01

    Carbohydrates have been investigated and developed as delivery vehicles for shuttling nucleic acids into cells. In this review, we present the state of the art in carbohydrate-based polymeric vehicles for nucleic acid delivery, with the focus on the recent successes in preclinical models, both in vitro and in vivo. Polymeric scaffolds based on the natural polysaccharides chitosan, hyaluronan, pullulan, dextran, and schizophyllan each have unique properties and potential for modification, and these results are discussed with the focus on facile synthetic routes and favorable performance in biological systems. Many of these carbohydrates have been used to develop alternative types of biomaterials for nucleic acid delivery to typical polyplexes, and these novel materials are discussed. Also presented are polymeric vehicles that incorporate copolymerized carbohydrates into polymer backbones based on polyethylenimine and polylysine and their effect on transfection and biocompatibility. Unique scaffolds, such as clusters and polymers based on cyclodextrin (CD), are also discussed, with the focus on recent successes in vivo and in the clinic. These results are presented with the emphasis on the role of carbohydrate and charge on transfection. Use of carbohydrates as molecular recognition ligands for cell-type specific delivery is also briefly reviewed. We contend that carbohydrates have contributed significantly to progress in the field of non-viral DNA delivery, and these new discoveries are impactful for developing new vehicles and materials for treatment of human disease. PMID:21504102

  15. Ocular Drug Delivery Using Ultrasound

    NASA Astrophysics Data System (ADS)

    Zderic, Vesna; Clark, John I.; Vaezy, Shahram

    2005-03-01

    Our goal was to evaluate ultrasound (US) enhancement of drug delivery through the cornea, and the histological appearance of the cornea, up to 24 h after treatment. The aqueous humor concentration of topically applied sodium fluorescein was determined quantitatively in US-treated and sham rabbit eyes in vivo. Gross and light microscopic examinations were used to observe structural changes in the cornea 0-24 h after US exposure. The increase in the dye concentration in aqueous humor, after the simultaneous application of 880 kHz US and the dye solution (for 5 min), was 2.4 times at 0.19 W/cm2, 3.8 times at 0.34 W/cm2, and 10.6 times at 0.56 W/m2 (p<0.05). The dye delivery was found to increase with increasing US intensity, which corresponded with an increase in cavitation activity. After the separate application of US and the dye solution, the increase in the dye concentration was 3.8 times at 0.56 W/cm2 (p<0.01), while no increase was achieved at 0.19-0.34 W/cm2. The majority of damaged cells were present in the surface layer of the corneal epithelium. Corneal pits, observed in the US-treated epithelium, completely disappeared within 90 min. The application of 880 kHz ultrasound provided enhancement in the delivery of a hydrophilic compound through the cornea while producing minor changes in the corneal epithelium.

  16. Ultrasound-mediated nail drug delivery system.

    PubMed

    Abadi, Danielle; Zderic, Vesna

    2011-12-01

    A novel ultrasound-mediated drug delivery system has been developed for treatment of a nail fungal disorder (onychomycosis) by improving delivery to the nail bed using ultrasound to increase the permeability of the nail. The slip-in device consists of ultrasound transducers and drug delivery compartments above each toenail. The device is connected to a computer, where a software interface allows users to select their preferred course of treatment. In in vitro testing, canine nails were exposed to 3 energy levels (acoustic power of 1.2 W and exposure durations of 30, 60, and 120 seconds). A stereo -microscope was used to determine how much of a drug-mimicking compound was delivered through the nail layers by measuring brightness on the cross section of each nail tested at each condition, where brightness level decreases coincide with increases in permeability. Each of the 3 energy levels tested showed statistical significance when compared to the control (P < .05) with a permeability factor of 1.3 after 30 seconds of exposure, 1.3 after 60 seconds, and 1.5 after 120 seconds, where a permeability factor of 1 shows no increase in permeability. Current treatments for onychomycosis include systemic, topical, and surgical. Even when used all together, these treatments typically take a long time to result in nail healing, thus making this ultrasound-mediated device a promising alternative. PMID:22124008

  17. Progress in antiretroviral drug delivery using nanotechnology

    PubMed Central

    Mallipeddi, Rama; Rohan, Lisa Cencia

    2010-01-01

    There are currently a number of antiretroviral drugs that have been approved by the Food and Drug Administration for use in the treatment of human immunodeficiency virus (HIV). More recently, antiretrovirals are being evaluated in the clinic for prevention of HIV infection. Due to the challenging nature of treatment and prevention of this disease, the use of nanocarriers to achieve more efficient delivery of antiretroviral drugs has been studied. Various forms of nanocarriers, such as nanoparticles (polymeric, inorganic, and solid lipid), liposomes, polymeric micelles, dendrimers, cyclodextrins, and cell-based nanoformulations have been studied for delivery of drugs intended for HIV prevention or therapy. The aim of this review is to provide a summary of the application of nanocarrier systems to the delivery of anti-HIV drugs, specifically antiretrovirals. For anti-HIV drugs to be effective, adequate distribution to specific sites in the body must be achieved, and effective drug concentrations must be maintained at those sites for the required period of time. Nanocarriers provide a means to overcome cellular and anatomical barriers to drug delivery. Their application in the area of HIV prevention and therapy may lead to the development of more effective drug products for combating this pandemic disease. PMID:20957115

  18. Recent Perspectives in Ocular Drug Delivery

    PubMed Central

    Gaudana, Ripal; Jwala, J.; Boddu, Sai H. S.; Mitra, Ashim K.

    2015-01-01

    Anatomy and physiology of the eye makes it a highly protected organ. Designing an effective therapy for ocular diseases, especially for the posterior segment, has been considered as a formidable task. Limitations of topical and intravitreal route of administration have challenged scientists to find alternative mode of administration like periocular routes. Transporter targeted drug delivery has generated a great deal of interest in the field because of its potential to overcome many barriers associated with current therapy. Application of nanotechnology has been very promising in the treatment of a gamut of diseases. In this review, we have briefly discussed several ocular drug delivery systems such as microemulsions, nanosuspensions, nanoparticles, liposomes, niosomes, dendrimers, implants, and hydrogels. Potential for ocular gene therapy has also been described in this article. In near future, a great deal of attention will be paid to develop non-invasive sustained drug release for both anterior and posterior segment eye disorders. A better understanding of nature of ocular diseases, barriers and factors affecting in vivo performance, would greatly drive the development of new delivery systems. Current momentum in the invention of new drug delivery systems hold a promise towards much improved therapies for the treatment of vision threatening disorders. PMID:18758924

  19. Treatment planning aspects and Monte Carlo methods in proton therapy

    NASA Astrophysics Data System (ADS)

    Fix, Michael K.; Manser, Peter

    2015-05-01

    Over the last years, the interest in proton radiotherapy is rapidly increasing. Protons provide superior physical properties compared with conventional radiotherapy using photons. These properties result in depth dose curves with a large dose peak at the end of the proton track and the finite proton range allows sparing the distally located healthy tissue. These properties offer an increased flexibility in proton radiotherapy, but also increase the demand in accurate dose estimations. To carry out accurate dose calculations, first an accurate and detailed characterization of the physical proton beam exiting the treatment head is necessary for both currently available delivery techniques: scattered and scanned proton beams. Since Monte Carlo (MC) methods follow the particle track simulating the interactions from first principles, this technique is perfectly suited to accurately model the treatment head. Nevertheless, careful validation of these MC models is necessary. While for the dose estimation pencil beam algorithms provide the advantage of fast computations, they are limited in accuracy. In contrast, MC dose calculation algorithms overcome these limitations and due to recent improvements in efficiency, these algorithms are expected to improve the accuracy of the calculated dose distributions and to be introduced in clinical routine in the near future.

  20. An extensive log-file analysis of step-and-shoot intensity modulated radiation therapy segment delivery errors.

    PubMed

    Stell, Anthony M; Li, Jonathan G; Zeidan, Omar A; Dempsey, James F

    2004-06-01

    We present a study to evaluate the monitor unit (MU), dosimetric, and leaf-motion errors found in the delivery of 91 step-and-shoot IMRT treatment plans performed at three nominal dose rates using a dual modality high energy Linac (Varian 2100 C/D, Varian Medical Systems Inc., Palo Alto, CA) equipped with a 120-leaf multileaf collimator (MLC). The analysis was performed by studying log files generated by the MLC controller system. Recent studies by our group have validated that the automatically generated MLC log files accurately record the actual system delivery. A total of 635 beams were delivered at three nominal dose rates: 100, 300, and 600 MU/min. The log files were manually retrieved and analysis software was developed to extract the recorded MU delivery and leaf positions for each segment. Our analysis revealed that the magnitude of segment MU errors were independent of the planned segment MUs. Segment MU errors were found to increase with dose rate having maximum errors per segment of +/-1.8 MU at 600 MU/min, +/-0.8 MU at 300 MU/min, and +/-0.5 MU at 100 MU/min. The total absolute MU error in each plan was observed to increase with the number of plan segments, with the trend increasing more rapidly for higher dose rates. Three dimensional dose distributions were recomputed based on the observed segment MU errors for three plans with large cumulative absolute MU errors. Comparison with the original treatment plans indicated no clinically significant consequences due to these errors. In addition, approximately 80% of the total segment deliveries reported at least one collimator leaf moving at least 1 mm (projected at isocenter) during segment delivery. Such errors occur near the end of segment delivery and have been previously observed by our group using a fast video-based electronic portal imaging device. At 600 MU/min, between 5% and 23% of the plan MUs were delivered during leaf motion that had exceeded a 1 mm position tolerance. These leaf motion errors were not included in the treatment plan recalculations performed in this study. PMID:15259664

  1. Transungual delivery: deliberations and creeds.

    PubMed

    Thatai, P; Sapra, B

    2014-10-01

    Although considered as trifling illness, nail diseases have a reasonably high occurrence and a noteworthy impact on the patients' quality of life. Furthermore, there is a need to improve the topical treatment for nail diseases to avoid drug interactions and to reduce side effects associated with oral therapy. Topical drug delivery to the nails has established amplified consideration lately. Strategies (such as chemical enhancers, formulation strategies, physical and mechanical methods) are being investigated in order to improve drug permeability across the nail plate. The rationale of this review is to present contemporary information on the structure of human nail along with its comparison with animal hooves. Precincts of nail permeability have been briefly discussed with respect to factors like permeant's molecular size, hydrophilicity, charge and the nature of the vehicle. These factors affect drug uptake and permeation through the nail. Formulations like nail lacquers which mimic cosmetic varnish and colloidal carriers along with nail substitutes that can be utilized for transungual delivery have also been discussed. PMID:24888698

  2. Infrared free electron laser enhanced transdermal drug delivery

    NASA Astrophysics Data System (ADS)

    Awazu, Kunio; Uchizono, Takeyuki; Suzuki, Sachiko; Yoshikawa, Kazushi

    2005-08-01

    It is necessary to control enhancement of transdermal drug delivery with non-invasive. The present study was investigated to assess the effectivity of enhancing the drug delivery by irradiating 6-?m region mid infrared free electron laser (MIR-FEL). The enhancement of transdermal drug (lidocaine) delivery of the samples (hairless mouse skin) irradiated with lasers was examined for flux (?g/cm2/h) and total penetration amount (?g/cm2) of lidocaine by High performance Liquid Chromatography (HPLC). The flux and total amount penatration date was enhanced 200-300 fold faster than the control date by the laser irradiation. FEL irradiating had the stratum corneum, and had the less thermal damage in epidermis. The effect of 6-?m region MIR-FEL has the enhancement of transdermal drug delivery without removing the stratum corneum because it has the less thermal damage. It leads to enhancement drug delivery system with non-invasive laser treatment.

  3. Silicon Nanowires for Bioadhesion and Drug Delivery

    E-print Network

    Fischer, Kathleen Elizabeth

    2010-01-01

    Generation Adhesive Drug Delivery Systems. Nano Letters 9,Drug Delivery Goals for Oral Delivery Micro- and Nanoparticles Microparticles Nanoparticles Bioadhesion Chemical Bioadhesives Physical Adhesives Nano-

  4. Transcutaneous antigen delivery system

    PubMed Central

    Lee, Mi-Young; Shin, Meong-Cheol; Yang, Victor C.

    2013-01-01

    Transcutaneous immunization refers to the topical application of antigens onto the epidermis. Transcutaneous immunization targeting the Langerhans cells of the skin has received much attention due to its safe, needle-free, and noninvasive antigen delivery. The skin has important immunological functions with unique roles for antigen-presenting cells such as epidermal Langerhans cells and dermal dendritic cells. In recent years, novel vaccine delivery strategies have continually been developed; however, transcutaneous immunization has not yet been fully exploited due to the penetration barrier represented by the stratum corneum, which inhibits the transport of antigens and adjuvants. Herein we review recent achievements in transcutaneous immunization, focusing on the various strategies for the enhancement of antigen delivery and vaccination efficacy. [BMB Reports 2013; 46(1): 17-24] PMID:23351379

  5. Telerobotic system concept for real-time soft-tissue imaging during radiotherapy beam delivery

    SciTech Connect

    Schlosser, Jeffrey; Salisbury, Kenneth; Hristov, Dimitre

    2010-12-15

    Purpose: The curative potential of external beam radiation therapy is critically dependent on having the ability to accurately aim radiation beams at intended targets while avoiding surrounding healthy tissues. However, existing technologies are incapable of real-time, volumetric, soft-tissue imaging during radiation beam delivery, when accurate target tracking is most critical. The authors address this challenge in the development and evaluation of a novel, minimally interfering, telerobotic ultrasound (U.S.) imaging system that can be integrated with existing medical linear accelerators (LINACs) for therapy guidance. Methods: A customized human-safe robotic manipulator was designed and built to control the pressure and pitch of an abdominal U.S. transducer while avoiding LINAC gantry collisions. A haptic device was integrated to remotely control the robotic manipulator motion and U.S. image acquisition outside the LINAC room. The ability of the system to continuously maintain high quality prostate images was evaluated in volunteers over extended time periods. Treatment feasibility was assessed by comparing a clinically deployed prostate treatment plan to an alternative plan in which beam directions were restricted to sectors that did not interfere with the transabdominal U.S. transducer. To demonstrate imaging capability concurrent with delivery, robot performance and U.S. target tracking in a phantom were tested with a 15 MV radiation beam active. Results: Remote image acquisition and maintenance of image quality with the haptic interface was successfully demonstrated over 10 min periods in representative treatment setups of volunteers. Furthermore, the robot's ability to maintain a constant probe force and desired pitch angle was unaffected by the LINAC beam. For a representative prostate patient, the dose-volume histogram (DVH) for a plan with restricted sectors remained virtually identical to the DVH of a clinically deployed plan. With reduced margins, as would be enabled by real-time imaging, gross tumor volume coverage was identical while notable reductions of bladder and rectal volumes exposed to large doses were possible. The quality of U.S. images obtained during beam operation was not appreciably degraded by radiofrequency interference and 2D tracking of a phantom object in U.S. images obtained with the beam on/off yielded no significant differences. Conclusions: Remotely controlled robotic U.S. imaging is feasible in the radiotherapy environment and for the first time may offer real-time volumetric soft-tissue guidance concurrent with radiotherapy delivery.

  6. Systems and Components Fuel Delivery System, Water Delivery System, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Systems and Components - Fuel Delivery System, Water Delivery System, Derrick Crane System, and Crane System Details - Marshall Space Flight Center, F-1 Engine Static Test Stand, On Route 565 between Huntsville and Decatur, Huntsville, Madison County, AL

  7. MRI-Guided Delivery of Viral Vectors.

    PubMed

    Salegio, Ernesto A; Bringas, John; Bankiewicz, Krystof S

    2016-01-01

    Gene therapy has emerged as a potential avenue of treatment for many neurological disorders. Technological advances in imaging techniques allow for the monitoring of real-time infusions into the brain of rodents, nonhuman primates, and humans. Here, we discuss the use of magnetic resonance imaging (MRI) as a tool in the delivery of adeno-associated viral (AAV) particles into brain of nonhuman primates. PMID:26611589

  8. Investigating parent delivery of the Lidcombe Program.

    PubMed

    Carr Swift, Michelle; O'Brian, Sue; Hewat, Sally; Onslow, Mark; Packman, Ann; Menzies, Ross

    2011-08-01

    The Lidcombe Program is an early childhood stuttering treatment delivered by parents in the child's everyday environment, under the guidance of a speech-language pathologist (SLP). Given the parents' central role in the treatment delivery, the way it is implemented away from the clinic and away from the SLP's input is very important. And yet, to date there has been very little investigation into this process. This study investigated to what extent parents deliver contingencies for stuttering and stutter-free speech, in structured and unstructured conversations, as directed in the treatment manual. Participants were three mothers and their children who were receiving the Lidcombe Program. They recorded two treatment sessions each week and completed a daily treatment diary. The recordings were analysed for the use of parent verbal contingencies (PVCs). This method detected differences in PVC delivery by the mothers both across and within cases over time. The results show that valuable information can be gained from analysing home treatment sessions in this way and with a few modifications this methodology would be useful in larger scale studies. The strengths and limitations of this methodology are discussed with future larger studies of this type recommended. PMID:21793776

  9. Redefining continuing education delivery.

    PubMed

    Carlton, K H

    1997-01-01

    Just as technology is transforming the delivery of education, the Internet and advanced telecommunication applications are changing the "face" of CE and the connotation of "lifelong learning." As late as the mid-1980s, a discussion of computer applications in nursing CE focused on the "timely" transition to microcomputers as tools for the enhancement of managerial tasks for increased productivity. Even as recently as 1990, there seemed to be "time" for those providers who were "slower to adopt innovation" to "catch up." Now, the CE provider who does not integrate the microcomputer and advanced telecommunications as an integral component of their delivery modalities may be outsourced rapidly by an educational or commercial competitive unit that is able to utilize the communication medium, mergers and partnerships, enterprise, and individual lifestyle and learning patterns that will epitomize the CE unit of the 21st century. As with the "re-engineering" of nursing education, the "re-engineered" delivery modalities of evolving CE entity might now best be conceptualized on a continuum from the traditional mode that time and place dependent to a mode of synchronous and asynchronous data and advanced telecommunication. Delivery methods will need to be selected according to the target populations, content, and situation. The health-care educational provider may discover, as in other industries, that a combination of distance and residential offerings will be the most successful medium for the delivery of CE to the progressively more "information and technologically savvy" lifelong learner of the 21st century. In addressing the dramatic effects of the information technology era on the refocused multimedia/interactive delivery method for student education, educators amply quoted Bob Dylan's phrase of the 1960s, "The times, they are a-changing." And so, we see that the times are also changing at an astronomical rate for the health-care educational provider as well as the individual health-care worker consumer. A number of national and world-wide trends are propelling rapid changes in the delivery modalities and types of emerging providers for health-care CE. Examples of these advanced telecommunications applications of CE opportunities for health-care personnel are becoming more prevalent in the literature and the pattern of CE marketing, and delivery evolution can be seen readily on the Internet. Continued program success and viability will belong to the individuals and organizations who are able to conceptualize and envision the positive transformations and opportunities that can occur from the evolving paradigm of education for the lifelong learner of the 21st century. PMID:9014388

  10. Micromachined therapeutic delivery systems: from concept to clinic

    NASA Astrophysics Data System (ADS)

    Desai, Tejal A.

    2001-05-01

    Microfabrication techniques which permit the creation of therapeutic delivery systems that possess a combination of structural, mechanical, and perhaps electronic features may surmount challenges associated with conventional delivery of therapy. In this review, delivery concepts are presented which capitalize on the strengths of microfabrication. Possible applications include micromachined silicon membranes to create implantable biocapsules for the immunoisolation of pancreatic islet cells--as a possible treatment for diabetes--and sustained release of injectable drugs needed over long time periods. Asymmetrical, drug- loaded microfabricated particles with specific ligands linked to the surface are proposed for improving oral bioavailability of peptide (and perhaps protein) drugs.

  11. Near-infrared light activated delivery platform for cancer therapy.

    PubMed

    Lin, Min; Gao, Yan; Hornicek, Francis; Xu, Feng; Lu, Tian Jian; Amiji, Mansoor; Duan, Zhenfeng

    2015-12-01

    Cancer treatment using conventional drug delivery platforms may lead to fatal damage to normal cells. Among various intelligent delivery platforms, photoresponsive delivery platforms are becoming popular, as light can be easily focused and tuned in terms of power intensity, wavelength, and irradiation time, allowing remote and precise control over therapeutic payload release both spatially and temporally. This unprecedented controlled delivery manner is important to improve therapeutic efficacy while minimizing side effects. However, most of the existing photoactive delivery platforms require UV/visible excitation to initiate their function, which suffers from phototoxicity and low level of tissue penetration limiting their practical applications in biomedicine. With the advanced optical property of converting near infrared (NIR) excitation to localized UV/visible emission, upconversion nanoparticles (UCNPs) have emerged as a promising photoactive delivery platform that provides practical applications for remote spatially and temporally controlled release of therapeutic payload molecules using low phototoxic and high tissue penetration NIR light as the excitation source. This article reviews the state-of-the-art design, synthesis and therapeutic molecular payload encapsulation strategies of UCNP-based photoactive delivery platforms for cancer therapy. Challenges and promises for engineering of advanced delivery platforms are also highlighted. PMID:26520243

  12. Micro- and nano-fabricated implantable drug-delivery systems

    PubMed Central

    Meng, Ellis; Hoang, Tuan

    2013-01-01

    Implantable drug-delivery systems provide new means for achieving therapeutic drug concentrations over entire treatment durations in order to optimize drug action. This article focuses on new drug administration modalities achieved using implantable drug-delivery systems that are enabled by micro- and nano-fabrication technologies, and microfluidics. Recent advances in drug administration technologies are discussed and remaining challenges are highlighted. PMID:23323562

  13. Chitosan Microspheres in Novel Drug Delivery Systems

    PubMed Central

    Mitra, Analava; Dey, Baishakhi

    2011-01-01

    The main aim in the drug therapy of any disease is to attain the desired therapeutic concentration of the drug in plasma or at the site of action and maintain it for the entire duration of treatment. A drug on being used in conventional dosage forms leads to unavoidable fluctuations in the drug concentration leading to under medication or overmedication and increased frequency of dose administration as well as poor patient compliance. To minimize drug degradation and loss, to prevent harmful side effects and to increase drug bioavailability various drug delivery and drug targeting systems are currently under development. Handling the treatment of severe disease conditions has necessitated the development of innovative ideas to modify drug delivery techniques. Drug targeting means delivery of the drug-loaded system to the site of interest. Drug carrier systems include polymers, micelles, microcapsules, liposomes and lipoproteins to name some. Different polymer carriers exert different effects on drug delivery. Synthetic polymers are usually non-biocompatible, non-biodegradable and expensive. Natural polymers such as chitin and chitosan are devoid of such problems. Chitosan comes from the deacetylation of chitin, a natural biopolymer originating from crustacean shells. Chitosan is a biocompatible, biodegradable, and nontoxic natural polymer with excellent film-forming ability. Being of cationic character, chitosan is able to react with polyanions giving rise to polyelectrolyte complexes. Hence chitosan has become a promising natural polymer for the preparation of microspheres/nanospheres and microcapsules. The techniques employed to microencapsulate with chitosan include ionotropic gelation, spray drying, emulsion phase separation, simple and complex coacervation. This review focuses on the preparation, characterization of chitosan microspheres and their role in novel drug delivery systems. PMID:22707817

  14. Nanotopography applications in drug delivery.

    PubMed

    Walsh, Laura A; Allen, Jessica L; Desai, Tejal A

    2015-12-01

    Refinement of micro- and nanofabrication in the semiconductor field has led to innovations in biomedical technologies. Nanotopography, in particular, shows great potential in facilitating drug delivery. The flexibility of fabrication techniques has created a diverse array of topographies that have been developed for drug delivery applications. Nanowires and nanostraws deliver drug cytosolically for in vitro and ex vivo applications. In vivo drug delivery is limited by the barrier function of the epithelium. Nanowires on microspheres increase adhesion and residence time for oral drug delivery, while also increasing permeability of the epithelium. Low aspect ratio nanocolumns increase paracellular permeability, and in conjunction with microneedles increase transdermal drug delivery of biologics in vivo. In summary, nanotopography is a versatile tool for drug delivery. It can deliver directly to cells or be used for in vivo delivery across epithelial barriers. This editorial highlights the application of nanotopography in the field of drug delivery. PMID:26512871

  15. Transorbital therapy delivery: phantom testing

    NASA Astrophysics Data System (ADS)

    Ingram, Martha-Conley; Atuegwu, Nkiruka; Mawn, Louise; Galloway, Robert L.

    2011-03-01

    We have developed a combined image-guided and minimally invasive system for the delivery of therapy to the back of the eye. It is composed of a short 4.5 mm diameter endoscope with a magnetic tracker embedded in the tip. In previous work we have defined an optimized fiducial placement for accurate guidance to the back of the eye and are now moving to system testing. The fundamental difficulty in testing performance is establishing a target in a manner which closely mimics the physiological task. We have to have a penetrable material which obscures line of sight, similar to the orbital fat. In addition we need to have some independent measure of knowing when a target has been reached to compare to the ideal performance. Lastly, the target cannot be rigidly attached to the skull phantom since the optic nerve lies buried in the orbital fat. We have developed a skull phantom with white cloth stellate balls supporting a correctly sized globe. Placed in the white balls are red, blue, orange and yellow balls. One of the colored balls has been soaked in barium to make it bright on CT. The user guides the tracked endoscope to the target as defined by the images and tells us its color. We record task accuracy and time to target. We have tested this with 28 residents, fellows and attending physicians. Each physician performs the task twice guided and twice unguided. Results will be presented.

  16. Delivery systems for {sup 252}Cf used in industrial applications

    SciTech Connect

    Rushton, R.O.

    2000-07-01

    Californium-252 is used in a variety of industrial applications to deliver neutron dose. The design of the delivery system, i.e., the system that places the {sup 252}Cf source next to the item being exposed, is a crucial part of a successful irradiator system. This paper reviews different types of delivery systems and discusses the benefits and limitations of each type of system. A recently installed irradiator uses a straight-line pneumatic tube and a multiple-source carousel to rapidly and accurately deliver different radioactive sources to the same position.

  17. Fluid delivery control system

    DOEpatents

    Hoff, Brian D.; Johnson, Kris William; Algrain, Marcelo C.; Akasam, Sivaprasad

    2006-06-06

    A method of controlling the delivery of fluid to an engine includes receiving a fuel flow rate signal. An electric pump is arranged to deliver fluid to the engine. The speed of the electric pump is controlled based on the fuel flow rate signal.

  18. Iontophoretic drug delivery.

    PubMed

    Kalia, Yogeshvar N; Naik, Aarti; Garrison, James; Guy, Richard H

    2004-03-27

    The composition and architecture of the stratum corneum render it a formidable barrier to the topical and transdermal administration of therapeutic agents. The physicochemical constraints severely limit the number of molecules that can be considered as realistic candidates for transdermal delivery. Iontophoresis provides a mechanism to enhance the penetration of hydrophilic and charged molecules across the skin. The principal distinguishing feature is the control afforded by iontophoresis and the ability to individualize therapies. This may become significant as the impact of interindividual variations in protein expression and the effect on drug metabolism and drug efficacy is better understood. In this review we describe the underlying mechanisms that drive iontophoresis and we discuss the impact of key experimental parameters-namely, drug concentration, applied current and pH-on iontophoretic delivery efficiency. We present a comprehensive and critical review of the different therapeutic classes and molecules that have been investigated as potential candidates for iontophoretic delivery. The iontophoretic delivery of peptides and proteins is also discussed. In the final section, we describe the development of the first pre-filled, pre-programmed iontophoretic device, which is scheduled to be commercialized during the course of 2004. PMID:15019750

  19. Vaccine delivery using nanoparticles

    PubMed Central

    Gregory, Anthony E.; Titball, Richard; Williamson, Diane

    2013-01-01

    Vaccination has had a major impact on the control of infectious diseases. However, there are still many infectious diseases for which the development of an effective vaccine has been elusive. In many cases the failure to devise vaccines is a consequence of the inability of vaccine candidates to evoke appropriate immune responses. This is especially true where cellular immunity is required for protective immunity and this problem is compounded by the move toward devising sub-unit vaccines. Over the past decade nanoscale size (<1000 nm) materials such as virus-like particles, liposomes, ISCOMs, polymeric, and non-degradable nanospheres have received attention as potential delivery vehicles for vaccine antigens which can both stabilize vaccine antigens and act as adjuvants. Importantly, some of these nanoparticles (NPs) are able to enter antigen-presenting cells by different pathways, thereby modulating the immune response to the antigen. This may be critical for the induction of protective Th1-type immune responses to intracellular pathogens. Their properties also make them suitable for the delivery of antigens at mucosal surfaces and for intradermal administration. In this review we compare the utilities of different NP systems for the delivery of sub-unit vaccines and evaluate the potential of these delivery systems for the development of new vaccines against a range of pathogens. PMID:23532930

  20. Revolutionary Impact of Nanodrug Delivery on Neuroscience

    PubMed Central

    Khanbabaie, Reza; Jahanshahi, Mohsen

    2012-01-01

    Brain research is the most expanding interdisciplinary research that is using the state of the art techniques to overcome limitations in order to conduct more accurate and effective experiments. Drug delivery to the target site in the central nervous system (CNS) is one of the most difficult steps in neuroscience researches and therapies. Taking advantage of the nanoscale structure of neural cells (both neurons and glia); nanodrug delivery (second generation of biotechnological products) has a potential revolutionary impact into the basic understanding, visualization and therapeutic applications of neuroscience. Current review article firstly provides an overview of preparation and characterization, purification and separation, loading and delivering of nanodrugs. Different types of nanoparticle bioproducts and a number of methods for their fabrication and delivery systems including (carbon) nanotubes are explained. In the second part, neuroscience and nervous system drugs are deeply investigated. Different mechanisms in which nanoparticles enhance the uptake and clearance of molecules form cerebrospinal fluid (CSF) are discussed. The focus is on nanodrugs that are being used or have potential to improve neural researches, diagnosis and therapy of neurodegenerative disorders. PMID:23730260

  1. PECTIN IN CONTROLLED DRUG DELIVERY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Controlled drug delivery remains a research focus for public health to enhance patient compliance, drug efficiency and to reduce the side effects of drugs. Pectin, an edible plant polysaccharide, has shown potential for the construction of drug delivery systems for site-specific drug delivery. Sev...

  2. What Is a Cesarean Delivery?

    MedlinePLUS

    ... delivered by cesarean delivery may experience more breathing problems than infants born by vaginal delivery. 5 More information on this topic can be found in the final statement from a 2006 NIH State-of-the-Science Conference on Cesarean Delivery by Maternal Request . If ...

  3. Bioengineered Nanoparticles for siRNA delivery

    PubMed Central

    Kozielski, Kristen L.; Tzeng, Stephany Y.; Green, Jordan J.

    2014-01-01

    Short interfering RNA (siRNA) has been an important laboratory tool in the last two decades and has allowed researchers to better understand the functions of non-protein-coding genes through RNA interference (RNAi). Although RNAi holds great promise for this purpose as well as for treatment of many diseases, efforts at using siRNA have been hampered by the difficulty of safely and effectively introducing it into cells of interest, both in vitro and in vivo. To overcome this challenge, many biomaterials and nanoparticles (NPs) have been developed and optimized for siRNA delivery, often taking cues from the DNA delivery field, although different barriers exist for these two types of molecules. In this review, we discuss general properties of biomaterials and nanoparticles that are necessary for effective nucleic acid delivery. We also discuss specific examples of bioengineered materials, including lipid-based NPs, polymeric NPs, inorganic NPs, and RNA-based NPs, which clearly illustrate the problems and successes in siRNA delivery. PMID:23821336

  4. Trans-ungual iontophoretic delivery of terbinafine.

    PubMed

    Nair, Anroop B; Vaka, Siva Ram K; Sammeta, Srinivasa M; Kim, Hyun D; Friden, Phillip M; Chakraborty, Bireswar; Murthy, S Narasimha

    2009-05-01

    Successful treatment of deep-seated nail infections remains elusive as the delivery of efficacious levels of antifungal drug to the site of action is very difficult. The aim of the present study was to attain rapid trans-ungual delivery of an antifungal agent, terbinafine, via the topical route using iontophoresis. Initial studies revealed that application of current (0.5 mA/cm(2)) could significantly enhance the trans-ungual delivery of terbinafine. An increase in the applied current or duration of current application enhanced the trans-ungual delivery of terbinafine. Permeation of terbinafine through the nail and drug load in the nail correlated well with the applied electrical dose. Release of drug from nails loaded using iontophoresis followed a two-phase release profile. Light microscopy studies substantiated the capability of iontophoresis to drive a charged molecule across the nail plate. The results of these studies indicate that iontophoresis could be developed as a potential technique for onychomycosis therapy. PMID:18781625

  5. Tuberculosis chemotherapy: current drug delivery approaches

    PubMed Central

    du Toit, Lisa Claire; Pillay, Viness; Danckwerts, Michael Paul

    2006-01-01

    Tuberculosis is a leading killer of young adults worldwide and the global scourge of multi-drug resistant tuberculosis is reaching epidemic proportions. It is endemic in most developing countries and resurgent in developed and developing countries with high rates of human immunodeficiency virus infection. This article reviews the current situation in terms of drug delivery approaches for tuberculosis chemotherapy. A number of novel implant-, microparticulate-, and various other carrier-based drug delivery systems incorporating the principal anti-tuberculosis agents have been fabricated that either target the site of tuberculosis infection or reduce the dosing frequency with the aim of improving patient outcomes. These developments in drug delivery represent attractive options with significant merit, however, there is a requisite to manufacture an oral system, which directly addresses issues of unacceptable rifampicin bioavailability in fixed-dose combinations. This is fostered by the need to deliver medications to patients more efficiently and with fewer side effects, especially in developing countries. The fabrication of a polymeric once-daily oral multiparticulate fixed-dose combination of the principal anti-tuberculosis drugs, which attains segregated delivery of rifampicin and isoniazid for improved rifampicin bioavailability, could be a step in the right direction in addressing issues of treatment failure due to patient non-compliance. PMID:16984627

  6. Long-Term Delivery of Protein Therapeutics

    PubMed Central

    Vaishya, Ravi; Khurana, Varun; Patel, Sulabh; Mitra, Ashim K

    2015-01-01

    Introduction Proteins are effective biotherapetics with applications in diverse ailments. Despite being specific and potent, their full clinical potential has not yet been realized. This can be attributed to short half-lives, complex structures, poor in vivo stability, low permeability frequent parenteral administrations and poor adherence to treatment in chronic diseases. A sustained release system, providing controlled release of proteins, may overcome many of these limitations. Areas covered This review focuses on recent development in approaches, especially polymer-based formulations, which can provide therapeutic levels of proteins over extended periods. Advances in particulate, gel based formulations and novel approaches for extended protein delivery are discussed. Emphasis is placed on dosage form, method of preparation, mechanism of release and stability of biotherapeutics. Expert opinion Substantial advancements have been made in the field of extended protein delivery via various polymer-based formulations over last decade despite the unique delivery-related challenges posed by protein biologics. A number of injectable sustained-release formulations have reached market. However, therapeutic application of proteins is still hampered by delivery related issues. A large number of protein molecules are under clinical trials and hence there is an urgent need to develop new methods to deliver these highly potent biologics. PMID:25251334

  7. On-demand controlled release of docetaxel from a battery-less MEMS drug delivery device.

    PubMed

    Pirmoradi, Fatemeh Nazly; Jackson, John K; Burt, Helen M; Chiao, Mu

    2011-08-21

    We report the development of a magnetically controlled MEMS device capable of on-demand release of defined quantities of an antiproliferative drug, docetaxel (DTX). Controlled release of DTX with a dosage suitable for the treatment of diabetic retinopathy has been achieved for 35 days. The device consists of a drug-loaded microreservoir (Ø6 mm ×?550 ?m), sealed by an elastic magnetic PDMS (polydimethylsiloxane) membrane (Ø6 mm × 40 ?m) with a laser-drilled aperture (?100 × 100 ?m(2)). By applying a magnetic field, the magnetic PDMS membrane deforms, causing the discharge of the drug solution from the device. Controlled DTX release at a rate of 171 ± 16.7 ng per actuation interval has been achieved for 35 days using a 255 mT magnetic field. The background leakage of drug solution through the aperture was negligible at 0.053 ± 0.014 ng min(-1). The biological activity of the released drug was investigated using a cytotoxicity assay (cell apoptosis) for two cell lines, HUVEC (human umbilical vein endothelial cells) and PC3 (prostate cancer) cells. Reproducible release rates have been achieved and DTX within the PDMS MEMS reservoir maintains full pharmacological efficacy for more than two months. This device is a proof-of-concept development for targeted delivery of hydrophobic drugs such as DTX and other taxane-based agents that require accurate delivery in nanomolar concentrations. PMID:21698338

  8. Application of Monodirectional Janus Patch to Oromucosal Delivery System.

    PubMed

    You, Jae Bem; Choi, Ah Young; Baek, Jieung; Oh, Myung Seok; Im, Sung Gap; Lee, Kyung Eun; Gwak, Hye Sun

    2015-10-01

    Drug delivery through mucosae has received huge research attention owing to its advantageous characteristics such as accurate dose control and the avoidance of premature metabolism of vulnerable drugs by oral administration. However, body fluid in mucosae may dissolve the drug, releasing it to unwanted directions. Here, a Janus drug delivery patch with monodirectional diffusion property is devised to deliver drugs efficiently and to overcome the issue of unwanted drug release. A polyester fabric is coated with a hydrophobic polymer, poly(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10-heptadecafluorodecyl methacrylate), via initiated chemical vapor deposition. Subsequently, hydrophilicity is rendered selectively on one surface by base-catalyzed hydrolysis to obtain a Janus substrate with both hydrophobic and hydrophilic surfaces. The hydrophilic surface of the Janus substrate is further coated with resveratrol-loaded hydrogel to produce a Janus drug delivery patch. The fabricated patch efficiently blocks fluid penetration from one side to the other in mucous environment. Delivery of resveratrol through hairless mouse skin and reconstructed human mucosae using Janus patch shows higher permeation flux compared to bare control patch. The Janus drug delivery patch shown in this study can be a useful tool for efficient transmucosal delivery of various kinds of drugs. PMID:26346613

  9. Superhydrophobic materials for drug delivery

    NASA Astrophysics Data System (ADS)

    Yohe, Stefan Thomas

    Superhydrophobicity is a property of material surfaces reflecting the ability to maintain air at the solid-liquid interface when in contact with water. These surfaces have characteristically high apparent contact angles, by definition exceeding 150°, as a result of the composite material-air surface formed under an applied water droplet. Superhydrophobic surfaces were first discovered on naturally occurring substrates, and have subsequently been fabricated in the last several decades to harness these favorable surface properties for a number of emerging applications, including their use in biomedical settings. This work describes fabrication and characterization of superhydrophobic 3D materials, as well as their use as drug delivery devices. Superhydrophobic 3D materials are distinct from 2D superhydrophobic surfaces in that air is maintained not just at the surface of the material, but also within the bulk. When the superhydrophobic 3D materials are submerged in water, water infiltrates slowly and continuously as a new water-air-material interface is formed with controlled displacement of air. Electrospinning and electrospraying are used to fabricate superhydrophobic 3D materials utilizing blends of the biocompatible polymers poly(epsilon-caprolactone) and poly(caprolactone-co-glycerol monostearate) (PGC-C18). PGC-C18 is significantly more hydrophobic than PCL (contact angle of 116° versus 83° for flat materials), and further additions of PGC-C18 into electrospun meshes and electrosprayed coatings affords increased stability of the entrapped air layer. For example, PCL meshes alone (500 mum thick) take 10 days to fully wet, and with 10% or 30% PGC-C18 addition wetting rates are dramatically slowed to 60% wetted by 77 days and 4% by 75 days, respectively. Stability of the superhydrophobic materials can be further probed with a variety of physio-chemical techniques, including pressure, surfactant containing solutions, and solvents of varying surface tension. Superhydrophobicity is shown to be enhanced with further increases in PGC-C18 content and surface roughness (a decrease in fiber size). We demonstrate the utility of superhydrophobicity as a method for drug delivery. When the camptothecin derivatives SN-38 and CPT-11 are encapsulated within electrospun meshes, changes in air layer stability (due to changes in PGC-C18 content) dictate the rate of drug release by controlling the rate in which water can permeate into the porous 3D electrospun structure. Drug release can be tuned from 2 weeks to >10 weeks from 300 mum meshes, and meshes effectively kill a variety of cancer cell lines (lung, colon, breast) when utilized in a cytotoxicity assay. After determining that air could be used to control the rate of drug release, superhydrophobic 3D materials are explored for three applications. First, meshes are considered as a potential combination reinforcement-drug delivery device for use in resectable colorectal cancer. Second, removal of the air layer in superhydrophobic meshes is used as a method to trigger drug release. The pressure generated from high-intensity focused ultrasound (0.75-4.25 MPa) can remove the air layer spatially and temporally, allowing drug release to be controlled with application of a sufficient treatment. Third, "connective" electrosprayed coatings are deposited on chemically distinct material surfaces, which are both three-dimensional and mechanically robust. In summary, superhydrophobic 3D materials are fabricated and characterized, and are utilized as drug delivery devices. Controlled air removal from these materials offers an entirely new strategy for drug delivery, and is promising for the applications considered in this work as well as many others.

  10. Extended Release Drug Delivery Strategies in Psychiatry

    PubMed Central

    2005-01-01

    Objective: An overview of the emerging field of long-term delivery strategies for improved convenience and adherence with psychiatric medications is provided. This review is motivated by the hypothesis that adherence to treatment is an important determinant of clinical outcomes in a wide range of settings and is particularly important in psychiatry practice where patients require treatment for months or years and premature discontinuation can have serious consequences for patient health and quality of life. Design: The author reviews the relevant literature and highlights several approaches to providing improved access to continuous medication through new and innovative delivery strategies ranging from days to annual intervals. Benefits and Disadvantages: Several solutions to the problem of discontinuous access to pharmacotherapy are being developed in the form of new, long-acting drug-delivery systems, which gradually release medication over a period of several days or weeks with a single application. Long-acting formulations of psychiatric medications offer a number of potential benefits in comparison with conventional immediate-release agents, including improved safety and effectiveness. Potential limitations to using long-acting formulations may include pain and discomfort at the injection site, perceived inconvenience of a new treatment method, preference for oral medications, and length of time to titrate down to the lowest effective dose. Conclusions: The introduction of new, long-acting drug formulations could provide significant improvements in clinical outcomes and patient satisfaction for many patients, including those with affective disorders, schizophrenia, and alcohol dependence. Switching from oral administration to these new agents requires careful monitoring to reach the optimal dose, and patient concerns regarding the use of new delivery methods must be addressed. Long-acting formulations are not intended to be a sole form of treatment, and the use of psychotherapy as an adjunct form of treatment is still required. Controlled clinical trials of these new formulations have only recently been completed, offering clinicians a new option in their treatment regimens; however, as technologies improve, several new formulations are likely to enter clinical trials during the next few years. Psychiatrists will need to become acquainted with these technologies and educate their patients about them so they may work together to determine the most effective treatment option. PMID:21152152

  11. Protease-mediated drug delivery

    NASA Astrophysics Data System (ADS)

    Dickson, Eva F.; Goyan, Rebecca L.; Kennedy, James C.; Mackay, M.; Mendes, M. A. K.; Pottier, Roy H.

    2003-12-01

    Drugs used in disease treatment can cause damage to both malignant and normal tissue. This toxicity limits the maximum therapeutic dose. Drug targeting is of high interest to increase the therapeutic efficacy of the drug without increasing systemic toxicity. Certain tissue abnormalities, disease processes, cancers, and infections are characterized by high levels of activity of specific extracellular and/or intracellular proteases. Abnormally high activity levels of specific proteases are present at sites of physical or chemical trauma, blood clots, malignant tumors, rheumatoid arthritis, inflammatory bowel disease, gingival disease, glomerulonerphritis, and acute pancreatitis. Abnormal protease activity is suspected in development of liver thrombosis, pulmonary emphysema, atherosclerosis, and muscular dystrophy. Inactiviating disease-associated proteases by the administration of appropriate protease inhibitors has had limited success. Instead, one could use such proteases to target drugs to treat the condition. Protease mediated drug delivery offers such a possibility. Solubilizing groups are attached to insoluble drugs via a polypeptide chain which is specifically cleavable by certian proteases. When the solubilized drug enounters the protease, the solubilizing moieties are cleaved, and the drug precipitates at the disease location. Thus, a smaller systemic dosage could result in a therapeutic drug concentration at the treatment site with less systemic toxicity.

  12. Electromechanical flowmeter accurately monitors fluid flow

    NASA Technical Reports Server (NTRS)

    Grant, D. J.

    1965-01-01

    Electromechanical flowmeter remotely and accurately monitors the flow rate and total volume of a transparent liquid discharged from a dispensing system. A dual dispensing tube system provides a relative reference level which permits compensation for temperature variations.

  13. 38 CFR 4.46 - Accurate measurement.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...the measurement of limitation of motion is indispensable in examinations conducted within the Department of Veterans Affairs. Muscle atrophy must also be accurately measured and reported. [41 FR 11294, Mar. 18,...

  14. 38 CFR 4.46 - Accurate measurement.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...the measurement of limitation of motion is indispensable in examinations conducted within the Department of Veterans Affairs. Muscle atrophy must also be accurately measured and reported. [41 FR 11294, Mar. 18,...

  15. 38 CFR 4.46 - Accurate measurement.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...the measurement of limitation of motion is indispensable in examinations conducted within the Department of Veterans Affairs. Muscle atrophy must also be accurately measured and reported. [41 FR 11294, Mar. 18,...

  16. 38 CFR 4.46 - Accurate measurement.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...the measurement of limitation of motion is indispensable in examinations conducted within the Department of Veterans Affairs. Muscle atrophy must also be accurately measured and reported. [41 FR 11294, Mar. 18,...

  17. Accurate capacitive metrology for atomic force microscopy

    E-print Network

    Mazzeo, Aaron D. (Aaron David), 1979-

    2005-01-01

    This thesis presents accurate capacitive sensing metrology designed for a prototype atomic force microscope (AFM) originally developed in the MIT Precision Motion Control Lab. The capacitive measurements use a set of ...

  18. Targeted drug delivery systems for pancreatic cancer.

    PubMed

    Khare, Vaibhav; Alam, Noor; Saneja, Ankit; Dubey, Ravindra Dhar; Gupta, Prem N

    2014-12-01

    Pancreatic cancer is usually diagnosed at the advanced stages, responds poorly to the available chemotherapeutics and constitutes the major factor for high mortality rate. Selective delivery of therapeutics to their cellular targets, without side effects is the foremost objective of the current investigations for effective treatment of pancreatic cancer. The development of the drugs which can selectively target pancreatic cancer along with carriers that can deliver drugs specifically to the rapidly dividing cells is considered as magic bullet for the efficient treatment of this fatal disease. This review describes various factors hampering the efficacy of drug targeting to pancreatic cancer including stromal fortress, hypocascularity, hyaluronan and interstitial fluid pressure, and exploration of various cellular targets for the site specific drug delivery. An account of burgeoning applications of novel drug delivery systems including nanoparticles, liposomes, quantum dots, micelles and drug conjugates in the management of pancreatic cancer is also provided. Additionally, potential of target based therapeutic agents and nanomedicines in clinical trials for the pancreatic cancer therapy are highlighted. PMID:26000366

  19. Practical SPECT technique for quantitation of drug delivery to human tumors and organ absorbed radiation dose

    SciTech Connect

    Iosilevsky, G.; Israel, O.; Frenkel, A.; Even-Sapir, E.; Ben-Haim, S.; Front, A.; Kolodny, G.M.; Front, D. )

    1989-01-01

    A practical quantitative single photon emission computed tomographic (SPECT) technique based on an empirical threshold analysis permits accurate measurements in humans of drug delivery and absorbed radiation dose. The limits of the method have been explored using a wide range of phantom volumes, concentrations, and target-to-nontarget ratios. A threshold of 43% was found to give the best results using volumes of 30 to 3,800 cc. An excellent correlation (r = .99 with a standard error of estimate (SEE) of 41 cc) was found between SPECT measured volumes and actual phantom volumes. A similarly high correlation (r = .98, SEE = 260 counts/voxel) was found in 77 measurements of concentrations between 0.01 and 3.6 microCi/cc. There was a direct relationship between the target-to-nontarget ratio of phantoms and the accuracy of volume measurements. The technique has been validated by an excellent in vivo/in vitro correlation of uptake in human tumors. The tumor cumulative concentration and tumor-to-blood ratio were used for assessment of drug delivery. In vivo quantitative measurements of the pharmacokinetics of technetium-99m (99mTc) glucoheptonate, cobalt-57 (57Co) bleomycin and platinum-195m (195mPt) cisplatin in human tumors in vivo indicates that, in contrast with tumor models in animals, there is a marked variability in drug delivery even in tumors with the same histology. Future development of labeled drugs should make it possible to use quantitative SPECT for predicting tumor response to therapy and for tailoring chemotherapy for the individual patient under treatment. SPECT quantitation of organ concentration was used for Medical Internal Radiation Dose committee (MIRD) calculations of organ absorbed radiation dose from 99mTc-labeled RBCs. 48 references.

  20. Semiconductor quantum dots as delivery and imaging platforms for intracellular assembly

    NASA Astrophysics Data System (ADS)

    Field, Lauren D.; Delehanty, James B.; Walper, Scott A.; Susumu, Kimihiro; Medintz, Igor L.

    2015-08-01

    Efficient and specific delivery of particles and drugs intracellularly is a critical area of research which can allow for further understanding of cellular processes and increased efficacy of therapeutic treatments. Visualizing these delivery mechanisms occurs through use of florescent molecules, some of which are bulky and can change the processes being studied. Alternatively, semiconductor nanocrystals called quantum dots (QDs) are nanoscale particles that provide a scaffold for drugs or targeting moieties while providing superior optical properties that include size-tunable photoluminescence and resistance to photobleaching. Utilizing these platforms, delivery methods and intracellular assembly can be studied. Potential delivery mechanisms include either specified delivery through attenuation to targeting ligands or systemic delivery through microinjection or electroporation. Once within the cytosol, the QDs can assemble to express proteins, a process that can be visualized through the use of FRET. The effectiveness of various delivery methods and QD surface chemistry has been analyzed and is described here.

  1. Mucoadhesive drug delivery systems

    PubMed Central

    Shaikh, Rahamatullah; Raj Singh, Thakur Raghu; Garland, Martin James; Woolfson, A David; Donnelly, Ryan F.

    2011-01-01

    Mucoadhesion is commonly defined as the adhesion between two materials, at least one of which is a mucosal surface. Over the past few decades, mucosal drug delivery has received a great deal of attention. Mucoadhesive dosage forms may be designed to enable prolonged retention at the site of application, providing a controlled rate of drug release for improved therapeutic outcome. Application of dosage forms to mucosal surfaces may be of benefit to drug molecules not amenable to the oral route, such as those that undergo acid degradation or extensive first-pass metabolism. The mucoadhesive ability of a dosage form is dependent upon a variety of factors, including the nature of the mucosal tissue and the physicochemical properties of the polymeric formulation. This review article aims to provide an overview of the various aspects of mucoadhesion, mucoadhesive materials, factors affecting mucoadhesion, evaluating methods, and finally various mucoadhesive drug delivery systems (buccal, nasal, ocular, gastro, vaginal, and rectal). PMID:21430958

  2. Delivery of RNA interference.

    PubMed

    Li, Charles X; Parker, Amy; Menocal, Ellen; Xiang, Shuanglin; Borodyansky, Laura; Fruehauf, Johannes H

    2006-09-01

    Over the last few years, RNA Interference (RNAi), a naturally occurring mechanism of gene regulation conserved in plant and mammalian cells, has opened numerous novel opportunities for basic research across the field of biology. While RNAi has helped accelerate discovery and understanding of gene functions, it also has great potential as a therapeutic and potentially prophylactic modality. Challenging diseases failing conventional therapeutics could become treatable by specific silencing of key pathogenic genes. More specifically, therapeutic targets previously deemed "undruggable" by small molecules, are now coming within reach of RNAi based therapy. For RNAi to be effective and elicit gene silencing response, the double-stranded RNA molecules must be delivered to the target cell. Unfortunately, delivery of these RNA duplexes has been challenging, halting rapid development of RNAi-based therapies. In this review we present current advancements in the field of siRNA delivery methods, including the pros and cons of each method. PMID:16940756

  3. Understanding the Code: keeping accurate records.

    PubMed

    Griffith, Richard

    2015-10-01

    In his continuing series looking at the legal and professional implications of the Nursing and Midwifery Council's revised Code of Conduct, Richard Griffith discusses the elements of accurate record keeping under Standard 10 of the Code. This article considers the importance of accurate record keeping for the safety of patients and protection of district nurses. The legal implications of records are explained along with how district nurses should write records to ensure these legal requirements are met. PMID:26418404

  4. Supplementary Data Drug delivery

    E-print Network

    Seroude, Laurent

    to polymerize and dry at room temperature for 12 to 36 hours depending on the ambient humidity. 2. "Yeast paste (0.01% molasses/8.2% cornmeal/3.4% killed yeast/0.94% agar/0.18% benzoic acid/0.66% propionic acic" delivery: Appropriate volumes of 25 mg/ml RU486 stock solution was mixed with yeast paste (60.4% water, 39

  5. Nanovehicular Intracellular Delivery Systems

    PubMed Central

    PROKOP, ALES; DAVIDSON, JEFFREY M.

    2013-01-01

    This article provides an overview of principles and barriers relevant to intracellular drug and gene transport, accumulation and retention (collectively called as drug delivery) by means of nanovehicles (NV). The aim is to deliver a cargo to a particular intracellular site, if possible, to exert a local action. Some of the principles discussed in this article apply to noncolloidal drugs that are not permeable to the plasma membrane or to the blood–brain barrier. NV are defined as a wide range of nanosized particles leading to colloidal objects which are capable of entering cells and tissues and delivering a cargo intracelullarly. Different localization and targeting means are discussed. Limited discussion on pharmacokinetics and pharmacodynamics is also presented. NVs are contrasted to micro-delivery and current nanotechnologies which are already in commercial use. Newer developments in NV technologies are outlined and future applications are stressed. We also briefly review the existing modeling tools and approaches to quantitatively describe the behavior of targeted NV within the vascular and tumor compartments, an area of particular importance. While we list “elementary” phenomena related to different level of complexity of delivery to cancer, we also stress importance of multi-scale modeling and bottom-up systems biology approach. PMID:18200527

  6. Transmembrane heme delivery systems

    PubMed Central

    Goldman, Barry S.; Beck, David L.; Monika, Elizabeth M.; Kranz, Robert G.

    1998-01-01

    Heme proteins play pivotal roles in a wealth of biological processes. Despite this, the molecular mechanisms by which heme traverses bilayer membranes for use in biosynthetic reactions are unknown. The biosynthesis of c-type cytochromes requires that heme is transported to the bacterial periplasm or mitochondrial intermembrane space where it is covalently ligated to two reduced cysteinyl residues of the apocytochrome. Results herein suggest that a family of integral membrane proteins in prokaryotes, protozoans, and plants act as transmembrane heme delivery systems for the biogenesis of c-type cytochromes. The complete topology of a representative from each of the three subfamilies was experimentally determined. Key histidinyl residues and a conserved tryptophan-rich region (designated the WWD domain) are positioned at the site of cytochrome c assembly for all three subfamilies. These histidinyl residues were shown to be essential for function in one of the subfamilies, an ABC transporter encoded by helABCD. We believe that a directed heme delivery pathway is vital for the synthesis of cytochromes c, whereby heme iron is protected from oxidation via ligation to histidinyl residues within the delivery proteins. PMID:9560218

  7. Single compartment drug delivery

    PubMed Central

    Cima, Michael J.; Lee, Heejin; Daniel, Karen; Tanenbaum, Laura M.; Mantzavinou, Aikaterini; Spencer, Kevin C.; Ong, Qunya; Sy, Jay C.; Santini, John; Schoellhammer, Carl M.; Blankschtein, Daniel; Langer, Robert S.

    2014-01-01

    Drug design is built on the concept that key molecular targets of disease are isolated in the diseased tissue. Systemic drug administration would be sufficient for targeting in such a case. It is, however, common for enzymes or receptors that are integral to disease to be structurally similar or identical to those that play important biological roles in normal tissues of the body. Additionally, systemic administration may not lead to local drug concentrations high enough to yield disease modification because of rapid systemic metabolism or lack of sufficient partitioning into the diseased tissue compartment. This review focuses on drug delivery methods that physically target drugs to individual compartments of the body. Compartments such as the bladder, peritoneum, brain, eye and skin are often sites of disease and can sometimes be viewed as “privileged,” since they intrinsically hinder partitioning of systemically administered agents. These compartments have become the focus of a wide array of procedures and devices for direct administration of drugs. We discuss the rationale behind single compartment drug delivery for each of these compartments, and give an overview of examples at different development stages, from the lab bench to phase III clinical trials to clinical practice. We approach single compartment drug delivery from both a translational and a technological perspective. PMID:24798478

  8. Novel antigen delivery systems

    PubMed Central

    Trovato, Maria; Berardinis, Piergiuseppe De

    2015-01-01

    Vaccines represent the most relevant contribution of immunology to human health. However, despite the remarkable success achieved in the past years, many vaccines are still missing in order to fight important human pathologies and to prevent emerging and re-emerging diseases. For these pathogens the known strategies for making vaccines have been unsuccessful and thus, new avenues should be investigated to overcome the failure of clinical trials and other important issues including safety concerns related to live vaccines or viral vectors, the weak immunogenicity of subunit vaccines and side effects associated with the use of adjuvants. A major hurdle of developing successful and effective vaccines is to design antigen delivery systems in such a way that optimizes antigen presentation and induces broad protective immune responses. Recent advances in vector delivery technologies, immunology, vaccinology and system biology, have led to a deeper understanding of the molecular and cellular mechanisms by which vaccines should stimulate both arms of the adaptive immune responses, offering new strategies of vaccinations. This review is an update of current strategies with respect to live attenuated and inactivated vaccines, DNA vaccines, viral vectors, lipid-based carrier systems such as liposomes and virosomes as well as polymeric nanoparticle vaccines and virus-like particles. In addition, this article will describe our work on a versatile and immunogenic delivery system which we have studied in the past decade and which is derived from a non-pathogenic prokaryotic organism: the “E2 scaffold” of the pyruvate dehydrogenase complex from Geobacillus stearothermophilus. PMID:26279977

  9. Novel antigen delivery systems.

    PubMed

    Trovato, Maria; De Berardinis, Piergiuseppe

    2015-08-12

    Vaccines represent the most relevant contribution of immunology to human health. However, despite the remarkable success achieved in the past years, many vaccines are still missing in order to fight important human pathologies and to prevent emerging and re-emerging diseases. For these pathogens the known strategies for making vaccines have been unsuccessful and thus, new avenues should be investigated to overcome the failure of clinical trials and other important issues including safety concerns related to live vaccines or viral vectors, the weak immunogenicity of subunit vaccines and side effects associated with the use of adjuvants. A major hurdle of developing successful and effective vaccines is to design antigen delivery systems in such a way that optimizes antigen presentation and induces broad protective immune responses. Recent advances in vector delivery technologies, immunology, vaccinology and system biology, have led to a deeper understanding of the molecular and cellular mechanisms by which vaccines should stimulate both arms of the adaptive immune responses, offering new strategies of vaccinations. This review is an update of current strategies with respect to live attenuated and inactivated vaccines, DNA vaccines, viral vectors, lipid-based carrier systems such as liposomes and virosomes as well as polymeric nanoparticle vaccines and virus-like particles. In addition, this article will describe our work on a versatile and immunogenic delivery system which we have studied in the past decade and which is derived from a non-pathogenic prokaryotic organism: the "E2 scaffold" of the pyruvate dehydrogenase complex from Geobacillus stearothermophilus. PMID:26279977

  10. Delivery Systems for {sup 252}Cf Used in Industrial Applications

    SciTech Connect

    R. O. Rushton

    2000-06-04

    Californium-252 is used in a variety of industrial applications to deliver neutron dose. The design of the delivery system, i.e., the system that places the {sup 252}Cf source next to the item being exposed, is a crucial part of a successful irradiator system. This paper reviews different types of delivery systems and discusses the benefits and limitations of each type of system. Several types of delivery systems are commercially available for {sup 252}Cf irradiators. The best design depends on the application for which it is used. For calibrating instruments and exposing dosimetry badges, the new straight-line, carousel system has proven to be effective, accurate, reliable, and safe.

  11. Development of Small RNA Delivery Systems for Lung Cancer Therapy

    PubMed Central

    Fujita, Yu; Kuwano, Kazuyoshi; Ochiya, Takahiro

    2015-01-01

    RNA interference (RNAi) has emerged as a powerful tool for studying target identification and holds promise for the development of therapeutic gene silencing. Recent advances in RNAi delivery and target selection provide remarkable opportunities for translational medical research. The induction of RNAi relies on small silencing RNAs, which affect specific messenger RNA (mRNA) degradation. Two types of small RNA molecules, small interfering RNAs (siRNAs) and microRNAs (miRNAs), have a central function in RNAi technology. The success of RNAi-based therapeutic delivery may be dependent upon uncovering a delivery route, sophisticated delivery carriers, and nucleic acid modifications. Lung cancer is still the leading cause of cancer death worldwide, for which novel therapeutic strategies are critically needed. Recently, we have reported a novel platform (PnkRNA™ and nkRNA®) to promote naked RNAi approaches through inhalation without delivery vehicles in lung cancer xenograft models. We suggest that a new class of RNAi therapeutic agent and local drug delivery system could also offer a promising RNAi-based strategy for clinical applications in cancer therapy. In this article, we show recent strategies for an RNAi delivery system and suggest the possible clinical usefulness of RNAi-based therapeutics for lung cancer treatment. PMID:25756380

  12. An intestinal Trojan horse for gene delivery

    NASA Astrophysics Data System (ADS)

    Peng, Haisheng; Wang, Chao; Xu, Xiaoyang; Yu, Chenxu; Wang, Qun

    2015-02-01

    The intestinal epithelium forms an essential element of the mucosal barrier and plays a critical role in the pathophysiological response to different enteric disorders and diseases. As a major enteric dysfunction of the intestinal tract, inflammatory bowel disease is a genetic disease which results from the inappropriate and exaggerated mucosal immune response to the normal constituents in the mucosal microbiota environment. An intestine targeted drug delivery system has unique advantages in the treatment of inflammatory bowel disease. As a new concept in drug delivery, the Trojan horse system with the synergy of nanotechnology and host cells can achieve better therapeutic efficacy in specific diseases. Here, we demonstrated the feasibility of encapsulating DNA-functionalized gold nanoparticles into primary isolated intestinal stem cells to form an intestinal Trojan horse for gene regulation therapy of inflammatory bowel disease. This proof-of-concept intestinal Trojan horse will have a wide variety of applications in the diagnosis and therapy of enteric disorders and diseases.

  13. An intestinal Trojan horse for gene delivery.

    PubMed

    Peng, Haisheng; Wang, Chao; Xu, Xiaoyang; Yu, Chenxu; Wang, Qun

    2015-03-14

    The intestinal epithelium forms an essential element of the mucosal barrier and plays a critical role in the pathophysiological response to different enteric disorders and diseases. As a major enteric dysfunction of the intestinal tract, inflammatory bowel disease is a genetic disease which results from the inappropriate and exaggerated mucosal immune response to the normal constituents in the mucosal microbiota environment. An intestine targeted drug delivery system has unique advantages in the treatment of inflammatory bowel disease. As a new concept in drug delivery, the Trojan horse system with the synergy of nanotechnology and host cells can achieve better therapeutic efficacy in specific diseases. Here, we demonstrated the feasibility of encapsulating DNA-functionalized gold nanoparticles into primary isolated intestinal stem cells to form an intestinal Trojan horse for gene regulation therapy of inflammatory bowel disease. This proof-of-concept intestinal Trojan horse will have a wide variety of applications in the diagnosis and therapy of enteric disorders and diseases. PMID:25619169

  14. Emerging Trends in Noninvasive Insulin Delivery

    PubMed Central

    Verma, Arun; Kumar, Nitin; Malviya, Rishabha; Sharma, Pramod Kumar

    2014-01-01

    This paper deals with various aspects of oral insulin delivery system. Insulin is used for the treatment of diabetes mellitus, which is characterized by the elevated glucose level (above the normal range) in the blood stream, that is, hyperglycemia. Oral route of administration of any drug is the most convenient route. Development of oral insulin is still under research. Oral insulin will cause the avoidance of pain during the injection (in subcutaneous administration), anxiety due to needle, and infections which can be developed. Different types of enzyme inhibitors, like sodium cholate, camostat, mesilate, bacitracin, leupeptin, and so forth, have been used to prevent insulin from enzymatic degradation. Subcutaneous route has been used for administration of insulin, but pain and itching at the site of administration can occur. That is why various alternative routes of insulin administration like oral route are under investigation. In this paper authors summarized advancement in insulin delivery with their formulation aspects. PMID:26556194

  15. Liquid and surfactant delivery into pulmonary airways

    PubMed Central

    Halpern, David; Fujioka, Hideki; Takayama, Shuichi; Grotberg, James B.

    2008-01-01

    We describe the mechanisms by which liquids and surfactants can be delivered into the pulmonary airways. These are instilled and transported throughout the lung in clinical therapies such as surfactant replacement therapy, partial liquid ventilation and drug delivery. The success of these treatments is contingent on the liquid distribution and the delivery to targeted regions of the lung. The targeting of a liquid plug can be influenced by a variety of factors such as the physical properties of the liquid, the interfacial activity, the gravitational orientation, instillation method and propagation speed. We provide a review of experimental and theoretical studies that examine these effects in single tubes or channels, in tubes with single bifurcations and in the whole lung. PMID:18585985

  16. Drug Delivery Nanoparticles in Skin Cancers

    PubMed Central

    Dianzani, Chiara; Zara, Gian Paolo; Maina, Giovanni; Pettazzoni, Piergiorgio; Pizzimenti, Stefania; Rossi, Federica; Gigliotti, Casimiro Luca; Ciamporcero, Eric Stefano; Daga, Martina; Barrera, Giuseppina

    2014-01-01

    Nanotechnology involves the engineering of functional systems at nanoscale, thus being attractive for disciplines ranging from materials science to biomedicine. One of the most active research areas of the nanotechnology is nanomedicine, which applies nanotechnology to highly specific medical interventions for prevention, diagnosis, and treatment of diseases, including cancer disease. Over the past two decades, the rapid developments in nanotechnology have allowed the incorporation of multiple therapeutic, sensing, and targeting agents into nanoparticles, for detection, prevention, and treatment of cancer diseases. Nanoparticles offer many advantages as drug carrier systems since they can improve the solubility of poorly water-soluble drugs, modify pharmacokinetics, increase drug half-life by reducing immunogenicity, improve bioavailability, and diminish drug metabolism. They can also enable a tunable release of therapeutic compounds and the simultaneous delivery of two or more drugs for combination therapy. In this review, we discuss the recent advances in the use of different types of nanoparticles for systemic and topical drug delivery in the treatment of skin cancer. In particular, the progress in the treatment with nanocarriers of basal cell carcinoma, squamous cell carcinoma, and melanoma has been reported. PMID:25101298

  17. Imaging Functional Nucleic Acid Delivery to Skin.

    PubMed

    Kaspar, Roger L; Hickerson, Robyn P; González-González, Emilio; Flores, Manuel A; Speaker, Tycho P; Rogers, Faye A; Milstone, Leonard M; Contag, Christopher H

    2016-01-01

    Monogenic skin diseases arise from well-defined single gene mutations, and in some cases a single point mutation. As the target cells are superficial, these diseases are ideally suited for treatment by nucleic acid-based therapies as well as monitoring through a variety of noninvasive imaging technologies. Despite the accessibility of the skin, there remain formidable barriers for functional delivery of nucleic acids to the target cells within the dermis and epidermis. These barriers include the stratum corneum and the layered structure of the skin, as well as more locally, the cellular, endosomal and nuclear membranes. A wide range of technologies for traversing these barriers has been described and moderate success has been reported for several approaches. The lessons learned from these studies include the need for combinations of approaches to facilitate nucleic acid delivery across these skin barriers and then functional delivery across the cellular and nuclear membranes for expression (e.g., reporter genes, DNA oligonucleotides or shRNA) or into the cytoplasm for regulation (e.g., siRNA, miRNA, antisense oligos). The tools for topical delivery that have been evaluated include chemical, physical and electrical methods, and the development and testing of each of these approaches has been greatly enabled by imaging tools. These techniques allow delivery and real time monitoring of reporter genes, therapeutic nucleic acids and also triplex nucleic acids for gene editing. Optical imaging is comprised of a number of modalities based on properties of light-tissue interaction (e.g., scattering, autofluorescence, and reflectance), the interaction of light with specific molecules (e.g., absorbtion, fluorescence), or enzymatic reactions that produce light (bioluminescence). Optical imaging technologies operate over a range of scales from macroscopic to microscopic and if necessary, nanoscopic, and thus can be used to assess nucleic acid delivery to organs, regions, cells and even subcellular structures. Here we describe the animal models, reporter genes, imaging approaches and general strategies for delivery of nucleic acids to cells in the skin for local expression (e.g., plasmid DNA) or gene silencing (e.g., siRNA) with the intent of developing nucleic acid-based therapies to treat diseases of the skin. PMID:26530911

  18. Stimuli-Responsive Nanomaterials for Therapeutic Protein Delivery

    PubMed Central

    Lu, Yue; Sun, Wujin; Gu, Zhen

    2014-01-01

    Protein therapeutics have emerged as a significant role in treatment of a broad spectrum of diseases, including cancer, metabolic disorders and autoimmune diseases. The efficacy of protein therapeutics, however, is limited by their instability, immunogenicity and short half-life. In order to overcome these barriers, tremendous efforts have recently been made in developing controlled protein delivery systems. Stimuli-triggered release is an appealing and promising approach for protein delivery and has made protein delivery with both spatiotemporal- and dosage-controlled manners possible. This review surveys recent advances in controlled protein delivery of proteins or peptides using stimuli-responsive nanomaterials. Strategies utilizing both physiological and external stimuli are introduced and discussed. PMID:25151983

  19. Exploring Different Strategies for Efficient Delivery of Colorectal Cancer Therapy

    PubMed Central

    Lin, Congcong; Ng, Huei Leng Helena; Pan, Weisan; Chen, Hubiao; Zhang, Ge; Bian, Zhaoxiang; Lu, Aiping; Yang, Zhijun

    2015-01-01

    Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer death in the world. Currently available chemotherapy of CRC usually delivers the drug to both normal as well as cancerous tissues, thus leading to numerous undesirable effects. Much emphasis is being laid on the development of effective drug delivery systems for achieving selective delivery of the active moiety at the anticipated site of action with minimized unwanted side effects. Researchers have employed various techniques (dependent on pH, time, pressure and/or bacteria) for targeting drugs directly to the colonic region. On the other hand, systemic drug delivery strategies to specific molecular targets (such as FGFR, EGFR, CD44, EpCAM, CA IX, PPAR? and COX-2) overexpressed by cancerous cells have also been shown to be effective. This review aims to put forth an overview of drug delivery technologies that have been, and may be developed, for the treatment of CRC. PMID:26569228

  20. Structural analysis of xSrO-(50-x)CaO-50P2O5 glasses with x=0, 5, or 10mol% for potential use in a local delivery system for osteomyelitis treatment.

    PubMed

    Comeau, P A; Filiaggi, M J

    2016-01-01

    The introduction of ions into a local delivery matrix is one method of managing degradation and subsequent release of the incorporated therapeutic agents. Of interest in this study was whether we could modify the structural nature of calcium polyphosphate (CPP) glass and the subsequent therapeutic potential of this local delivery matrix with inclusion of strontium (Sr). We found that adding 10mol% Sr significantly increased the density and chain length of the glass. There was no significant impact of Sr doping on the subsequent loading of vancomycin into the matrix, or the matrix porosity. The noted differences in structural stability, ion release, and vancomycin release between the un-doped CPP matrices and 10mol% Sr-doped CPP matrices in vitro are likely a result of a decrease in glass disorder upon Sr addition to the glass and preferential retention of Sr over Ca during matrix degradation. This study has provided further evidence that Sr incorporation may serve to both manipulate antibiotic release from the amorphous CPP matrix and provide a potential source of therapeutic ions for enhanced bone regeneration. PMID:26478355

  1. Delivery of therapeutic radioisotopes using nanoparticle platforms: potential benefit in systemic radiation therapy

    PubMed Central

    Zhang, Longjiang; Chen, Hongwei; Wang, Liya; Liu, Tian; Yeh, Julie; Lu, Guangming; Yang, Lily; Mao, Hui

    2010-01-01

    Radiation therapy is an effective cancer treatment option in conjunction with chemotherapy and surgery. Emerging individualized internal and systemic radiation treatment promises significant improvement in efficacy and reduction of normal tissue damage; however, it requires cancer cell targeting platforms for efficient delivery of radiation sources. With recent advances in nanoscience and nanotechnology, there is great interest in developing nanomaterials as multifunctional carriers to deliver therapeutic radioisotopes for tumor targeted radiation therapy, to monitor their delivery and tumor response to the treatment. This paper provides an overview on developing nanoparticles for carrying and delivering therapeutic radioisotopes for systemic radiation treatment. Topics discussed in the review include: selecting nanoparticles and radiotherapy isotopes, strategies for targeting nanoparticles to cancers, together with challenges and potential solutions for the in vivo delivery of nanoparticles. Some examples of using nanoparticle platforms for the delivery of therapeutic radioisotopes in preclinical studies of cancer treatment are also presented. PMID:24198480

  2. Methods and metrics challenges of delivery-system research

    PubMed Central

    2012-01-01

    Background Many delivery-system interventions are fundamentally about change in social systems (both planned and unplanned). This systems perspective raises a number of methodological challenges for studying the effects of delivery-system change--particularly for answering questions related to whether the change will work under different conditions and how the change is integrated (or not) into the operating context of the delivery system. Methods The purpose of this paper is to describe the methodological and measurement challenges posed by five key issues in delivery-system research: (1) modeling intervention context; (2) measuring readiness for change; (3) assessing intervention fidelity and sustainability; (4) assessing complex, multicomponent interventions; and (5) incorporating time in delivery-system models to discuss recommendations for addressing these issues. For each issue, we provide recommendations for how research may be designed and implemented to overcome these challenges. Results and conclusions We suggest that a more refined understanding of the mechanisms underlying delivery-system interventions (treatment theory) and the ways in which outcomes for different classes of individuals change over time are fundamental starting points for capturing the heterogeneity in samples of individuals exposed to delivery-system interventions. To support the research recommendations outlined in this paper and to advance understanding of the "why" and "how" questions of delivery-system change and their effects, funding agencies should consider supporting studies with larger organizational sample sizes; longer duration; and nontraditional, mixed-methods designs. A version of this paper was prepared under contract with the Agency for Healthcare Research and Quality (AHRQ), US Department of Health and Human Services for presentation and discussion at a meeting on "The Challenge and Promise of Delivery System Research," held in Sterling, VA, on February 16-17, 2011. The opinions in the paper are those of the author and do not represent the views or recommendations of AHRQ or the US Department of Health and Human Services.1 PMID:22409885

  3. Polymers for Drug Delivery Systems

    PubMed Central

    Liechty, William B.; Kryscio, David R.; Slaughter, Brandon V.; Peppas, Nicholas A.

    2012-01-01

    Polymers have played an integral role in the advancement of drug delivery technology by providing controlled release of therapeutic agents in constant doses over long periods, cyclic dosage, and tunable release of both hydrophilic and hydrophobic drugs. From early beginnings using off-the-shelf materials, the field has grown tremendously, driven in part by the innovations of chemical engineers. Modern advances in drug delivery are now predicated upon the rational design of polymers tailored for specific cargo and engineered to exert distinct biological functions. In this review, we highlight the fundamental drug delivery systems and their mathematical foundations and discuss the physiological barriers to drug delivery. We review the origins and applications of stimuli-responsive polymer systems and polymer therapeutics such as polymer-protein and polymer-drug conjugates. The latest developments in polymers capable of molecular recognition or directing intracellular delivery are surveyed to illustrate areas of research advancing the frontiers of drug delivery. PMID:22432577

  4. A Solvent-Free Thermosponge Nanoparticle Platform for Efficient Delivery of Labile Proteins

    E-print Network

    von Andrian, Ulrich H.

    A Solvent-Free Thermosponge Nanoparticle Platform for Efficient Delivery of Labile Proteins Won Il the development of a novel polymeric thermosponge nanoparticle for efficient delivery of labile proteins using Supporting Information ABSTRACT: Protein therapeutics have gained attention recently for treatment

  5. DELIVERY OF THERAPEUTIC PROTEINS

    PubMed Central

    Pisal, Dipak S.; Kosloski, Matthew P.; Balu-Iyer, Sathy V.

    2009-01-01

    The safety and efficacy of protein therapeutics are limited by three interrelated pharmaceutical issues, in vitro and in vivo instability, immunogenicity and shorter half-lives. Novel drug modifications for overcoming these issues are under investigation and include covalent attachment of poly(ethylene glycol) (PEG), polysialic acid, or glycolic acid, as well as developing new formulations containing nanoparticulate or colloidal systems (e.g. liposomes, polymeric microspheres, polymeric nanoparticles). Such strategies have the potential to develop as next generation protein therapeutics. This review includes a general discussion on these delivery approaches. PMID:20049941

  6. Delivery methods for LVSD systems

    NASA Astrophysics Data System (ADS)

    Kasner, James H.; Brower, Bernard V.

    2011-06-01

    In this paper we present formats and delivery methods of Large Volume Streaming Data (LVSD) systems. LVSD systems collect TBs of data per mission with aggregate camera sizes in the 100 Mpixel to several Gpixel range at temporal rates of 2 - 60 Hz. We present options and recommendations for the different stages of LVSD data collection and delivery, to include the raw (multi-camera) data, delivery of processed (stabilized mosaic) data, and delivery of user-defined region of interest windows. Many LVSD systems use JPEG 2000 for the compression of raw and processed data. We explore the use of the JPEG 2000 Interactive Protocol (JPIP) for interactive client/server delivery to thick-clients (desktops and laptops) and MPEG-2 and H.264 to handheld thin-clients (tablets, cell phones). We also explore the use of 3D JPEG 2000 compression, defined in ISO 15444-2, for storage and delivery as well. The delivery of raw, processed, and region of interest data requires different metadata delivery techniques and metadata content. Beyond the format and delivery of data and metadata we discuss the requirements for a client/server protocol that provides data discovery and retrieval. Finally, we look into the future as LVSD systems perform automated processing to produce "information" from the original data. This information may include tracks of moving targets, changes of the background, snap shots of targets, fusion of multiple sensors, and information about "events" that have happened.

  7. Dendrimer Advances for the Central Nervous System Delivery of Therapeutics

    PubMed Central

    2013-01-01

    The effectiveness of noninvasive treatment for central nervous system (CNS) diseases is generally limited by the poor access of therapeutic agents into the CNS. Most CNS drugs cannot permeate into the brain parenchyma because of the blood-brain barrier (BBB), and overcoming this has become one of the most significant challenges in the development of CNS therapeutics. Rapid advances in nanotechnology have provided promising solutions to this challenge. This review discusses the latest applications of dendrimers in the treatment of CNS diseases with an emphasis on brain tumors. Dendrimer-mediated drug delivery, imaging, and diagnosis are also reviewed. The toxicity, biodistribution, and transport mechanisms in dendrimer-mediated delivery of CNS therapeutic agents bypassing or crossing the BBB are also discussed. Future directions and major challenges of dendrimer-mediated delivery of CNS therapeutic agents are included. PMID:24274162

  8. Vaginal Birth After Cesarean Delivery: Deciding on a Trial of Labor After a Cesarean Delivery (TOLAC)

    MedlinePLUS

    ... Vaginal Birth After Cesarean Delivery: Deciding on a Trial of Labor After Cesarean Delivery • What is a ... birth after cesarean delivery ( VBAC) ? • What is a trial of labor after cesarean delivery ( TOLAC) ? • What are ...

  9. Analytical verification of waterborne chemical treatment regimens in hatchery raceways

    USGS Publications Warehouse

    Rach, J.J.; Ramsay, R.T.

    2000-01-01

    Chemical therapy for control and prevention of fish diseases is a necessary and common practice in aquaculture. Many factors affect the accuracy of a chemical treatment application, such as the functioning of the chemical delivery system, calculation of chemical quantities to be delivered, water temperature, geometry of the culture unit, inlet-outlet structure, the influence of aerators, wind movement, and measurement of water volumes and flow rates. Three separate trials were conducted at the Osceola Fish Hatchery, a facility of the Wisconsin Department of Natural Resources, evaluating the accuracy of flow-through hydrogen peroxide treatments applied to 1, 3, or 9 raceways that were connected in series. Raceways were treated with 50 or 75 ??L/L of hydrogen peroxide for 30 min. Chemical concentrations were determined titrimetrically. The target treatment regimen was not realized in any of the applications. Chemical concentrations dropped and exposure times increased with each additional raceway treated in series. Single introduction of a therapeutant to more than three raceways in series is not recommended. Factors that interfered with the accuracy of the treatments were culture unit configuration, aeration, and flow rates. Several treatment modifications were identified that would result in more accurate chemical treatments.

  10. Clinical implementation of target tracking by breathing synchronized delivery

    SciTech Connect

    Tewatia, Dinesh; Zhang Tiezhi; Tome, Wolfgang; Paliwal, Bhudatt; Metha, Minesh

    2006-11-15

    Target-tracking techniques can be categorized based on the mechanism of the feedback loop. In real time tracking, breathing-delivery phase correlation is provided to the treatment delivery hardware. Clinical implementation of target tracking in real time requires major hardware modifications. In breathing synchronized delivery (BSD), the patient is guided to breathe in accordance with target motion derived from four-dimensional computed tomography (4D-CT). Violations of mechanical limitations of hardware are to be avoided at the treatment planning stage. Hardware modifications are not required. In this article, using sliding window IMRT delivery as an example, we have described step-by-step the implementation of target tracking by the BSD technique: (1) A breathing guide is developed from patient's normal breathing pattern. The patient tries to reproduce this guiding cycle by following the display in the goggles; (2) 4D-CT scans are acquired at all the phases of the breathing cycle; (3) The average tumor trajectory is obtained by deformable image registration of 4D-CT datasets and is smoothed by Fourier filtering; (4) Conventional IMRT planning is performed using the images at reference phase (full exhalation phase) and a leaf sequence based on optimized fluence map is generated; (5) Assuming the patient breathes with a reproducible breathing pattern and the machine maintains a constant dose rate, the treatment process is correlated with the breathing phase; (6) The instantaneous average tumor displacement is overlaid on the dMLC position at corresponding phase; and (7) DMLC leaf speed and acceleration are evaluated to ensure treatment delivery. A custom-built mobile phantom driven by a computer-controlled stepper motor was used in the dosimetry verification. A stepper motor was programmed such that the phantom moved according to the linear component of tumor motion used in BSD treatment planning. A conventional plan was delivered on the phantom with and without motion. The BSD plan was also delivered on the phantom that moved with the prescheduled pattern and synchronized with the delivery of each beam. Film dosimetry showed underdose and overdose in the superior and inferior regions of the target, respectively, if the tumor motion is not compensated during the delivery. BSD delivery resulted in a dose distribution very similar to the planned treatments.

  11. Helical tomotherapy with dynamic running-start-stop delivery compared to conventional tomotherapy delivery

    SciTech Connect

    Rong, Yi; Chen, Yu; Lu, Weiguo; Shang, Lu; Zuo, Li; Chen, Quan

    2014-05-15

    Purpose: Despite superior target dose uniformity, helical tomotherapy{sup ®} (HT) may involve a trade-off between longitudinal dose conformity and beam-on time (BOT), due to the limitation of only three available jaw sizes with the conventional HT (1.0, 2.5, and 5.0 cm). The recently introduced dynamic running-start-stop (RSS) delivery allows smaller jaw opening at the superior and inferior ends of the target when a sharp penumbra is needed. This study compared the dosimetric performance of RSS delivery with the fixed jaw HT delivery. Methods: Twenty patient cases were selected and deidentified prior to treatment planning, including 16 common clinical cases (brain, head and neck (HN), lung, and prostate) and four special cases of whole brain with hippocampus avoidance (WBHA) that require a high degree of dose modulation. HT plans were generated for common clinical cases using the fixed 2.5 cm jaw width (HT2.5) and WBHA cases using 1.0 cm (HT1.0). The jaw widths for RSS were preset with a larger size (RSS5.0 vs HT2.5 and RSS2.5 vs HT1.0). Both delivery techniques were planned based on identical contours, prescriptions, and planning objectives. Dose indices for targets and critical organs were compared using dose-volume histograms, BOT, and monitor units. Results: The average BOT was reduced from 4.8 min with HT2.5 to 2.5 min with RSS5.0. Target dose homogeneity with RSS5.0 was shown comparable to HT2.5 for common clinical sites. Superior normal tissue sparing was observed in RSS5.0 for optic nerves and optic chiasm in brain and HN cases. RSS5.0 demonstrated improved dose sparing for cord and esophagus in lung cases, as well as penile bulb in prostate cases. The mean body dose was comparable for both techniques. For the WBHA cases, the target homogeneity was significantly degraded in RSS2.5 without distinct dose sparing for hippocampus, compared to HT1.0. Conclusions: Compared to the fixed jaw HT delivery, RSS combined with a larger jaw width provides faster treatment delivery and improved cranial-caudal target dose conformity. The target coverage achieved by RSS with a large jaw width is comparable to the fixed jaw HT delivery for common cancer sites, but may deteriorate for cases where complex geometry is present in the middle part of the target.

  12. RNA-Catalyzed RNA Polymerization: Accurate and

    E-print Network

    Bartel, David

    for general polymerization (7). De- rivatives of self-splicing introns are able to join oligonucleotidesRNA-Catalyzed RNA Polymerization: Accurate and General RNA-Templated Primer Extension Wendy K. Johnston, Peter J. Unrau,* Michael S. Lawrence, Margaret E. Glasner, David P. Bartel The RNA world

  13. LETTERS TO NATURE Accurate prediction of the

    E-print Network

    Levitt, Michael

    LETTERS TO NATURE Accurate prediction of the stability and activity effects of site to be more stable than the wild type. Free-energy stability calculations for several single-site muta- tions-chains allowed to move in the prediction is shown as solid lines (predicted wild-type structure (thin lines

  14. APT: Accurate Outdoor Pedestrian Tracking with Smartphones

    E-print Network

    Li, Qun

    APT: Accurate Outdoor Pedestrian Tracking with Smartphones Xiaojun Zhu, Qun Li, Guihai Chen§ State pedestrians with smartphones. APT performs better than the built-in GPS module of the smartphone in terms for map matching. When the user is walking with the smartphone, the dead reckoning algorithm monitors

  15. Accurate Electrothermal Modeling of Thermoelectric Generators

    E-print Network

    Pedram, Massoud

    Accurate Electrothermal Modeling of Thermoelectric Generators Mohammad Javad Dousti1 , Antonio Janeiro, Brazil 1 {dousti,pedram}@usc.edu and 2 antonio@pads.ufrj.br Abstract--Thermoelectric generators of thermoelectric generators (TEGs). TEGs work based on the Seebeck effect, which converts a temperature gradient

  16. Fast and Accurate Business Process Drift Detection

    E-print Network

    Liang, Huizhi "Elly"

    Fast and Accurate Business Process Drift Detection Abderrahmane Maaradji1 , Marlon Dumas2.larosa,alireza.ostovar}@qut.edu.au Abstract. Business processes are prone to continuous and unexpected changes. Process workers may start or regulations for example. Early detection of business process changes based on their event logs ­ also known

  17. Accurate pointing of tungsten welding electrodes

    NASA Technical Reports Server (NTRS)

    Ziegelmeier, P.

    1971-01-01

    Thoriated-tungsten is pointed accurately and quickly by using sodium nitrite. Point produced is smooth and no effort is necessary to hold the tungsten rod concentric. The chemically produced point can be used several times longer than ground points. This method reduces time and cost of preparing tungsten electrodes.

  18. Accurate Assessment--Compelling Evidence for Practice

    ERIC Educational Resources Information Center

    Flynn, Regina T.; Anderson, Ludmila; Martin, Nancy R.

    2010-01-01

    Childhood overweight and obesity is a public health concern not just because of its growing prevalence but also for its serious and lasting health consequences. Though height and weight measures are easy to obtain and New Hampshire Head Start sites measure height and weight of their enrollees, there are numerous challenges related to accurate

  19. Accurate Weather Forecasting for Radio Astronomy

    E-print Network

    Groppi, Christopher

    Accurate Weather Forecasting for Radio Astronomy Ronald J Maddalena October, 2009 #12;Outline Very-3 days #12;The influence of the weather at cm- and mm-wavelengths Opacity Calibration System, telescope productivity Past conditions Calibration Weather statistics Telescope productivity, hardware

  20. Do Workers Accurately Perceive Gender Wage Discrimination?

    ERIC Educational Resources Information Center

    Hampton, Mary B.; Heywood, John S.

    1993-01-01

    Analysis of data from 529 female and 1,343 male physicians found a strong positive correlation between women's perceptions of the gender income differences they experienced and econometric estimates of those differences. Women accurately perceived wage discrimination and used their perception in determining the amount they were underpaid. (SK)

  1. Comparing two models of voice care delivery.

    PubMed

    Gamberini, L J; Carding, P N; Drinnan, M D

    2007-04-01

    Voice care is an important aspect in the successful treatment of patients with non-organic dysphonia. No previous study has examined the specific effect of voice care programmes or the comparative effectiveness of the delivery of these programmes across two healthcare professionals (speech and language therapists and ENT nurses). We describe a pilot study that provides preliminary data that suggests a short, easily deliverable voice care programme is (i) effective in reducing patients' perception of their dysphonia and (ii) equally effectively administered by an ENT nurse compared with a speech and language therapist. The study provides a firm base for continued research. PMID:17403232

  2. Waste feed delivery planning at Hanford

    SciTech Connect

    Certa, Paul J.; West, Elizha B.; Rodriguez, Juissepp S.; Hohl, Ted M.; Larsen, Douglas C.; Ritari, Jaakob S.; Kelly, James W.

    2013-01-10

    The Integrated Waste Feed Delivery Plan (IWFDP) describes how waste feed will be delivered to the Waste Treatment and Immobilization Plant (WTP) to safely and efficiently accomplish the River Protection Project (RPP) mission. The IWFDP, which is integrated with the Baseline Case operating scenario, is comprised of three volumes. Volume 1 - Process Strategy provides an overview of waste feed delivery (WFD) and describes how the WFD system will be used to prepare and deliver feed to the WTP based on the equipment configuration and functional capabilities of the WFD system. Volume 2 - Campaign Plan describes the plans for the first eight campaigns for delivery to the WTP, evaluates projected feed for systematic issues, projects 242-A Evaporator campaigns, and evaluates double-shell tank (DST) space and availability of contingency feed. Volume 3 - Project Plan identifies the scope and timing of the DST and infrastructure upgrade projects necessary to feed the WTP, and coordinates over 30 projectized projects and operational activities that comprise the needed WFD upgrades.

  3. Ultrasound-Propelled Nanocups for Drug Delivery

    PubMed Central

    Kwan, James J; Myers, Rachel; Coviello, Christian M; Graham, Susan M; Shah, Apurva R; Stride, Eleanor; Carlisle, Robert C; Coussios, Constantin C

    2015-01-01

    Ultrasound-induced bubble activity (cavitation) has been recently shown to actively transport and improve the distribution of therapeutic agents in tumors. However, existing cavitation-promoting agents are micron-sized and cannot sustain cavitation activity over prolonged time periods because they are rapidly destroyed upon ultrasound exposure. A novel ultrasound-responsive single-cavity polymeric nanoparticle (nanocup) capable of trapping and stabilizing gas against dissolution in the bloodstream is reported. Upon ultrasound exposure at frequencies and intensities achievable with existing diagnostic and therapeutic systems, nanocups initiate and sustain readily detectable cavitation activity for at least four times longer than existing microbubble constructs in an in vivo tumor model. As a proof-of-concept of their ability to enhance the delivery of unmodified therapeutics, intravenously injected nanocups are also found to improve the distribution of a freely circulating IgG mouse antibody when the tumor is exposed to ultrasound. Quantification of the delivery distance and concentration of both the nanocups and coadministered model therapeutic in an in vitro flow phantom shows that the ultrasound-propelled nanocups travel further than the model therapeutic, which is itself delivered to hundreds of microns from the vessel wall. Thus nanocups offer considerable potential for enhanced drug delivery and treatment monitoring in oncological and other biomedical applications. PMID:26296985

  4. Nanoparticles in the ocular drug delivery

    PubMed Central

    Zhou, Hong-Yan; Hao, Ji-Long; Wang, Shuang; Zheng, Yu; Zhang, Wen-Song

    2013-01-01

    Ocular drug transport barriers pose a challenge for drug delivery comprising the ocular surface epithelium, the tear film and internal barriers of the blood-aqueous and blood-retina barriers. Ocular drug delivery efficiency depends on the barriers and the clearance from the choroidal, conjunctival vessels and lymphatic. Traditional drug administration reduces the clinical efficacy especially for poor water soluble molecules and for the posterior segment of the eye. Nanoparticles (NPs) have been designed to overcome the barriers, increase the drug penetration at the target site and prolong the drug levels by few internals of drug administrations in lower doses without any toxicity compared to the conventional eye drops. With the aid of high specificity and multifunctionality, DNA NPs can be resulted in higher transfection efficiency for gene therapy. NPs could target at cornea, retina and choroid by surficial applications and intravitreal injection. This review is concerned with recent findings and applications of NPs drug delivery systems for the treatment of different eye diseases. PMID:23826539

  5. Lipid-Based Nanocarriers for RNA Delivery

    PubMed Central

    Xue, Hui Yi; Guo, Pengbo; Wen, Wu-Cheng; Wong, Ho Lun

    2015-01-01

    RNA-interference (RNAi) agents such as small-interfering RNA (siRNA) and micro-RNA (miRNA) have strong potential as therapeutic agents for the treatment of a broad range of diseases such as malignancies, infections, autoimmune diseases and neurological diseases that are associated with undesirable gene expression. In recent years, several clinical trials of RNAi therapeutics especially siRNAs have been conducted with limited success so far. For systemic administration of these poorly permeable and easily degradable macromolecules, it is obvious that a safe and efficient delivery platform is highly desirable. Because of high biocompatibility, biodegradability and solid track record for clinical use, nanocarriers made of lipids and/or phospholipids have been commonly employed to facilitate RNA delivery. In this article, the key features of the major sub-classes of lipid-based nanocarriers, e.g. liposomes, lipid nanoparticles and lipid nanoemulsions, will be reviewed. Focus of the discussion is on the various challenges researchers face when developing lipid-based RNA nanocarriers, such as the toxicity of cationic lipids and issues related to PEGylated lipids, as well as the strategies employed in tackling these challenges. It is hoped that by understanding more about the pros and cons of these most frequently used RNA delivery systems, the pharmaceutical scientists, biomedical researchers and clinicians will be more successful in overcoming some of the obstacles that currently limit the clinical translation of RNAi therapy. PMID:26027572

  6. Polysaccharides for colon targeted drug delivery.

    PubMed

    Chourasia, M K; Jain, S K

    2004-01-01

    Colon targeted drug delivery has the potential to deliver bioactive agents for the treatment of a variety of colonic diseases and to deliver proteins and peptides to the colon for their systemic absorption. Various strategies, currently available to target the release of drugs to colon, include formation of prodrug, coating of pH-sensitive polymers, use of colon-specific biodegradable polymers, timed released systems, osmotic systems, and pressure controlled drug delivery systems. Among the different approaches to achieve targeted drug release to the colon, the use of polymers especially biodegradable by colonic bacteria holds great promise. Polysaccharidases are bacterial enzymes that are available in sufficient quantity to be exploited in colon targeting of drugs. Based on this approach, various polysaccharides have been investigated for colon-specific drug release. These polysaccharides include pectin, guar gum, amylose, inulin, dextran, chitosan, and chondroitin sulphate. This family of natural polymers has an appeal to drug delivery as it is comprised of polymers with a large number of derivatizable groups, a wide range of molecular weights, varying chemical compositions, and, for the most part, low toxicity and biodegradability yet high stability. The most favorable property of these materials is their approval as pharmaceutical excipients. PMID:15200012

  7. Waste Feed Delivery Planning at Hanford - 13232

    SciTech Connect

    Certa, Paul J.; Hohl, Ted M.; Kelly, James W.; Larsen, Douglas C.; West, Elizha B.; Ritari, Jaakob S.; Rodriguez, Juissepp S.

    2013-07-01

    The Integrated Waste Feed Delivery Plan (IWFDP) describes how waste feed will be delivered to the Waste Treatment and Immobilization Plant (WTP) to safely and efficiently accomplish the River Protection Project (RPP) mission. The IWFDP, which is integrated with the Baseline Case operating scenario, is comprised of three volumes. Volume 1 - Process Strategy provides an overview of waste feed delivery (WFD) and describes how the WFD system will be used to prepare and deliver feed to the WTP based on the equipment configuration and functional capabilities of the WFD system. Volume 2 - Campaign Plan describes the plans for the first eight campaigns for delivery to the WTP, evaluates projected feed for systematic issues, projects 242-A Evaporator campaigns, and evaluates double-shell tank (DST) space and availability of contingency feed. Volume 3 - Project Plan identifies the scope and timing of the DST and infrastructure upgrade projects necessary to feed the WTP, and coordinates over 30 projectized projects and operational activities that comprise the needed WFD upgrades. (authors)

  8. A high-speed scintillation-based electronic portal imaging device to quantitatively characterize IMRT delivery.

    PubMed

    Ranade, Manisha K; Lynch, Bart D; Li, Jonathan G; Dempsey, James F

    2006-01-01

    We have developed an electronic portal imaging device (EPID) employing a fast scintillator and a high-speed camera. The device is designed to accurately and independently characterize the fluence delivered by a linear accelerator during intensity modulated radiation therapy (IMRT) with either step-and-shoot or dynamic multileaf collimator (MLC) delivery. Our aim is to accurately obtain the beam shape and fluence of all segments delivered during IMRT, in order to study the nature of discrepancies between the plan and the delivered doses. A commercial high-speed camera was combined with a terbium-doped gadolinium-oxy-sulfide (Gd2O2S:Tb) scintillator to form an EPID for the unaliased capture of two-dimensional fluence distributions of each beam in an IMRT delivery. The high speed EPID was synchronized to the accelerator pulse-forming network and gated to capture every possible pulse emitted from the accelerator, with an approximate frame rate of 360 frames-per-second (fps). A 62-segment beam from a head-and-neck IMRT treatment plan requiring 68 s to deliver was recorded with our high speed EPID producing approximately 6 Gbytes of imaging data. The EPID data were compared with the MLC instruction files and the MLC controller log files. The frames were binned to provide a frame rate of 72 fps with a signal-to-noise ratio that was sufficient to resolve leaf positions and segment fluence. The fractional fluence from the log files and EPID data agreed well. An ambiguity in the motion of the MLC during beam on was resolved. The log files reported leaf motions at the end of 33 of the 42 segments, while the EPID observed leaf motions in only 7 of the 42 segments. The static IMRT segment shapes observed by the high speed EPID were in good agreement with the shapes reported in the log files. The leaf motions observed during beam-on for step-and-shoot delivery were not temporally resolved by the log files. PMID:16485415

  9. Value-Based Delivery of Education: MOOCs as Messengers

    ERIC Educational Resources Information Center

    Gilfoil, David M.; Focht, Jeffrey W.

    2015-01-01

    Value-based delivery of healthcare has been discussed in the literature for almost a decade. The concept focuses on the patient and defines value as the improvement of patient outcomes divided by healthcare costs. Further refinements, called the Triple Aim model, focus on improving patient outcomes, reducing treatment costs, and improving patient…

  10. Feedback about More Accurate versus Less Accurate Trials: Differential Effects on Self-Confidence and Activation

    ERIC Educational Resources Information Center

    Badami, Rokhsareh; VaezMousavi, Mohammad; Wulf, Gabriele; Namazizadeh, Mahdi

    2012-01-01

    One purpose of the present study was to examine whether self-confidence or anxiety would be differentially affected by feedback from more accurate rather than less accurate trials. The second purpose was to determine whether arousal variations (activation) would predict performance. On Day 1, participants performed a golf putting task under one of…

  11. Using prediction to facilitate patient flow in a health care delivery chain

    E-print Network

    Peck, Jordan S. (Jordan Shefer)

    2013-01-01

    A health care delivery chain is a series of treatment steps through which patients flow. The Emergency Department (ED)/Inpatient Unit (IU) chain is an example chain, common to many hospitals. Recent literature has suggested ...

  12. 21 CFR 876.5600 - Sorbent regenerated dialysate delivery system for hemodialysis.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...delivery system for hemodialysis is a device that is part of an artificial kidney system for the treatment of patients with renal failure or toxemic conditions, and that consists of a sorbent cartridge and the means to circulate dialysate...

  13. 21 CFR 876.5600 - Sorbent regenerated dialysate delivery system for hemodialysis.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...delivery system for hemodialysis is a device that is part of an artificial kidney system for the treatment of patients with renal failure or toxemic conditions, and that consists of a sorbent cartridge and the means to circulate dialysate...

  14. Biomimetic nanoassembly for targeted antigen delivery and enhanced Th1-type immune response.

    PubMed

    Li, Zhenhua; Dong, Kai; Zhang, Yan; Ju, Enguo; Chen, Zhaowei; Ren, Jinsong; Qu, Xiaogang

    2015-11-14

    A new type of biomimetic nanoassembly for targeted antigen delivery and enhanced Th1-type response is reported for the first time, to combat the major challenges in the treatment of infected cells. PMID:26383825

  15. Development of a multilayered association polymer system for sequential drug delivery

    NASA Astrophysics Data System (ADS)

    Chinnakavanam Sundararaj, Sharath kumar

    As all the physiological processes in our body are controlled by multiple biomolecules, comprehensive treatment of certain disease conditions may be more effectively achieved by administration of more than one type of drug. Thus, the primary objective of this research was to develop a multilayered, polymer-based system for sequential delivery of multiple drugs. This particular device was designed aimed at the treatment of periodontitis, a highly prevalent oral inflammatory disease that affects 90% of the world population. This condition is caused by bacterial biofilm on the teeth, resulting in a chronic inflammatory response that leads to loss of alveolar bone and, ultimately, the tooth. Current treatment methods for periodontitis address specific parts of the disease, with no individual treatment serving as a complete therapy. The polymers used for the fabrication of this multilayered device consists of cellulose acetate phthalate (CAP) complexed with Pluronic F-127 (P). After evaluating morphology of the resulting CAPP system, in vitro release of small molecule drugs and a model protein was studied from both single and multilayered devices. Drug release from single-layered CAPP films followed zero-order kinetics related to surface erosion property of the association polymer. Release studies from multilayered CAPP devices showed the possibility of achieving intermittent release of one type of drug as well as sequential release of more than one type of drug. Mathematical modeling accurately predicted the release profiles for both single layer and multilayered devices. After the initial characterization of the CAPP system, the device was specifically modified to achieve sequential release of drugs aimed at the treatment of periodontitis. The four types of drugs used were metronidazole, ketoprofen, doxycycline, and simvastatin to eliminate infection, inhibit inflammation, prevent tissue destruction, and aid bone regeneration, respectively. To obtain different erosion times and achieve appropriate release profiles specific to the disease condition, the device was modified by increasing the number of layers or by inclusion of a slower eroding polymer layer. In all the cases, the device was able to release the four different drugs in the designed temporal sequence. Analysis of antibiotic and antiinflammatory bioactivity showed that drugs released from the devices retained 100% bioactivity. Following extensive studies on the in vitro sequential drug release from these devices, the in vivo drug release profiles were investigated. The CAPP devices with different release rates and dosage formulations were implanted in a rat calvarial onlay model, and the in vivo drug release and erosion was compared with in vitro results. In vivo studies showed sequential release of drugs comparable to those measured in vitro, with some difference in drug release rates observed. The present CAPP association polymer-based multilayer devices can be used for localized, sequential delivery of multiple drugs for the possible treatment of complex disease conditions, and perhaps for tissue engineering applications, that require delivery of more than one type of biomolecule. KEYWORDS: Multiple drug delivery, Periodontitis, Cellulose acetate phthalate, Pluronic F-127, Sequential drug release, in vitro drug release, in vivo drug release.

  16. Novel Approaches in Formulation and Drug Delivery using Contact Lenses

    PubMed Central

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

    2011-01-01

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

  17. Hydrogen Delivery Technical Team Roadmap

    SciTech Connect

    2013-06-01

    The mission of the Hydrogen Delivery Technical Team (HDTT) is to enable the development of hydrogen delivery technologies, which will allow for fuel cell competitiveness with gasoline and hybrid technologies by achieving an as-produced, delivered, and dispensed hydrogen cost of $2-$4 per gallon of gasoline equivalent of hydrogen.

  18. Hydrogen Distribution and Delivery Infrastructure

    SciTech Connect

    2008-11-01

    This 2-page fact sheet provides a brief introduction to hydrogen delivery technologies. Intended for a non-technical audience, it explains how hydrogen is transported and delivered today, the challenges to delivering hydrogen for use as a widespread energy carrier, and the research goals for hydrogen delivery.

  19. Drug Delivery Systems, CNS Protection, and the Blood Brain Barrier

    PubMed Central

    Upadhyay, Ravi Kant

    2014-01-01

    Present review highlights various drug delivery systems used for delivery of pharmaceutical agents mainly antibiotics, antineoplastic agents, neuropeptides, and other therapeutic substances through the endothelial capillaries (BBB) for CNS therapeutics. In addition, the use of ultrasound in delivery of therapeutic agents/biomolecules such as proline rich peptides, prodrugs, radiopharmaceuticals, proteins, immunoglobulins, and chimeric peptides to the target sites in deep tissue locations inside tumor sites of brain has been explained. In addition, therapeutic applications of various types of nanoparticles such as chitosan based nanomers, dendrimers, carbon nanotubes, niosomes, beta cyclodextrin carriers, cholesterol mediated cationic solid lipid nanoparticles, colloidal drug carriers, liposomes, and micelles have been discussed with their recent advancements. Emphasis has been given on the need of physiological and therapeutic optimization of existing drug delivery methods and their carriers to deliver therapeutic amount of drug into the brain for treatment of various neurological diseases and disorders. Further, strong recommendations are being made to develop nanosized drug carriers/vehicles and noninvasive therapeutic alternatives of conventional methods for better therapeutics of CNS related diseases. Hence, there is an urgent need to design nontoxic biocompatible drugs and develop noninvasive delivery methods to check posttreatment clinical fatalities in neuropatients which occur due to existing highly toxic invasive drugs and treatment methods. PMID:25136634

  20. Intranasal delivery bypasses the blood-brain barrier to target therapeutics to the CNS William H. Frey II, Ph.D., Senior Director

    E-print Network

    Thomas, David D.

    Intranasal delivery bypasses the blood-brain barrier to target therapeutics to the CNS Speaker, Stanford University, HealthPartners Research Foundation and others, target delivery of therapeutic agents. His intranasal therapeutic cell delivery and treatment methods have been validated in animals

  1. Real-time DMLC IMRT delivery for mobile and deforming targets

    SciTech Connect

    Papiez, Lech; Rangaraj, Dharanipathy; Keall, Paul

    2005-09-15

    In numerous cases of radiotherapy delivery to moving targets, simplifying assumptions of identical pattern of motions of tissue for each fraction are not satisfied. Therefore, algorithms capable to respond in real time to motions of target registered at treatment should be developed to improve the precision of radiation intensity delivery. The DMLC delivery of predetermined intensity maps to moving and deforming targets in real time is developed in this paper. Algorithms are constructed so that constraints on maximum admissible speed of leaves are preserved during delivery. A sequence of examples is presented to illustrate behavior of leaf trajectories for representative cases of [dynamic multileaf collimator] (DMLC) [intensity modulated radiation therapy] (IMRT) real-time delivery. The examples presented show real-time deliveries to targets moving as rigid bodies and targets deforming uniformly over their volumes. Examples are admitting random perturbations of predefined target motions that are time dependent only, i.e., target motion perturbations are identical for all target points.

  2. Economical ground data delivery

    NASA Technical Reports Server (NTRS)

    Markley, Richard W.; Byrne, Russell H.; Bromberg, Daniel E.

    1994-01-01

    Data delivery in the Deep Space Network (DSN) involves transmission of a small amount of constant, high-priority traffic and a large amount of bursty, low priority data. The bursty traffic may be initially buffered and then metered back slowly as bandwidth becomes available. Today both types of data are transmitted over dedicated leased circuits. The authors investigated the potential of saving money by designing a hybrid communications architecture that uses leased circuits for high-priority network communications and dial-up circuits for low-priority traffic. Such an architecture may significantly reduce costs and provide an emergency backup. The architecture presented here may also be applied to any ground station-to-customer network within the range of a common carrier. The authors compare estimated costs for various scenarios and suggest security safeguards that should be considered.

  3. Secondary fuel delivery system

    DOEpatents

    Parker, David M. (Oviedo, FL); Cai, Weidong (Oviedo, FL); Garan, Daniel W. (Orlando, FL); Harris, Arthur J. (Orlando, FL)

    2010-02-23

    A secondary fuel delivery system for delivering a secondary stream of fuel and/or diluent to a secondary combustion zone located in the transition piece of a combustion engine, downstream of the engine primary combustion region is disclosed. The system includes a manifold formed integral to, and surrounding a portion of, the transition piece, a manifold inlet port, and a collection of injection nozzles. A flowsleeve augments fuel/diluent flow velocity and improves the system cooling effectiveness. Passive cooling elements, including effusion cooling holes located within the transition boundary and thermal-stress-dissipating gaps that resist thermal stress accumulation, provide supplemental heat dissipation in key areas. The system delivers a secondary fuel/diluent mixture to a secondary combustion zone located along the length of the transition piece, while reducing the impact of elevated vibration levels found within the transition piece and avoiding the heat dissipation difficulties often associated with traditional vibration reduction methods.

  4. Rhythmomimetic drug delivery

    E-print Network

    Calderer, M Carme; Siegel, Ronald A; Yao, Lingxing

    2015-01-01

    We present modeling, analysis and numerical simulation of a prototype glucose driven drug delivery device based on chemomechanical interactions and volume phase transitions in polyelectrolyte gels. The device consists of two fluid compartments, an external cell (I) mimicking the physiological environment, and a closed chamber (II), separated by a hydrogel membrane. Cell I, which is held at constant pH and ionic strength, provides a constant supply of glucose to cell II, and also serves as clearance station for reaction products. Cell II contains the drug to be delivered to the body, an enzyme that catalyzes conversion of glucose into hydrogen ions, and a piece of marble to remove excess hydrogen ions that would otherwise overwhelm the system. When the membrane is swollen, glucose flux into Cell II is high, leading to rapid production of hydrogen ions. However, the hydrogen ions are not immediately released to Cell I but react, instead, with the negatively charged carboxyl groups of the membrane, which collaps...

  5. Targeted delivery of nanomedicines.

    PubMed

    Kumar Khanna, Vinod

    2012-01-01

    The role of targeting of the diseased region by a drug is emphasized. The rationale for resorting to nanomaterials as drug carriers is explained. A clear understanding of the biological environment, its degradation in diseased condition, and the interaction of the drug with it in normal condition and during illness lie at the core of successful drug delivery. Passive and active drug targeting approaches are differentiated. Commonly used drug targets, targeting ligands, and nanoscale systems are elaborated. Mechanisms of internalization of nanomedicines and circumventing P-glycoprotein mediated resistance are outlined. The paper presents an overview of the current scenario of targeted transportation of nanomedicines to the affected organ and suggests future research directions. PMID:22577576

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

    PubMed Central

    Philip, Anil K.; Philip, Betty

    2010-01-01

    The colon is a site where both local and systemic delivery of drugs can take place. Local delivery allows topical treatment of inflammatory bowel disease. However, treatment can be made effective if the drugs can be targeted directly into the colon, thereby reducing the systemic side effects. This review, mainly compares the primary approaches for CDDS (Colon Specific Drug Delivery) namely prodrugs, pH and time dependent systems, and microbially triggered systems, which achieved limited success and had limitations as compared with newer CDDS namely pressure controlled colonic delivery capsules, CODESTM, and osmotic controlled drug delivery which are unique in terms of achieving in vivo site specificity, and feasibility of manufacturing process. PMID:22125706

  7. Nanoparticles as Drug Delivery Systems in Cancer Medicine: Emphasis on RNAi-Containing Nanoliposomes

    PubMed Central

    Rivera Díaz, Mónica; Vivas-Mejia, Pablo E.

    2013-01-01

    Nanomedicine is a growing research field dealing with the creation and manipulation of materials at a nanometer scale for the better treatment, diagnosis and imaging of diseases. In cancer medicine, the use of nanoparticles as drug delivery systems has advanced the bioavailability, in vivo stability, intestinal absorption, solubility, sustained and targeted delivery, and therapeutic effectiveness of several anticancer agents. The expansion of novel nanoparticles for drug delivery is an exciting and challenging research filed, in particular for the delivery of emerging cancer therapies, including small interference RNA (siRNA) and microRNA (miRNAs)-based molecules. In this review, we focus on the currently available drug delivery systems for anticancer agents. In addition, we will discuss the promising use of nanoparticles for novel cancer treatment strategies. PMID:24287462

  8. TIGER -- A technology to improve the delivery capability of nuclear bombs and the survivability of the delivery aircraft

    SciTech Connect

    1980-12-31

    The TIGER (Terminal guided and Extended-Range) Program was initiated in 1972 to study improved delivery capabilities for stockpiled tactical nuclear bombs. The Southeast Asia conflict fostered the development of air-delivered standoff conventional weapons utilizing terminal guidance systems. SNL initiated the TIGER program to determine if current nuclear bombs could be provided with a similarly accurate standoff capabilities. These conventional weapon delivery techniques, while allowing highly accurate attack, generally require entering the target area at high altitude to establish line of sight to the target. In parallel with the TIGER program, system studies analyzed this concept and showed marked improvement in aircraft and weapon survivability with moderate standoff (10--20 km) if low level deliveries (60 m) could be accomplished. As a result of this work, the TIGER program was redirected in early 1974 to demonstrate a standoff bomb with good accuracy (90 m CEP) when delivered from low flying aircraft. This program redirection resulted in the selection of an inertial guidance system to replace the earlier terminal guidance systems. This program was called the Extended-Range Bomb (ERB). In May 1974, a joint Air Force/DOE study identified the desirability of having a single tactical weapon which could be employed against either fixed, preselected targets, or mobile battlefield targets. Studies conducted on the ERB system showed that the inertially guided weapon could fly not only the standoff mission but also a return-to-target mission against the mobile battlefield targets whose locations are not known accurately enough to use a standoff delivery. The ERB program evolved from these initial investigations into an exploratory program to develop the hardware and demonstrate the technology required to fly standoff and return-to-target trajectories. The application of this technology in the form of field retrofit kits to the B61 bomb is called TIGER II.

  9. An accurate registration technique for distorted images

    NASA Technical Reports Server (NTRS)

    Delapena, Michele; Shaw, Richard A.; Linde, Peter; Dravins, Dainis

    1990-01-01

    Accurate registration of International Ultraviolet Explorer (IUE) images is crucial because the variability of the geometrical distortions that are introduced by the SEC-Vidicon cameras ensures that raw science images are never perfectly aligned with the Intensity Transfer Functions (ITFs) (i.e., graded floodlamp exposures that are used to linearize and normalize the camera response). A technique for precisely registering IUE images which uses a cross correlation of the fixed pattern that exists in all raw IUE images is described.

  10. Breath powered nasal delivery: a new route to rapid headache relief.

    PubMed

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

    2013-09-01

    The nose offers an attractive noninvasive alternative for drug delivery. Nasal anatomy, with a large mucosal surface area and high vascularity, allows for rapid systemic absorption and other potential benefits. However, the complex nasal geometry, including the narrow anterior valve, poses a serious challenge to efficient drug delivery. This barrier, plus the inherent limitations of traditional nasal delivery mechanisms, has precluded achievement of the full potential of nasal delivery. Breath Powered bi-directional delivery, a simple but novel nasal delivery mechanism, overcomes these barriers. This innovative mechanism has now been applied to the delivery of sumatriptan. Multiple studies of drug deposition, including comparisons of traditional nasal sprays to Breath Powered delivery, demonstrate significantly improved deposition to superior and posterior intranasal target sites beyond the nasal valve. Pharmacokinetic studies in both healthy subjects and migraineurs suggest that improved deposition of sumatriptan translates into improved absorption and pharmacokinetics. Importantly, the absorption profile is shifted toward a more pronounced early peak, representing nasal absorption, with a reduced late peak, representing predominantly gastrointestinal (GI) absorption. The flattening and "spreading out" of the GI peak appears more pronounced in migraine sufferers than healthy volunteers, likely reflecting impaired GI absorption described in migraineurs. In replicated clinical trials, Breath Powered delivery of low-dose sumatriptan was well accepted and well tolerated by patients, and onset of pain relief was faster than generally reported in previous trials with noninjectable triptans. Interestingly, Breath Powered delivery also allows for the potential of headache-targeted medications to be better delivered to the trigeminal nerve and the sphenopalatine ganglion, potentially improving treatment of various types of headache. In brief, Breath Powered bi-directional intranasal delivery offers a new and more efficient mechanism for nasal drug delivery, providing an attractive option for improved treatment of headaches by enabling or enhancing the benefits of current and future headache therapies. PMID:24024605

  11. Investigating the accuracy of microstereotactic-body-radiotherapy utilizing anatomically accurate 3D printed rodent-morphic dosimeters

    SciTech Connect

    Bache, Steven T.; Juang, Titania; Belley, Matthew D.; Koontz, Bridget F.; Yoshizumi, Terry T.; Kirsch, David G.; Oldham, Mark; Adamovics, John

    2015-02-15

    Purpose: Sophisticated small animal irradiators, incorporating cone-beam-CT image-guidance, have recently been developed which enable exploration of the efficacy of advanced radiation treatments in the preclinical setting. Microstereotactic-body-radiation-therapy (microSBRT) is one technique of interest, utilizing field sizes in the range of 1–15 mm. Verification of the accuracy of microSBRT treatment delivery is challenging due to the lack of available methods to comprehensively measure dose distributions in representative phantoms with sufficiently high spatial resolution and in 3 dimensions (3D). This work introduces a potential solution in the form of anatomically accurate rodent-morphic 3D dosimeters compatible with ultrahigh resolution (0.3 mm{sup 3}) optical computed tomography (optical-CT) dose read-out. Methods: Rodent-morphic dosimeters were produced by 3D-printing molds of rodent anatomy directly from contours defined on x-ray CT data sets of rats and mice, and using these molds to create tissue-equivalent radiochromic 3D dosimeters from Presage. Anatomically accurate spines were incorporated into some dosimeters, by first 3D printing the spine mold, then forming a high-Z bone equivalent spine insert. This spine insert was then set inside the tissue equivalent body mold. The high-Z spinal insert enabled representative cone-beam CT IGRT targeting. On irradiation, a linear radiochromic change in optical-density occurs in the dosimeter, which is proportional to absorbed dose, and was read out using optical-CT in high-resolution (0.5 mm isotropic voxels). Optical-CT data were converted to absolute dose in two ways: (i) using a calibration curve derived from other Presage dosimeters from the same batch, and (ii) by independent measurement of calibrated dose at a point using a novel detector comprised of a yttrium oxide based nanocrystalline scintillator, with a submillimeter active length. A microSBRT spinal treatment was delivered consisting of a 180° continuous arc at 225 kVp with a 20 × 10 mm field size. Dose response was evaluated using both the Presage/optical-CT 3D dosimetry system described above, and independent verification in select planes using EBT2 radiochromic film placed inside rodent-morphic dosimeters that had been sectioned in half. Results: Rodent-morphic 3D dosimeters were successfully produced from Presage radiochromic material by utilizing 3D printed molds of rat CT contours. The dosimeters were found to be compatible with optical-CT dose readout in high-resolution 3D (0.5 mm isotropic voxels) with minimal artifacts or noise. Cone-beam CT image guidance was possible with these dosimeters due to sufficient contrast between high-Z spinal inserts and tissue equivalent Presage material (CNR ?10 on CBCT images). Dose at isocenter measured with optical-CT was found to agree with nanoscintillator measurement to within 2.8%. Maximum dose in line profiles taken through Presage and film dose slices agreed within 3%, with FWHM measurements through each profile found to agree within 2%. Conclusions: This work demonstrates the feasibility of using 3D printing technology to make anatomically accurate Presage rodent-morphic dosimeters incorporating spinal-mimicking inserts. High quality optical-CT 3D dosimetry is feasible on these dosimeters, despite the irregular surfaces and implanted inserts. The ability to measure dose distributions in anatomically accurate phantoms represents a powerful useful additional verification tool for preclinical microSBRT.

  12. Investigating the accuracy of microstereotactic-body-radiotherapy utilizing anatomically accurate 3D printed rodent-morphic dosimeters

    PubMed Central

    Bache, Steven T.; Juang, Titania; Belley, Matthew D.; Koontz, Bridget F.; Adamovics, John; Yoshizumi, Terry T.; Kirsch, David G.; Oldham, Mark

    2015-01-01

    Purpose: Sophisticated small animal irradiators, incorporating cone-beam-CT image-guidance, have recently been developed which enable exploration of the efficacy of advanced radiation treatments in the preclinical setting. Microstereotactic-body-radiation-therapy (microSBRT) is one technique of interest, utilizing field sizes in the range of 1–15 mm. Verification of the accuracy of microSBRT treatment delivery is challenging due to the lack of available methods to comprehensively measure dose distributions in representative phantoms with sufficiently high spatial resolution and in 3 dimensions (3D). This work introduces a potential solution in the form of anatomically accurate rodent-morphic 3D dosimeters compatible with ultrahigh resolution (0.3 mm3) optical computed tomography (optical-CT) dose read-out. Methods: Rodent-morphic dosimeters were produced by 3D-printing molds of rodent anatomy directly from contours defined on x-ray CT data sets of rats and mice, and using these molds to create tissue-equivalent radiochromic 3D dosimeters from Presage. Anatomically accurate spines were incorporated into some dosimeters, by first 3D printing the spine mold, then forming a high-Z bone equivalent spine insert. This spine insert was then set inside the tissue equivalent body mold. The high-Z spinal insert enabled representative cone-beam CT IGRT targeting. On irradiation, a linear radiochromic change in optical-density occurs in the dosimeter, which is proportional to absorbed dose, and was read out using optical-CT in high-resolution (0.5 mm isotropic voxels). Optical-CT data were converted to absolute dose in two ways: (i) using a calibration curve derived from other Presage dosimeters from the same batch, and (ii) by independent measurement of calibrated dose at a point using a novel detector comprised of a yttrium oxide based nanocrystalline scintillator, with a submillimeter active length. A microSBRT spinal treatment was delivered consisting of a 180° continuous arc at 225 kVp with a 20 × 10 mm field size. Dose response was evaluated using both the Presage/optical-CT 3D dosimetry system described above, and independent verification in select planes using EBT2 radiochromic film placed inside rodent-morphic dosimeters that had been sectioned in half. Results: Rodent-morphic 3D dosimeters were successfully produced from Presage radiochromic material by utilizing 3D printed molds of rat CT contours. The dosimeters were found to be compatible with optical-CT dose readout in high-resolution 3D (0.5 mm isotropic voxels) with minimal artifacts or noise. Cone-beam CT image guidance was possible with these dosimeters due to sufficient contrast between high-Z spinal inserts and tissue equivalent Presage material (CNR ?10 on CBCT images). Dose at isocenter measured with optical-CT was found to agree with nanoscintillator measurement to within 2.8%. Maximum dose in line profiles taken through Presage and film dose slices agreed within 3%, with FWHM measurements through each profile found to agree within 2%. Conclusions: This work demonstrates the feasibility of using 3D printing technology to make anatomically accurate Presage rodent-morphic dosimeters incorporating spinal-mimicking inserts. High quality optical-CT 3D dosimetry is feasible on these dosimeters, despite the irregular surfaces and implanted inserts. The ability to measure dose distributions in anatomically accurate phantoms represents a powerful useful additional verification tool for preclinical microSBRT. PMID:25652497

  13. Sterile Delivery of Pigs 

    E-print Network

    Unknown

    2011-08-17

    (sterilization) and trap and translocation (deer removal) efforts in managing white-tailed deer on JSC. In general, single treatments of removals or sterilization (less than 75 percent of female deer treated) were not effective in reducing population growth (R...

  14. Nanomaterials as Non-viral siRNA Delivery Agents for Cancer Therapy

    PubMed Central

    Singh, Sanjay

    2013-01-01

    Gene therapy has been recently shown as a promising tool for cancer treatment as nanotechnology-based safe and effective delivery methods are developed. Generally, genes are wrapped up in extremely tiny nanoparticles which could be taken up easily by cancer cells, not to their healthy neighboring cells. Several nanoparticle systems have been investigated primarily to address the problems involved in other methods of gene delivery and observed improved anticancer efficacy suggesting that nanomedicine provides novel opportunities to safely deliver genes, thus treat cancer. In this review, various nanoparticle types and related strategies, used in gene delivery for cancer treatment, have been discussed. PMID:23878788

  15. High Frequency QRS ECG Accurately Detects Cardiomyopathy

    NASA Technical Reports Server (NTRS)

    Schlegel, Todd T.; Arenare, Brian; Poulin, Gregory; Moser, Daniel R.; Delgado, Reynolds

    2005-01-01

    High frequency (HF, 150-250 Hz) analysis over the entire QRS interval of the ECG is more sensitive than conventional ECG for detecting myocardial ischemia. However, the accuracy of HF QRS ECG for detecting cardiomyopathy is unknown. We obtained simultaneous resting conventional and HF QRS 12-lead ECGs in 66 patients with cardiomyopathy (EF = 23.2 plus or minus 6.l%, mean plus or minus SD) and in 66 age- and gender-matched healthy controls using PC-based ECG software recently developed at NASA. The single most accurate ECG parameter for detecting cardiomyopathy was an HF QRS morphological score that takes into consideration the total number and severity of reduced amplitude zones (RAZs) present plus the clustering of RAZs together in contiguous leads. This RAZ score had an area under the receiver operator curve (ROC) of 0.91, and was 88% sensitive, 82% specific and 85% accurate for identifying cardiomyopathy at optimum score cut-off of 140 points. Although conventional ECG parameters such as the QRS and QTc intervals were also significantly longer in patients than controls (P less than 0.001, BBBs excluded), these conventional parameters were less accurate (area under the ROC = 0.77 and 0.77, respectively) than HF QRS morphological parameters for identifying underlying cardiomyopathy. The total amplitude of the HF QRS complexes, as measured by summed root mean square voltages (RMSVs), also differed between patients and controls (33.8 plus or minus 11.5 vs. 41.5 plus or minus 13.6 mV, respectively, P less than 0.003), but this parameter was even less accurate in distinguishing the two groups (area under ROC = 0.67) than the HF QRS morphologic and conventional ECG parameters. Diagnostic accuracy was optimal (86%) when the RAZ score from the HF QRS ECG and the QTc interval from the conventional ECG were used simultaneously with cut-offs of greater than or equal to 40 points and greater than or equal to 445 ms, respectively. In conclusion 12-lead HF QRS ECG employing RAZ scoring is a simple, accurate and inexpensive screening technique for cardiomyopathy. Although HF QRS ECG is highly sensitive for cardiomyopathy, its specificity may be compromised in patients with cardiac pathologies other than cardiomyopathy, such as uncomplicated coronary artery disease or multiple coronary disease risk factors. Further studies are required to determine whether HF QRS might be useful for monitoring cardiomyopathy severity or the efficacy of therapy in a longitudinal fashion.

  16. Transurethral light delivery for prostate photoacoustic imaging

    NASA Astrophysics Data System (ADS)

    Lediju Bell, Muyinatu A.; Guo, Xiaoyu; Song, Danny Y.; Boctor, Emad M.

    2015-03-01

    Photoacoustic imaging has broad clinical potential to enhance prostate cancer detection and treatment, yet it is challenged by the lack of minimally invasive, deeply penetrating light delivery methods that provide sufficient visualization of targets (e.g., tumors, contrast agents, brachytherapy seeds). We constructed a side-firing fiber prototype for transurethral photoacoustic imaging of prostates with a dual-array (linear and curvilinear) transrectal ultrasound probe. A method to calculate the surface area and, thereby, estimate the laser fluence at this fiber tip was derived, validated, applied to various design parameters, and used as an input to three-dimensional Monte Carlo simulations. Brachytherapy seeds implanted in phantom, ex vivo, and in vivo canine prostates at radial distances of 5 to 30 mm from the urethra were imaged with the fiber prototype transmitting 1064 nm wavelength light with 2 to 8 mJ pulse energy. Prebeamformed images were displayed in real time at a rate of 3 to 5 frames per second to guide fiber placement and beamformed offline. A conventional delay-and-sum beamformer provided decreasing seed contrast (23 to 9 dB) with increasing urethra-to-target distance, while the short-lag spatial coherence beamformer provided improved and relatively constant seed contrast (28 to 32 dB) regardless of distance, thus improving multitarget visualization in single and combined curvilinear images acquired with the fiber rotating and the probe fixed. The proposed light delivery and beamforming methods promise to improve key prostate cancer detection and treatment strategies.

  17. Nanomedicines for Back of the Eye Drug Delivery, Gene Delivery, and Imaging

    PubMed Central

    Kompella, Uday B.; Amrite, Aniruddha C.; Ravi, Rashmi Pacha; Durazo, Shelley A.

    2013-01-01

    Treatment and management of diseases of the posterior segment of the eye such as diabetic retinopathy, retinoblastoma, retinitis pigmentosa, and choroidal neovascularization is a challenging task due to the anatomy and physiology of ocular barriers. For instance, traditional routes of drug delivery for therapeutic treatment are hindered by poor intraocular penetration and/or rapid ocular elimination. One possible approach to improve ocular therapy is to employ nanotechnology. Nanomedicines, products of nanotechnology, having at least one dimension in the nanoscale include nanoparticles, micelles, nanotubes, and dendrimers, with and without targeting ligands, are making a significant impact in the fields of ocular drug delivery, gene delivery, and imaging, the focus of this review. Key applications of nanotechnology discussed in this review include a) bioadhesive nanomedicines; b) functionalized nanomedicines that enhance target recognition and/or cell entry; c) nanomedicines capable of controlled release of the payload; d) nanomedicines capable of enhancing gene transfection and duration of transfection; f) nanomedicines responsive to stimuli including light, heat, ultrasound, electrical signals, pH, and oxidative stress; g) diversely sized and colored nanoparticles for imaging, and h) nanowires for retinal prostheses. Additionally, nanofabricated delivery systems including implants, films, microparticles, and nanoparticles are described. Although the above nanomedicines may be administered by various routes including topical, intravitreal, intravenous, transscleral, suprachoroidal, and subretinal routes, each nanomedicine should be tailored for the disease, drug, and site of administration. In addition to the nature of materials used in nanomedicine design, depending on the site of nanomedicine administration, clearance and toxicity are expected to differ. PMID:23603534

  18. The Scientific and Societal Need for Accurate Global Remote Sensing of Marine Suspended Sediments

    NASA Technical Reports Server (NTRS)

    Acker, James G.

    2006-01-01

    Population pressure, commercial development, and climate change are expected to cause continuing alteration of the vital oceanic coastal zone environment. These pressures will influence both the geology and biology of the littoral, nearshore, and continental shelf regions. A pressing need for global observation of coastal change processes is an accurate remotely-sensed data product for marine suspended sediments. The concentration, delivery, transport, and deposition of sediments is strongly relevant to coastal primary production, inland and coastal hydrology, coastal erosion, and loss of fragile wetland and island habitats. Sediment transport and deposition is also related to anthropogenic activities including agriculture, fisheries, aquaculture, harbor and port commerce, and military operations. Because accurate estimation of marine suspended sediment concentrations requires advanced ocean optical analysis, a focused collaborative program of algorithm development and assessment is recommended, following the successful experience of data refinement for remotely-sensed global ocean chlorophyll concentrations.

  19. Introducing the Healthcare Delivery Research Program | Healthcare Delivery Research Blog

    Cancer.gov

    Understanding the many challenges of cancer care is the focus of the new Healthcare Delivery Research Program in the Division of Cancer Control and Population Sciences at the National Cancer Institute (NCI).

  20. Space age health care delivery

    NASA Technical Reports Server (NTRS)

    Jones, W. L.

    1977-01-01

    Space age health care delivery is being delivered to both NASA astronauts and employees with primary emphasis on preventive medicine. The program relies heavily on comprehensive health physical exams, health education, screening programs and physical fitness programs. Medical data from the program is stored in a computer bank so epidemiological significance can be established and better procedures can be obtained. Besides health care delivery to the NASA population, NASA is working with HEW on a telemedicine project STARPAHC, applying space technology to provide health care delivery to remotely located populations.

  1. Transmucosal macromolecular drug delivery.

    PubMed

    Prego, C; García, M; Torres, D; Alonso, M J

    2005-01-01

    Mucosal surfaces are the most common and convenient routes for delivering drugs to the body. However, macromolecular drugs such as peptides and proteins are unable to overcome the mucosal barriers and/or are degraded before reaching the blood stream. Among the approaches explored so far in order to optimize the transport of these macromolecules across mucosal barriers, the use of nanoparticulate carriers represents a challenging but promising strategy. The present paper aims to compare the characteristics and potential of nanostructures based on the mucoadhesive polysaccharide chitosan (CS). These are CS nanoparticles, CS-coated oil nanodroplets (nanocapsules) and CS-coated lipid nanoparticles. The characteristics and behavior of CS nanoparticles and CS-coated lipid nanoparticles already reported [A. Vila, A. Sanchez, M. Tobio, P. Calvo, M.J. Alonso, Design of biodegradable particles for protein delivery, J. Control. Rel. 78 (2002) 15-24; R. Fernandez-Urrusuno, P. Calvo, C. Remunan-Lopez, J.L. Vila-Jato, M.J. Alonso, Enhancement of nasal absorption of insulin using chitosan nanoparticles, Pharm. Res. 16 (1999) 1576-1581; M. Garcia-Fuentes, D. Torres, M.J. Alonso, New surface-modified lipid nanoparticles as delivery vehicles for salmon calcitonin (submitted for publication).] are compared with those of CS nanocapsules originally reported here. The three types of systems have a size in the nanometer range and a positive zeta potential that was attributed to the presence of CS on their surface. They showed an important capacity for the association of peptides such as insulin, salmon calcitonin and proteins, such as tetanus toxoid. Their mechanism of interaction with epithelia was investigated using the Caco-2 model cell line. The results showed that CS-coated systems caused a concentration-dependent reduction in the transepithelial resistance of the cell monolayer. Moreover, within the range of concentrations investigated, these systems were internalized in the monolayer in a concentration-dependent manner. This uptake was slightly enhanced by the presence of the CS coating but, as compared with previously published results [M. Garcia-Fuentes, C. Prego, D. Torres, M.J. Alonso, Triglyceride-chitosan nanostructures for oral calcitonin delivery: evaluation in the Caco-2 cell model and in vivo (submitted for publication)], highly dependent on the nature of the lipid core. Nevertheless, these differences in the uptake of the CS-coated systems (solid lipid core or oily core) by the Caco-2 cells did not have a consequence in the in vivo behaviour. Indeed, both CS-coated systems (nanocapsules and CS-coated nanoparticles) showed an important capacity to enhance the intestinal absorption of the model peptide, salmon calcitonin, as shown by the important and long-lasting decrease in the calcemia levels observed in rats. PMID:15588901

  2. Accurate upwind methods for the Euler equations

    NASA Technical Reports Server (NTRS)

    Huynh, Hung T.

    1993-01-01

    A new class of piecewise linear methods for the numerical solution of the one-dimensional Euler equations of gas dynamics is presented. These methods are uniformly second-order accurate, and can be considered as extensions of Godunov's scheme. With an appropriate definition of monotonicity preservation for the case of linear convection, it can be shown that they preserve monotonicity. Similar to Van Leer's MUSCL scheme, they consist of two key steps: a reconstruction step followed by an upwind step. For the reconstruction step, a monotonicity constraint that preserves uniform second-order accuracy is introduced. Computational efficiency is enhanced by devising a criterion that detects the 'smooth' part of the data where the constraint is redundant. The concept and coding of the constraint are simplified by the use of the median function. A slope steepening technique, which has no effect at smooth regions and can resolve a contact discontinuity in four cells, is described. As for the upwind step, existing and new methods are applied in a manner slightly different from those in the literature. These methods are derived by approximating the Euler equations via linearization and diagonalization. At a 'smooth' interface, Harten, Lax, and Van Leer's one intermediate state model is employed. A modification for this model that can resolve contact discontinuities is presented. Near a discontinuity, either this modified model or a more accurate one, namely, Roe's flux-difference splitting. is used. The current presentation of Roe's method, via the conceptually simple flux-vector splitting, not only establishes a connection between the two splittings, but also leads to an admissibility correction with no conditional statement, and an efficient approximation to Osher's approximate Riemann solver. These reconstruction and upwind steps result in schemes that are uniformly second-order accurate and economical at smooth regions, and yield high resolution at discontinuities.

  3. Utility and translatability of mathematical modeling, cell culture and small and large animal models in magnetic nanoparticle hyperthermia cancer treatment research

    NASA Astrophysics Data System (ADS)

    Hoopes, P. J.; Petryk, Alicia A.; Misra, Adwiteeya; Kastner, Elliot J.; Pearce, John A.; Ryan, Thomas P.

    2015-03-01

    For more than 50 years, hyperthermia-based cancer researchers have utilized mathematical models, cell culture studies and animal models to better understand, develop and validate potential new treatments. It has been, and remains, unclear how and to what degree these research techniques depend on, complement and, ultimately, translate accurately to a successful clinical treatment. In the past, when mathematical models have not proven accurate in a clinical treatment situation, the initiating quantitative scientists (engineers, mathematicians and physicists) have tended to believe the biomedical parameters provided to them were inaccurately determined or reported. In a similar manner, experienced biomedical scientists often tend to question the value of mathematical models and cell culture results since those data typically lack the level of biologic and medical variability and complexity that are essential to accurately study and predict complex diseases and subsequent treatments. Such quantitative and biomedical interdependence, variability, diversity and promise have never been greater than they are within magnetic nanoparticle hyperthermia cancer treatment. The use of hyperthermia to treat cancer is well studied and has utilized numerous delivery techniques, including microwaves, radio frequency, focused ultrasound, induction heating, infrared radiation, warmed perfusion liquids (combined with chemotherapy), and, recently, metallic nanoparticles (NP) activated by near infrared radiation (NIR) and alternating magnetic field (AMF) based platforms. The goal of this paper is to use proven concepts and current research to address the potential pathobiology, modeling and quantification of the effects of treatment as pertaining to the similarities and differences in energy delivered by known external delivery techniques and iron oxide nanoparticles.

  4. The first accurate description of an aurora

    NASA Astrophysics Data System (ADS)

    Schröder, Wilfried

    2006-12-01

    As technology has advanced, the scientific study of auroral phenomena has increased by leaps and bounds. A look back at the earliest descriptions of aurorae offers an interesting look into how medieval scholars viewed the subjects that we study.Although there are earlier fragmentary references in the literature, the first accurate description of the aurora borealis appears to be that published by the German Catholic scholar Konrad von Megenberg (1309-1374) in his book Das Buch der Natur (The Book of Nature). The book was written between 1349 and 1350.

  5. Accurate multiplication with noisy spiking neurons

    NASA Astrophysics Data System (ADS)

    Nezis, Panagiotis; van Rossum, Mark C. W.

    2011-06-01

    Multiplication is an operation which is fundamental in mathematics, but it is also relevant for many sensory computations in the nervous system. Nevertheless, despite a number of suggestions in the literature, it is not known how multiplication is implemented in neural circuitry. We propose a simple feedforward circuit that combines a rate model of neural activity and a realistic neural input-output relation to accurately and efficiently implement multiplication of two rate-coded quantities. By simulating a network of integrate and fire neurons, we demonstrate the functional efficiency of the circuit. Finally we discuss how the model can be tested experimentally.

  6. [Delivery of premature infants].

    PubMed

    Eckman, A; Mottet, N; Ramanah, R; Riethmuller, D

    2015-10-01

    Prematurity is a frequent event and clearly raises an issue concerning how these fetuses with multiple weaknesses should be delivered. Although, a systematic abdominal approach has no scientific basis, there are cases where the caesarean is chosen because of other factors associated to prematurity such as any maternal or fetal indication to terminate the pregnancy while labour induction remains impossible. However, in case of breech presentation, which is often delivered by caesarean, the literature does recommend neither the vaginal nor the abdominal approach. Caesarean in case of prematurity is more difficult because of the absence of any inferior segment and implies making a large incision so as to easily extract these weak fetuses. Increased maternal morbidity related to preterm caesarean sections has been reported through out literature. The viability gestational age limit represents a confounding factor in most studies since caesarean is rarely chosen for these fetuses because of a very low expected survival rate, while it is probably in this situation that the abdominal approach could provide a real benefit. Larger studies are required to show potential advantages. Systematic use of episiotomies or instrumental deliveries in case of vaginal births is not recommended in case of prematurity. Protecting the fetal head with spatulas still requires further evaluations. PMID:26139037

  7. Electronic Nicotine Delivery Systems.

    PubMed

    2015-11-01

    Electronic nicotine delivery systems (ENDS) are rapidly growing in popularity among youth. ENDS are handheld devices that produce an aerosolized mixture from a solution typically containing concentrated nicotine, flavoring chemicals, and propylene glycol to be inhaled by the user. ENDS are marketed under a variety of names, most commonly electronic cigarettes and e-cigarettes. In 2014, more youth reported using ENDS than any other tobacco product. ENDS pose health risks to both users and nonusers. Nicotine, the major psychoactive ingredient in ENDS solutions, is both highly addictive and toxic. In addition to nicotine, other toxicants, carcinogens, and metal particles have been detected in solutions and aerosols of ENDS. Nonusers are involuntarily exposed to the emissions of these devices with secondhand and thirdhand aerosol. The concentrated and often flavored nicotine in ENDS solutions poses a poisoning risk for young children. Reports of acute nicotine toxicity from US poison control centers have been increasing, with at least 1 child death reported from unintentional exposure to a nicotine-containing ENDS solution. With flavors, design, and marketing that appeal to youth, ENDS threaten to renormalize and glamorize nicotine and tobacco product use. There is a critical need for ENDS regulation, legislative action, and counter promotion to protect youth. ENDS have the potential to addict a new generation of youth to nicotine and reverse more than 50 years of progress in tobacco control. PMID:26504128

  8. Bioresponsive matrices in drug delivery

    PubMed Central

    2010-01-01

    For years, the field of drug delivery has focused on (1) controlling the release of a therapeutic and (2) targeting the therapeutic to a specific cell type. These research endeavors have concentrated mainly on the development of new degradable polymers and molecule-labeled drug delivery vehicles. Recent interest in biomaterials that respond to their environment have opened new methods to trigger the release of drugs and localize the therapeutic within a particular site. These novel biomaterials, usually termed "smart" or "intelligent", are able to deliver a therapeutic agent based on either environmental cues or a remote stimulus. Stimuli-responsive materials could potentially elicit a therapeutically effective dose without adverse side effects. Polymers responding to different stimuli, such as pH, light, temperature, ultrasound, magnetism, or biomolecules have been investigated as potential drug delivery vehicles. This review describes the most recent advances in "smart" drug delivery systems that respond to one or multiple stimuli. PMID:21114841

  9. Cellular delivery using peptoid carriers 

    E-print Network

    Escher, Geraldine

    2013-06-29

    Efficient delivery into cells is essential for many applications. However, cellular access of “cell-impermeable” molecules, such as drugs, sensors, proteins and oligonucleotides, can often be severely limited due to the ...

  10. Workplace Learning and Flexible Delivery.

    ERIC Educational Resources Information Center

    Smith, Peter J.

    2003-01-01

    Reviews some of the conceptualizations of workplace learning and its cognitive bases and examines workplaces as learning environments. Also considers the special challenges involved in the flexible delivery of training to workplaces. (SLD)

  11. Nonviral Vectors for Gene Delivery

    E-print Network

    Baoum, Abdulgader Ahmed

    2011-04-26

    , two nonviral gene delivery systems using either biodegradable poly(D,L-lactide-co-glycolide) (PLG) nanoparticles or cell penetrating peptide (CPP) complexes have been designed and studied using A549 human lung epithelial cells. PLG nanoparticles were...

  12. conferences | Healthcare Delivery Research Blog

    Cancer.gov

    Over the course of my career I have often been frustrated with the gap between the research I was conducting and the clinical operations of the health care delivery systems with which I was affiliated.

  13. Variable delivery, fixed displacement pump

    DOEpatents

    Sommars, Mark F. (Sparland, IL)

    2001-01-01

    A variable delivery, fixed displac