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Sample records for intravenously drug application

  1. Intravenous Antiepileptic Drugs in Russia

    Directory of Open Access Journals (Sweden)

    P. N. Vlasov

    2014-01-01

    Full Text Available Launching four intravenous antiepileptic drugs: valproate (Depakene and Convulex, lacosamide (Vimpat, and levetiracetam (Keppra – into the Russian market has significantly broadened the possibilities of rendering care to patients in seizure emergency situations. The chemi- cal structure, mechanisms of action, indications/contraindications, clinical effectiveness and tolerability, advantages/disadvantages, and adverse events of using these drugs in urgent and elective neurology are discussed. 

  2. INFECTIVE ENDOCARDITIS IN INTRAVENOUS DRUGS ABUSED PATIENT

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    E. Y. Ponomareva

    2014-07-01

    Full Text Available Three-year observation of acute tricuspid infective endocarditis in intravenous drug abused patient: diagnosis, clinical features, visceral lesions, the possibility of cardiac surgery and conservative treatment, outcome.

  3. INFECTIVE ENDOCARDITIS IN INTRAVENOUS DRUGS ABUSED PATIENT

    Directory of Open Access Journals (Sweden)

    E. Y. Ponomareva

    2011-01-01

    Full Text Available Three-year observation of acute tricuspid infective endocarditis in intravenous drug abused patient: diagnosis, clinical features, visceral lesions, the possibility of cardiac surgery and conservative treatment, outcome.

  4. Administration costs of intravenous biologic drugs for rheumatoid arthritis

    OpenAIRE

    Soini, Erkki J; Leussu, Miina; Hallinen, Taru

    2013-01-01

    Background Cost-effectiveness studies explicitly reporting infusion times, drug-specific administration costs for infusions or real-payer intravenous drug cost are few in number. Yet, administration costs for infusions are needed in the health economic evaluations assessing intravenously-administered drugs. Objectives To estimate the drug-specific administration and total cost of biologic intravenous rheumatoid arthritis (RA) drugs in the adult population and to compare the obtained costs wit...

  5. Potential intravenous drug interactions in intensive care

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    Maiara Benevides Moreira

    Full Text Available Abstract OBJECTIVE To analyze potential intravenous drug interactions, and their level of severity associated with the administration of these drugs based on the prescriptions of an intensive care unit. METHOD Quantitative study, with aretrospective exploratory design, and descriptive statistical analysis of the ICU prescriptions of a teaching hospital from March to June 2014. RESULTS The sample consisted of 319 prescriptions and subsamples of 50 prescriptions. The mean number of drugs per patient was 9.3 records, and a higher probability of drug interaction inherent to polypharmacy was evidenced. The study identified severe drug interactions, such as concomitant administration of Tramadol with selective serotonin reuptake inhibitor drugs (e.g., Metoclopramide and Fluconazole, increasing the risk of seizures due to their epileptogenic actions, as well as the simultaneous use of Ranitidine-Fentanyl®, which can lead to respiratory depression. CONCLUSION A previous mapping of prescriptions enables the characterization of the drug therapy, contributing to prevent potential drug interactions and their clinical consequences.

  6. MYCOTIC FEMORAL PSEUDOANEURYSMS FROM INTRAVENOUS DRUG ABUSE

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    Vojko Flis

    2004-04-01

    Full Text Available Background. Parenteral drug abuse is the most common cause of infected femoral artery pseudoaneurysms (IFAP. This complication of intravenous drug abuse is not only limb threatening but can also be life threatening. The management of the IFAP is difficult and controversial. Generally speaking, ligation and excision of the pseudoaneurysm without revascularization is accepted procedure in majority of the patients. However it is not regarded as an appropriate procedure for cases where the high probability of amputation is expected from acute interruption of the femoral artery flow.Patients, methods and results. We present three cases of young (average 20 years, range 18–24 patients with IFAP, in which a primary reconstruction was performed due to absence of doppler signal over pedal arteries after ligation of common femoral artery. In two of them complications in form of haemorrhage and repeated infection developed in late postoperative period. The first one, had an excision and ligation while the second one had a reconstruction made by means of a silver impregnated dacron prosthesis. None of the patients required an amputation.Conclusions. Overall prognosis and prognosis of the reconstruction in parenteral drug abuse patients is uncertain because there is a high incidence of postoperative drug injection despite aggressive drug rehabilitation.

  7. Potential intravenous drug interactions in intensive care.

    Science.gov (United States)

    Moreira, Maiara Benevides; Mesquita, Maria Gefé da Rosa; Stipp, Marluci Andrade Conceição; Paes, Graciele Oroski

    2017-07-20

    To analyze potential intravenous drug interactions, and their level of severity associated with the administration of these drugs based on the prescriptions of an intensive care unit. Quantitative study, with aretrospective exploratory design, and descriptive statistical analysis of the ICU prescriptions of a teaching hospital from March to June 2014. The sample consisted of 319 prescriptions and subsamples of 50 prescriptions. The mean number of drugs per patient was 9.3 records, and a higher probability of drug interaction inherent to polypharmacy was evidenced. The study identified severe drug interactions, such as concomitant administration of Tramadol with selective serotonin reuptake inhibitor drugs (e.g., Metoclopramide and Fluconazole), increasing the risk of seizures due to their epileptogenic actions, as well as the simultaneous use of Ranitidine-Fentanyl®, which can lead to respiratory depression. A previous mapping of prescriptions enables the characterization of the drug therapy, contributing to prevent potential drug interactions and their clinical consequences. Analisar as potenciais interações medicamentosas intravenosas e seu grau de severidade associadas à administração desses medicamentos a partir das prescrições do Centro de Terapia Intensiva. Estudo quantitativo, tipologia retrospectiva exploratória, com análise estatística descritiva das prescrições medicamentosas do Centro de Terapia Intensiva de um Hospital Universitário, no período de março-junho/2014. A amostra foi composta de 319 prescrições e subamostras de 50 prescrições. Constatou-se que a média de medicamentos por paciente foi de 9,3 registros, e evidenciou-se maior probabilidade para ocorrência de interação medicamentosa inerente à polifarmácia. O estudo identificou interações medicamentosas graves, como a administração concomitante de Tramadol com medicamentos inibidores seletivos da recaptação da serotonina, (exemplo: Metoclopramida e Fluconazol

  8. Illicit intravenous drug use in Johannesburg - medical complications ...

    African Journals Online (AJOL)

    mortality and prevalence of HIV infection. Design. We conducted a ... Table I. Other complications of intravenous drug abuse ... In 2 cases (2%) an initial screen positivity .... patients with Gram-negative, anaerobic or fungal organisms. Our study ...

  9. HIV antibodies among intravenous drug users in Bahrain.

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    al-Haddad, M K; Khashaba, A S; Baig, B Z; Khalfan, S

    1994-09-01

    A 12-month study was conducted to identify risk factors for human immunodeficiency virus (HIV) infections among intravenous drug users (IDU) attending drug rehabilitation clinic of the Psychiatric Hospital, Manama, Bahrain. Patients provided demographic and behavioural information based on a questionnaire. Two hundred and forty male IDUs participated in the study on voluntary basis. The seroprevalence of HIV was 21.1 per cent. The presence of HIV antibody was associated with educational status, frequency of injecting drugs and needle sharing.

  10. Mycotic aneurysms in intravenous drug abusers: the utility of intravenous digital subtraction angiography

    International Nuclear Information System (INIS)

    Shetty, P.C.; Krasicky, G.A.; Sharma, R.P.; Vemuri, B.R.; Burke, M.M.

    1985-01-01

    Two-hundred thirteen intravenous digital subtraction angiographic (DSA) examinations were performed on 195 intravenous drug abusers to rule out the possibility of a mycotic aneurysm in a groin, neck, or upper extremity infection. Twenty-three surgically proved cases of mycotic aneurysm were correctly identified with no false positive results. In addition, six cases of major venous occlusion were documented. The authors present the results of their experience and conclude that DSA is an effective and cost-efficient method of examining this high risk patient population

  11. Candida costochondritis associated with recent intravenous drug use

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    Simeon J. Crawford

    2016-01-01

    Full Text Available Candida osteoarticular infections are being reported with increasing frequency, possibly due to an expanding population at risk. However, Candida costochondritis is uncommon. We report two cases of Candida costochondritis in patients who presented with subacute-onset chest wall swelling and whose only identifiable risk factor was a history of recent intravenous drug use.

  12. Secondary venous aneurysm following intravenous drug abuse: A case report

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    Marković Miroslav

    2016-01-01

    Full Text Available Introduction. Venous aneurysm (VA is a rare condition that can be presented in both superficial and deep venous system. Secondary VAs as well as pseudoaneurysms are usually caused by external spontaneous or iatrogenic trauma. They are often misdiagnosed and inadequately treated. Complications include thrombosis, phlebitis, eventual pulmonary embolism and rupture. Case report. We presented a case of secondary VA of the great saphenous vein developed in a young addict following chronic intravenous drug application in the groin region. Aneurysm required urgent surgical treatment due to bleeding complication as it was previously misdiagnosed for hematoma (or abscess and punctuated by a general surgeon. Complete resection of VA with successful preservation of continuity of the great saphenous vein was performed. Postoperative course was uneventful. Regular venous flow through the great saphenous vein was confirmed on control ultrasound examination. Conclusion. VAs are uncommon, among them secondary VA being extremely rare. In cases with a significant diameter or threatening complications surgical treatment is recommended. [Projekat Ministarstva nauke Republike Srbije, br. ON175008 i br. III41007

  13. The intravenous injection of illicit drugs and needle sharing: an historical perspective.

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    Zule, W A; Vogtsberger, K N; Desmond, D P

    1997-01-01

    This study reviewed the literature on the history of needle sharing and intravenous drug abuse. Reports suggest that needle sharing was practiced by drug abusers as early as 1902 in China and 1914 in the United States. Intravenous drug abuse was first mentioned in the literature in 1925. However other references suggest that some opioid users were injecting intravenously prior to 1920. Outbreaks of malaria in Egypt, the United States, and China between 1929 and 1937 were attributed to needle sharing and intravenous injection of opioids. These reports suggest that both needle sharing and intravenous drug use were common by 1937. Factors such as medical use of intravenous injections, enactment and zealous enforcement of antinarcotic laws, and interactions among drug users in institutional settings such as regional hospitals and prisons may have contributed to the spread of both needle sharing and the intravenous technique among drug abusers.

  14. Why not to ''pocket shoot'': Radiology of intravenous drug abuse

    International Nuclear Information System (INIS)

    McCarroll, K.A.; Fisher, D.R.; Cawthon, L.A.; Donovan, K.R.; Roszler, M.H.; Kling, G.A.

    1987-01-01

    Our large population of intravenous drug abusers has increasingly resorted to supraclavicular central venous injection for vascular access. Few reports of complications associated with the practice of supraclavicular ''pocket'' injection have appeared in the radiologic literature. The authors describe the complications associated with this practice, including pneumothorax, mycotic aneurysm, arteriovenous fistula, jugular vein thrombosis, cellulitis, foreign body reaction, and neck abscess. In addition, the authors provide examples of sternoclavicular osteomyelitis. The anatomy of the ''pocket,'' and the pathophysiology and radiographic manifestations of these complications, are reviewed

  15. Potential intravenous drug incompatibilities in a pediatric unit.

    Science.gov (United States)

    Leal, Karla Dalliane Batista; Leopoldino, Ramon Weyler Duarte; Martins, Rand Randall; Veríssimo, Lourena Mafra

    2016-01-01

    To investigate potential intravenous drug incompatibilities and related risk factors in a pediatric unit. A cross-sectional analytical study conducted in the pediatric unit of a university hospital in Brazil. Data on prescriptions given to children aged 0-15 years from June to October 2014 were collected. Prescriptions that did not include intravenous drugs and prescriptions with incomplete dosage regimen or written in poor handwriting were excluded. Associations between variables and the risk of potential incompatibility were investigated using the Student's t test and ANOVA; the level of significance was set at 5% (ppenicilina G e ceftriaxona. Quase 85% das crianças apresentaram ao menos uma potencial incompatibilidade, razão de 1,2 incompatibilidades/paciente. Os tipos de incompatibilidades mais comuns foram: não testada (93,4%), precipitação (5,5%), turbidez (0,7%) e decomposição química (0,4%). Os fatores associados a potenciais incompatibilidades foram: número de medicamentos e a prescrição dos medicamentos diazepam, fenitoína, fenobarbital e metronidazol. A maioria das prescrições pediátricas apresentou potenciais incompatibilidades e a incompatibilidade não testada foi o tipo mais comum. O número de medicamentos e a prescrição dos medicamentos diazepam, fenobarbital, fenitoína e metronidazol foram fatores de risco para potenciais incompatibilidades.

  16. Hepatitis C seroprevalence among intravenous drug users in Tehran

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    Mohammad Mahdi Mir-Nasseri

    2008-12-01

    Full Text Available

    • BACKGROUND: Hepatitis C (HCV is increasing worldwide including Iran. HCV is more prevalent among intravenous drug abusers (IDU, especially if imprisoned, mostly due to needle sharing. We determined the rate of HCV seropositivity among IDU prisoners and compared it with those of non-prisoners.
    • METHODS: A cross-sectional study was conducted on consenting IDUs inhabiting two prisons and attending three rehabilitation centers in Tehran, Iran. A questionnaire was completed for each subject and 5 ml blood was drawn. The samples were kept at 2-8°C until the sera were separated and stored at -70°C. HCVAb (ELISA was checked by a single technician. Chi-square, Fisher's exact test and multivariate analysis were used where appropriate.
    • RESULTS: Five-hundred and eighteen subjects were enrolled. About 74.5% were prisoners and 89.6% were male. Overall, 59.5% were positive for HCVAb (93.2% males and 6.8% females, P < 0.02. HCV seropositivity was higher among prisoners compared to non-prisoners (78.3% vs. 30.6%, respectively, P < 0.001. Also, it was higher in IUD older than 45 year-old compared to those younger than 30 year-old (77.8% vs.54.2%, respectively, P = 0.002. Multivariate analysis showed significant association of HCV seropositivity with imprisonment (OR: 9.32, 95% CI: 5.60-15.51, sharing syringes (OR: 2.00, 95% CI: 1.26-3.17 and duration of intravenous drug use (OR: 0.86, 95% CI: 0.80-0.92.
    • CONCLUSIONS: HCV is rather common among IDU prisoners. Imprisonment is an independent risk factor for HCV and the infected IDUs going back to the society could be an important source of HCV. Taking effective strategies (education of high risk groups, provision of sterile syringes, identification and treatment of infected IDUs to reduce the risk of this public health problem is needed urgently.
    • KEYWORDS: Hepatitis C, intravenous drug

    • Severe Osteomalacia Related to Long-Term Intravenous Drug Abuse

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      Leslie Gamache MD

      2014-09-01

      Full Text Available Objective . We present the clinical, biochemical, and imaging findings of a woman with vitamin D deficiency and severe osteomalacia related to intravenous heroin addiction. Results . A 54-year-old woman with a medical history significant for long-standing heroin abuse presented with complaints of bone pain, muscle cramping, and a left hip ulcer. She had been bed bound for approximately 1 year secondary to pain of uncertain etiology, and her husband was bringing her both food and drugs. She was admitted to the hospital for debridement of a right ischial ulcer. Further workup revealed osteomyelitis of the left hip and severe vitamin D deficiency. Radiologic evaluation demonstrated diffuse osteopenia with pseudofractures, as well as true fractures. Conclusion . This is the first case reported in the English literature of advanced osteomalacia resulting from a debilitating narcotic dependency. Vitamin D deficiency should be considered in patients with poor nutrition and prolonged sunlight deprivation from any cause.

    • Safety of Intravenous Application of Mistletoe (Viscum album L. Preparations in Oncology: An Observational Study

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      Megan L. Steele

      2014-01-01

      Full Text Available Background. Traditional mistletoe therapy in cancer patients involves subcutaneous applications of Viscum album L. preparations, with doses slowly increasing based on patient responses. Intravenous infusion of high doses may improve therapeutic outcomes and is becoming more common. Little is known about the safety of this “off-label” application of mistletoe. Methods. An observational study was performed within the Network Oncology. Treatment with intravenous mistletoe applications is described. The frequency of adverse drug reactions (ADRs to intravenous mistletoe applications was calculated and compared to ADR data from a study on subcutaneous applications. Results. Of 475 cancer patients who received intravenous infusions of Helixor, Abnoba viscum, or Iscador mistletoe preparations, 22 patients (4.6% reported 32 ADRs of mild (59.4% or moderate severity (40.6%. No serious ADRs occurred. ADRs were more frequently reported to i.v. mistletoe administered alone (4.3%, versus prior to chemotherapy (1.6%. ADR frequency differed with respect to preparation type, with Iscador preparations showing a higher relative frequency, compared to Abnoba viscum and Helixor. Overall, patients were almost two times less likely to experience an ADR to intravenous compared to subcutaneous application of mistletoe. Conclusion. Intravenous mistletoe therapy was found to be safe and prospective studies for efficacy are recommended.

    • Effect of intravenous drug administration mode on drug distribution in a tumor slab: a finite Fourier transform analysis.

      Science.gov (United States)

      Subramaniam, B; Claudius, J S

      1990-03-08

      Cancer therapy using chemotherapeutic drugs frequently involves injection of the drug into the body through some intravenous mode of administration, viz, continuous (drip) infusion or single/multiple bolus injection(s). An understanding of the effect of the various modes of administration upon tumor penetration of drug is essential to rational design of drug therapy. This paper investigates drug penetration into a model tumor of slab geometry (between two capillaries) in which the overall transport rate of drug is limited by intra-tumor transport characterized by an effective diffusion coefficient. Employing the method of Finite Fourier Transforms (FFT), analytical solutions have been obtained for transient drug distribution in both the plasma and the tumor following three modes of administration, viz, continuous infusion, single bolus injection and equally-spaced equal-dose multiple bolus injections, of a given amount of drug. The qualitative trends exhibited by the plasma drug distribution profiles are consistent with reported experimental studies. Two concepts, viz, the dimensionless decay constant and the plasma/tumor drug concentration trajectories, are found to be particularly useful in the rational design of drug therapy. The dimensionless decay constant provides a measure of the rate of drug decay in the plasma relative to the rate of drug diffusion into the tumor and is thus characteristic of the tumor/drug system. The magnitude of this parameter dictates the choice of drug administration mode for minimizing drug decay in the plasma while simultaneously maximizing drug transport into the tumor. The concentration trajectories provide a measure of the plasma drug concentration relative to the tumor drug concentration at various times following injection. When the tumor drug concentration exceeds the plasma drug concentration, the drug will begin to diffuse out of the tumor. Knowledge of the time at which this diffusion reversal occurs is especially useful

    • Gallium-67 detection of intramammary injection sites secondary to intravenous drug abuse

      International Nuclear Information System (INIS)

      Swayne, L.C.

      1989-01-01

      A case of gallium localization within the breast occurred secondary to intravenous drug abuse. In the appropriate clinical setting, prior self-administered injections should be considered as a cause of Ga-67 accumulation at unusual sites

  1. Biochemical sensor tubing for point-of-care monitoring of intravenous drugs and metabolites.

    Science.gov (United States)

    Choi, Charles J; Wu, Hsin-Yu; George, Sherine; Weyhenmeyer, Jonathan; Cunningham, Brian T

    2012-02-07

    In medical facilities, there is strong motivation to develop detection systems that can provide continuous analysis of fluids in medical tubing used to either deliver or remove fluids from a patient's body. Possible applications include systems that increase the safety of intravenous (IV) drug injection and point-of-care health monitoring. In this work, we incorporated a surface-enhanced Raman scattering (SERS) sensor comprised of an array of closely spaced metal nanodomes into flexible tubing commonly used for IV drug delivery and urinary catheters. The nanodome sensor was fabricated by a low-cost, large-area process that enables single use disposable operation. As exemplary demonstrations, the sensor was used to kinetically detect promethazine (pain medication) and urea (urinary metabolite) within their clinically relevant concentration ranges. Distinct SERS peaks for each analyte were used to demonstrate separate detection and co-detection of the analytes.

  2. Stability of Reconstituted Telavancin Drug Product in Frozen Intravenous Bags.

    Science.gov (United States)

    Gu, Zhengtian; Wong, Anissa; Raquinio, Elvira; Nguyen, Alice

    2015-07-01

    Intravenous (IV) infusions of telavancin for injection are generally administered in-hospital, but in some circumstances they may be administered in an outpatient environment. In that setting, antibiotics may be premixed and frozen. This study determined the chemical stability of nonpreserved telavancin in various commonly used reconstitution diluents stored in IV bags (polyvinyl chloride [PVC] and PVC-free) at -20°C (-4°F) without light. Telavancin (750 mg/vial) was reconstituted with 5% dextrose injection USP (D5W) or 0.9% sodium chloride injection USP (NS) to obtain drug solutions at approximately 15 mg/mL. Infusion solutions of telavancin at diluted concentrations of 0.6 mg/mL and 8.0 mg/mL covering the range utilized in clinical practice were prepared in both PVC and PVC-free IV bags using D5W or NS solutions. The infusion solutions were stored under frozen conditions (-20°C ± 5°C [-4°F ± 41°F]) and the chemical stability was evaluated for up to 32 days. Telavancin concentration, purity, and degradant levels were determined using a stability-indicating high-performance liquid chromatography (HPLC) method. Telavancin IV infusion solutions in D5W or NS at 0.6 mg/mL and 8 mg/mL and stored at -20°C (-4°F) met the chemical stability criteria when tested on days 0, 7, 14, and 32. The assayed telavancin concentration at each time point was within 97% to 103% of the initial mean assay value. The total degradants quantified by the HPLC stability-indicating method did not show any significant change over the 32-day study period. Telavancin IV infusion solutions (in D5W or NS) in both PVC and PVC-free IV bags were stable for at least 32 days when stored at -20°C (-4°F) without light. These results provide prolonged frozen stability data further to that previously established for 7 days under refrigerated conditions (2°C-8°C [36°F -46°F]), and for 12 hours at room temperature when diluted into IV bags containing D5W, NS, or lactated Ringer's solution.

  3. Iris abscess a rare presentation of intravenous drug abuse associated Candida endophthalmitis

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    Jonathan Pierce

    2016-12-01

    Conclusions and importance: An iris abscess is a rare clinical presentation of intravenous drug use-associated endogenous endophthalmitis and as a result may present a diagnostic challenge as it requires a high level of clinical suspicion and a detailed social history to elicit the drug abuse. Early diagnosis and aggressive therapy is the key to better visual outcomes in these patients.

  4. Intravenous dipyridamole thallium-201 SPECT imaging methodology, applications, and interpretations

    International Nuclear Information System (INIS)

    Rockett, J.F.; Magill, H.L.; Loveless, V.S.; Murray, G.L.

    1990-01-01

    Dipyridamole TI-201 imaging is an ideal alternative to exercise TI-201 scintigraphy in patients who are unwilling or unable to perform maximum exercise stress. The use of intravenous dipyridamole, alone or in combination with exercise, has not been approved for clinical practice by the Food and Drug Administration. Once approval is granted, the test will become a widely used and important component of the cardiac work-up. The indications, methodology, side effects, and utility of dipyridamole cardiac imaging in the clinical setting are discussed and a variety of examples presented.59 references

  5. Hemolytic Disease of the Fetus and Newborn due to Intravenous Drug Use.

    Science.gov (United States)

    Markham, Kara B; Scrape, Scott R; Prasad, Mona; Rossi, Karen Q; O'Shaughnessy, Richard W

    2016-03-01

    Objectives The objective is to present a pregnancy complication associated with intravenous drug use, namely, that of red blood cell alloimmunization and hemolytic disease of the fetus and newborn. Methods An observational case series is presented including women with red blood cell alloimmunization most likely secondary to intravenous drug abuse Results Five pregnancies were identified that were complicated by red blood cell alloimmunization and significant hemolytic disease of the fetus and newborn, necessitating intrauterine transfusion, an indicated preterm birth, or neonatal therapy. Conclusions As opioid abuse continues to increase in the United States, clinicians should be aware of the potential for alloimmunization to red blood cell antibodies as yet another negative outcome from intravenous drug abuse.

  6. Incidence of intravenous drug incompatibilities in intensive care units

    Czech Academy of Sciences Publication Activity Database

    Machotka, O.; Maňák, J.; Kuběna, Aleš Antonín; Vlček, J.

    2015-01-01

    Roč. 159, č. 4 (2015), s. 652-656 ISSN 1213-8118 Institutional support: RVO:67985556 Keywords : medical error * graph theory * graph coloring * drug administration * drug incompatibilities * applied combinatorics * decision theory * medical * medication safety * intensive care units Subject RIV: FN - Epidemiology, Contagious Diseases ; Clinical Immunology Impact factor: 0.924, year: 2015 http://library.utia.cas.cz/separaty/2014/E/kubena-0437509.pdf

  7. Epidural versus intravenous steroids application following percutaneous endoscopic lumbar discectomy.

    Science.gov (United States)

    Hu, Annan; Gu, Xin; Guan, Xiaofei; Fan, Guoxin; He, Shisheng

    2018-05-01

    Retrospectively study.The purpose of this study was to compare the effects of intraoperative epidural steroids and single dose intravenous steroids following a percutaneous endoscopic lumbar discectomy (PELD).Inflammatory irritation of dorsal root ganglia or sensory nerve roots may cause postoperative pain. Epidural steroids have been applied after a lumbar discectomy for more than 20 years. Epidural steroid application after a PELD is easier to perform and safer because the operations are under observation of the scope.We retrospectively reviewed the medical records of patients with lumbar intervertebral disc herniation who had undergone transforaminal PELD at our department. There are 60 patients in epidural steroid group, intravenous steroid group, and control group, respectively. Visual analog scores (VAS) and the Oswestry Disability Index (ODI) were collected. Successful pain control is defined as 50% or more reduction in back and leg pain (VAS scores).VAS scores (back and leg) and ODI showed a significant decrease in all groups when comparing pre- and postoperatively. Epidural steroid group had a significant improvement in successful pain control compared with the control group at 2 weeks of follow-up. VAS scores (leg) in the epidural steroid group showed a significant decrease compared with the intravenous steroids group at 1, 3, and 7 days after the surgery, but this difference had no statistical significance at 1, 6, and 12 months of follow-up. All groups did not show a significant difference in ODI at 1, 6, and 12 months follow-up.Epidural application of steroid has a better effect on controlling the postoperative pain of PELD in the short term. The epidural application of steroid did not show a tendency to cause infection.

  8. ECMO for Cardiac Rescue after Accidental Intravenous Mepivacaine Application

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    Michael Froehle

    2012-01-01

    Full Text Available Mepivacaine is a potent local anaesthetic and used for infiltration and regional anaesthesia in adults and pediatric patients. Intoxications with mepivacaine affect mainly the CNS and the cardiovascular system. We present a case of accidental intravenous mepivacaine application and intoxication of an infant resulting in seizure, broad complex bradyarrhythmia, arterial hypotension and finally cardiac arrest. The patient could be rescued by prolonged resuscitations and a rapid initiation of ECMO and survived without neurological damage. The management strategies of this rare complication including promising other treatment options with lipid emulsions are discussed.

  9. Clinical and Molecular Epidemiology of Infective Endocarditis in Intravenous Drug Users

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    Pei-Jiuan Chao

    2009-12-01

    Conclusion: Our results suggest that coinfection with hepatitis C was common in intravenous drug users with IE, and that molecular patterns of MRSA isolates had high similarity. SCCmec type III, which is usually hospital-acquired, could have caused the community-associated MRSA endocarditis in our patients.

  10. Treatment of early AIDS dementia in intravenous drug users : High versus low dose peptide T

    NARCIS (Netherlands)

    Kosten, TR; Rosen, MI; McMahon, TL; Bridge, TP; OMalley, SS; Pearsall, R; OConnor, PG

    1997-01-01

    This placebo-controlled, double blind, cross-over study tested the efficacy of two different doses of Peptide T in the treatment of nine intravenous drug users with early AIDS dementia who were also receiving methadone and AZT. Subjects received Peptide T doses of either 15 or 1.5 mg daily for four

  11. Surgical treatment of infective endocarditis in active intravenous drug users: a justified procedure?

    Science.gov (United States)

    Weymann, Alexander; Borst, Tobias; Popov, Aron-Frederik; Sabashnikov, Anton; Bowles, Christopher; Schmack, Bastian; Veres, Gabor; Chaimow, Nicole; Simon, Andre Rüdiger; Karck, Matthias; Szabo, Gábor

    2014-03-24

    Infective endocarditis is a life threatening complication of intravenous drug abuse, which continues to be a major burden with inadequately characterised long-term outcomes. We reviewed our institutional experience of surgical treatment of infective endocarditis in active intravenous drug abusers with the aim of identifying the determinants long-term outcome of this distinct subgroup of infective endocarditis patients. A total of 451 patients underwent surgery for infective endocarditis between January 1993 and July 2013 at the University Hospital of Heidelberg. Of these patients, 20 (7 female, mean age 35 ± 7.7 years) underwent surgery for infective endocarditis with a history of active intravenous drug abuse. Mean follow-up was 2504 ± 1842 days. Staphylococcus aureus was the most common pathogen detected in preoperative blood cultures. Two patients (10%) died before postoperative day 30. Survival at 1, 5 and 10 years was 90%, 85% and 85%, respectively. Freedom from reoperation was 100%. Higher NYHA functional class, higher EuroSCORE II, HIV infection, longer operating time, postoperative fever and higher requirement for red blood cell transfusion were associated with 90-day mortality. In active intravenous drug abusers, surgical treatment for infective endocarditis should be performed as extensively as possible and be followed by an aggressive postoperative antibiotic therapy to avoid high mortality. Early surgical intervention is advisable in patients with precipitous cardiac deterioration and under conditions of staphylococcal endocarditis. However, larger studies are necessary to confirm our preliminary results.

  12. DISTINGUISHED CHARACTERISTICS OF INFECTIVE ENDOCARDITIS IN HIV/AIDS AMONG INTRAVENOUS DRUGS ABUSED

    Directory of Open Access Journals (Sweden)

    E. Y. Ponomareva

    2011-01-01

    Full Text Available The aim – definition of distinguished characteristics of the right-sided infective endocarditis (IE inintravenous drugs abused with human immunodeficiency virus (HIV/acquired immunodeficiency syndrome (AIDS.Materials and methods. The study included 10 patients with right-sided IE in conjunction with HIV/AIDS. All patients were male, age – from 28to 36 years.Results. Course of the IE in HIV/AIDS among intravenous drugs abused in general corresponds to features specific to IE in intravenous drug users without HIV infection. Distinctive features of IE in these patients are a large burden of lung disease, its disseminated character, more tissue oxygenation disorders and marked pulmonary hypertension and haematological disorders (lymphopenia, anemia, and late diagnosis of IE.Conclusion. Features of the current right-sided IE in intravenous drugs abused with HIV/AIDS are distinguished . Difficulties in diagnosis of IE inHIV infection are due to variety of causes of prolonged fever, which should guide doctors to more frequent use of transthoracic echocardiography during prolonged fever in HIV-infected patients.

  13. Stent-Graft Placement with Early Debridement and Antibiotic Treatment for Femoral Pseudoaneurysms in Intravenous Drug Addicts

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    Fu, Qining; Meng, Xiyun; Li, Fenghe; Wang, Xuehu; Cheng, Jun; Huang, Wen; Ren, Wei; Zhao, Yu

    2015-01-01

    PurposeExplore the application of endovascular covered stent-graft (SG) placement in femoral pseudoaneurysms in intravenous drug addicts.Materials and MethodsWe evaluated a consecutive series of pseudoaneurysm in intravenous drug addicts treated with SGs from August 2010 to December 2013.Results15 patients with 16 arterial pseudoaneurysms were enrolled in this study. All were males with a mean age of 36.9 years. Hemorrhage was the most common reason (93.8 %) for seeking medical care, and 3 of these patients were in hemorrhagic shock at admission. All patients received broad-spectrum antibiotics, and debridement and drainage were implemented after SG placement. 7 of the 13 cases which had microbiologic results showed mixed infections, while gram-negative bacteria were the major pathogens. Except for 2 patients, who were lost to follow-up, two new pseudoaneurysms formed due to delayed debridement, and one stent thrombosis occurred, none of the remaining cases had SG infection or developed claudication.ConclusionsSG placement controls massive hemorrhage rapidly, gives enough time for subsequent treatment for pseudoaneurysms due to intravenous drug abuse, and reduces the incidence of postoperative claudication. With appropriate broad-spectrum antibiotics and early debridement, the incidence of SG infection is relatively low. It is an effective alternative especially as temporary bridge measure for critical patients. However, the high cost, uncertain long-term prospects, high demand for medical adherence, and the risk of using the conduits for re-puncture call for a cautious selection of patients. More evidence is required for the application of this treatment

  14. Stent-Graft Placement with Early Debridement and Antibiotic Treatment for Femoral Pseudoaneurysms in Intravenous Drug Addicts

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Qining, E-mail: cqmufqn@163.com; Meng, Xiyun, E-mail: 383274177@qq.com; Li, Fenghe, E-mail: lfh-cqmu@gmail.com; Wang, Xuehu, E-mail: 184037696@qq.co; Cheng, Jun, E-mail: cqdcj@163.com; Huang, Wen, E-mail: dhuangwen@hotmail.com; Ren, Wei, E-mail: renwei9771@yahoo.com.cn; Zhao, Yu, E-mail: zhaoyu-cqmu@126.com [The First Affiliated Hospital of Chongqing Medical University, Department of Vascular Surgery (China)

    2015-06-15

    PurposeExplore the application of endovascular covered stent-graft (SG) placement in femoral pseudoaneurysms in intravenous drug addicts.Materials and MethodsWe evaluated a consecutive series of pseudoaneurysm in intravenous drug addicts treated with SGs from August 2010 to December 2013.Results15 patients with 16 arterial pseudoaneurysms were enrolled in this study. All were males with a mean age of 36.9 years. Hemorrhage was the most common reason (93.8 %) for seeking medical care, and 3 of these patients were in hemorrhagic shock at admission. All patients received broad-spectrum antibiotics, and debridement and drainage were implemented after SG placement. 7 of the 13 cases which had microbiologic results showed mixed infections, while gram-negative bacteria were the major pathogens. Except for 2 patients, who were lost to follow-up, two new pseudoaneurysms formed due to delayed debridement, and one stent thrombosis occurred, none of the remaining cases had SG infection or developed claudication.ConclusionsSG placement controls massive hemorrhage rapidly, gives enough time for subsequent treatment for pseudoaneurysms due to intravenous drug abuse, and reduces the incidence of postoperative claudication. With appropriate broad-spectrum antibiotics and early debridement, the incidence of SG infection is relatively low. It is an effective alternative especially as temporary bridge measure for critical patients. However, the high cost, uncertain long-term prospects, high demand for medical adherence, and the risk of using the conduits for re-puncture call for a cautious selection of patients. More evidence is required for the application of this treatment.

  15. Deep vein thrombosis of the lower limbs in intravenous drug users

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    Wiesława Kwiatkowska

    2015-04-01

    Full Text Available Addiction to intravenously administered drugs has been a serious epidemiological problem for years. Among the related health complications, deep vein thrombosis (DVT is one of the most important. This paper provides an illustrative presentation of DVT in intravenous drug users (IDUs, HIV-positive subjects among them.We searched PubMed, Ovid Journals, Scopus, ScienceDirect, Cochrane Library, Google Scholar and references from articles obtained. The main terms used to identify appropriate studies of DVT in IDUs were ‘intravenous drug users’, ‘substance-related disorders’ and ‘deep vein thrombosis’.No guidelines exist for DVT in intravenous drug users. As many as 47.6% of IDUs report having suffered from DVT. IDUs may constitute approx. 50% of patients under 40 years of age with DVT, this being promoted by multiple vein punctures, groin injections, lack of sterility, insoluble microparticles and other factors. The clinical appearance is more complex than in the general population, which also makes prognosis more difficult. HIV infection can worsen DVT. It often appears as proximal iliofemoral thrombosis, accompanied by local and general complications. Ultrasound with a compression test is an objective method of choice, but must often be complemented with computed tomography. Antithrombotic therapy in IDUs needs to be applied individually. The optimal method is supervised therapy at addiction treatment services.Individual and public preventive measures, among them locally prepared guidelines for DVT in IDUs, may be the most important processes capable of effectively reducing the morbidity of septic and non-septic DVT.

  16. Optimal primary surgical management of infected pseudoaneurysm in intravenous drug abusers: ligation or reconstruction?

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    Jamil, M.; Usman, R.; Afzal, M.; Malik, N.I.

    2017-01-01

    Objective: To find out the optimal primary surgical treatment options for infected pseudoaneurysm in intravenous drug abusers. Study Design: Cross sectional descriptive study. Place and Duration of Study: Department of Vascular Surgery, Combined Military Hospital Lahore, from Jan 2010 to Jun 2015. Material and Methods: A total of 31 consecutive patients with a history of intravenous drug abuse and an infected pseudoaneurysm in the groin or elbow, presenting in emergency department; were included in this study. All patients were primarily treated with ligation of the artery, excision of infected pseudoaneurysm and debridement of necrotic tissues. Only one patient underwent additional revascularization procedure. Results: All patients who underwent ligation and excision procedures did well initially. One (3.2%) patient developed severe distal ischemia after ligation of femoral artery within first 24 hours, so extra anatomic revascularization procedure was performed. Five (16.1%) patients required revascularization procedure after 16 weeks due to disabling distal ischemia. No amputation was needed and mortality rate was zero. Conclusion: Primary ligation of the artery with excision of infected pseudoaneurysm and necrotic material was found the optimal initial management for infected pseudoaneurysm in intravenous drug addicts. Ischemic complications if develop should be treated with early or late revascularization.

  17. Seroprevalence study of HCV among hospitalized intravenous drug users in Ahvaz, Iran (2001–2006

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    Seyed Mohammad Alavi

    Full Text Available Summary: Background and aims: Prevalence of hepatitis C virus (HCV in intravenous drug users (IDU varies in different areas according to socioeconomic and geographical circumstances. The present study was performed to determine seroprevalence of HCV in IDU individuals in Ahvaz, Iran. Materials and methods: 142 IDU patients were included in this retrospective study in Ahvaz southwest Iran from 2001 to 2006. Patients were placed in two groups determined by HCV Ab positive or negative status. Data were analyzed using SPSS for Windows (version 11.5; SPSS Inc., USA software. Results: Out of total 142 cases, 74 persons (52.11% had a positive HCV-Ab test according to the ELISA method. There was no difference in age, sex, level of education, residency and co-infection with HIV and hepatitis B virus between HCV-Ab positive (HAP and HCV-Ab negative (HAN groups (p > 0.05. HCV-Ab positivity was significantly related to imprisonment and duration spent in prison [OR: 3.22, 95% (CI 2.61–3.76, p < 0.0001]. Conclusion: Patients with IDU constitute a high-risk group for acquisition of HCV infection. Transmission of HCV via sharing syringe and needle as well as blood transfusion has been a significant source of hepatitis C infection for patients with intravenous drug addiction. Keywords: Intravenous drug user, Hepatitis C virus, Seroprevalence, Ahvaz

  18. Intravenous Drug Abuse by Patients Inside the Hospital: A Cause for Sustained Bacteremia

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    Noopur Goel

    2016-01-01

    Full Text Available Patients with history of intravenous drug abuse are noted to be at risk of several infections including HIV, endocarditis, and other opportunistic infections. We report the case of a patient with sustained Bacillus cereus bacteremia despite use of multiple antibiotic regimens during his inpatient stay. Our case highlights the importance of high suspicion for active drug use inside the hospital in such patients. This is important in order to minimize unnecessary diagnostic workup and provide adequate treatment and safe hospital stay for these patients.

  19. Relationship between Individual Characteristics and High Risk Behavior in Intravenous Drug Addicts in Ardabil, 2012

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    Nasrin Fouladi

    2014-12-01

    Full Text Available Background & objectives: Addiction is one of the problems in world threating the social, economic and culture factors. It is essential to have an accurate knowledge about the characteristics of drug users in order to diminish the high-risk behaviors of intravenous drug addicts. This research has been done to assess relationship between individual characteristics and high risk behavior in intravenous drug addicts.   Method: In this descriptive-analytic research, 360 drug users were selected from different places in Ardabil city and interviewed by a prepared questionnaire. The data were analyzed using descriptive and analytical tests including t-test, Pearson correlation and ANOVA with SPSS statistical software.   Results: The results showed that the age, gender, material status, job position, age of addiction start, age of injection start, injection frequency, injection frequency per day, syringe supply place and the partner’s gender during recent few months had no significant difference compared to drug users with needle sharing and without needle sharing. The educational level of drug users with needle sharing was lower (P=0.037 and the number of new syringe usage per month was also lesser (P=0.001. They predicted to be more likely infected with AIDS (P=0.001 and had a less argument with their partner about using condom, also mostly have not used condom at their last sexual relationship (P=0.001. The average number of their partners during last three months was high (P=0.003 and there was a meaningful relationship between true sense of peril and using condom in drug users with needle sharing group (p=0.001.   Conclusion: There is a significant relationship between the true sense of danger and the using condom. It is necessary to have an appropriate advertising to increase using condoms among injecting drug users.

  20. Rhizobium radiobacter Endocarditis in an Intravenous Drug User: Clinical Presentation, Diagnosis, and Treatment.

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    Zahoor, Bilal A

    2016-08-01

    Rhizobium radiobacter, a soil-based organism, is not, usually, pathogenic unless in the immunecompromised. Endocarditis, in the immunocompromised, is a typical presentation generally as a result of catheter-based infections. We describe the presentation of R. radiobacter prosthetic valve endocarditis and the inherent challenges in its presentation and diagnosis. A patient presented with acute limb ischemia secondary to R. radiobacter-mediated endocarditis and subsequent thromboembolization of the distal superior femoral and proximal popliteal arteries in the left lower limb. He underwent an uneventful thrombolectomy that restored blood flow distal to the occlusion and restored the patency of the affected arteries. Postoperatively, the patient maintained several unexplained febrile episodes. Blood cultures remained negative for infection. A cardiac work-up demonstrated the presence of vegetative growth on the prosthetic mitral and native aortic valves. Histopathologic analysis of the extracted thrombus confirmed the presence of R. radiobacter. On further history, it was elucidated that the patient was an intravenous drug user who routinely stored drug paraphernalia in plant beds. The patient recovered uneventfully after Piptazobactam was administered. R. radiobacter, and similarly other soil-based pathogens, should be considered as a potential source of endocarditic infection and thromboembolization in patients who similarly describe a history of intravenous drug use. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Enzymatic assays for detecting lactose and sucrose in urine to reveal intravenous drug abuse with emphasis on buprenorphine.

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    Keltanen, T; Mariottini, C; Walta, A M; Rahikainen, A L; Ojanperä, I

    2017-06-01

    Buprenorphine and methadone are commonly used medications for opioid maintenance treatment (OMT), using sublingual and oral administration, respectively. Although beneficial for OMT, these drugs can also be abused by intravenous administration. In intravenous abuse cases, the adjuvants lactose and sucrose are excreted in urine without hydrolysis to monosaccharides, since there are no disaccharidases in the blood. We validated enzymatic methods for the analysis of lactose and sucrose in urine. The analytical performance of both assays was considered appropriate for detecting intravenous drug abuse. The principle was proven by analyzing 93 postmortem (PM) urine samples for lactose, following comprehensive toxicological drug screening. In addition, 32 clinical urine samples from potential drug abusers were analyzed to assess the effect of PM changes on the assay. The mean level of lactose was low in clinical samples and relatively low in PM samples in which no drugs were found. Markedly elevated levels were seen in many of the buprenorphine positive samples, suggesting intravenous administration. Enzymatic methods could provide a simple and cost effective way to assess the intravenous administration of OMT drugs or drugs of abuse. Very high levels of glucose in urine may interfere with the assays. Furthermore, other causes for elevated urine disaccharides, such as hypolactasia and increased intestinal permeability, need to be considered in the interpretation of the results. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  2. Docetaxel-loaded PLGA and PLGA-PEG nanoparticles for intravenous application: pharmacokinetics and biodistribution profile.

    Science.gov (United States)

    Rafiei, Pedram; Haddadi, Azita

    2017-01-01

    Docetaxel is a highly potent anticancer agent being used in a wide spectrum of cancer types. There are important matters of concern regarding the drug's pharmacokinetics related to the conventional formulation. Poly(lactide- co -glycolide) (PLGA) is a biocompatible/biodegradable polymer with variable physicochemical characteristics, and its application in human has been approved by the United States Food and Drug Administration. PLGA gives polymeric nanoparticles with unique drug delivery characteristics. The application of PLGA nanoparticles (NPs) as intravenous (IV) sustained-release delivery vehicles for docetaxel can favorably modify pharmacokinetics, biofate, and pharmacotherapy of the drug in cancer patients. Surface modification of PLGA NPs with poly(ethylene glycol) (PEG) can further enhance NPs' long-circulating properties. Herein, an optimized fabrication approach has been used for the preparation of PLGA and PLGA-PEG NPs loaded with docetaxel for IV application. Both types of NP formulations demonstrated in vitro characteristics that were considered suitable for IV administration (with long-circulating sustained-release purposes). NP formulations were IV administered to an animal model, and docetaxel's pharmacokinetic and biodistribution profiles were determined and compared between study groups. PLGA and PEGylated PLGA NPs were able to modify the pharmacokinetics and biodistribution of docetaxel. Accordingly, the mode of changes made to pharmacokinetics and biodistribution of docetaxel is attributed to the size and surface properties of NPs. NPs contributed to increased blood residence time of docetaxel fulfilling their role as long-circulating sustained-release drug delivery systems. Surface modification of NPs contributed to more pronounced docetaxel blood concentration, which confirms the role of PEG in conferring long-circulation properties to NPs.

  3. Successful lung transplantation for talcosis secondary to intravenous abuse of oral drug

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    Dekel Shlomi

    2008-06-01

    Full Text Available Dekel Shlomi1, David Shitrit1, Daniele Bendayan1, Gidon Sahar2, Yitshak Shechtman3, Mordechai R Kramer11Pulmonary Institute, Departments of 2Cardiothoracic Surgery and 3Pathology, Rabin Medical Center, Beilinson Campus, Petah Tiqwa, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelAbstract: Talcosis due to intravenous injection of oral drugs can cause severe pulmonary disease with progressive dyspnea even when drug use is discontinued. We describe a 54-yearold woman with severe emphysema who underwent left lung transplantation. The patient had a remote history of intravenous injection of crushed methylphenidate (Ritalin tablets. Chest computed tomography showed severe emphysematous changes, more prominent in the lower lobes. Microscopic examination of the extracted lung demonstrated multinucleated giant cells with birefringent crystals, compatible with talcosis. At follow-up, daily symptoms were completely alleviated and lung function was good. We recommend that lung transplantation be considered as a viable option in the treatment of talcosis.Keywords: methylphenidate (Ritalin, emphysema

  4. Reemergence of Intravenous Drug Use as Risk Factor for Candidemia, Massachusetts, USA

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    Poowanawittayakom, Nongnooch; Dutta, Anamika; Stock, Shannon; Touray, Sunkaru; Ellison, Richard T.

    2018-01-01

    The epidemic of illicit intravenous drug use (IVDU) in the United States has been accompanied by a surge in drug overdose deaths and infectious sequelae. Candida albicans infections were associated with injection of contaminated impure brown heroin in the 1970s–1990s; however, candidiasis accompanying IVDU became considerably rarer as the purity of the heroin supply increased. We reviewed cases of candidemia occurring over a recent 7-year period in persons >14 years of age at a tertiary care hospital in central Massachusetts. Of the 198 patients with candidemia, 24 cases occurred in patients with a history of IVDU. Compared with non-IVDU patients, those with a history of IVDU were more likely to have non-albicans Candida, be co-infected with hepatitis C, and have end-organ involvement, including endocarditis and osteomyelitis. Thus, IVDU appears to be reemerging as a risk factor for invasive candidiasis. PMID:29553923

  5. Impact of repeated intravenous cocaine administration on incentive motivation depends on mode of drug delivery.

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    LeBlanc, Kimberly H; Maidment, Nigel T; Ostlund, Sean B

    2014-11-01

    The incentive sensitization theory of addiction posits that repeated exposure to drugs of abuse, like cocaine, can lead to long-term adaptations in the neural circuits that support motivated behavior, providing an account of pathological drug-seeking behavior. Although pre-clinical findings provide strong support for this theory, much remains unknown about the conditions that support incentive sensitization. The current study examined whether the mode of cocaine administration is an important factor governing that drug's long-term impact on behavior. Separate groups of rats were allowed either to self-administer intravenous cocaine or were given an equivalent number and distribution of unsignaled cocaine or saline infusions. During the subsequent test of incentive motivation (Pavlovian-to-instrumental transfer), we found that rats with a history of cocaine self-administration showed strong cue-evoked food seeking, in contrast to rats given unsignaled cocaine or saline. This finding indicates that the manner in which cocaine is administered can determine its lasting behavioral effects, suggesting that subjective experiences during drug use play a critical role in the addiction process. Our findings may therefore have important implications for the study and treatment of compulsive drug seeking. © 2013 Society for the Study of Addiction.

  6. A lyophilized etoposide submicron emulsion with a high drug loading for intravenous injection: preparation, evaluation, and pharmacokinetics in rats.

    Science.gov (United States)

    Chen, Hao; Shi, Shuai; Zhao, Mingming; Zhang, Ling; He, Haibing; Tang, Xing

    2010-12-01

    To develop a submicron emulsion for etoposide with a high drug loading capacity using a drug-phospholipid complex combined with drug freeze-drying techniques. An etoposide-phospholipid complex (EPC) was prepared and its structure was confirmed by X-ray diffraction and differential scanning calorimetry analysis. A freeze-drying technique was used to produce lyophilized etoposide emulsions (LEPE), and LEPE was investigated with regard to their appearance, particle size, and zeta potential. The pharmacokinetic study in vivo was determined by the UPLC/MS/MS system. It showed that EPC significantly improved the liposolubility of etoposide, indicating a high drug loading intravenous emulsion could be easily prepared by EPC. Moreover, the obtained loading of etoposide in the submicron emulsion was 3.0 mg/mL, which was three times higher than that of the previous liquid emulsions. The optimum cryoprotectant was trehalose (15%) in freeze-drying test. The median diameter, polydispersity index, and zeta potential of the optimum formulation of LEPE were 226.1 ± 5.1 nm, 0.107 ± 0.011, and -36.20 ± 1.13 mV, respectively. In addition, these parameters had no significant change during 6 months storage at 4 ± 2°C. The main pharmacokinetic parameters exhibited no significant differences between LEPE and etoposide commercial solution except for area under the concentration-time curve and clearance. The stable etoposide emulsion with a high drug loading was successfully prepared, indicating the amount of excipients such as the oil phase and emulsifiers significantly decreased following administration of the same dose of drug, effectively reducing the metabolism by patients while increasing their compliance. Therefore, LEPE has a great potential for clinical applications.

  7. Intravenous Immunoglobulin: A Drug Utilization Review at Shahid Sadoughi Hospital in Yazd

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    SeyedMojtaba Sohrevardi

    2015-10-01

    Full Text Available  Background: Drug use evaluation (DUE aims at improving the patients’ care. Studying the administration pattern of intravenous immunoglobulin (IVIG is an important research topic due to its significant role in the treatment and controlling of many disorders, high prices, and limited availability of this drug.  Methods:This observational cross-sectional study was conducted at Shahid Sadoughi Hospital in Yazd, central Iran, from May to September 2014. The orders of different wards in the hospital for IVIG given to the hospital central pharmacy were surveyed. Also, a special form developed for evaluation the method of administration. The related physician and nurse were consulted on drug complications and the causes. Finally, the gleaned data were compared to the available standards on the prescription and administration of IVIG.Results:A total of 75 patients received IVIG during this study. 58.7% of the prescriptions belonged to the cases approved by Food and Drug Administration (FDA. The most frequent cause of the use of IVIG was idiopathic thrombocytopenic purpura (ITP. The rate and dose of administration was suitable in most of the patients, yet, the measurement of laboratory parameters required for IVIG were observed in only a few cases. Complications occurred in 26.7% of the patients receiving it, which was mostly related to infusion-related reactions. On the whole, 3922 g IVIG was used during this study of which 1848 g belonged to the cases approved by FDA.Conclusion:Regarding the high costs of IVIG, complications, and limited information on the quality of the effect of this drug in the treatment of many cases, physicians should be cautious enough with its appropriate use. Besides, the presence of a clinical pharmacist in the health-care team not only improves the quality of drug therapy and treatment results, but also plays an important part in decreasing the treatment costs for the patients.

  8. HIV-1 subtype A infection in a community of intravenous drug users in Pakistan

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    Khan Muhammad N

    2006-11-01

    Full Text Available Abstract Background Data on the subtypes of HIV in a population help in predicting the potential foci of epidemic, tracking the routes of infection and following the patterns of the virus' genetic divergence. Globally, the most prevalent HIV infection is the HIV-1 subtype C. In Asia, predominant subtypes of HIV-1 are B, C, and CRF-01AE. During the last few years, HIV prevalence in Pakistan has taken the form of a concentrated epidemic in at least two high risk groups, namely, Intravenous Drug Users (IDUs and Male Sex Workers (MSWs. Factors that have facilitated the proliferation of HIV infection include transmission through a large number of repatriates and needle-sharing intravenous drug users, unscreened blood transfusions, and sexual illiteracy. The HIV subtypes infecting Pakistani populations have not been explored to date. In this study, we analyzed HIV-1 subtypes from in a high-risk community of IDUs in Karachi, the largest city of Pakistan. Methods Samples were collected from 34 IDUs after their informed consent. In addition, the study subjects were administered a questionnaire regarding their sexual behavior and travel history. For HIV analysis, DNA was extracted from the samples and analyzed for HIV types and subtypes using subtype-specific primers in a nested polymerase chain reaction (PCR. The results from this PCR were further confirmed using the Heteroduplex Mobility Assay (HMA. Results We found HIV-1 subtype A in all the 34 samples analyzed. A few of the study subjects were found to have a history of travel and stay in the United Arab Emirates. The same subjects also admitted to having contact with commercial sex workers during their stay abroad. Conclusion Our study therefore shows clade A HIV-1 to be prevalent among the IDUs in Karachi. As the prevalence of HIV in Pakistan continues to rise, more work needs to be done to track the infection, and to analyze the strains of HIV spreading through the country.

  9. Contrasting effects of cord injury on intravenous and oral pharmacokinetics of diclofenac: a drug with intermediate hepatic extraction.

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    Cruz-Antonio, L; Arauz, J; Franco-Bourland, R E; Guízar-Sahagún, G; Castañeda-Hernández, G

    2012-08-01

    Laboratory investigation in rats submitted to experimental spinal cord injury (SCI). To determine the effect of acute SCI on the pharmacokinetics of diclofenac, a marker drug of intermediate hepatic extraction, administered by the intravenous and the oral routes. Female Wistar rats were submitted to complete section of the spinal cord at the T8 level. SCI and sham-injured rats received 3.2 mg kg(-1) of diclofenac sodium either intravenously or orally, diclofenac concentration was measured in whole blood samples and pharmacokinetic parameters were estimated. Diclofenac was not selected as test drug because of its therapeutic properties, but because to its biopharmaceutical properties, that is, intermediate hepatic extraction. Diclofenac bioavailability after intravenous administration was increased in injured rats compared with controls due to a reduced clearance. In contrast, oral diclofenac bioavailability was diminished in SCI animals due to a reduction in drug absorption, which overrides the effect on clearance. Acute SCI induces significant pharmacokinetic changes for diclofenac, a marker drug with intermediate hepatic extraction. SCI-induced pharmacokinetic changes are not only determined by injury characteristics, but also by the route of administration and the biopharmaceutical properties of the studied drug.

  10. Multicentric Castleman's Disease in a Hepatitis C-Positive Intravenous Drug User: A Case Report

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    D. Y. Talukder

    2011-01-01

    Full Text Available Introduction. We report a rare presentation of Castleman's disease in a hepatitis C-positive patient and present a short review of treatments described in other similar case reports and studies. Case Presentation. A 46-year-old male with untreated hepatitis C and a 16-year history of intravenous drug use presented with pleuritic chest pain and bony pain in the knee, hip, and lower back, on a background of unexplained weight loss of 40 kilograms, fevers, night sweats, and repeated infections over the last two years. Examination discovered tender hepatomegaly, a warm right knee effusion, and painless lymphadenopathy. The patient was reactive to Epstein Barr virus and cytomegalovirus; however, HIV and HHV-8 viral testing was negative. Osteomyelitis of vertebrae T8–T11 and septic arthritis of the knee were found on investigation. A lymph node biopsy revealed histology suggestive of plasmacytic Castleman's disease. The patient is to commence rituximab treatment. Conclusion. Castleman's disease continues to present in novel ways, which may lead to difficulties in clinicopathologic diagnosis. A growing body of evidence suggests larger studies are required to determine the best treatment for multicentric Castleman's disease, particularly in patients with a concomitant disease, including hepatitis C.

  11. Influenza vaccination of HIV-1-positive and HIV-1-negative former intravenous drug users.

    Science.gov (United States)

    Amendola, A; Boschini, A; Colzani, D; Anselmi, G; Oltolina, A; Zucconi, R; Begnini, M; Besana, S; Tanzi, E; Zanetti, A R

    2001-12-01

    The immunogenicity of an anti-influenza vaccine was assessed in 409 former intravenous drug user volunteers and its effect on the levels of HIV-1 RNA, proviral DNA and on CD4+ lymphocyte counts in a subset HIV-1-positive subjects was measured. HIV-1-positive individuals (n = 72) were divided into three groups on the basis of their CD4+ lymphocyte counts, while the 337 HIV-1-negative participants were allocated into group four. Haemagglutination inhibiting (HI) responses varied from 45.8 to 70% in the HIV-1-positive subjects and were significantly higher in group four (80.7% responses to the H1N1 strain, 81.6% to the H3N2 strain, and 83% to the B strain). The percentage of subjects with HI protective antibody titres (> or = 1:40) increased significantly after vaccination, especially in HIV-1 uninfected subjects. Immunization caused no significant changes in CD4+ counts and in neither plasma HIV-1 RNA nor proviral DNA levels. Therefore, vaccination against influenza may benefit persons infected by HIV-1. Copyright 2001 Wiley-Liss, Inc.

  12. A Model for the Application of Target-Controlled Intravenous Infusion for a Prolonged Immersive DMT Psychedelic Experience

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    Andrew Robert Gallimore

    2016-07-01

    Full Text Available The state of consciousness induced by N,N-dimethyltryptamine (DMT is one of the most extraordinary of any naturally-occurring psychedelic substance. Users consistently report the complete replacement of normal subjective experience with a novel alternate universe, often densely populated with a variety of strange objects and other highly complex visual content, including what appear to be sentient beings. The phenomenology of the DMT state is of great interest to psychology and calls for rigorous academic enquiry. The extremely short duration of DMT effects—less than 20 minutes—militates against single dose administration as the ideal model for such enquiry. Using pharmacokinetic modelling and DMT blood sampling data, we demonstrate that the unique pharmacological characteristics of DMT, which also include a rapid onset and lack of acute tolerance to its subjective effects, make it amenable to administration by target-controlled intravenous infusion. This is a technology developed to maintain a stable brain concentration of anaesthetic drugs during surgery. Simulations of our model demonstrate that this approach will allow research subjects to be induced into a stable and prolonged DMT experience, making it possible to carefully observe its psychological contents, and provide more extensive accounts for subsequent analyses. This model would also be valuable in performing functional neuroimaging, where subjects are required to remain under the influence of the drug for extended periods. Finally, target-controlled intravenous infusion of DMT may aid the development of unique psychotherapeutic applications of this psychedelic agent.

  13. Transmission of hepatitis C virus among intravenous drug users in the Uppsala region of Sweden

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    Axel Danielsson

    2014-01-01

    Full Text Available Background: Epidemiology and transmission patterns of hepatitis C virus (HCV are important subjects as we enter a new era of treatment with directly acting antivirals (DAAs. The highest prevalence of HCV in developed countries is found among intravenous drug users (IDUs, where unsafe needle sharing practices provide the main route of infection. Efforts to prohibit the continuous spread of HCV among these groups have been initiated by the community services and health care providers. Our goal was to understand how HCV was transmitted among IDUs within a limited population group. We provide a retrospective study (2005–2007 of the HCV transmission patterns in a population of IDUs in the Uppsala region of Sweden. Method: Eighty-two serum samples were collected from IDUs in Uppsala County. Our reverse transcription nested polymerase chain reaction (RT-nested PCR and sequencing method enabled a comprehensive genetic analysis for a broad spectrum of genotypes of two relatively conserved regions, NS5B and NS3, that encodes for the viral polymerase and protease, respectively. HCV RNA in serum samples was amplified and sequenced with in-house primers. Sequence similarities between individuals and subgroups were analyzed with maximum likelihood (ML phylogenetic trees. Published HCV reference sequences from other geographic regions and countries were also included for clarity. Results: Phylogenetic analysis was possible for 59 NS5B (72% and 29 NS3 (35% sequences from Uppsala patients. Additionally, we also included 15 NS3 sequences from Örebro patients, making a total of 44 NS3 sequences for the analysis. By analyzing the NS3 sequences, two transmission sets were found between the IDUs (>98% sequence identity, with one set consisting of two individuals and another set consisting of three individuals. In addition, the phylogenetic analysis done with our serum samples displayed clusters that distinguished them from the reference sequences. Conclusion: Our

  14. Point-of-care detection and real-time monitoring of intravenously delivered drugs via tubing with an integrated SERS sensor.

    Science.gov (United States)

    Wu, Hsin-Yu; Cunningham, Brian T

    2014-05-21

    We demonstrate an approach for detection, identification, and kinetic monitoring of drugs flowing within tubing, through the use of a plasmonic nanodome array (PNA) surface. The PNA structures are fabricated using a low-cost nanoreplica molding process upon a flexible plastic substrate that is subsequently integrated with a flow cell that connects in series with ordinary intravenous (IV) drug delivery tubing. To investigate the potential clinical applications for point-of-care detection and real-time monitoring, we perform SERS detection of ten pharmaceutical compounds (hydrocodone, levorphanol, morphine, oxycodone, methadone, phenobarbital, dopamine, diltiazem, promethazine, and mitoxantrone). We demonstrate dose-dependent SERS signal magnitude, resulting in detection limits (ng ml(-1)) well below typical administered dosages (mg ml(-1)). Further, we show that the detected drugs are not permanently attached to the PNA surface, and thus our approach is capable of performing continuous monitoring of drug delivery as materials flow through IV tubing that is connected in series with the sensor. Finally, we demonstrate the potential co-detection of multiple drugs when they are mixed together, and show excellent reproducibility and stability of SERS measurements for periods extending at least five days. The capabilities reported here demonstrate the potential to use PNA SERS surfaces for enhancing the safety of IV drug delivery.

  15. Clinical application of electron beam computed tomography in intravenous three-dimensional coronary angiography

    International Nuclear Information System (INIS)

    Luo Chufan; Du Zhimin; Hu Chengheng; Li Yi; Zeng Wutao; Ma Hong; Li Xiangmin; Zhou Xuhui

    2002-01-01

    Objective: To investigate the clinical application of intravenous three-dimensional coronary angiography using electron beam computed tomography (EBCT) as compared with selective coronary angiography. Methods: Intravenous EBCT and selective coronary angiography were performed during the same period in 38 patients. The value of EBCT angiography for diagnosing coronary artery disease was evaluated. Results: The number of coronary arteries adequately evaluated by EBCT angiography was 134 out of 152 vessels (88.2%), including 100% of the left main coronary arteries, 94.7% of the left anterior descending arteries, 81.6% of the left circumflex arteries and 76.3 % of the right coronary arteries. Significantly more left main and heft anterior descending coronary arteries were adequately visualized than the left circumflex and right coronary arteries (P < 0.05). The sensitivity, specificity, accuracy, and positive and negative predictive value of EBCT angiography for diagnosing coronary artery disease were 88.0%, 84.6%, 86.8%, 91.7% and 78.6%, respectively. Of the 38 arteries with ≥ 50% stenosis, EBCT underestimated 8, for a sensitivity of 78.9%. Of the 96 arteries without significant stenosis, EBCT overestimated 7 stenosis, for a specificity of 92.7%. Conclusion: Intravenous electron beam computed tomographic coronary angiography is a promising noninvasive method for diagnosing coronary artery disease

  16. Procrastination and Self-Efficacy Among Intravenous Drug Users on a Methadone Maintenance Program in Sari City, Iran, 2013.

    Science.gov (United States)

    Taghizadeh, Fatemeh; Yazdani Cherati, Jamshid

    2015-12-01

    Self-efficacy is the belief that one has the ability to implement the behaviors needed to produce a desired effect. There has been growing interest in the role of self-efficacy as a predictor and/or mediator of treatment outcome in a number of domains. Procrastination is a self-regulatory failure, defined as the voluntary delay of an intended course of action despite expecting to be worse off for the delay. Behavioral procrastination is a self-sabotage strategy that allows people to shift blame and avoid action; the decisional procrastination strategy is to put off making a decision when dealing with conflicts or choices. Procrastination has a great role in quitting drug addiction. The aim of this study was to determine the relationship between procrastination and self-efficacy and other factors among intravenous drug users. This cross-sectional study was conducted on 178 intravenous drug users in the behavioral disease counseling, health center in Sari city, Mazandaran province, Iran, in 2013. The samples were selected through census sampling, descriptive and inferential statistics were used to measure the properties of distribution that depicts a set of data shown as frequency distribution tables, while for the mean and standard deviation, chi-square, Fisher and Spearman-Brown coefficients were used to analyze the data. The mean age of the participants was 43 years. Seventy-two percent of them were married and opium was the first drug used. The first substance used in them was 54% of opium, 33% cannabis and 5% alcohol and 79% smoking. The reason of the first drug use in 32% of the subjects was temptation and in 10% a friend's influence. The mean age of the first drug use was 23 years, and the frequency was 2 times per day. All of them had relapse at least once. Seven percent of them currently use other materials (2% crystal, 5% alcohol and opium and crack) both in methadone treatment. Behavioral procrastination in 60.5% of them and decisional procrastination in

  17. HIV-1 subtypes among intravenous drug users from two neighboring cities in São Paulo State, Brazil

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    M.A.A. Rossini

    2001-01-01

    Full Text Available In order to assess the molecular epidemiology of HIV-1 in two neighboring cities located near the epicenter of the HIV-1 epidemics in Brazil (Santos and São Paulo, we investigated 83 HIV-1 strains obtained from samples collected in 1995 from intravenous drug users. The V3 through V5 region of the envelope of gp 120 was analyzed by heteroduplex mobility analysis. Of the 95 samples, 12 (12.6% were PCR negative (6 samples from each group; low DNA concentration was the reason for non-amplification in half of these cases. Of the 42 typed cases from São Paulo, 34 (81%, 95% confidence limits 74.9 to 87.0% were B and 8 (19%, 95% confidence limits 12.9 to 25.0% were F, whereas of the 41 typed cases from Santos, 39 (95%, 95% confidence limits 91.6 to 98.4% were B and 2 (5%, 95% confidence limits 1.6 to 8.4% were C. We therefore confirm the relationship between clade F and intravenous drug use in São Paulo, and the presence of clade C in Santos. The fact that different genetic subtypes of HIV-1 are co-circulating indicates a need for continuous surveillance for these subtypes as well as for recombinant viruses in Brazil.

  18. The RIA studies on the changes of serum hormone levels during induction stage of intravenous anesthesia with three different drugs

    International Nuclear Information System (INIS)

    Lan Changsheng; Huang Jianmin; Pan Liping; Li Dongxue; Feng Rongfang

    2002-01-01

    Objective: To investigate of effects of propofol, thiopental and etomidate on pituitary adrenal functions during the induction stage of intravenous anaesthesia with them. Methods: Forty-eight patients undergoing elective surgery were randomly divided into three groups, propofol (group I), thipental (group II) and etomidate (group III). Peripheral blood samples were taken for the measurement of E, NE, PRL, GH, B-EP and cortisone before induction (T 0 ), During induction (T 1 ) and 2, 5, 15 min after intubation with RIA. Results: The study showed that none of the three drugs could inhibit increase in E and NE during induction and intubation, but propofol was significantly better than the other two. Conclusion: Propofol has less effects on pituitary-adrenal functions and is the drug of choice for induction

  19. The effects of cyclodextrins on the disposition of intravenously injected drugs in the rat

    NARCIS (Netherlands)

    Frijlink, H W; Franssen, E J; Eissens, Anko; Oosting, Roelof; Lerk, C F; Meijer, D K

    Naproxen and flurbiprofen form complexes with hydroxypropyl-beta-cyclodextrin; with stability constants of 2207 and 12515 M-1, respectively. However, only small fractions of the drug remain complexed when the drug-cyclodextrin complex is added to plasma in vitro. This result can be explained by

  20. Efficacy of Core Decompression of Femoral Head to Treat Avascular Necrosis in Intravenous Drug Users

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    Hossein Soleimani

    2013-04-01

    Full Text Available Core decompression (CD of the femoral head is one of the effective treatments of avascular necrosis (AVN, especially in the early stages of the disease. To investigate further the value of CD in treating the AVN, this study was performed on patients with symptomatic AVN with different etiologies who were treated with CD. This study was carried out on 25 patients (with the total number of 37 femoral head who were diagnosed AVN using X-Ray and MRI. The CD treatments for these patients were started soon after the diagnosis. The results were considered as a success if there was no progression of disease confirmed by X Ray or no subsequent operation was required. Modified Ficat staging was used to record changes before and 2 years after CD treatment. Twenty five patients were participated in this study in which 68% (n=17 were female, 32% (n=8 were male, and the average of the age of the patients were 29.58±4.58. Eight of these patients had systemic lupus erythematous (SLE (32%, 4 rheumatoid arthritis (RA (16%, 3 with kidney transplant (12%, 1 Takayasu’s vasculitis (4% and 1 Wegner vasculitis (4%. Eight of patients had a history of intravenous injection of Temgesic (32%. In patients using Temgesic the changes in Modified Ficat staging were significantly different before and after CD treatment (P=0.03 in comparison with other groups. And in all 8 Temgesic users AVN progressed to the stage 3 and 4 after CD treatment. This study demonstrated that CD treatment to prevent the changes in the femoral head has been more effective in patients with collagen vascular diseases and kidney transplant than patients using intravenous Temgesic. These patients, in spite of early operation, showed no benefit of CD to prevent the changes in the femoral head.

  1. Combined application versus topical and intravenous application of tranexamic acid following primary total hip arthroplasty: a meta-analysis.

    Science.gov (United States)

    Zhang, Pei; Liang, Yuan; Chen, Pengtao; Fang, Yongchao; He, Jinshan; Wang, Jingcheng

    2017-02-21

    The use of intravenous (IV) or topical tranexamic acid (TXA) in total hip arthroplasty has been proven to be effective and safe in total hip arthroplasty. However, which of these two administration routes is better has not been determined. The combined administration of TXA has been used in total knee arthroplasty with satisfactory results. We hypothesized that combined application of TXA may be the most effective way without increased rate of thrombotic events such as deep vein thrombosis (DVT) and pulmonary embolisms (PE) in patients subjected to primary total hip replacement (THA). A meta-analysis was conducted to compare the efficacy and safety of the combined use of tranexamic acid (TXA) relative to topical or intravenous (IV) use alone for treatment of primary THA. The outcomes included total blood loss, postoperative hemoglobin decline, transfusion rates, and the incidence rates of deep vein thrombosis (DVT) and pulmonary embolisms (PE). We searched electronic databases including PubMed, EMBASE, the Cochrane Library, Web of Science, the Chinese Biomedical Literature database, the CNKI database, and Wanfang Data until September 2016. The references of the included articles were also checked for additional potentially relevant studies. There were no language restrictions for the search. The data of the included studies were analyzed using RevMan 5.3 software. Seven studies met the inclusion criteria, encompassing a total of 1762 patients. Our meta-analysis demonstrated that total blood loss, postoperative hemoglobin decline, and transfusion rates were significantly lower for patients that received the combined treatment compared to patients that received either topical or intravenous administration of TXA. No statistical differences were found in the incidence of deep venous thrombosis (DVT) or pulmonary embolism (PE). The group that received the combined treatment had lower total blood loss, postoperative hemoglobin decline, and transfusion rates without an

  2. Intravenous contrast medium application in elderly patients - evaluation of Iopentol (Imagopaque trademark 300)

    International Nuclear Information System (INIS)

    Rathsmann, P.; Jacobs, G.F.; Mueller, R.D.

    2004-01-01

    Purpose: We examined the subjective compatibility of elderly patients who received the intravenous contrast medium Iopentol (Imagopaque trademark 300). In addition, objective data were acquired to show possible interactions between contrast media and organ systems in old patients. Methods and materials: A CT scan with intravenous application of contrast media was performed on 132 patients ranging in age from 75 to 96 years. The patients were questioned about their individual sensations. In addition, blood pressure, creatinine and CT-densitometry were acquired as objective date. Results: The patients' individual sensations and clinical data show a very low rate of complications. Mild allergic reactions were noticed in two patients. No severe anaphylactic reactions were encountered. Statistically significant changes in blood pressure before and after administration of the contrast medium were not observed. The serum creatinine concentration was unchanged after application of contrast media. For CT-densitometry, the patients were divided into two groups, one group with patients 75-84 years and the other group with patients 85-96 years of age. CT-densitometry showed no age-related differences. The protocol of contrast administration resulted in excellent opacification of the examined regions, only the liver did not enhance in some cases before the opacification of the portal vein. Conclusion: It is shown that old age alone is no reason to withhold contrast media containing iodine when performing CT. For the evaluation of the liver, however, the peculiarities of old age have to be taken into account and the interval between injection of the contrast medium and beginning of the spiral-CT has to be extended. (orig.)

  3. Incidence of drug-induced torsades de pointes with intravenous amiodarone

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    Jayaprakash Shenthar

    2017-11-01

    Conclusion: The incidence of drug-induced TdP with IV amiodarone is about 1.5%. Risk factors include female sex, left ventricular dysfunction, electrolyte abnormalities, baseline prolonged QTc, concomitant beta-blocker, and digoxin therapy. Amiodarone induced TdP has favorable prognosis if recognized and treated promptly, and these patients should not receive amiodarone by any route in future.

  4. Gender differences in HIV risk behaviours among intravenous drug users in Catalonia, Spain.

    Science.gov (United States)

    Folch, Cinta; Casabona, Jordi; Espelt, Albert; Majó, Xavier; Meroño, Mercè; Gonzalez, Victoria; Brugal, Maria Teresa

    2013-01-01

    To describe gender differences in injection and sexual risks behaviours, and human immunodeficiency virus (HIV) and hepatitis C (HCV) prevalence among injecting drug users (IDU) in Catalonia, Spain. Cross-sectional studies in 2008-2009 (n=748) and 2010-2011 (n=597) in the network of harm reduction centres. Face to face interviews were conducted and oral fluid samples were collected to estimate HIV/HCV prevalence. Female were more likely than male IDU to have had a steady sexual partner (68.2% versus 44.9%), to have had an IDU steady sexual partner (46.6% versus 15.1%) and to have exchanged sex for money or drugs in the last 6 months (25.5% versus 2.3%). There were no gender differences in injecting risk behaviours. HIV prevalence was 38.7% (91/235) in women and 31.5% (347/1103) in men (p=0.031). HIV prevalence among female IDU who reported having exchange sex for money or drugs was 53.3% (32/60). The prevalence of HCV was 67.4% (159/236) and 73.6% (810/1101) in female and male IDU, respectively (p=0.053). After adjustment by immigrant status, age and years of injection, differences among HIV/HCV prevalence by gender were not significant. This study demonstrated differences in sexual risk behaviours between male and female IDU, but failed to find gender differences in injecting risk behaviours. Apart from that, the higher prevalence of HIV among women than among men, together with a lower prevalence of HCV, provides evidence that sexual transmission of HIV is important among female IDU. Additional studies are needed to analyze in-depth these specific risk factors for women in order to develop appropriate prevention and health education programs. Copyright © 2012 SESPAS. Published by Elsevier Espana. All rights reserved.

  5. Drug Use Evaluation of Human Intravenous Immunoglobulin (IVIG in a Teaching Hospital in East of Iran

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    Mandana Moradi

    2018-02-01

    Full Text Available different indications that only a few of them is now approved by the Food and Drug Administration (FDA as primary immunodeficiency, idiopathic thrombocytopenic purpura (ITP. Although it has been approved for selected indications, the list of its clinical indications, particularly off-labels, has grown considerably. Unfortunately, many of these conditions, lack sufficient clinical data of efficacy and might not always be appropriate.Method: It was a cross sectional study performed in Amir-al-momenin teaching hospital affiliated to Zabol University of medical sciences. All hospitalized patients who received IVIG during a 6 month period (autumn and winter 2015 were included in this study. We used predesigned data collection forms for data gathering as patient’s demographics, diagnoses, as well as drug related data, such as dose regimen, duration, rate of infusion, any related lab test.Results: In this study total of 49 patients received IVIG. Only in 25 cases, the mentioned indications were FDA approved (51%.Total of 189 IVIG vials (945 grams that cost 146,475,000 Tomans (39481 USD was administered during this study period, of which 560 grams (112vials (59.2% were used for FDA approved indications. From 19 ITP patients only 6 (12.2% fulfilled the criteria for IVIG therapy. Considering cases of wrong doses and whom were not indicated to receive IVIG therapy, total of (93 vials 465 grams, that cost 72,075,000 Tomans (19427 USD were spent irrationally.Conclusion: We concluded that IVIG was widely used irrationally in our institution and cost of this irrational administration is huge. This fact justifies the need for establishing multidisciplinary supervisory procedure in our hospital.

  6. [Groin abscesses and vascular catastrophes in intravenous drug users--strategy and results].

    Science.gov (United States)

    Scheuerlein, H; Ruff, S; Haage, P; Zirngibl, H; Fraunhofer, S; Settmacher, U

    2008-02-01

    Drug addiction is a global medical and public health-care problem. Infections of the groin and fossa cubitalis are a common clinical problem in these patients. Severe vascular complications are rare but if they occur, therapy is difficult and requires emergency management and surgery because of bleeding problems. In a retrospective case series, we report on patients treated within an emergency setting in our hospital because of groin abscesses with vascular involvement between 2003 and 2006. The therapeutic concepts and results are reported and discussed in the context of a review of the international literature. We report on 4 patients with a long-standing history of i. v. drug abuse (average age 33, range 29-36 years). All were hepatitis C Ag positive and HIV negative. The general health and nutritional status were not compromised, all patients had one or more DVT in their medical history. In two cases, emergency surgery with revascularisation was necessary (after 2 days in one case and 4 weeks in the other) because of septic bleeding subsequent to abscess incision. Two patients underwent primary revascularisation because of pseudoaneurysms. The grafts were a saphenous vein patch and a superficial femoral artery patch in one and deep vein segments in two cases. In two cases, a sartorius muscle flap and VAC therapy were used to cover the defect. All patients survived, minor amputation became necessary in one case. Abscess excision and debridement have to be as complete as possible and primary revascularisation is the procedure of choice in cases of severe groin infection. In the case of large vessel involvement, abscess incision alone without revision of the vascular structures is dangerous because of subsequent complications like secondary ruptures. For this reason, these patients require intensive care and close monitoring. Successful treatment exclusively based on ligation is described in literature with regard to isolated lesions of the superficial or deep

  7. Experimental research on preventing mechanical phlebitis arising from indwelling needles in intravenous therapy by external application of mirabilite.

    Science.gov (United States)

    Lu, Yanyan; Hao, Chunyan; He, Wubin; Tang, Can; Shao, Zhenya

    2018-01-01

    Various types of complications arising from intravenous indwelling needles have become a challenge in clinical care. It is urgent to seek a simple and cost-effective method for prevention and treatment of phlebitis. We investigated the roles of mirabilite in preventing and treating phlebitis caused by intravenous indwelling needles and provide guidance for prevention and treatment of mechanical phlebitis caused by intravenous indwelling needles. A total of 57 healthy congeneric big-eared New Zealand rabbits were randomly divided into 3 groups: blank control, indwelling needle, and group with external application of mirabilite. The ear vein of each rabbit was punctured with an intravenous indwelling needle. The ear vein specimens were taken at 3, 5, and 7 days after indwelling. The hematoxylin and eosin stained pathological tissue sections of the ear veins of the rabbits in each group were observed. The expression levels of IL-1 and IL-6, and tumour necrosis factor-α (TNF-α) in the vascular tissue of the ear veins of the rabbits in each group were detected with the immunofluorescence method. In the blank control group, there was no inflammatory cellular infiltration and no proliferation of fibrous tissue around the vascular wall. With the increase of the indwelling time, proliferation of fibrous tissue in vascular wall, increased inflammatory cellular infiltration and organized thrombus in the vascular tissue occurred in the ear veins of the rabbits in the indwelling needle group and group with external application of mirabilite. Compared with the indwelling needle group, the group with external application of mirabilite had significantly decreased fibrous tissue in the vascular wall and significantly decreased inflammatory cellular infiltration. At the same point in indwelling time, the expression levels of IL-1, IL-6, and TNF-α in the indwelling needle and group with external application of mirabilite were significantly higher than that in the blank control

  8. Generation and Characterization of HIV-1 Transmitted and Founder Virus Consensus Sequence from Intravenous Drug Users in Xinjiang, China.

    Science.gov (United States)

    Li, Fan; Ma, Liying; Feng, Yi; Hu, Jing; Ni, Na; Ruan, Yuhua; Shao, Yiming

    2017-06-01

    HIV-1 transmission in intravenous drug users (IDUs) has been characterized by high genetic multiplicity and suggests a greater challenge for HIV-1 infection blocking. We investigated a total of 749 sequences of full-length gp160 gene obtained by single genome sequencing (SGS) from 22 HIV-1 early infected IDUs in Xinjiang province, northwest China, and generated a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON). The T/F virus was classified as subtype CRF07_BC and predicted to be CCR5-tropic virus. The variable region (V1, V2, and V4 loop) of IDU.CON showed length variation compared with the heterosexual T/F virus consensus sequence (HSX.CON) and homosexual T/F virus consensus sequence (MSM.CON). A total of 26 N-linked glycosylation sites were discovered in the IDU.CON sequence, which is less than that of MSM.CON and HSX.CON. Characterization of T/F virus from IDUs highlights the genetic make-up and complexity of virus near the moment of transmission or in early infection preceding systemic dissemination and is important toward the development of an effective HIV-1 preventive methods, including vaccines.

  9. Spontaneous Pneumothorax as a Complication of Septic Pulmonary Embolism in an Intravenous Drug User: A Case Report

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    Chau-Chyun Sheu

    2006-02-01

    Full Text Available Infective endocarditis has been the major cause of morbidity and mortality among intravenous drug users (IDUs with infections, mostly involving the tricuspid valve and presenting multiple septic pulmonary embolisms. Numerous pulmonary complications of septic pulmonary embolism have been described, but only a few have reported spontaneous pneumothorax. Our patient, a 23-year-old heroin addict, was hospitalized for tricuspid endocarditis and septic pulmonary embolism. Acute onset of respiratory distress occurred on his seventh hospital day and rapidly resulted in hypoxemia. Immediate bedside chest radiograph demonstrated left pneumothorax. It was thought to be a spontaneous pneumothorax, because he had not undergone any invasive procedure before the occurrence of pneumothorax. His clinical condition improved after the insertion of an intercostal chest tube. He later underwent surgery to replace the tricuspid valve as a result of the large size of the vegetation and poor control of infection. He ultimately survived. Pneumothorax is a possible lethal complication of septic pulmonary embolism in IDUs with right-sided endocarditis and should be considered in such patients when respiratory distress occurs acutely during their hospitalization.

  10. Efficacy of combined antiviral therapy with pegylated interferon α-2a and ribavirin for chronic hepatitis C infection in intravenous drug users

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    Ružić Maja

    2010-01-01

    Full Text Available Introduction. Hepatitis C Virus infection represents not just a medical, but also a socio-economic problem. It is estimated that among 170 million infected, 60% belongs to the category of intravenous drug users (IDUs. Objective. The aim of this paper was to compare the response to the combined therapy of pegylated interferon alfa 2a and ribavirin, in the group of patients with HCV infection who were intravenous drug users (IDUs and in patients who were identified in the other way of transmission of HCV. Also to identify the influence of the therapy on diseases of addiction, during the course of HCV infection and on the effects of the combined therapy of pegylated interferon alfa 2a and ribavirin. Methods. We conducted a retrospective-prospective study, on 60 patients, treated with combined antiviral therapy-pegylated interferon alfa 2a and ribavirin. 30 patients were from the group of IDUs, and 30 patients from other epidemiological groups. Results. There were significant differences between the age of the patients (30.2±7.1 vs. 39.3±11.2 years; p=0.002, but no significant difference in the duration of the HCV infection between the two groups of patients (8.9±7.4 vs. 13.1±7.0 years; p>0.05. A large number of the patients in the group of IDUs had a problem with the abstinence of the drug abuse. In this group, there was the influence of alcohol (30% and other substances with potential hepatotoxicity: marihuana (23.3% and psycho-active drugs (73.6%. Staging of the liver fibrosis was not influenced by those two parameters and was similar in both groups (p>0.05. The genotype 3a was dominant in intravenous drug users (50.0% and genotype 1b in the control group of the patients (76.6%. In both groups, SVR was achieved at a higher percentage (86% vs. 70.00%; p>0.05, but among the intravenous drug users the relapses of HCV infection were at a lower percentage (3.3% vs. 20.0%; p=0.044. Side effects were noticed in solitary cases in both of the examined

  11. Angiographic CT with intravenous contrast agent application for monitoring of intracranial flow diverting stents

    International Nuclear Information System (INIS)

    Saake, Marc; Struffert, Tobias; Goelitz, Philipp; Ott, Sabine; Doerfler, Arnd; Seifert, Frank; Ganslandt, Oliver

    2012-01-01

    Intracranial flow diverting devices are increasingly used to treat cerebral aneurysms. A reliable, non-invasive follow-up modality would be desirable. Our aim was to compare intra-arterial digital subtraction angiography (ia DSA) to angiographic computed tomography with intravenous contrast agent application (iv ACT) in the visualisation of flow diverting devices and aneurysm lumina. Follow-up monitoring by iv ACT (n = 36) and ia DSA (n = 25) in 14 patients treated with flow diverting devices for intracranial aneurysms was evaluated retrospectively. Images were evaluated by two neuroradiologists in anonymous consensus reading regarding the device deployment, wall apposition, neck coverage of the aneurysm, opacification of the vessel and device lumen, as well as the degree of aneurysm occlusion. Corresponding ia DSA and iv ACT images were scored identically in all patients regarding the stent deployment, wall apposition and neck coverage, as well as the degree of aneurysm occlusion and patency status of the device and parent artery. Opacification of the parent vessel lumen and perfused parts of the aneurysm was considered slightly inferior for iv ACT in comparison with ia DSA (seven of 36 cases), without impact on diagnosis. We demonstrated the feasibility and diagnostic value of iv ACT in follow-up imaging of intracranial flow diverting devices. Due to its high spatial resolution and non-invasive character, this novel technique might become a valuable imaging modality in these patients. (orig.)

  12. Chiron Vision files FDA application to market intraocular implant for CMV retinitis. Food and Drug Administration.

    Science.gov (United States)

    1995-07-01

    Chiron Corporation and Hoffman-LaRoche announced a filing of a New Drug Application with the Food and Drug Administration (FDA) to market Vitrasert, its intraocular implant which delivers ganciclovir directly to the eye for treatment of CMV retinitis. Clinical trials show that Vitrasert offers a clinical improvement versus intravenous ganciclovir in further delaying progression of CMV retinitis in the treated eye. One study reported that the median time to progression of CMV retinitis was 186 days for eyes receiving Vitrasert compared to 72 days for eyes receiving intravenous ganciclovir therapy. Chiron's intraocular implant contains ganciclovir embedded in a polymer-based system that slowly releases the drug into the eye for up to eight months. Two additional trials are underway. For further information contact the Professional Services Group at Chiron Corporation at (800) 244-7668, select 2.

  13. Demographic characteristics and intravenous drug use among hepatitis C patients in the Kota Setar district, Kedah, Malaysia

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    Wei Leong Tan

    2015-07-01

    Full Text Available OBJECTIVES: This study explored the demographic characteristics of hepatitis C patients in the Kota Setar (KS district, Kedah, Malaysia, the prevalence of intravenous drug use (IVDU as a risk factor among these patients, and the associations between IVDU and demographic characteristics. METHODS: Retrospective data pertaining to 713 patients from January 2009 to December 2013 were retrieved from hospital and disease notification records for analysis. The risk factors for hepatitis C virus (HCV infection were grouped into IVDU and non-IVDU risk factors for analysis using multiple logistic regression. RESULTS: Of the hepatitis C patients included in this study, the most common age group was 31 to 40 years (30.2%, and male patients (91.2% made up the overwhelming majority. Ethnic Malays constituted approximately 80.4% of the patients, and IVDU was the main risk factor (77.8% for HCV infection. Multiple logistic regression showed that male patients were 59 times more likely to have IVDU as a risk factor for HCV infection. Single patients were 2.5 times more likely to have IVDU as a risk factor. Patients aged ≥71 years were much less likely than patients aged ≤30 years to have IVDU as a risk factor for HCV infection. CONCLUSIONS: IVDU was found to be an important risk factor for HCV infection among patients in the KS district. The factors associated with IVDU included age, sex, and marital status. Appropriate preventive measures should be developed to target the groups in which IVDU is most likely to be a risk factor for HCV infection.

  14. Multiple Introduction and Naturally Occuring Drug Resistance of HCV among HIV-Infected Intravenous Drug Users in Yunnan: An Origin of China's HIV/HCV Epidemics.

    Directory of Open Access Journals (Sweden)

    Min Chen

    Full Text Available The human immunodeficiency virus 1 (HIV-1 epidemic in China historically stemmed from intravenous drug users (IDUs in Yunnan. Due to a shared transmission route, hepatitis C virus (HCV/HIV-1 co-infection is common. Here, we investigated HCV genetic characteristics and baseline drug resistance among HIV-infected IDUs in Yunnan.Blood samples of 432 HIV-1/HCV co-infected IDUs were collected from January to June 2014 in six prefectures of Yunnan Province. Partial E1E2 and NS5B genes were sequenced. Phylogenetic, evolutionary and genotypic drug resistance analyses were performed.Among the 293 specimens successfully genotyped, seven subtypes were identified, including subtypes 3b (37.9%, 111/293, 3a (21.8%, 64/293, 6n (14.0%, 41/293, 1b (10.6%, 31/293, 1a (8.2%, 24/293, 6a (5.1%, 15/293 and 6u (2.4%, 7/293. The distribution of HCV subtypes was mostly related to geographic location. Subtypes 3b, 3a, and 6n were detected in all six prefectures, however, the other four subtypes were detected only in parts of the six prefectures. Phylogeographic analyses indicated that 6n, 1a and 6u originated in the western prefecture (Dehong and spread eastward and showed genetic relatedness with those detected in Burmese. However, 6a originated in the southeast prefectures (Honghe and Wenshan bordering Vietnam and was transmitted westward. These subtypes exhibited different evolutionary rates (between 4.35×10-4 and 2.38×10-3 substitutions site-1 year-1 and times of most recent common ancestor (tMRCA, between 1790.3 and 1994.6, suggesting that HCV was multiply introduced into Yunnan. Naturally occurring resistance-associated mutations (C316N, A421V, C445F, I482L, V494A, and V499A to NS5B polymerase inhibitors were detected in direct-acting antivirals (DAAs-naïve IDUs.This work reveals the temporal-spatial distribution of HCV subtypes and baseline HCV drug resistance among HIV-infected IDUs in Yunnan. The findings enhance our understanding of the characteristics and

  15. Sustained Release Drug Delivery Applications of Polyurethanes

    Directory of Open Access Journals (Sweden)

    Michael B. Lowinger

    2018-05-01

    Full Text Available Since their introduction over 50 years ago, polyurethanes have been applied to nearly every industry. This review describes applications of polyurethanes to the development of modified release drug delivery. Although drug delivery research leveraging polyurethanes has been ongoing for decades, there has been renewed and substantial interest in the field in recent years. The chemistry of polyurethanes and the mechanisms of drug release from sustained release dosage forms are briefly reviewed. Studies to assess the impact of intrinsic drug properties on release from polyurethane-based formulations are considered. The impact of hydrophilic water swelling polyurethanes on drug diffusivity and release rate is discussed. The role of pore formers in modulating drug release rate is examined. Finally, the value of assessing mechanical properties of the dosage form and approaches taken in the literature are described.

  16. Clinical Efficiency of Application of Intravenous Immunoglobulin in Pregnant Women with Intrauterine Infection

    Directory of Open Access Journals (Sweden)

    O.L. Ishchenko

    2016-02-01

    Full Text Available The problem of intrauterine infection (IUI is still relevant today. Ineffective treatment of this pathology is associated with physiological decline of the immunity in these patients. We have proposed the additional use of intravenous immunoglobulin for the treatment of pregnant women with IUI. There were examined 75 patients with IUI, which was diagnosed in the II trimester. The I group consisted of 40 individuals who received conventional treatment, the II group was formed from 35 women who additionally received intravenous immunoglobulin. On the background of IUI, pregnancy was characterized by an increased incidence of threatened miscarriage and premature labor, gestosis and placental dysfunction; during delivery, premature rupture of amniotic membrane and fetal distress were more common. These patients had placenta with both ultrasonic and histological signs of infection. Among newborns, there was a significant increase in the incidence of pathology associated with intrauterine infection. Additional use of intravenous immunoglobulin in the treatment of IUI during the II trimester of pregnancy in comparison with conventional therapy leads to a significant reduction in the incidence of both obstetric complications and perinatal pathology.

  17. Drug-induced MR urography: the effects of furosemide and intravenous saline injection on MR urography of obstructed and non-obstructed urinary tract

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jeong Ha; Lee, Myung Jun; Lee, Chang Joon [National Medical Center, Seoul (Korea, Republic of)

    2001-10-01

    To determine the usefulness of MR urography technique for the evaluation of urinary systems in patients with obstructed urinary tract and normal volunteers with non-obstructed urinary tract after intravenous normal saline and diuretic injection. Three normal volunteers and 12 patients with urinary tract obstruction [ureteral calculi (n=8), extraurinary mass (n=1), ureteral tumor invasion (n=3)] underwent MR urography using a 1.0T scanner and a 2D non-breath-hold heavily T2-weighted fast spin-cho sequence. These acquisition were post-processed with a maximum intensity projection (MIP) algorithm. Two acquisitions were performed, the first prior to saline solution infusion following standard MR urography procedures, and the second, within 2-3 minutes of the infusion of 250 ml saline solution followed by 20 mg of Lasix administered intravenously. For this latter, drug-induced MR urography procedures were followed. In healthy volunteer (n=3) and those experiencing partial obstruction (n=4) by a urinary stone, drug-induced MR urography provided better images of the urinary tract than did standard MR urography. In those in whom a urinary stone or tumor had caused complete obstruction (n=8), standard MR urography provided good images, as did drug-induced MR urography. In patients with a partially or non-obstructed urinary tract, drug-induced MR urography provided better anatomic and functional details of the kidney and urinary tract than did standard MR urography. In those experiencing complete obstruction of the urinary tract, however, standard or drug-induced MR urography permitted very adequate evaluation of the tract, and drug-induced MR urography was unnecessary.

  18. Comparison of self-administration behavior and responsiveness to drug-paired cues in rats running an alley for intravenous heroin and cocaine.

    Science.gov (United States)

    Su, Zu-In; Wenzel, Jennifer; Baird, Rebeccah; Ettenberg, Aaron

    2011-04-01

    Evidence suggests that responsiveness to a drug-paired cue is predicted by the reinforcing magnitude of the drug during prior self-administration. It remains unclear, however, if this principle holds true when comparisons are made across drug reinforcers. The current study was therefore devised to test the hypothesis that differences in the animals' responsiveness to a cocaine- or heroin-paired cue presented during extinction would reflect differences in the patterns of prior cocaine and heroin runway self-administration. Rats ran a straight alley for single intravenous injections of either heroin (0.1 mg/kg/inj) or cocaine (1.0 mg/kg/inj) each paired with a distinct olfactory cue. Animals experienced 15 trials with each drug reinforcer in a counterbalanced manner. Start latencies, run times, and retreat behaviors (a form of approach-avoidance conflict) provided behavioral indices of the subjects' motivation to seek the reinforcer on each trial. Responsiveness to each drug-paired cue was assessed after 7, 14, or 21 days of non-reinforced extinction trials. Other animals underwent conditioned place preference (CPP) testing to ensure that the two drug reinforcers were capable of producing drug-cue associations. While both drugs produced comparable CPPs, heroin served as a stronger incentive stimulus in the runway as evidenced by faster start and run times and fewer retreats. In contrast, cocaine- but not heroin-paired cues produced increases in drug-seeking behavior during subsequent extinction trials. The subjects' responsiveness to drug-paired cues during extinction was not predicted by differences in the motivation to seek heroin versus cocaine during prior drug self-administration.

  19. Toxicological study of DTPA as a drug, (4). Effect of intravenously injected DTPA on cardiovascular system in beagle dogs

    Energy Technology Data Exchange (ETDEWEB)

    Fukuda, Satoshi; Iida, Haruzo

    1988-09-01

    We have previously reported that the side effects on cardiovascular system such as the heart failure, increases of blood pressure and pulse accompanied with hypocalcemia occurred in rats when Zn-DTPA was injected intravenously, but those did not occur by Ca-DTPA. This is in the reverse that it is generally said that Zn-DTPA is more safe than Ca-DTPA. This study was carried out to examine whether the same side effects occurred in different animal species or not. Zn-DTPA or Ca-DTPA (30, 150, 300 and 600 ..mu..mol/kg) was injected intravenously to beagle dogs. The hypocalcemia was observed in the dogs by Zn-DTPA injection, but it was not by Ca-DTPA. After Zn-DTPA injection, the increase of blood pressure and pulse, and heart failure was observed in 3 out of 5 dogs at 300 ..mu..mol/kg dose, and in 3 out of 8 dogs at 600 ..mu..mol/kg dose. These changes were the same degrees as those in rats. In the present study, it is suggested that the side effects induced by Zn-DTPA intravenous injection occur independently of animal species and the data obtained from animal experiments can be available to estimate DTPA toxicity in humans.

  20. Comparison of oral versus intravenous application of tranexamic acid in total knee and hip arthroplasty: A systematic review and meta-analysis.

    Science.gov (United States)

    Zhang, Lu-Kai; Ma, Jian-Xiong; Kuang, Ming-Jie; Zhao, Jie; Wang, Ying; Lu, Bin; Sun, Lei; Ma, Xin-Long

    2017-09-01

    Tranexamic acid (TXA) is regarded as one of the most important drugs in reducing blood loss and hemoglobin (Hb) drop after total knee arthroplasty (TKA) or total hip arthroplasty (THA). Treatment with tranexamic acid (TXA) by intravenous application has been discussed extensively. Recently, several studies have reported that oral administration has an effect on blood sparing. Therefore, we performed a meta-analysis to investigate the efficacy and safety between oral TXA and intravenous TXA (IV-TXA) for blood sparing in total knee and hip arthroplasty. Randomized controlled trials (RCTs) or retrospective cohort studies (RCSs) about relevant research were searched for by using PubMed (1996-April 2017), Embase (1980-April 2017), and the Cochrane Library (CENTRAL, April 2017). Five studies that compared oral with IV administration of TXA were included in our meta-analysis. Meta-analysis results were collected and analyzed by the software Review Manager 5.3 (Copenhagen: The Nordic Cochrane Center, The Collaboration, 2014). Five studies containing 3474 patients met the inclusion criteria. Our pooled data analysis indicated that oral TXA was as effective as the IV-TXA in terms of the average Hb drop (P = 0.88), total Hb loss (P = 0.57), total blood loss (P = 0.42), transfusion rate (P = 0.16), complications (P = 0.61), and length of hospital stay (P = 1.00). Compared with the IV-TXA method, oral TXA shows similar blood-sparing efficacy for preventing hemoglobin drop, total hemoglobin loss, and total blood loss following TKA or THA. In addition, no significant differences of transfusion rate, complications, or length of hospital stay were found between the 2 groups. However, because of the limited number of included studies, more studies of high quality are needed to further identify the optimal administration time for oral TXA. Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

  1. Intravenous Therapy: Hazards, Complications and Their Prevention ...

    African Journals Online (AJOL)

    Breaks in aseptic techniques, faulty handling of parenteral fluid containers, failure to discard out-dated intravenous solutions and tubings contribute to occurrence of intravenous-associated sepsis. Improper technique and lack of pharmaceutical knowledge when adding drugs into intravenous fluids contribute to ...

  2. Intravenous application of an anticalin dramatically lowers plasma digoxin levels and reduces its toxic effects in rats

    Energy Technology Data Exchange (ETDEWEB)

    Eyer, Florian, E-mail: Florian.Eyer@mac.com [Department of Toxicology, Klinikum rechts der Isar, Munich (Germany); Steimer, Werner [Institute of Clinical Chemistry and Pathobiochemistry, Klinikum rechts der Isar, Munich (Germany); Nitzsche, Thomas [Munich Center for Integrated Protein Science (CIPS-M), Freising-Weihenstephan (Germany); Lehrstuhl für Biologische Chemie, Technische Universität München, Freising-Weihenstephan (Germany); Jung, Nicole; Neuberger, Heidi [Department of Toxicology, Klinikum rechts der Isar, Munich (Germany); Müller, Christine [Institute of Clinical Chemistry and Pathobiochemistry, Klinikum rechts der Isar, Munich (Germany); Schlapschy, Martin [Munich Center for Integrated Protein Science (CIPS-M), Freising-Weihenstephan (Germany); Lehrstuhl für Biologische Chemie, Technische Universität München, Freising-Weihenstephan (Germany); Zilker, Thomas [Department of Toxicology, Klinikum rechts der Isar, Munich (Germany); Skerra, Arne [Munich Center for Integrated Protein Science (CIPS-M), Freising-Weihenstephan (Germany); Lehrstuhl für Biologische Chemie, Technische Universität München, Freising-Weihenstephan (Germany)

    2012-09-15

    Lipocalins tailored with high affinity for prescribed ligands, so-called anticalins, constitute promising candidates as antidotes. Here, we present an animal study to investigate both pharmacokinetic and clinical effects of an anticalin specific for the digitalis compound digoxin. Intravenous digoxin (2.5–50 μg/kg/min) was administered to rats until first changes in the ECG occurred (dose finding study) or a priori for 30 min (kinetic study). The anticalin DigA16(H86N), dubbed DigiCal, was administered intravenously at absolute doses of 1, 5, 10 and 20 mg, while the control group received isotonic saline. Hemodynamic changes, several ECG parameters and digoxin concentration in plasma were monitored at given time intervals. After DigiCal administration free digoxin concentration in plasma ultrafiltrate declined dramatically within 1 min to the presumably non-toxic range. There was also a significant and DigiCal dose-dependent effect on longer survival, less ECG alterations, arrhythmia, and improved hemodynamics. Infusion of a lower digoxin dose (2.5 μg/kg/min) resulted in a more sustained reduction of free digoxin in plasma after DigiCal administration compared to a higher digoxin dose (25 μg/kg/min), whereas ECG and hemodynamic parameters did not markedly differ, reflecting the known relative insensitivity of rats towards digoxin toxicity. Notably, we observed a re-increase of free digoxin in plasma some time after bolus administration of DigiCal, which was presumably due to toxin redistribution from tissue in combination with the relatively fast renal clearance of the rather small protein antidote. We conclude that anticalins with appropriately engineered drug-binding activities and, possibly, prolonged plasma half-life offer prospects for next-generation antidotal therapy. -- Highlights: ► We provide an advanced model of digoxin toxicity in rats. ► We report on binding of digoxin to a novel designed anticalin. ► We report on pharmacokinetics of digoxin

  3. Doxorubicin conjugation and drug linker chemistry alter the intravenous and pulmonary pharmacokinetics of a PEGylated Generation 4 polylysine dendrimer in rats.

    Science.gov (United States)

    Leong, Nathania J; Mehta, Dharmini; McLeod, Victoria M; Kelly, Brian D; Pathak, Rashmi; Owen, David J; Porter, Christopher Jh; Kaminskas, Lisa M

    2018-05-28

    PEGylated polylysine dendrimers have demonstrated potential as inhalable drug delivery systems that can improve the treatment of lung cancers. Their treatment potential may be enhanced by developing constructs that display prolonged lung retention, together with good systemic absorption, the capacity to passively target lung tumours from the blood and highly selective, yet rapid liberation in the tumour microenvironment. This study sought to characterise how the nature of cathepsin B cleavable peptide linkers, used to conjugate doxorubicin to a PEGylated (PEG570) G4 polylysine dendrimer, affect drug liberation kinetics and intravenous and pulmonary pharmacokinetics in rats. The construct bearing a self-emolative diglycolic acid-V-Citrulline linker exhibited faster doxorubicin release kinetics compared to constructs bearing self emolative diglycolic acid-GLFG, or non-self emolative glutaric acid-GLFG linkers. The V-Citrulline construct exhibited slower plasma clearance, but faster absorption from the lungs than a GLFG construct, although mucociliary clearance and urinary elimination were unchanged. Doxorubicin-conjugation enhanced localisation in the bronchoalveolar lavage fluid compared to lung tissue, suggesting that projection of doxorubicin from the dendrimer surface reduced tissue uptake. These data show that the linker chemistry employed to conjugate drugs to PEGylated carriers can affect drug release profiles and systemic and lung disposition. Copyright © 2018. Published by Elsevier Inc.

  4. 77 FR 8262 - Draft Guidance on Investigational New Drug Applications for Positron Emission Tomography Drugs...

    Science.gov (United States)

    2012-02-14

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0081] Draft Guidance on Investigational New Drug Applications for Positron Emission Tomography Drugs; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug...

  5. 75 FR 32482 - Investigational New Drug Applications; Co-development of Investigational Drugs

    Science.gov (United States)

    2010-06-08

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0247] Investigational New Drug Applications; Co-development of Investigational Drugs AGENCY: Food and Drug Administration, HHS. ACTION: Notice; establishment of docket; request for comments. SUMMARY: The Food and Drug...

  6. 78 FR 52429 - New Animal Drugs; Withdrawal of Approval of New Animal Drug Applications; Diethylcarbamazine...

    Science.gov (United States)

    2013-08-23

    ... 558 [Docket No. FDA-2013-N-0839] New Animal Drugs; Withdrawal of Approval of New Animal Drug...: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect the withdrawal of approval of three new animal drug applications (NADAs) at the sponsors' request...

  7. HIV-1 A1 Subtype Epidemic in Italy Originated from Africa and Eastern Europe and Shows a High Frequency of Transmission Chains Involving Intravenous Drug Users.

    Directory of Open Access Journals (Sweden)

    Alessia Lai

    Full Text Available Subtype A accounts for only 12% of HIV-1 infections worldwide but predominates in Russia and Former Soviet Union countries of Eastern Europe. After an early propagation via heterosexual contacts, this variant spread explosively among intravenous drug users. A distinct A1 variant predominates in Greece and Albania, which penetrated directly from Africa. Clade A1 accounts for 12.5% of non-B subtypes in Italy, being the most frequent after F1 subtype.Aim of this study was to investigate the circulation of A1 subtype in Italy and trace its origin and diffusion through phylogenetic and phylodynamic approaches.The phylogenetic analysis of 113 A1 pol sequences included in the Italian ARCA database, indicated that 71 patients (62.8% clustered within 5 clades. A higher probability to be detected in clusters was found for patients from Eastern Europe and Italy (88.9% and 60.4%, respectively compared to those from Africa (20% (p < .001. Higher proportions of clustering sequences were found in intravenous drug users with respect to heterosexuals (85.7% vs. 59.3%, p = .056 and in women with respect to men (81.4% vs. 53.2%, p < .006. Subtype A1 dated phylogeny indicated an East African origin around 1961. Phylogeographical reconstruction highlighted 3 significant groups. One involved East European and some Italian variants, the second encompassed some Italian and African strains, the latter included the majority of viruses carried by African and Italian subjects and all viral sequences from Albania and Greece.Subtype A1 originated in Central Africa and spread among East European countries in 1982. It entered Italy through three introduction events: directly from East Africa, from Albania and Greece, and from the area encompassing Moldavia and Ukraine. As in previously documented A1 epidemics of East European countries, HIV-1 A1 subtype spread in Italy in part through intravenous drug users. However, Eastern European women contributed to the penetration of

  8. Nanodiamond and its application to drug delivery

    Directory of Open Access Journals (Sweden)

    Eiji Osawa

    2012-08-01

    Full Text Available Quasi-spherical diamond crystals having an average diameter of 3.7±0.6 nm are attracting much attention as an ideal material in carbon nanotechnology. In contrast to the other popular nanocarbons including fullerenes, carbon nanotubes and graphenes, our single-nanodiamond can be produced in uniform shape/size on industrial scale. Thus, the most serious problem in nanocarbon industry that persisted in the past 25 years, namely the technical failure to produce highly crystalline nanocarbons in narrow shape/size range does not exist in our diamond from the beginning. Among potential applications of the single-nanodiamond under development, this review concentrates on its highly promising role as a drug carrier, especially for therapeutic-resistant cancer. An interesting possibility of intercalation is proposed as the mechanism of drug transport through blood, which takes into accounts of the spontaneous formation of nanographene layer on the [111] facets, which is then extensively oxidized during oxidative soot removal process to give nanographene oxide partial surface, capable of intercalating drug molecules to prevent them from leaking and causing undesirable side effects during transportation to target malignant cells. A perspective of quantifying the drug delivery process by anticipating orders of magnitude in the number of administered detonation nanodiamond (DND particles is suggested.

  9. Intravenous contrast media application using cone-beam computed tomography in a rabbit model

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Min Sung; Kim, Bok Yeol; Choi, Hwa Young [Dept. of Oral and Maxillofacial Radiology, School of Dentistry, Kyung Hee University, Seoul (Korea, Republic of); and others

    2015-03-15

    This study was performed to evaluate the feasibility of visualizing soft tissue lesions and vascular structures using contrast-enhanced cone-beam computed tomography (CE-CBCT) after the intravenous administration of a contrast medium in an animal model. CBCT was performed on six rabbits after a contrast medium was administered using an injection dose of 2 mL/kg body weight and an injection rate of 1 mL/s via the ear vein or femoral vein under general anesthesia. Artificial soft tissue lesions were created through the transplantation of autologous fatty tissue into the salivary gland. Volume rendering reconstruction, maximum intensity projection, and multiplanar reconstruction images were reconstructed and evaluated in order to visualize soft tissue contrast and vascular structures. The contrast enhancement of soft tissue was possible using all contrast medium injection parameters. An adequate contrast medium injection parameter for facilitating effective CE-CBCT was a 5-mL injection before exposure combined with a continuous 5-mL injection during scanning. Artificial soft tissue lesions were successfully created in the animals. The CE-CBCT images demonstrated adequate opacification of the soft tissues and vascular structures. Despite limited soft tissue resolution, the opacification of vascular structures was observed and artificial soft tissue lesions were visualized with sufficient contrast to the surrounding structures. The vascular structures and soft tissue lesions appeared well delineated in the CE-CBCT images, which was probably due to the superior spatial resolution of CE-CBCT compared to other techniques, such as multislice computed tomography.

  10. Intravenous contrast media application using cone-beam computed tomography in a rabbit model

    International Nuclear Information System (INIS)

    Kim, Min Sung; Kim, Bok Yeol; Choi, Hwa Young

    2015-01-01

    This study was performed to evaluate the feasibility of visualizing soft tissue lesions and vascular structures using contrast-enhanced cone-beam computed tomography (CE-CBCT) after the intravenous administration of a contrast medium in an animal model. CBCT was performed on six rabbits after a contrast medium was administered using an injection dose of 2 mL/kg body weight and an injection rate of 1 mL/s via the ear vein or femoral vein under general anesthesia. Artificial soft tissue lesions were created through the transplantation of autologous fatty tissue into the salivary gland. Volume rendering reconstruction, maximum intensity projection, and multiplanar reconstruction images were reconstructed and evaluated in order to visualize soft tissue contrast and vascular structures. The contrast enhancement of soft tissue was possible using all contrast medium injection parameters. An adequate contrast medium injection parameter for facilitating effective CE-CBCT was a 5-mL injection before exposure combined with a continuous 5-mL injection during scanning. Artificial soft tissue lesions were successfully created in the animals. The CE-CBCT images demonstrated adequate opacification of the soft tissues and vascular structures. Despite limited soft tissue resolution, the opacification of vascular structures was observed and artificial soft tissue lesions were visualized with sufficient contrast to the surrounding structures. The vascular structures and soft tissue lesions appeared well delineated in the CE-CBCT images, which was probably due to the superior spatial resolution of CE-CBCT compared to other techniques, such as multislice computed tomography.

  11. Histopathological confirmation of similar intramucosal distribution of fluorescein in both intravenous administration and local mucosal application for probe-based confocal laser endomicroscopy of the normal stomach.

    Science.gov (United States)

    Nonaka, Kouichi; Ohata, Ken; Ban, Shinichi; Ichihara, Shin; Takasugi, Rumi; Minato, Yohei; Tashima, Tomoaki; Matsuyama, Yasushi; Takita, Maiko; Matsuhashi, Nobuyuki; Neumann, Helmut

    2015-12-16

    Probe-based confocal laser endomicroscopy (pCLE) is capable of acquiring in vivo magnified cross-section images of the gastric mucosa. Intravenous injection of fluorescein sodium is used for confocal imaging. However, it is still under debate if local administration of the dye to the mucosa is also effective for confocal imaging as it is not yet clear if topical application also reveals the intramucosal distribution of fluorescein. The objective of this study was to evaluate the intramucosal distribution of fluorescein sodium after topical application and to compare the distribution to the conventional intravenous injection used for confocal imaging. pCLE of the stomach uninfected with Helicobacter pylori was performed in a healthy male employing intravenous administration and local mucosal application of fluorescein. The mucosa of the lower gastric body was biopsied 1 min and 5 min after intravenous administration or local mucosal application of fluorescein, and the distribution of fluorescein in the biopsy samples was examined histologically. Green fluorescence was already observed in the cytoplasm of fundic glandular cells in the biopsied deep mucosa 1 min after local mucosal application of fluorescein. It was also observed in the foveolar lumen and inter-foveolar lamina propria, although it was noted at only a few sites. In the tissue biopsied 5 min after the local mucosal application of fluorescein, green fluorescence was more frequently noted in the cytoplasm of fundic glandular cells than in that 1 min after the local mucosal application of fluorescein, although obvious green fluorescence was not identified in the foveolar lumen or inter-foveolar lamina propria. The distribution of intravenously administered fluorescein in the cytoplasm of fundic glandular cells was also clearly observed similarly to that after local mucosal application of fluorescein. Green fluorescence in more cells was observed in many cells 5 min after intravenous administration compared

  12. Antimicrobial Peptides: Multifunctional Drugs for Different Applications

    Directory of Open Access Journals (Sweden)

    Lea-Jessica Albrecht

    2012-02-01

    Full Text Available Antimicrobial peptides (APs are an important part of the innate immune system in epithelial and non-epithelial surfaces. So far, many different antimicrobial peptides from various families have been discovered in non-vertebrates and vertebrates. They are characterized by antibiotic, antifungal and antiviral activities against a variety of microorganisms. In addition to their role as endogenous antimicrobials, APs participate in multiple aspects of immunity. They are involved in septic and non-septic inflammation, wound repair, angiogenesis, regulation of the adaptive immune system and in maintaining homeostasis. Due to those characteristics AP could play an important role in many practical applications. Limited therapeutic efficiency of current antimicrobial agents and the emerging resistance of pathogens require alternate antimicrobial drugs. The purpose of this review is to highlight recent literature on functions and mechanisms of APs. It also shows their current practical applications as peptide therapeutics and bioactive polymers and discusses the possibilities of future clinical developments.

  13. 77 FR 71802 - Guidance on Investigational New Drug Applications for Positron Emission Tomography Drugs...

    Science.gov (United States)

    2012-12-04

    ... Positron Emission Tomography (PET) Drugs.'' The guidance is intended to assist manufacturers of PET drugs... one self-addressed adhesive label to assist that office in processing your requests. See the... ``Investigational New Drug Applications for Positron Emission Tomography (PET) Drugs.'' The guidance summarizes the...

  14. Intravenous Immunoglobulins: Mechanism of Action and Limitations of Clinical Application in Pediatrics

    Directory of Open Access Journals (Sweden)

    S.O. Mokiia-Serbina

    2016-02-01

    IVIG consumption is increasing due to the fact that in many cases the drugs are being used off-label. IVIG were more likely to be used in autoimmune and systemic inflammatory diseases. However, in randomized clinical trials, a good effect was achieved only in Kawasaki disease and immune thrombocytopenic purpura. Current clinical guidelines narrowed the indications for IVIG, limiting their use in sepsis. Immunoglobulin replacement therapy is recommended for children with physiological delay of immunoglobulin production only in repeated infections, which can not be controlled or prevented with antibiotics. In secondary ID, replacement therapy must be carried out if the cause of hypogammaglobulinemia can not be eliminated or elimination is contraindicated, as well as in association with β-cell cancers, in which severe infections caused by encapsulated bacteria persist despite preventive antibiotic therapy.

  15. Accidents and Incidents Related to Intravenous Drug Administration: A Pre-Post Study Following Implementation of Smart Pumps in a Teaching Hospital.

    Science.gov (United States)

    Guérin, Aurélie; Tourel, Julien; Delage, Emmanuelle; Duval, Stéphanie; David, Marie-Johanne; Lebel, Denis; Bussières, Jean-François

    2015-08-01

    Smart pumps are expected to prevent and reduce medication errors. The implementation of smart pumps requires a significant effort and collaboration of physicians, nurses, pharmacists, and other stakeholders. The main objective of this study was to evaluate the impact of new smart pumps on reported drug-related accidents and incidents (AIs). This is a descriptive retrospective pre-post study conducted at a women's and pediatric hospital with 500 beds. A strong multidisciplinary team (nurse, pharmacist, pharmacy resident, physician, biomedical technician, information technology technician, patient safety officer, manager) was involved in the planning, implementation, and monitoring technology implementation. A total of 1045 smart pumps were implemented in 2011 in our hospital. The reported number of AIs related to intravenous drug administration (AIIV) before and after the implementation of 1045 smart pumps were collected. A total of 2911 AI events related to medications, devices, and equipment were self-reported by clinical staff in the pre-phase (Y0), 3523 in the post-phase (Y1), and 2788 in the post-phase (Y2). The total AIIV increased from 1432 in Y0 to 1834 in Y1 and decreased to 1389 in Y2. We observed no risk reduction associated with the implementation of smart pumps in a 500 bed mother-child hospital. Further studies are required to explore the details of the potential risk reduction associated with the use of smart pumps.

  16. Broadly Applicable Nanowafer Drug Delivery System for Treating Eye Injuries

    Science.gov (United States)

    2015-09-01

    Systems in Systemic , Dermal, Transdermal , and Ocular Drug Delivery . Crit. Rev. Ther. Drug 2008, 25, 545–584. 14. Choy, Y. B.; Park, J.-H.; McCarey, B...AWARD NUMBER: W81XWH-13-1-0146 TITLE: Broadly Applicable Nanowafer Drug Delivery System for Treating Eye Injuries PRINCIPAL INVESTIGATOR: Dr...Broadly Applicable Nanowafer Drug Delivery System for Treating Eye Injuries” 5b. GRANT NUMBER W81XWH-13-1-0146 5c. PROGRAM ELEMENT NUMBER 6

  17. Functionalization of protein-based nanocages for drug delivery applications.

    Science.gov (United States)

    Schoonen, Lise; van Hest, Jan C M

    2014-07-07

    Traditional drug delivery strategies involve drugs which are not targeted towards the desired tissue. This can lead to undesired side effects, as normal cells are affected by the drugs as well. Therefore, new systems are now being developed which combine targeting functionalities with encapsulation of drug cargo. Protein nanocages are highly promising drug delivery platforms due to their perfectly defined structures, biocompatibility, biodegradability and low toxicity. A variety of protein nanocages have been modified and functionalized for these types of applications. In this review, we aim to give an overview of different types of modifications of protein-based nanocontainers for drug delivery applications.

  18. Post-marketing safety and effectiveness evaluation of the intravenous anti-influenza neuraminidase inhibitor peramivir (I): a drug use investigation.

    Science.gov (United States)

    Komeda, Takuji; Ishii, Shingo; Itoh, Yumiko; Ariyasu, Yasuyuki; Sanekata, Masaki; Yoshikawa, Takayoshi; Shimada, Jingoro

    2014-11-01

    Peramivir is the only intravenous formulation among anti-influenza neuraminidase inhibitors currently available. Peramivir was approved for manufacturing and marketing in Japan in January 2010. We conducted a drug use investigation of peramivir from October 2010 to February 2012 and evaluated its safety and effectiveness under routine clinical settings. We collected data of 1309 patients from 189 facilities across Japan and examined safety in 1174 patients and effectiveness in 1158 patients. In total, 143 adverse events were observed with an incidence rate of 7.33% (86/1174). Of these, 78 events were adverse drug reactions (ADRs) with an incidence rate of 4.34% (51/1174). The most frequently reported ADRs were diarrhea, vomiting, and nausea, with incidence rates of 1.87% (22/1174), 0.85% (10/1174), and 0.68% (8/1174), respectively. Moreover, no ADR was reported as serious. ADR onset was within 3 days after the start of peramivir administration in 91.0% (71 events) of the 78 ADRs, and ADRs were resolved or improved within 7 days after onset in 96.2% (75 events) of the 78 ADRs. Neither patient characteristics nor treatment factors appeared to significantly affect drug safety. With regard to effectiveness, the median time to alleviation of both influenza symptoms and fever was 3 days, including the first day of administration. The present study demonstrates the safety and effectiveness of peramivir under routine clinical settings. Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  19. Intra-articular versus intravenous tranexamic acid application in total knee arthroplasty: a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Mi, Bobin; Liu, Guohui; Zhou, Wu; Lv, Huijuan; Liu, Yi; Zha, Kun; Wu, Qipeng; Liu, Jing

    2017-07-01

    The purpose of this meta-analysis was to compare the blood loss and complications of intra-articular (IA) with intravenous (IV) tranexamic acid (TXA) for total knee arthroplasty (TKA). A comprehensive search of studies was conducted to identify related articles in Pubmed, Embase, Cochrane central Register of Controlled Trials, springerLink, OVID and the Research published from January 1980 to September 2016. All studies that compared IA TXA with IV TXA application on TKA were included. Main outcomes of the two methods were collected and analyzed by using Review Manager 5.3. There were 16 randomized controlled trials with 1308 cases met the criteria. Compared with IV TXA, IA TXA had similar blood volume of drainage, hidden blood loss, transfusion rate and complications (P > 0.05). IA TXA had lower total blood loss than IV TXA, and there was significant difference (P  0.05) when compared with IA TXA. Both IA TXA and single dose of IV TXA are effective in reducing total blood loss and postoperative hemoglobin drop without increasing complications of DVT or PE. The current meta-analysis suggests that 1.5 g TXA by IA administration or 1 g TXA by IV administration 10 min before tourniquet deflation is effective and safe in patients undergoing TKA.

  20. Drug-Target Interactions: Prediction Methods and Applications.

    Science.gov (United States)

    Anusuya, Shanmugam; Kesherwani, Manish; Priya, K Vishnu; Vimala, Antonydhason; Shanmugam, Gnanendra; Velmurugan, Devadasan; Gromiha, M Michael

    2018-01-01

    Identifying the interactions between drugs and target proteins is a key step in drug discovery. This not only aids to understand the disease mechanism, but also helps to identify unexpected therapeutic activity or adverse side effects of drugs. Hence, drug-target interaction prediction becomes an essential tool in the field of drug repurposing. The availability of heterogeneous biological data on known drug-target interactions enabled many researchers to develop various computational methods to decipher unknown drug-target interactions. This review provides an overview on these computational methods for predicting drug-target interactions along with available webservers and databases for drug-target interactions. Further, the applicability of drug-target interactions in various diseases for identifying lead compounds has been outlined. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. The influence of psychological variables on health-related quality of life among HIV-positive individuals with a history of intravenous drug use.

    Science.gov (United States)

    Psaros, Christina; O'Cleirigh, Conall; Bullis, Jacqueline R; Markowitz, Sarah M; Safren, Steven A

    2013-01-01

    Intravenous drug use (IDU) remains a prominent pathway of HIV transmission in the United States, though little is known about modifiable factors influencing quality of life among IDUs. The goal of this study was to evaluate the influence of psychological variables (e.g., depression and anxiety) on health-related quality of life among HIV-positive individuals with a history of IDU who were enrolled in outpatient treatment for opioid dependence. 108 HIV-positive individuals with a history of IDU and participating in current outpatient treatment for opiate dependence who were screened for participation in a depression and adherence study reported sociodemographic data, depressive and anxiety symptoms, and health-related quality of life (HRQoL; Multidimensional Health Assessment using the ACTG-SF 21). Multiple regression models controlling for disease stage and background characteristics identified significant negative relationships between General Health Perception and Functioning without Pain for anxiety and depression, and between Role Functioning and Physical Functioning for anxiety. CD4 cell count was significantly related to Physical Functioning only. Results indicate that distress (both depression and anxiety) contribute significantly to variation in HRQoL over and above the effects of disease variables. Effective depression and anxiety treatment may result in improved overall functioning.

  2. Inaccuracy of transthoracic echocardiography for the identification of right-sided vegetation in patients with no history of intravenous drug abuse or cardiac device insertion.

    Science.gov (United States)

    Xie, Jiang; Liu, Shuang; Yang, Jinghua; Xu, Jie; Zhu, Guangfa

    2014-06-01

    The use of transthoracic echocardiography (TTE) to identify right-sided infective endocarditis (RSIE) vegetation is controversial. Data are scarce for patients with no history of intravenous drug abuse (IVDA) or cardiac device insertion. This study analysed the consistency of presurgical echocardiographic results with surgical findings for vegetation identification, and the factors that influence accuracy of echocardiography. This retrospective trial divided infective endocarditis (IE) patients into three subgroups according to the results of their presurgical TTE: left-sided native IE (LSNIE), left-sided prosthetic valve IE (LSPIE) and RSIE. The accuracy of TTE was tested by comparing vegetation (number and location), detected presurgery by TTE, with actual findings during surgery. In total, 416 patients were analysed, 322 with LSNIE, 31 with LSPIE and 63 with RSIE. Consistency between TTE findings and surgical results was lower in the RSIE group compared with the LSPIE and LSNIE groups. Consistency was lowered by the presence of vegetation in multiple locations and atypical distribution--both of which were increased in the RSIE group. The chance of vegetation in both sides of the heart rose with increased numbers of vegetation locations in RSIE patients. A high proportion of RSIE patients had congenital heart defects, mostly ventricular septal defects. TTE may be unsuitable for RSIE patients with no history of IVDA or cardiac device insertion, because multifocal and atypically distributed vegetation may influence detection accuracy. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  3. Post-marketing safety and effectiveness evaluation of the intravenous anti-influenza neuraminidase inhibitor peramivir. II: a pediatric drug use investigation.

    Science.gov (United States)

    Komeda, Takuji; Ishii, Shingo; Itoh, Yumiko; Ariyasu, Yasuyuki; Sanekata, Masaki; Yoshikawa, Takayoshi; Shimada, Jingoro

    2015-03-01

    Peramivir is the only intravenous formulation among anti-influenza neuraminidase inhibitors currently available. Peramivir was approved for manufacturing and marketing in Japan in January 2010. In October 2010, an additional indication for pediatric use was approved. We conducted a pediatric drug use investigation of peramivir from October 2010 to February 2012 and evaluated its real-world safety and effectiveness in pediatric patients. We collected the data of 1254 peramivir-treated pediatric patients from 161 facilities across Japan and examined the safety in 1199 patients and effectiveness in 1188 patients. In total, 245 adverse events were observed with an incidence rate of 14.01% (168/1199). Of these, 115 events were adverse drug reactions (ADRs) with an incidence rate of 7.67% (92/1199). Common ADRs were diarrhea and abnormal behavior, with incidence rates of 2.50% (30/1199) and 2.25% (27/1199), respectively. Fourteen serious ADRs were observed in 12 patients (1.00%), including 5 cases each of abnormal behavior and neutrophil count decreased. While 87.0% (100 events) of ADRs occurred within 3 days after the initiation of peramivir administration, 87.8% (101 events) resolved or improved within 7 days after onset. Multivariate analyses indicated that the presence or absence of underlying diseases/complications was significantly related to ADR incidence. With regard to effectiveness, the median time to alleviation of both influenza symptoms and fever was 3 days, including the first day of administration. Thus, this study confirms the pediatric safety of peramivir without any concerns about effectiveness under routine clinical settings. Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  4. Application of nanohydrogels in drug delivery systems: recent patents review.

    Science.gov (United States)

    Dalwadi, Chintan; Patel, Gayatri

    2015-01-01

    Nanohydrogel combines the advantages of hydrogel and nano particulate systems. Similar to the hydrogel and macrogel, nanohydrogel can protect the drug and control drug release by stimuli responsive conformation or biodegradable bond into the polymer networks. Nanohydrogel has drawn huge interest due to their potential applications, such as carrier in target-specific controlled drug delivery, absorbents, chemical/biological sensors, and bio-mimetic materials. Similar to the nanoparticles, stimuli responsive nanohydrogel can easily be delivered in the liquid form for parenteral drug delivery application. This review highlights the methods to prepare nanohydrogel based on natural and synthetic polymers for diverse applications in drug delivery. It also encompasses the drug loading and drug release mechanism of the nanohydrogel formulation and patents related to the composition and chemical methods for preparation of nanohydrogel formulation with current status in clinical trials.

  5. Applications of polymeric nanocapsules in field of drug delivery systems.

    Science.gov (United States)

    Rong, Xinyu; Xie, Yinghua; Hao, Xiaomei; Chen, Tao; Wang, Yingming; Liu, Yuanyuan

    2011-09-01

    Drug-loaded polymeric nanocapsules have exhibited potential applications in the field of drug delivery systems in recent years. This article entails the biodegradable polymers generally used for preparing nanocapsules, which include both natural polymers and synthetic polymers. Furthermore, the article presents a general review of the different preparation methods: nanoprecipitation method, emulsion-diffusion method, double emulsification method, emulsion-coacervation method, layer-by-layer assembly method. In addition, the analysis methods of nanocapsule characteristics, such as mean size, morphology, surface characteristics, shell thickness, encapsulation efficiency, active substance release, dispersion stability, are mentioned. Also, the applications of nanocapsules as carriers for use in drug delivery systems are reviewed, which primarily involve targeting drug delivery, controlled/sustained release drug delivery systems, transdermal drug delivery systems and improving stability and bioavailability of drugs. Nanocapsules, prepared with different biodegradable polymers, have received more and more attention and have been regarded as one of the most promising drug delivery systems.

  6. 10 CFR 707.8 - Applicant drug testing.

    Science.gov (United States)

    2010-01-01

    ... DEPARTMENT OF ENERGY WORKPLACE SUBSTANCE ABUSE PROGRAMS AT DOE SITES Procedures § 707.8 Applicant drug... final selection for employment or assignment to such a position. Provisions of this part do not prohibit contractors from conducting drug testing on applicants for employment in any position. ...

  7. Drug nanocrystals for the formulation of poorly soluble drugs and its application as a potential drug delivery system

    International Nuclear Information System (INIS)

    Gao Lei; Zhang Dianrui; Chen Minghui

    2008-01-01

    Formulation of poorly soluble drugs is a general intractable problem in pharmaceutical field, especially those compounds poorly soluble in both aqueous and organic media. It is difficult to resolve this problem using conventional formulation approaches, so many drugs are abandoned early in discovery. Nanocrystals, a new carrier-free colloidal drug delivery system with a particle size ranging from 100 to 1000 nm, is thought as a viable drug delivery strategy to develop the poorly soluble drugs, because of their simplicity in preparation and general applicability. In this article, the product techniques of the nanocrystals were reviewed and compared, the special features of drug nanocrystals were discussed. The researches on the application of the drug nanocrystals to various administration routes were described in detail. In addition, as introduced later, the nanocrystals could be easily scaled up, which was the prerequisite to the development of a delivery system as a market product

  8. Prediction of drug terminal half-life and terminal volume of distribution after intravenous dosing based on drug clearance, steady-state volume of distribution, and physiological parameters of the body.

    Science.gov (United States)

    Berezhkovskiy, Leonid M

    2013-02-01

    The steady state, V(ss), terminal volume of distribution, V(β), and the terminal half-life, t(1/2), are commonly obtained from the drug plasma concentration-time profile, C(p)(t), following intravenous dosing. Unlike V(ss) that can be calculated based on the physicochemical properties of drugs considering the equilibrium partitioning between plasma and organ tissues, t(1/2) and V(β) cannot be calculated that way because they depend on the rates of drug transfer between blood and tissues. Considering the physiological pharmacokinetic model pertinent to the terminal phase of drug elimination, a novel equation that calculates t(1/2) (and consequently V(β)) was derived. It turns out that V(ss), the total body clearance, Cl, equilibrium blood-plasma concentration ratio, r; and the physiological parameters of the body such as cardiac output, and blood and tissue volumes are sufficient for determination of terminal kinetics. Calculation of t(1/2) by the obtained equation appears to be in good agreement with the experimentally observed vales of this parameter in pharmacokinetic studies in rat, monkey, dog, and human. The equation for the determination of the pre-exponent of the terminal phase of C(p)(t) is also found. The obtained equation allows to predict t(1/2) in human assuming that V(ss) and Cl were either obtained by allometric scaling or, respectively, calculated in silico or based on in vitro drug stability measurements. For compounds that have high clearance, the derived equation may be applied to calculate r just using the routine data on Cl, V(ss), and t(1/2), rather than doing the in vitro assay to measure this parameter. Copyright © 2012 Wiley Periodicals, Inc.

  9. INTRAVENOUS IMMUNOGLOBULIN IN PEDIATRIC RHEUMATOLOGY PRACTICE

    Directory of Open Access Journals (Sweden)

    E. I. Alexeeva

    2015-01-01

    Full Text Available Modern successful treatment of rheumatic diseases is impossible without the use of intravenous immunoglobulin. The use of intravenous immunoglobulin is based on strict indications developed as a result of long-term multicenter controlled studies. The article highlights the issues of using immunoglobulin in pediatric rheumatology practice, and provides the review of literature with the results from the evaluation of the efficiency of intravenous immunoglobulin confirming the efficiency of the drug only for certain rheumatic diseases. 

  10. The Effects of a Normal Rate versus a Slow Intervalled Rate of Oral Nutrient Intake and Intravenous Low Rate Macronutrient Application on Psychophysical Function – Two Pilot Studies

    Directory of Open Access Journals (Sweden)

    Melanie Y. Denzer-Lippmann

    2017-06-01

    Full Text Available Stomach distension and energy per time are factors influencing satiety. Moreover, different rates of nutrient intake induce different stomach distension. The goal of our studies was to elucidate the influence of different oral rates of nutrient intake (normal rate versus slow intervalled rate; study I and intravenous low rate macronutrient application (protein, carbohydrate, fat or placebo (study II on psychophysical function. The pilot studies investigated the effects of 1 study I: a mixed nutrient solution (1/3 protein, 1/3 fat, 1/3 carbohydrates 2 study II: intravenous macronutrient infusions (protein, carbohydrate, fat or placebo on psychophysical function (mood, hunger, food craving, alertness, smell intensity ratings and hedonic ratings in human subjects. In study I 10 male subjects (age range: 21–30 years completed the study protocol participating in both test conditions and in study II 20 male subjects (age range: 19–41 years completed the study protocol participating in all test conditions. Additionally, metabolic function was analyzed and cognitive and olfactory tests were conducted twice starting 100 min before the beginning of the intervention and 240 min after. Psychophysical (mood, hunger, fat-, protein-, carbohydrate-, sweets- and vegetable-craving, alertness and metabolic function tests were performed seven times on each examination day. Greater effects on hunger and food cravings were observed for normal rate of intake compared to slow intervalled rate of intake and intravenous low rate macronutrient application. Our findings potentially confirm that volume of the food ingested and a higher rate of energy per time contribute to satiety during normal rate of food intake, while slow intervalled rate of food intake and intravenous low rate macronutrient application showed no effects on satiation. Our results motivate the view that a certain amount of volume of the food ingested and a certain energy per time ratio are necessary

  11. Multifunctional Nanoparticles for Drug Delivery Applications Imaging, Targeting, and Delivery

    CERN Document Server

    Prud'homme, Robert

    2012-01-01

    This book clearly demonstrates the progression of nanoparticle therapeutics from basic research to applications. Unlike other books covering nanoparticles used in medical applications, Multifunctional Nanoparticles for Drug Delivery Applications presents the medical challenges that can be reduced or even overcome by recent advances in nanoscale drug delivery. Each chapter highlights recent progress in the design and engineering of select multifunctional nanoparticles with topics covering targeting, imaging, delivery, diagnostics, and therapy.

  12. Isavuconazole absorption following oral administration in healthy subjects is comparable to intravenous dosing, and is not affected by food, or drugs that alter stomach pH.

    Science.gov (United States)

    Schmitt-Hoffmann, Anne; Desai, Amit; Kowalski, Donna; Pearlman, Helene; Yamazaki, Takao; Townsend, Robert

    2016-08-01

    Two openlabel, single-dose, randomized crossover studies and one open-label, multiple-dose, parallel group study in healthy volunteers were conducted with the prodrug, isavuconazonium sulfate, to determine absolute bioavailability of the active triazole, isavuconazole (EudraCT 2007-004949-15; n = 14), and the effect of food (EudraCT 2007- 004940-63; n = 26), and pH (NCT02128893; n = 24) on the absorption of isavuconazole. Isavuconazonium sulfate 744 mg designed to deliver 400 mg of the active triazole isavuconazole was administered in the absolute bioavailability (oral or intravenous (IV) (2-hour infusion)) and food-effect studies (oral). In the pH-effect study, isavuconazonium sulfate 372 mg designed to deliver 200 mg of isavuconazole was administered orally three times daily (t.i.d.) for 2 days, followed by a single daily oral dose for 3 days, in the presence of steady state esomeprazole dosed orally at 40 mg/day. Isavuconazole was well tolerated in each study. Bioavailability: Geometric least squares mean ratios (GLSMR; oral/IV) for isavuconazole AUC∞, and Cmax were 98% (90% confidence interval (CI): 94, 101) and 78% (90% CI: 72, 85), respectively. Food-effect: GLSMR (fed/fasted) for AUC∞ and Cmax of isavuconazole in plasma were 110% (90% CI: 102, 118) and 92% (90% CI: 86, 98), respectively. Median tmax was 5 hours with food and 3 hours under fasted conditions. pH-effect: GLSMR for isavuconazole AUCtau and Cmax were 108% (90% CI: 89, 130) and 105% (90% CI: 89, 124), respectively. Orally administered isavuconazonium sulfate effectively delivers isavuconazole, as evidenced by the fact that oral isavuconazole is bioequivalent to the IV formulation. Dose adjustments are not required when switching between oral and IV formulations, regardless of food or drugs that increase gastric pH.

  13. Trends in HIV seroprevalence, AIDS and prevention policy among intravenous drug users and men who have sex with men, before and after 1990 in Austria

    International Nuclear Information System (INIS)

    Piribauer, Franz; Duer, Wolfgang

    1998-01-01

    This study reports for the first time on secular trends in human immunodeficiency virus (HIV) infection and AIDS, and possible associations with prevention policy in Austria. We analysed HIV seroprevalence and AIDS cases among intravenous drug users (IDU) and men who have sex with men (MSM). In this study we found a diminished rate of increase in new cases of AIDS and a decline in HIV seroprevalence among IDU but not among MSM. Among clients visiting HIV counselling and testing centres in Austria between 1987 and 1990, seroprevalence among IDU was estimated at 27.9% as compared to 19.6% between 1990 and 1992 (odds ratio: 0.62; 95% confidence interval (CI): 0.45-0.85). Among MSM corresponding prevalence for these two periods was 12.1% and 10.9%, respectively, which was not a significant decline. In the period 1990 to 1994, the increase in AIDS cases per half-year levelled off for IDU (incidence rate ratio (IRR): 1.00; 95% CI: 0.99-1.01) but to a lesser extent among MSM (IRR: 1.01; 95% CI: 1.01-1.02). The most effective prevention policy intervention was considered to be the national methadone maintenance program (MMTP), started in 1987, and the provision of sterile injection equipment. We observed that in the recent period there was a decline in the frequency of attendance among young (less than 28 years of age) MSM at counselling centres (odds ratio (OR): 1.27; 95% CI: 1.08-1.49), accompanied by the observation that the rate of seroprevalence among this group did not decline. This is in contrast to young IDU where attendance did not decline but seroprevalence did. Although inference is limited from cross sectional studies, we argue for a reoriented and effectively monitored HIV prevention policy focused on young MSM

  14. Infective endocarditis not related to intravenous drug abuse in HIV-1-infected patients: report of eight cases and review of the literature.

    Science.gov (United States)

    Losa, J E; Miro, J M; Del Rio, A; Moreno-Camacho, A; Garcia, F; Claramonte, X; Marco, F; Mestres, C A; Azqueta, M; Gatell, J M

    2003-01-01

    To add to the limited information on infective endocarditis (IE) not related to intravenous drug abuse (IVDA) in HIV-1-infected patients. We have reviewed the characteristics of eight cases of IE in non-IVDA HIV-1 infected patients diagnosed in our institution between 1979 and 1999 as well as cases in the literature. All our patients were male, and the mean age was 44 years (range 29-64). HIV-1 risk factors were: homosexuality in five, heterosexuality in two, and the use of blood products in one. HIV stage C was found in six cases, and the median (range) CD4 cell count was 22/microL (4-274 cells/microL). IE was caused by Enterococcus faecalis in three cases, staphylococci in two cases, and Salmonella enteritidis, viridans group streptococci and Coxiella burnetii in one case each. Three patients acquired IE while in the hospital. All IE cases involved a native valve, and underlying valve disease was found in three patients. The aortic valve was the most frequently affected (five cases). Two patients underwent surgery, with a good outcome, and one patient died. Fourteen cases of IE not related to IVDA in HIV-1-infected patients were found in the literature review. The most common causative agents were Salmonella spp. and fungi (four cases each). Two patients had prosthetic valve IE, and the mitral valve was the most frequently affected (10 cases). The remaining clinical characteristics and the outcome were similar to those in the present series. IE not related to IVDA is rare in HIV-1-infected patients. In more than half of the cases, IE develops in patients with advanced HIV-1 disease. A wide etiologic range is found, reflecting different clinical and environmental conditions. None of the patients who underwent surgery died, and the overall mortality rate was not higher than in non-HIV-1-infected patients with IE.

  15. Albumin and its application in drug delivery.

    Science.gov (United States)

    Sleep, Darrell

    2015-05-01

    Rapid clearance of drugs from the body results in short therapeutic half-life and is an integral property of many protein and peptide-based drugs. To maintain the desired therapeutic effect patients are required to administer higher doses more frequently, which is inconvenient and risks undesirable side effects. Drug delivery technologies aim to minimise the number of administrations and dose-related toxicity while maximising therapeutic efficacy. This review describes albumin's inherent biochemical and biophysical properties, which make it an attractive drug delivery platform and the developmental status of drugs that are associated, conjugated or genetically fused with albumin. Albumin interacts with a number of cell surface receptors including gp18, gp30, gp60, FcRn, cubilin and megalin. The importance of albumin's interaction with the FcRn receptor, the basis for albumin's long circulatory half-life, is described, as are engineered albumins with improved pharmacokinetics. Albumin naturally accumulates at tumours and sites of inflammation, a characteristic which can be augmented by the addition of targeting ligands. The development of albumin drug conjugates which reply upon this property is described. Albumin's inherent biochemical and biophysical properties make it an ideal drug delivery platform. Recent advances in our understanding of albumin physiology and the improvement in albumin-based therapies strongly suggest that albumin-based therapies have a significant advantage over alternative technologies in terms of half-life, stability, versatility, safety and ease of manufacture. Given the importance of the albumin:FcRn interaction, the interpretation of the pharmacokinetic and pharmacodynamic profiles of albumin-based therapeutics with disturbed albumin:FcRn interaction may have to be reassessed. The FcRn receptor has additional functionality, especially in relation to immunology, antigen presentation and delivery of proteins across mucosal membranes

  16. Drug-targeting methodologies with applications: A review

    Science.gov (United States)

    Kleinstreuer, Clement; Feng, Yu; Childress, Emily

    2014-01-01

    Targeted drug delivery to solid tumors is a very active research area, focusing mainly on improved drug formulation and associated best delivery methods/devices. Drug-targeting has the potential to greatly improve drug-delivery efficacy, reduce side effects, and lower the treatment costs. However, the vast majority of drug-targeting studies assume that the drug-particles are already at the target site or at least in its direct vicinity. In this review, drug-delivery methodologies, drug types and drug-delivery devices are discussed with examples in two major application areas: (1) inhaled drug-aerosol delivery into human lung-airways; and (2) intravascular drug-delivery for solid tumor targeting. The major problem addressed is how to deliver efficiently the drug-particles from the entry/infusion point to the target site. So far, most experimental results are based on animal studies. Concerning pulmonary drug delivery, the focus is on the pros and cons of three inhaler types, i.e., pressurized metered dose inhaler, dry powder inhaler and nebulizer, in addition to drug-aerosol formulations. Computational fluid-particle dynamics techniques and the underlying methodology for a smart inhaler system are discussed as well. Concerning intravascular drug-delivery for solid tumor targeting, passive and active targeting are reviewed as well as direct drug-targeting, using optimal delivery of radioactive microspheres to liver tumors as an example. The review concludes with suggestions for future work, considereing both pulmonary drug targeting and direct drug delivery to solid tumors in the vascular system. PMID:25516850

  17. The human experience with intravenous levodopa

    Directory of Open Access Journals (Sweden)

    Shan H Siddiqi

    2016-01-01

    Full Text Available Objective: To compile a comprehensive summary of published human experience with levodopa given intravenously, with a focus on information required by regulatory agencies.Background: While safe intravenous (IV use of levodopa has been documented for over 50 years, regulatory supervision for pharmaceuticals given by a route other than that approved by the U.S. Food and Drug Administration (FDA has become increasingly cautious. If delivering a drug by an alternate route raises the risk of adverse events, an investigational new drug (IND application is required, including a comprehensive review of toxicity data.Methods: Over 200 articles referring to IV levodopa were examined for details of administration, pharmacokinetics, benefit and side effects.Results: We identified 142 original reports describing IVLD use in humans, beginning with psychiatric research in 1959-1960 before the development of peripheral decarboxylase inhibitors. Over 2750 subjects have received IV levodopa, and reported outcomes include parkinsonian signs, sleep variables, hormone levels, hemodynamics, CSF amino acid composition, regional cerebral blood flow, cognition, perception and complex behavior. Mean pharmacokinetic variables were summarized for 49 healthy subjects and 190 with Parkinson’s disease. Side effects were those expected from clinical experience with oral levodopa and dopamine agonists. No articles reported deaths or induction of psychosis.Conclusion: Over 2750 patients have received IV levodopa with a safety profile comparable to that seen with oral administration.

  18. Transdermal microneedles for drug delivery applications

    International Nuclear Information System (INIS)

    Teo, Ai Ling; Shearwood, Christopher; Ng, Kian Chye; Lu Jia; Moochhala, Shabbir

    2006-01-01

    Transdermal drug delivery (TDD) has many advantages, the main one being the ability to maintain the prolonged release of drugs to attain optimal blood concentrations. Unfortunately, nature has provided a very effective protective barrier, the stratum corneum (sc), which limits TDD to certain types of drugs with specific properties. In order to enhance TDD, the idea of using microneedles to painlessly penetrate the sc barrier has previously been proposed. In this paper, we will review the different microneedles that are currently being developed as well as our own efforts in this area. Based on our experiences, we will offer our view on the key parameters for effective transdermal microneedle design as well as future directions in this area

  19. Transdermal microneedles for drug delivery applications

    Energy Technology Data Exchange (ETDEWEB)

    Teo, Ai Ling [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117510 (Singapore); Shearwood, Christopher [School of Mechanical and Aerospace Engineering, 50 Nanyang Avenue, Singapore 639798 (Singapore); Ng, Kian Chye [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117510 (Singapore); Lu Jia [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117510 (Singapore); Moochhala, Shabbir [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117510 (Singapore)]. E-mail: mshabbir@dso.org.sg

    2006-07-25

    Transdermal drug delivery (TDD) has many advantages, the main one being the ability to maintain the prolonged release of drugs to attain optimal blood concentrations. Unfortunately, nature has provided a very effective protective barrier, the stratum corneum (sc), which limits TDD to certain types of drugs with specific properties. In order to enhance TDD, the idea of using microneedles to painlessly penetrate the sc barrier has previously been proposed. In this paper, we will review the different microneedles that are currently being developed as well as our own efforts in this area. Based on our experiences, we will offer our view on the key parameters for effective transdermal microneedle design as well as future directions in this area.

  20. Abbreviated New Drug Applications (ANDAS): Future trend in radiopharmaceuticals

    International Nuclear Information System (INIS)

    Kishore, R.

    1990-01-01

    The Drug Price Competition and Patent Term Restoration Act (commonly called Waxman Hatch Amendment) of 1984, to the Federal Food, Drug, and Cosmetic Act provided for abbreviated new drug applications (ANDAs) if the conditions specified in the Code of Federal Regulations (CFR) Title 21, subsection 312.55 are met. Under this subsection, reports of nonclinical laboratory studies and clinical investigations can be omitted. New drugs approved under these regulations are so called generic drugs as opposed to listed or pioneer (innovator) drugs. As the patents on more and more radiopharmaceuticals reach their expiration, the radiopharmaceutical industry is likely to produce more of these generic versions of innovator drugs. The ANDAs are required to contain information specified under subsections 314.50(a), (b), (d)(1) and (3), (e), and (g)

  1. Drug knowledge bases and their applications in biomedical informatics research.

    Science.gov (United States)

    Zhu, Yongjun; Elemento, Olivier; Pathak, Jyotishman; Wang, Fei

    2018-01-03

    Recent advances in biomedical research have generated a large volume of drug-related data. To effectively handle this flood of data, many initiatives have been taken to help researchers make good use of them. As the results of these initiatives, many drug knowledge bases have been constructed. They range from simple ones with specific focuses to comprehensive ones that contain information on almost every aspect of a drug. These curated drug knowledge bases have made significant contributions to the development of efficient and effective health information technologies for better health-care service delivery. Understanding and comparing existing drug knowledge bases and how they are applied in various biomedical studies will help us recognize the state of the art and design better knowledge bases in the future. In addition, researchers can get insights on novel applications of the drug knowledge bases through a review of successful use cases. In this study, we provide a review of existing popular drug knowledge bases and their applications in drug-related studies. We discuss challenges in constructing and using drug knowledge bases as well as future research directions toward a better ecosystem of drug knowledge bases. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. Biodegradable multiblock copolymers for drug delivery applications

    NARCIS (Netherlands)

    van Dijkhuizen-Radersma, Riemke

    2004-01-01

    With rapid advances in genomic research and biotechnology, an increasing number of pharmaceutical proteins and peptides become available for a variety of diseases. However, the efficient delivery of these drugs is hampered by their large size and (biological) instability. Consequently, to obtain a

  3. Drug delivery and nanoparticles: Applications and hazards

    Directory of Open Access Journals (Sweden)

    Wim H De Jong

    2008-06-01

    Full Text Available Wim H De Jong1, Paul JA Borm2,31Laboratory for Toxicology, Pathology and Genetics, National Institute for Public Health and the Environment (RIVM, Bilthoven, The Netherlands; 2Zuyd University, Centre of Expertise in Life Sciences, Heerlen, The Netherlands; 3Magnamedics GmbH, Aachen, GermanyAbstract: The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifically for cancer therapy. Interestingly pharmaceutical sciences are using nanoparticles to reduce toxicity and side effects of drugs and up to recently did not realize that carrier systems themselves may impose risks to the patient. The kind of hazards that are introduced by using nanoparticles for drug delivery are beyond that posed by conventional hazards imposed by chemicals in classical delivery matrices. For nanoparticles the knowledge on particle toxicity as obtained in inhalation toxicity shows the way how to investigate the potential hazards of nanoparticles. The toxicology of particulate matter differs from toxicology of substances as the composing chemical(s may or may not be soluble in biological matrices, thus influencing greatly the potential exposure of various internal organs. This may vary from a rather high local exposure in the lungs and a low or neglectable exposure for other organ systems after inhalation. However, absorbed species may also influence the potential toxicity of the inhaled particles. For nanoparticles the situation is different as their size opens the potential for crossing the various biological barriers within the body. From a positive viewpoint, especially the potential to cross the blood brain barrier may open new ways for drug delivery into the brain. In addition, the nanosize also allows for access into the cell and various cellular compartments including the nucleus. A multitude of substances are currently under investigation

  4. Self-Assembled Hydrogel Nanoparticles for Drug Delivery Applications

    Directory of Open Access Journals (Sweden)

    Miguel Gama

    2010-02-01

    Full Text Available Hydrogel nanoparticles—also referred to as polymeric nanogels or macromolecular micelles—are emerging as promising drug carriers for therapeutic applications. These nanostructures hold versatility and properties suitable for the delivery of bioactive molecules, namely of biopharmaceuticals. This article reviews the latest developments in the use of self-assembled polymeric nanogels for drug delivery applications, including small molecular weight drugs, proteins, peptides, oligosaccharides, vaccines and nucleic acids. The materials and techniques used in the development of self-assembling nanogels are also described.

  5. Development of a two-dimensional imaging system for clinical applications of intravenous coronary angiography using intense synchrotron radiation produced by a multipole wiggler

    International Nuclear Information System (INIS)

    Hyodo, K.; Ando, M.; Oku, Y.; Yamamoto, S.; Takeda, T.; Itai, Y.; Ohtsuka, S.; Sugishita, Y.; Tada, J.

    1998-01-01

    A two-dimensional clinical intravenous coronary angiography system, comprising a large-size View area produced by asymmetrical reflection from a silicon crystal using intense synchrotron radiation from a multipole wiggler and a two-dimensional detector with an image intensifier, has been completed. An advantage of the imaging system is that two-dimensional dynamic imaging of the cardiovascular system can be achieved due to its two-dimensional radiation field. This world-first two-dimensional system has been successfully adapted to clinical applications. Details of the imaging system are described in this paper

  6. Development of a two-dimensional imaging system for clinical applications of intravenous coronary angiography using intense synchrotron radiation produced by a multipole wiggler

    Energy Technology Data Exchange (ETDEWEB)

    Hyodo, K.; Ando, M. [High Energy Accelerator Research Organization, Inst. of Material Structure Sciences, Tsukuba (Japan); Oku, Y.; Yamamoto, S. [Graduated School for Advanced Sciences, Tsukuba (Japan); Takeda, T.; Itai, Y.; Ohtsuka, S.; Sugishita, Y. [The Univ. of Tsukuba, Inst. of Clinical Medicine, Tsukuba (Japan); Tada, J. [The Univ. of Tsukuba, Inst. of Basic Medical Sciences, Tsukuba (Japan)

    1998-05-01

    A two-dimensional clinical intravenous coronary angiography system, comprising a large-size View area produced by asymmetrical reflection from a silicon crystal using intense synchrotron radiation from a multipole wiggler and a two-dimensional detector with an image intensifier, has been completed. An advantage of the imaging system is that two-dimensional dynamic imaging of the cardiovascular system can be achieved due to its two-dimensional radiation field. This world-first two-dimensional system has been successfully adapted to clinical applications. Details of the imaging system are described in this paper. 18 refs.

  7. Retrospective analysis of non-laboratory-based adverse drug reactions induced by intravenous radiocontrast agents in a Joint Commission International-accredited academic medical center hospital in China

    Directory of Open Access Journals (Sweden)

    Chen QL

    2017-04-01

    Full Text Available Qin-lan Chen,1 Xiao-ying Zhao,2 Xiao-mi Wang,1 Na Lv,2 Ling-ling Zhu,3 Hui-min Xu,4 Quan Zhou4 1Radiology Nursing Unit, Division of Nursing, 2Department of Quality Management, 3Geriatric VIP Care Ward, Division of Nursing, 4Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China Abstract: The authors retrospectively analyzed the pattern and characteristics of non-laboratory-based adverse drug reactions (ADRs induced by intravenous radiocontrast agents in a large-scale hospital in China during 2014–2015. There were 314 ADR cases among 118,208 patients receiving enhanced CT or MRI examinations. The frequency of moderate/severe ADRs defined by Chinese Society of Radiology (ie, severe vomiting, systematic urticaria, facial swelling, dyspnea, vasovagal reaction, laryngeal edema, seizure, trembling, convulsions, unconsciousness, shock, death, and other unexpected adverse reactions was rare (0.0431%, whereas the mild ADRs were uncommon (0.2225% and accounted for 83.76% of ADRs. Frequency of ADRs induced by iodinated contrast agents was related with examination site, sex, and type of patient settings (P<0.01 and was higher compared with gadolinium contrast agents (0.3676% vs 0.0504%, P<0.01. From 2014 to 2015, frequencies of total and moderate/severe ADRs induced by iodinated contrast agents decreased significantly (0.4410% vs 0.2947%, P<0.01; 0.0960% vs 0.0282%, P<0.01, respectively. Frequency of ADRs differed among different iodinated contrast and gadolinium contrast (P<0.05 agents. Iopromide’s ADR frequency in 2014 was significantly higher compared with iopamidol, ioversol, or iohexol (P<0.01. Frequency of moderate/severe ADRs induced by iodixanol was 4.1–5.4 times that of iohexol, iopromide, or iopamidol. Rash was the predominant ADR subtype (84.39% and occurred more frequently with iodixanol compared with iohexol, iopamidol, or ioversol (P<0

  8. 76 FR 54473 - Guidance on Positron Emission Tomography Drug Applications-Content and Format for New Drug...

    Science.gov (United States)

    2011-09-01

    ... (formerly Docket No. 00D-0892)] Guidance on Positron Emission Tomography Drug Applications-- Content and... the availability of a guidance for industry entitled ``PET Drug Applications--Content and Format for... guidance for industry entitled ``PET Drug Applications--Content and Format for NDAs and ANDAs.'' The...

  9. Treatment of post-operative pain in old oncology patients with intravenous application of 50% glucose solution

    Directory of Open Access Journals (Sweden)

    Jovanović Nikola Č.

    2003-01-01

    Full Text Available Postoperative pain is the most important factor od so called "tumor promotive effect of surgery" ie. of endocrine-metabolic changes having the consequence drop in immune, antiinfective and antitumor defense. Due to presence of organic involutive changes, old people (≥ 65 years, often have serious side effects during application of usual analgetics. Since hypertonic glucose (33% given i.v. or per os, works analgesically in small children there is assumption that it can be used in treatment of postoperative pain in old oncology patients. We tested the hypothesis that postoperative pain in old oncology patients can be treated with i.v. application of 50% of glucose solution. 37 oncology patients over 65 years, 26 females and 11 males, operated for breast cancer and soft tissue cancer, werw investigated. Average age of the patients was 72±4 years. 50% Glucose solution was given in two boluses of 20 ml each: the first bolus was given to all patients at the end of anesthesia and the other bolus was given individually after appearance of post-operative pain. Pain intensity (in coefficients of the visual analogue scale VAK = 1-100 and its characteristics were tested by oral testing of operated patients: after weaking from anesthesia, after the first appearance of the pain and 15 minutes after giving of the second glucose bolus. None patient had pain weaking from anesthesia. All tested patients experienced pain during the first 70 minutes and it could be categorized as very strong pain (=82 VAK. The pain was decreased with another glucose bolus by approximately (=56% VAK so it was classifies in category of bearable pains (=36 VAK. In 9 patients (24,3% the pain had neuropatic component (filing of "burning" which could not be eliminated by hypertonic glucose but only with application of tramadol. Activation of the central cholinergic transmission is the most significant mechanism of analgesic glucose effect, but, probably there is another one

  10. Asymmetrical Polymer Vesicles for Drug delivery and Other Applications

    Directory of Open Access Journals (Sweden)

    Yi Zhao

    2017-06-01

    Full Text Available Scientists have been attracted by polymersomes as versatile drug delivery systems since the last two decades. Polymersomes have the potential to be versatile drug delivery systems because of their tunable membrane formulations, stabilities in vivo, various physicochemical properties, controlled release mechanisms, targeting abilities, and capacities to encapsulate a wide range of drugs and other molecules. Asymmetrical polymersomes are nano- to micro-sized polymeric capsules with asymmetrical membranes, which means, they have different outer and inner coronas so that they can exhibit better endocytosis rate and endosomal escape ability than other polymeric systems with symmetrical membranes. Hence, asymmetrical polymersomes are highly promising as self-assembled nano-delivery systems in the future for in vivo therapeutics delivery and diagnostic imaging applications. In this review, we prepared a summary about recent research progresses of asymmetrical polymersomes in the following aspects: synthesis, preparation, applications in drug delivery and others.

  11. The role of drug profiles as similarity metrics: applications to repurposing, adverse effects detection and drug-drug interactions.

    Science.gov (United States)

    Vilar, Santiago; Hripcsak, George

    2017-07-01

    Explosion of the availability of big data sources along with the development in computational methods provides a useful framework to study drugs' actions, such as interactions with pharmacological targets and off-targets. Databases related to protein interactions, adverse effects and genomic profiles are available to be used for the construction of computational models. In this article, we focus on the description of biological profiles for drugs that can be used as a system to compare similarity and create methods to predict and analyze drugs' actions. We highlight profiles constructed with different biological data, such as target-protein interactions, gene expression measurements, adverse effects and disease profiles. We focus on the discovery of new targets or pathways for drugs already in the pharmaceutical market, also called drug repurposing, in the interaction with off-targets responsible for adverse reactions and in drug-drug interaction analysis. The current and future applications, strengths and challenges facing all these methods are also discussed. Biological profiles or signatures are an important source of data generation to deeply analyze biological actions with important implications in drug-related studies. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. 3D printing applications for transdermal drug delivery.

    Science.gov (United States)

    Economidou, Sophia N; Lamprou, Dimitrios A; Douroumis, Dennis

    2018-06-15

    The role of two and three-dimensional printing as a fabrication technology for sophisticated transdermal drug delivery systems is explored in literature. 3D printing encompasses a family of distinct technologies that employ a virtual model to produce a physical object through numerically controlled apparatuses. The applicability of several printing technologies has been researched for the direct or indirect printing of microneedle arrays or for the modification of their surface through drug-containing coatings. The findings of the respective studies are presented. The range of printable materials that are currently used or potentially can be employed for 3D printing of transdermal drug delivery (TDD) systems is also reviewed. Moreover, the expected impact and challenges of the adoption of 3D printing as a manufacturing technique for transdermal drug delivery systems, are assessed. Finally, this paper outlines the current regulatory framework associated with 3D printed transdermal drug delivery systems. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Continuous infusion versus intermittent flushing to prevent loss of function of peripheral intravenous catheters used for drug administration in newborn infants.

    Science.gov (United States)

    Flint, A; McIntosh, D; Davies, M W

    2005-10-19

    The use of peripheral intravenous cannulae is common in newborn babies. Many of them require an intravenous line only for medications and not for fluid. Currently there is little uniformity in methods used to maintain cannula patency. The object of this review was to determine which method was better for maintaining intravenous lines used in neonates for intravenous medication only: intermittent flushing or continuous infusion We searched The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2004), CINAHL (from 1982 to June 2004) and MEDLINE (from 1966 to June 2004) . Randomised controlled trials comparing continuous infusion to intermittent flushing to maintain patency of intravenous cannulas. Units of randomisation might include individual catheters or individual babies. Three reviewers independently assessed trial quality and extracted data. Two studies were eligible for inclusion. In one study only one of our primary outcomes was available: the duration of cannula patency for the first cannula used per infant was slightly longer in the continuous infusion group, but not significantly so, with a mean difference of -4.3 hours (95% CI -18.2 to 9.7). In the second study, only one of our primary outcomes was available: the mean (SD) number cannulas used per infant in the first 48 hours was less in the intermittent flush group with a mean difference of -0.76 cannulas (95% CI -1.37 to -0.15). No results were available for any of our other primary outcomes: in the published report, results were reported per catheter rather than per infant, a number of infants received more than one intravenous catheter (39 infants received an unknown number of catheters). The overall duration of cannula patency was significantly longer in the intermittent flush group with a mean duration of patency in the intermittent flush group of 2.1 days (SD 1.0) compared with the continuous infusion group where the mean duration of patency was 1.0 days (SD 0

  14. Electrospinning of polymeric nanofibers for drug delivery applications.

    Science.gov (United States)

    Hu, Xiuli; Liu, Shi; Zhou, Guangyuan; Huang, Yubin; Xie, Zhigang; Jing, Xiabin

    2014-07-10

    Electrospinning has been recognized as a simple and versatile method for fabrication of polymer nanofibers. Various polymers that include synthetic, natural, and hybrid materials have been successfully electrospun into ultrafine fibers. The inherently high surface to volume ratio of electrospun fibers can enhance cell attachment, drug loading, and mass transfer properties. Drugs ranging from antibiotics and anticancer agents to proteins, DNA, RNA, living cells, and various growth factors have been incorporated into electrospun fibers. This article presents an overview of electrospinning techniques and their application in drug delivery. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Determination of Relative Frequency of HBS Ag, HCV and HIV Antibodies Serum Markers among Admitted Intravenous Drug Users in Infectious Disease Ward of Razi Hospital in Ahvaz, 2004-2005

    Directory of Open Access Journals (Sweden)

    Abdolrasool Nikkhooy

    2012-07-01

    Full Text Available Introduction: Intravenous drug users as a serious health problem in communities have economical and social effects as well as health and hygienic complications. Viral infections may be transmitted through drug injection by shared syringes among users. The aim of this study has been to determine the relative frequency of HBV, HCV and HIV infection’s markers as epidemiological data in Ahvaz. Materials & Methods: This retrospective cross sectional study was conducted on IV drug users (IVDUs who were admitted in infectious diseases ward of Razi Ahvaz Hospital in 2004-2005. The collected data of serum markers of these patients were coded, and statistical analyses were conducted. Results: 1890 patients were evaluated and 258 patients were IVDUs (14.6%. 154 patients (59.98% were tested for anti HCV-Ab of whom 65 patients were HCV-Ab positive (42.2%. 205 patients (79.45% were tested for anti HIV-Ab of whom 38 patients were HIV-Ab positive (18.53%. 67 patients (25.96% were tested for HBs-Ag of whom 15 patients were HBs-Ag positive (22.67%. 12 patients (4.65% were tested for anti HBc-Ab of whom 8 patients were HBc-Ab positive (66.66%. Conclusion: In this study, high infection rate relates to different causes such as increasing consumes of opium substances and recent differences in fumigated opium substances pattern toward injecting drug use in society level, which increases the prevalence of these infections, The present study determined some critical information about the prevalence of serum markers HBS Ag, HCV and HIV antibodies among intravenous drug users in southwestern of Iran.

  16. Application of radioimmunoassay for virus and anticancer drugs

    Energy Technology Data Exchange (ETDEWEB)

    Toyoshima, S. (Keio Univ., Tokyo (Japan). School of Medicine)

    1980-05-01

    Recent progress in RIA for virus and anticancer drugs was described. DNA and RNA virus and antivirus antibody which could be detected by RIA were mentioned, and then causes of arteriosclerosis, Paget's disease, multiple sclerosis, and diabetus mellitus were analysed virologically. Diagnostic significance of RIA was also described. Application of RIA to the measurement of interferon and carcinogenic virus at substantial level and recent information of viral hepatitis obtained by RIA were stated. Finally, application of RIA to the measurement of anticancer drugs acting on protective mechanism of the living body and measurement range by RIA were stated.

  17. Application of radioimmunoassay for virus and anticancer drugs

    Energy Technology Data Exchange (ETDEWEB)

    Toyoshima, S [Keio Univ., Tokyo (Japan). School of Medicine

    1980-05-01

    Recent progress in RIA for virus and anticancer drugs was described. DNA and RNA virus and antivirus antibody which could be detected by RIA were mentioned, and then causes of arteriosclerosis, Paget's disease, multiple sclerosis, and diabetus mellitus were analysed virologically. Diagnostic significance of RIA was also described. Application of RIA to the measurement of interferon and carcinogenic virus at substantial level and recent information of viral hepatitis obtained by RIA were stated. Finally, application of RIA to the measurement of anticancer drugs acting on protective mechanism of the living body and measurement range by RIA were stated.

  18. [Pharmaceutical application of cyclodextrins as multi-functional drug carriers].

    Science.gov (United States)

    Uekama, Kaneto

    2004-12-01

    Owing to the increasingly globalized nature of the cyclodextrin (CyD)-related science and technology, development of the CyD-based pharmaceutical formulation is rapidly progressing. The pharmaceutically useful CyDs are classified into hydrophilic, hydrophobic, and ionic derivatives. Because of the multi-functional characteristics and bioadaptability, these CyDs are capable of alleviating the undesirable properties of drug molecules through the formation of inclusion complexes or the form of CyD/drug conjugates. This review outlines the current application of CyDs in drug delivery and pharmaceutical formulation, focusing on the following evidences. 1) The hydrophilic CyDs enhance the rate and extent of bioavailability of poorly water-soluble drugs. 2) The amorphous CyDs such as 2-hydroxypropyl-beta-CyD are useful for inhibition of polymorphic transition and crystallization rates of drugs during storage. 3) The delayed release formulation can be obtained by the use of enteric type CyDs such as O-carboxymethyl-O-ethyl-beta-CyD. 4) The hydrophobic CyDs are useful for modification of the release site and/or time profile of water-soluble drugs with prolonged therapeutic effects. 5) The branched CyDs are particularly effective in inhibiting the adsorption to hydrophobic surface of containers and aggregation of polypeptide and protein drugs. 6) The combined use of different CyDs and/or pharmaceutical additives can serve as more functional drug carriers, improving efficacy and reducing side effects. 7) The CyD/drug conjugates may provide a versatile means for the constructions of not only colonic delivery system but also site-specific drug release system, including gene delivery. On the basis of the above-mentioned knowledge, the advantages and limitations of CyDs in the design of advanced dosage forms will be discussed.

  19. Breast abscess after intravenous methamphetamine injection into the breast.

    Science.gov (United States)

    Kistler, Amanda; Ajkay, Nicolas

    2018-05-01

    Intravenous drug use is a problem plaguing our society. We present a case of a young female who injected methamphetamine into her mammary vein, resulting in the formation of a breast abscess. This case demonstrates a rare but dangerous complication of intravenous drug use and a possible differential diagnosis in a patient presenting with a breast abscess. © 2017 Wiley Periodicals, Inc.

  20. Drug disposition and drug-drug interaction data in 2013 FDA new drug applications: a systematic review.

    Science.gov (United States)

    Yu, Jingjing; Ritchie, Tasha K; Mulgaonkar, Aditi; Ragueneau-Majlessi, Isabelle

    2014-12-01

    The aim of the present work was to perform a systematic review of drug metabolism, transport, pharmacokinetics, and DDI data available in the NDAs approved by the FDA in 2013, using the University of Washington Drug Interaction Database, and to highlight significant findings. Among 27 NMEs approved, 22 (81%) were well characterized with regard to drug metabolism, transport, or organ impairment, in accordance with the FDA drug interaction guidance (2012) and were fully analyzed in this review. In vitro, a majority of the NMEs were found to be substrates or inhibitors/inducers of at least one drug metabolizing enzyme or transporter. However, in vivo, only half (n = 11) showed clinically relevant drug interactions, with most related to the NMEs as victim drugs and CYP3A being the most affected enzyme. As perpetrators, the overall effects for NMEs were much less pronounced, compared with when they served as victims. In addition, the pharmacokinetic evaluation in patients with hepatic or renal impairment provided useful information for further understanding of the drugs' disposition. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  1. Electrosprayed nanoparticles for drug delivery and pharmaceutical applications

    Science.gov (United States)

    Sridhar, Radhakrishnan; Ramakrishna, Seeram

    2013-01-01

    Nanotechnology based Pharma has emerged significantly and has influenced the Pharma industry up to a considerable extent. Nanoparticles technology holds a good share of the nanotech Pharma and is significant in comparison with the other domains. Electrospraying technology answers the potential needs of nanoparticle production such as scalability, reproducibility, effective encapsulation etc. Many drugs have been electrosprayed with and without polymer carriers. Drug release characteristics are improved with the incorporation of biodegradable polymer carriers which sustain the release of encapsulated drug. Electrospraying is acknowledged as an important technique for the preparation of nanoparticles with respect to pharmaceutical applications. Herein we attempted to consolidate the reports pertaining to electrospraying and their corresponding therapeutic application area. PMID:23512013

  2. Microencapsulation of protein drugs for drug delivery: strategy, preparation, and applications.

    Science.gov (United States)

    Ma, Guanghui

    2014-11-10

    Bio-degradable poly(lactide) (PLA)/poly(lactide-glycolide) (PLGA) and chitosan microspheres (or microcapsules) have important applications in Drug Delivery Systems (DDS) of protein/peptide drugs. By encapsulating protein/peptide drugs in the microspheres, the serum drug concentration can be maintained at a higher constant value for a prolonged time, or injection formulation can be changed to orally or mucosally administered formulation. PLA/PLGA and chitosan are most often used in injection formulation and oral formulation. However, in the preparation and applications of PLA/PLGA and chitosan microspheres containing protein/peptide drugs, the problems of broad size distribution and poor reproducibility of microspheres, and deactivation of protein during the preparation, storage and release, are still big challenges. In this article, the techniques for control of the diameter of microspheres and microcapsules will be introduced at first, then the strategies about how to maintain the bioactivity of protein drugs during preparation and drug release will be reviewed and developed in our research group. The membrane emulsification techniques including direct membrane emulsification and rapid membrane emulsification processes were developed to prepare uniform-sized microspheres, the diameter of microspheres can be controlled from submicron to 100μm by these two processes, and the reproducibility of products can be guaranteed. Furthermore, compared with conventional stirring method, the big advantages of membrane emulsification process were that the uniform microspheres with much higher encapsulation efficiency can be obtained, and the release behavior can be adjusted by selecting microsphere size. Mild membrane emulsification condition also can prevent the deactivation of proteins, which frequently occurred under high shear force in mechanical stirring, sonification, and homogenization methods. The strategies for maintaining the bioactivity of protein drug were

  3. Intravenous contrast medium application in elderly patients - evaluation of Iopentol (Imagopaque trademark 300); Intravenoese Kontrastmittel-Applikation bei aelteren Patienten - Anwendungsbeobachtung von Iopentol (Imagopaque trademark 300)

    Energy Technology Data Exchange (ETDEWEB)

    Rathsmann, P.; Jacobs, G.F.; Mueller, R.D. [Zentrum fuer Klinische Radiologie, Kliniken Essen-Sued (Germany)

    2004-12-01

    Purpose: We examined the subjective compatibility of elderly patients who received the intravenous contrast medium Iopentol (Imagopaque trademark 300). In addition, objective data were acquired to show possible interactions between contrast media and organ systems in old patients. Methods and materials: A CT scan with intravenous application of contrast media was performed on 132 patients ranging in age from 75 to 96 years. The patients were questioned about their individual sensations. In addition, blood pressure, creatinine and CT-densitometry were acquired as objective date. Results: The patients' individual sensations and clinical data show a very low rate of complications. Mild allergic reactions were noticed in two patients. No severe anaphylactic reactions were encountered. Statistically significant changes in blood pressure before and after administration of the contrast medium were not observed. The serum creatinine concentration was unchanged after application of contrast media. For CT-densitometry, the patients were divided into two groups, one group with patients 75-84 years and the other group with patients 85-96 years of age. CT-densitometry showed no age-related differences. The protocol of contrast administration resulted in excellent opacification of the examined regions, only the liver did not enhance in some cases before the opacification of the portal vein. Conclusion: It is shown that old age alone is no reason to withhold contrast media containing iodine when performing CT. For the evaluation of the liver, however, the peculiarities of old age have to be taken into account and the interval between injection of the contrast medium and beginning of the spiral-CT has to be extended. (orig.)

  4. Biocompatibility of Chitosan Carriers with Application in Drug Delivery

    Directory of Open Access Journals (Sweden)

    Ana Grenha

    2012-09-01

    Full Text Available Chitosan is one of the most used polysaccharides in the design of drug delivery strategies for administration of either biomacromolecules or low molecular weight drugs. For these purposes, it is frequently used as matrix forming material in both nano and micron-sized particles. In addition to its interesting physicochemical and biopharmaceutical properties, which include high mucoadhesion and a great capacity to produce drug delivery systems, ensuring the biocompatibility of the drug delivery vehicles is a highly relevant issue. Nevertheless, this subject is not addressed as frequently as desired and even though the application of chitosan carriers has been widely explored, the demonstration of systems biocompatibility is still in its infancy. In this review, addressing the biocompatibility of chitosan carriers with application in drug delivery is discussed and the methods used in vitro and in vivo, exploring the effect of different variables, are described. We further provide a discussion on the pros and cons of used methodologies, as well as on the difficulties arising from the absence of standardization of procedures.

  5. [Application of Imaging Mass Spectrometry for Drug Discovery].

    Science.gov (United States)

    Hayasaka, Takahiro

    2016-01-01

    Imaging mass spectrometry (IMS) can reveal the distribution of biomolecules on tissue sections. In this process, the biomolecules are directly ionized within tissue sections using matrix-assisted laser desorption/ionization, and then their distribution is visualized by pseudo-color based on the relative signal intensity. The biomolecules, such as fatty acids, phospholipids, glycolipids, peptides, proteins, and neurotransmitters, have been analyzed at a spatial resolution of 5 μm. A special instrument for IMS analysis was developed by Shimadzu. The IMS analysis does not require the labeling of biomolecules and is capable of analyzing all the ionized biomolecules. Interest in this method has expanded to many research fields, including biology, agriculture, medicine, and pharmacology. The technique is especially relevant to the drug discovery process. As practiced currently, drug discovery is expensive and time consuming, requiring the preparation of probes for each drug and its metabolites, followed by systematic probe tracking in animal models. The IMS technique is expected to overcome these drawbacks by revealing the distribution of drugs and their metabolites using only a single analysis. In this symposium, I introduced the methodology and applications of IMS and discussed the feasibility of its application to drug discovery in the near future.

  6. Recent advances in inkjet dispensing technologies: applications in drug discovery.

    Science.gov (United States)

    Zhu, Xiangcheng; Zheng, Qiang; Yang, Hu; Cai, Jin; Huang, Lei; Duan, Yanwen; Xu, Zhinan; Cen, Peilin

    2012-09-01

    Inkjet dispensing technology is a promising fabrication methodology widely applied in drug discovery. The automated programmable characteristics and high-throughput efficiency makes this approach potentially very useful in miniaturizing the design patterns for assays and drug screening. Various custom-made inkjet dispensing systems as well as specialized bio-ink and substrates have been developed and applied to fulfill the increasing demands of basic drug discovery studies. The incorporation of other modern technologies has further exploited the potential of inkjet dispensing technology in drug discovery and development. This paper reviews and discusses the recent developments and practical applications of inkjet dispensing technology in several areas of drug discovery and development including fundamental assays of cells and proteins, microarrays, biosensors, tissue engineering, basic biological and pharmaceutical studies. Progression in a number of areas of research including biomaterials, inkjet mechanical systems and modern analytical techniques as well as the exploration and accumulation of profound biological knowledge has enabled different inkjet dispensing technologies to be developed and adapted for high-throughput pattern fabrication and miniaturization. This in turn presents a great opportunity to propel inkjet dispensing technology into drug discovery.

  7. Intravenous application of HI-6 salts (dichloride and dimethansulphonate) in pigs: comparison with pharmacokinetics profile after intramuscular administration.

    Science.gov (United States)

    Zdarova Karasova, Jana; Zemek, Filip; Kunes, Martin; Kvetina, Jaroslav; Chladek, Jaroslav; Jun, Daniel; Bures, Jan; Tachecí, Ilja; Kuca, Kamil

    2013-01-01

    Oxime HI-6 is an acetylcholinesterase reactivator therapeutically efficient against nerve agents. Because of their physico-chemical properties, oximes are typically applied intramuscularly (i.m.). This route of administration has also some disadvantages, and alternative strategies ought to be examined. We evaluated the pharmacokinetic profiles of two HI-6 salts after their intravenous (i.v.) administration, and compare the results with the known pharmacokinetics after i.m. administration. Pigs were administered with HI-6 salts (i.v), either HI-6 dichloride (10.71 mg/kg) or molar equivalent HI-6 dimethansulphonate (13.59 mg/kg). Doses of the HI-6 salts corresponded with a standard HI-6 dichloride dose in one autoinjector (500 mg) and were recalculated for one kilogram of body weight. The main pharmacokinetic parameters are comparable after i.v. and i.m. HI-6 administration. The compared pharmacokinetic parameters were half-life, terminal rate constant, mean residence time of the molecule in the body, clearance, and the apparent volume in the terminal phase. The bioavailability after i.m. administration was comparable with that of i.v.; these results suggest that the oxime is well released from the muscle depot. Significant differences were found in parameters Cmax and Tmax which are important in cases of emergency when rapidity and bioavailability are paramount for the success of treatment. I.v. administration should solve the problem of rapid clearance. Infusion or bolus administration may be considered as a logical subsequent step in oxime treatment strategy. The main advantage is in maintenance of an effective therapeutic plasma concentration, a more easily achievable effective therapeutic concentration, and fewer local adverse reactions.

  8. Tourniquet application after local forearm warming to improve venodilation for peripheral intravenous cannulation in young and middle-aged adults: A single-blind prospective randomized controlled trial.

    Science.gov (United States)

    Yamagami, Yuki; Tomita, Kohei; Tsujimoto, Tomomi; Inoue, Tomoko

    2017-07-01

    Local forearm warming before tourniquet application is often used to promote venodilation for peripheral intravenous cannulation; however, few studies have compared the effect of tourniquet application with and without local warming on vein size. To evaluate the effectiveness of tourniquet application after local forearm warming with that of tourniquet application alone in young and middle-aged adults. A single-blind, prospective, parallel group, randomized controlled trial. A national university in Japan. Seventy-two volunteers aged 20-64 years. Participants were randomly allocated to one of two groups: tourniquet application for 30s after forearm application of a heat pack warmed to 40°C±2°C for 15min (active warming group; n=36) or tourniquet application for 30s after applying a non-warmed heat pack for 15min (passive warming group; n=36). The primary outcomes were vein cross-sectional area on the forearm, measured after the intervention by blinded research assistants using ultrasound. Secondary outcomes were shortest diameter, and longest diameter of vein on the forearm, forearm skin temperature, body temperature, pulse, systolic blood pressure, and diastolic blood pressure. All outcomes were assessed at the same site before and immediately after the intervention, once per participant. Vein cross-sectional area, shortest vein diameter, and longest vein diameter were significantly increased in the active warming group compared with the passive warming group (p application after local warming was superior to tourniquet application alone in increasing vein cross-sectional, shortest diameter, and longest diameter (between-group differences of 2.2mm 2 , 0.5mm, and 0.5mm, respectively), and in raising skin temperature (between-group difference: 5.2°C). However, there were no significant differences in body temperature, pulse, or systolic or diastolic blood pressure between the groups. There were no adverse events associated with either intervention. Tourniquet

  9. Intentional intravenous mercury injection

    African Journals Online (AJOL)

    In this case report, intravenous complications, treatment strategies and possible ... Mercury toxicity is commonly associated with vapour inhalation or oral ingestion, for which there exist definite treatment options. Intravenous mercury ... personality, anxiousness, irritability, insomnia, depression and drowsi- ness.[1] However ...

  10. Applications of fiber-optics-based nanosensors to drug discovery.

    Science.gov (United States)

    Vo-Dinh, Tuan; Scaffidi, Jonathan; Gregas, Molly; Zhang, Yan; Seewaldt, Victoria

    2009-08-01

    Fiber-optic nanosensors are fabricated by heating and pulling optical fibers to yield sub-micron diameter tips and have been used for in vitro analysis of individual living mammalian cells. Immobilization of bioreceptors (e.g., antibodies, peptides, DNA) selective to targeting analyte molecules of interest provides molecular specificity. Excitation light can be launched into the fiber, and the resulting evanescent field at the tip of the nanofiber can be used to excite target molecules bound to the bioreceptor molecules. The fluorescence or surface-enhanced Raman scattering produced by the analyte molecules is detected using an ultra-sensitive photodetector. This article provides an overview of the development and application of fiber-optic nanosensors for drug discovery. The nanosensors provide minimally invasive tools to probe subcellular compartments inside single living cells for health effect studies (e.g., detection of benzopyrene adducts) and medical applications (e.g., monitoring of apoptosis in cells treated with anticancer drugs).

  11. 75 FR 65565 - Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of New Animal Drug Applications...

    Science.gov (United States)

    2010-10-26

    ... 558 [Docket No. FDA-2010-N-0002] Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of New Animal Drug Applications; Aklomide; Levamisole Hydrochloride; Nitromide and Sulfanitran AGENCY...) is amending the animal drug regulations by removing those portions that reflect approval of eight new...

  12. Potential applications for halloysite nanotubes based drug delivery systems

    Science.gov (United States)

    Sun, Lin

    could be released in a sustained manner; (2) cytotoxicity test confirmed the biocompatibility of HNTs and methotrexate coated HNTs; (3) proliferation test confirmed the growth inhibition of released methotrexate on osteosarcoma cells; and (4) nylon-6 could prolong the sustained release of methotrexate from polyelectrolytes coated HNTs. Another application comes from the prevention of surgical site infection. It is a common complication in surgery, which may prolong hospital stay, increase mortality rate, and cause additional financial burden for patients. By directly releasing antibiotics at the surgical site, it is supposed to enhance the drug efficacy and improve the treatment outcome. Therefore, the same HNTs based system was tested with E. coli in vitro to show the potential of delivering antibiotics to enhance the prevention of surgical site infection. Nitrofurantoin was incorporated within HNTs using the layer-by-layer coating technique, and the drug coated HNTs were filled into nylon-6 again. Results showed that (1) nitrofurantoin could be incorporated with this HNTs based drug delivery system, and released in a sustained manner; (2) nylon-6 could prolong the sustained release of nitrofurantoin from polyelectrolytes coated HNTs; and (3) released nitrofurantoin could severely inhibit E. coil growth. Therefore, a tunable drug delivery system based on HNTs was developed, and a great potential of medical application in drug delivery was shown.

  13. Development of novel drug delivery systems using phage display technology for clinical application of protein drugs.

    Science.gov (United States)

    Nagano, Kazuya; Tsutsumi, Yasuo

    2016-01-01

    Attempts are being made to develop therapeutic proteins for cancer, hepatitis, and autoimmune conditions, but their clinical applications are limited, except in the cases of drugs based on erythropoietin, granulocyte colony-stimulating factor, interferon-alpha, and antibodies, owing to problems with fundamental technologies for protein drug discovery. It is difficult to identify proteins useful as therapeutic seeds or targets. Another problem in using bioactive proteins is pleiotropic actions through receptors, making it hard to elicit desired effects without side effects. Additionally, bioactive proteins have poor therapeutic effects owing to degradation by proteases and rapid excretion from the circulatory system. Therefore, it is essential to establish a series of novel drug delivery systems (DDS) to overcome these problems. Here, we review original technologies in DDS. First, we introduce antibody proteomics technology for effective selection of proteins useful as therapeutic seeds or targets and identification of various kinds of proteins, such as cancer-specific proteins, cancer metastasis-related proteins, and a cisplatin resistance-related protein. Especially Ephrin receptor A10 is expressed in breast tumor tissues but not in normal tissues and is a promising drug target potentially useful for breast cancer treatment. Moreover, we have developed a system for rapidly creating functional mutant proteins to optimize the seeds for therapeutic applications and used this system to generate various kinds of functional cytokine muteins. Among them, R1antTNF is a TNFR1-selective antagonistic mutant of TNF and is the first mutein converted from agonist to antagonist. We also review a novel polymer-conjugation system to improve the in vivo stability of bioactive proteins. Site-specific PEGylated R1antTNF is uniform at the molecular level, and its bioactivity is similar to that of unmodified R1antTNF. In the future, we hope that many innovative protein drugs will be

  14. Comparison of the effects of preoperative and intraoperative intravenous application of dexketoprofen on postoperative analgesia in septorhinoplasty patients: randomised double blind clinical trial.

    Science.gov (United States)

    Ozer, A B; Erhan, O L; Keles, E; Demirel, I; Bestas, A; Gunduz, G

    2012-11-01

    Postoperative analgesia is important because it prevents the adverse effects of pain. To study the effect of preoperative or intraoperative application of dexketoprofen on postoperative analgesia and patient comfort in patients undergoing septorhinoplasty. A randomized, double-blind, placebo-controlled study. The study included 100 patients randomly assigned to four groups. Patients from group 50/0 got 50 mg dexketoprofen 30 minutes prior to the operation; patients from group 0/50 got 50 mg dexketoprofen 30 minutes after the operation, and patients from group 25/25 got 25 mg dexketoprofen both 30 minutes prior and 30 minutes after the operation. Dexketoprofen was not applied to any of the patients from group C. Once in the recovery room, patient-controlled analgesia was received to all patients. The patients' visual analog scale (VAS), sedation, nausea and vomiting and dyspepsia complaints were recorded at 1, 2, 3, 4, 5, 6, 7, 8, 12 and 24 hours. In addition, patient satisfaction, intraoperative fentanyl and consumption of tramadol in the postoperative 24 hour period were recorded. The VAS, nausea and vomiting, sedation and patient satisfaction scores were lower in patients from all groups that had received dexketoprofen compared to the controls. There was no difference in intraoperative fentanyl consumption between the groups. The consumption of tramadol was significantly higher in group C compared to all other groups. Dexketoprofen provides good postoperative analgesia and patient satisfaction if applied intravenously to septorhinoplasty patients. However, there is no significant difference between preoperative and intraoperative applications of dexketoprofen.

  15. Current Challenges and Future of Lipid nanoparticles formulations for topical drug application to oral mucosa, skin, and eye.

    Science.gov (United States)

    Guilherme, Viviane A; Ribeiro, Ligia N M; Tofoli, Giovana Radomille; Franz-Montan, Michelle; de Paula, Eneida; de Jesus, Marcelo Bispo

    2017-11-21

    Topical drug administration offers an attractive route with minimal invasiveness. It also avoids limitations of intravenous administration such as the first pass metabolism and presystemic elimination within the gastrointestinal tract. Furthermore, topical drug administration is safe, have few side effects, is easy to apply, and offers a fast onset of action. However, the development of effective topical formulations still represents a challenge for the desired effect to be reached, locally or systemically. Solid lipid nanoparticles and nanostructured lipid carriers are particular candidates to overcome the problem of topical drug administration. The nanometric particle size of lipid nanoparticles favors the physical adhesion to the skin or mucosal, what can also be attained with the formation of hybrid (nanoparticles/polymer) systems. In this review, we discuss the major challenges for lipid nanoparticles formulations for topical application to oral mucosa, skin, and eye, highlighting the strategies to improve the performance of lipid nanoparticles for topical applications. Next, we critically analyzed the in vitro and in vivo approaches used to evaluate lipid nanoparticles performance and toxicity. We addressed some major drawbacks related to lipid nanoparticle topical formulations and concluded the key points that have to be overcome to help them to reach the market in topical formulations to oral mucosa, skin and eye. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. 76 FR 6143 - Draft Guidance on Positron Emission Tomography Drug Applications-Content and Format for New Drug...

    Science.gov (United States)

    2011-02-03

    ...; formerly Docket No. 00D-0892] Draft Guidance on Positron Emission Tomography Drug Applications--Content and... Applications for Certain Positron Emission Tomography Drug Products; Availability,'' issued on March 10, 2000... and ANDAs.'' The draft guidance is intended to assist manufacturers of certain positron emission...

  17. Application of Stable Isotope in Detection of Veterinary Drug Residues

    International Nuclear Information System (INIS)

    Wang Wei; Liu Zhanfeng; Du Xiaoning

    2010-01-01

    In recent years, there has happened a series of significant food safety events worldwide, which lower down consumers' confidence in food safety, and they are taking increasing care about the sources of their foods. The safety problem of animal-origin foods has become a global topic for discussion. Therefore, it is a pressing task to establish a precise, sensitive and reliable method for analyzing veterinary drug residue. An introduction of the present status regarding veterinary drug residue analysis was made in the paper, and it briefly summarized the limit of detection (LOD) and quantification (LOQ) which could be reached in veterinary drug residue analysis by isotopic internal standard method domestically and abroad. The paper also made a review of the progress in applied research of stable isotope labeled compound in veterinary drug residue analysis of, such as, antibiotic medicines, furans and sulfonamides. The paper elucidated the great importance of the application of stable isotopes in the sane development of China's food safety system. (authors)

  18. Manufacture and Drug Delivery Applications of Silk Nanoparticles.

    Science.gov (United States)

    Wongpinyochit, Thidarat; Johnston, Blair F; Seib, F Philipp

    2016-10-08

    Silk is a promising biopolymer for biomedical and pharmaceutical applications due to its outstanding mechanical properties, biocompatibility and biodegradability, as well its ability to protect and subsequently release its payload in response to a trigger. While silk can be formulated into various material formats, silk nanoparticles are emerging as promising drug delivery systems. Therefore, this article covers the procedures for reverse engineering silk cocoons to yield a regenerated silk solution that can be used to generate stable silk nanoparticles. These nanoparticles are subsequently characterized, drug loaded and explored as a potential anticancer drug delivery system. Briefly, silk cocoons are reverse engineered first by degumming the cocoons, followed by silk dissolution and clean up, to yield an aqueous silk solution. Next, the regenerated silk solution is subjected to nanoprecipitation to yield silk nanoparticles - a simple but powerful method that generates uniform nanoparticles. The silk nanoparticles are characterized according to their size, zeta potential, morphology and stability in aqueous media, as well as their ability to entrap a chemotherapeutic payload and kill human breast cancer cells. Overall, the described methodology yields uniform silk nanoparticles that can be readily explored for a myriad of applications, including their use as a potential nanomedicine.

  19. Nano-Star-Shaped Polymers for Drug Delivery Applications.

    Science.gov (United States)

    Yang, Da-Peng; Oo, Ma Nwe Nwe Linn; Deen, Gulam Roshan; Li, Zibiao; Loh, Xian Jun

    2017-11-01

    With the advancement of polymer engineering, complex star-shaped polymer architectures can be synthesized with ease, bringing about a host of unique properties and applications. The polymer arms can be functionalized with different chemical groups to fine-tune the response behavior or be endowed with targeting ligands or stimuli responsive moieties to control its physicochemical behavior and self-organization in solution. Rheological properties of these solutions can be modulated, which also facilitates the control of the diffusion of the drug from these star-based nanocarriers. However, these star-shaped polymers designed for drug delivery are still in a very early stage of development. Due to the sheer diversity of macromolecules that can take on the star architectures and the various combinations of functional groups that can be cross-linked together, there remain many structure-property relationships which have yet to be fully established. This review aims to provide an introductory perspective on the basic synthetic methods of star-shaped polymers, the properties which can be controlled by the unique architecture, and also recent advances in drug delivery applications related to these star candidates. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. [Phlebitis associated to intravenous/infusional therapy].

    Science.gov (United States)

    Nicotera, Raffaela

    2011-01-01

    Phlebitis is a common problem associated to intravenous therapies, it may cause pain, sepsis and increased duration of hospitalization. Several factors can increase the risk of phlebitis. The literature review addresses the mechanisms of chemical phlebitis, the characteristics of drugs likely to cause a phlebitis and the main measures to be adopted for prevention and treatment.

  1. Intravenous paracetamol overdose in a paediatric patient

    NARCIS (Netherlands)

    Broeks, Ilse J.; Van Roon, Eric N.; Van Pinxteren-Nagler, Evelyn; De Vries, Tjalling W.

    2013-01-01

    BACKGROUND: Paracetamol is a widely used drug in children. In therapeutic doses, paracetamol has an excellent safety profile. Since the introduction of the intravenous form in 2004, only three reports of accidental overdose in children have been published. The low number probably is due to

  2. Administration and monitoring of intravenous anesthetics

    NARCIS (Netherlands)

    Sahinovic, Marko M.; Absalom, Anthony R.; Struys, Michel M. R. F.

    2010-01-01

    Purpose of review The importance of accuracy in controlling the dose-response relation for intravenous anesthetics is directly related to the importance of optimizing the efficacy and quality of anesthesia while minimizing adverse drug effects. Therefore, it is important to measure and control all

  3. Designing an intuitive web application for drug discovery scientists.

    Science.gov (United States)

    Karamanis, Nikiforos; Pignatelli, Miguel; Carvalho-Silva, Denise; Rowland, Francis; Cham, Jennifer A; Dunham, Ian

    2018-01-11

    We discuss how we designed the Open Targets Platform (www.targetvalidation.org), an intuitive application for bench scientists working in early drug discovery. To meet the needs of our users, we applied lean user experience (UX) design methods: we started engaging with users very early and carried out research, design and evaluation activities within an iterative development process. We also emphasize the collaborative nature of applying lean UX design, which we believe is a foundation for success in this and many other scientific projects. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Chemical functionalization of hyaluronic acid for drug delivery applications

    Energy Technology Data Exchange (ETDEWEB)

    Vasi, Ana-Maria [“Gheorghe Asachi” Technical University of Iasi, Faculty of Chemical Engineering and Environmental Protection, 73 Prof. dr. docent Dimitrie Mangeron Street, 700050 Iasi (Romania); Popa, Marcel Ionel, E-mail: mipopa@ch.tuiasi.ro [“Gheorghe Asachi” Technical University of Iasi, Faculty of Chemical Engineering and Environmental Protection, 73 Prof. dr. docent Dimitrie Mangeron Street, 700050 Iasi (Romania); Butnaru, Maria [“Grigore T. Popa” University of Medicine Pharmacy, Faculty of Medical Bioengineering, 9-13 Kogalniceanu Street, 700454 Iasi (Romania); Dodi, Gianina [“Gheorghe Asachi” Technical University of Iasi, Faculty of Chemical Engineering and Environmental Protection, 73 Prof. dr. docent Dimitrie Mangeron Street, 700050 Iasi (Romania); SCIENT — Research Center for Instrumental Analysis, S.C. CROMATEC PLUS, 18 Sos. Cotroceni, 060114 Bucharest (Romania); Verestiuc, Liliana [“Grigore T. Popa” University of Medicine Pharmacy, Faculty of Medical Bioengineering, 9-13 Kogalniceanu Street, 700454 Iasi (Romania)

    2014-05-01

    Functionalized hyaluronic acid (HA) derivatives were obtained by ring opening mechanism of maleic anhydride (MA). FTIR and H{sup 1} NMR spectroscopy were used to confirm the chemical linkage of MA on the hyaluronic acid chains. Thermal analysis (TG-DTG and DSC) and GPC data for the new products revealed the formation of new functional groups, without significant changes in molecular weight and thermal stability. New gels based on hyaluronic acid modified derivatives were obtained by acrylic acid copolymerization in the presence of a redox initiation system. The resulted circular and interconnected pores of the gels were visualized by SEM. The release profiles of an ophthalmic model drug, pilocarpine from tested gels were studied in simulated media. Evaluation of the cytotoxicity and cell proliferation properties indicates the potential of the new systems to be used in contact with biological media in drug delivery applications. - Highlights: • New functionalized hyaluronic acid was prepared by ring opening of maleic anhydride. • Gels with circular pores based on acrylic acid copolymerization were formulated. • In vitro drug loading/release profile was evaluated in simulated ophthalmic media. • The cytotoxicity indicates the potential of derivatives to be used in vivo.

  5. Application of ion exchange resin in floating drug delivery system.

    Science.gov (United States)

    Upadhye, Abhijeet A; Ambike, Anshuman A; Mahadik, Kakasaheb R; Paradkar, Anant

    2008-10-01

    The purpose of this study was to explore the application of low-density ion exchange resin (IER) Tulsion(R) 344, for floating drug delivery system (FDDS), and study the effect of its particle size on rate of complexation, water uptake, drug release, and in situ complex formation. Batch method was used for the preparation of complexes, which were characterized by physical methods. Tablet containing resin with high degree of crosslinking showed buoyancy lag time (BLT) of 5-8 min. Decreasing the particle size of resin showed decrease in water uptake and drug release, with no significant effect on the rate of complexation and in situ complex formation for both preformed complexes (PCs) and physical mixtures (PMs). Thus, low-density and high degree of crosslinking of resin and water uptake may be the governing factor for controlling the initial release of tablet containing PMs but not in situ complex formation. However, further sustained release may be due to in situ complex formation.

  6. MRI Based Localisation and Quantification of Abscesses following Experimental S. aureus Intravenous Challenge: Application to Vaccine Evaluation.

    Directory of Open Access Journals (Sweden)

    Elizabeth R Allen

    Full Text Available To develop and validate a sensitive and specific method of abscess enumeration and quantification in a preclinical model of Staphylococcus aureus infection.S. aureus infected murine kidneys were fixed in paraformaldehyde, impregnated with gadolinium, and embedded in agar blocks, which were subjected to 3D magnetic resonance microscopy on a 9.4T MRI scanner. Image analysis techniques were developed, which could identify and quantify abscesses. The result of this imaging was compared with histological examination. The impact of a S. aureus Sortase A vaccination regime was assessed using the technique.Up to 32 murine kidneys could be imaged in a single MRI run, yielding images with voxels of about 25 μm3. S. aureus abscesses could be readily identified in blinded analyses of the kidneys after 3 days of infection, with low inter-observer variability. Comparison with histological sections shows a striking correlation between the two techniques: all presumptive abscesses identified by MRI were confirmed histologically, and histology identified no abscesses not evident on MRI. In view of this, simulations were performed assuming that both MRI reconstruction, and histology examining all sections of the tissue, were fully sensitive and specific at abscess detection. This simulation showed that MRI provided more sensitive and precise estimates of abscess numbers and volume than histology, unless at least 5 histological sections are taken through the long axis of the kidney. We used the MRI technique described to investigate the impact of a S. aureus Sortase A vaccine.Post mortem MRI scanning of large batches of fixed organs has application in the preclinical assessment of S. aureus vaccines.

  7. Quantum dots in imaging, drug delivery and sensor applications.

    Science.gov (United States)

    Matea, Cristian T; Mocan, Teodora; Tabaran, Flaviu; Pop, Teodora; Mosteanu, Ofelia; Puia, Cosmin; Iancu, Cornel; Mocan, Lucian

    2017-01-01

    Quantum dots (QDs), also known as nanoscale semiconductor crystals, are nanoparticles with unique optical and electronic properties such as bright and intensive fluorescence. Since most conventional organic label dyes do not offer the near-infrared (>650 nm) emission possibility, QDs, with their tunable optical properties, have gained a lot of interest. They possess characteristics such as good chemical and photo-stability, high quantum yield and size-tunable light emission. Different types of QDs can be excited with the same light wavelength, and their narrow emission bands can be detected simultaneously for multiple assays. There is an increasing interest in the development of nano-theranostics platforms for simultaneous sensing, imaging and therapy. QDs have great potential for such applications, with notable results already published in the fields of sensors, drug delivery and biomedical imaging. This review summarizes the latest developments available in literature regarding the use of QDs for medical applications.

  8. Effects of intravenous nonsteroidal antiinflammatory drugs on a C-fiber reflex elicited by a wide range of stimulus intensities in the rat.

    Science.gov (United States)

    Bustamante, D; Paeile, C; Willer, J C; Le Bars, D

    1996-03-01

    A C-fiber reflex elicited by electrical stimulation within the territory of the sural nerve, was recorded from the ipsilateral biceps femoris muscle in anesthetized rats. The temporal evolution of the response was studied using a constant stimulus intensity (3 x threshold) and recruitment curves were built by varying stimulus intensity from 0 to 7 x threshold. The i.v. administration of aspirin, indomethacin, ketoprofen, paracetamol (= acetaminophen) and lysine clonixinate resulted in dose-dependent depressions of the C-fiber reflex by up to 30 to 40%. By contrast, saline was ineffective. High doses of the effective drugs that produced large disturbances in heart rate and/or acid-base equilibrium were not considered in the pharmacological analysis. When a constant level of stimulation was used, different dose-dependent profiles of drug action were observed. Aspirin induced a slow and gradual depression, although indomethacin, ketoprofen and paracetamol produced a peak effect within the first 10-min period and then reached a steady state phase for up to 30 min. The depressive effects of lysine clonixinate appeared more stable. When recruitment curves were built with a range of nociceptive stimulus intensities, all the drugs produced a dose-dependent decrease in the slopes and the areas under the recruitment curves without any major modification in the thresholds. The order of potency was the same for both stimulation paradigms, e.g., aspirin lysine clonixinate = ketoprofen < indomethacin. It is concluded that NSAID elicit significant antinociceptive effects at a central level, which do not depend on the existence of a hyperalgesic or inflammatory state.

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

    NARCIS (Netherlands)

    Ojha, Tarun; Rizzo, Larissa; Storm, Gerrit; Kiessling, Fabian; Lammers, Twan Gerardus Gertudis Maria

    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, including for monitoring biodistribution, target site accumulation, off-target localization, drug release and drug efficacy.

  10. Use of intravenous immunoglobulins in clinical practice

    Directory of Open Access Journals (Sweden)

    E.K. Donyush

    2011-01-01

    Full Text Available Immunoglobulins are main component of immune defense; they take part in anti-infectious resistance of organism and regulate processes of different immune reactions. Intravenous immunoglobulins are the most frequently used products made from donor blood plasma. The need in these drugs is steadily increasing during last 15–20 years, and indications are widening due to modern hightechnology methods of production and cleaning. The article presents modern data on formula, mechanisms of action and indications for different groups of intravenous immunoglobulins (standard, hyperimmune, fortified and description of possible adverse events.Key words: immuglobulines, prophylaxis, treatment, unfavorable reaction, children.

  11. Microbiological quality of some brands of intravenous fluids ...

    African Journals Online (AJOL)

    SERVER

    2007-10-04

    Oct 4, 2007 ... Food, Drug Administration and Control (NAFDAC), have on many occasions ... products from 8 manufacturers were tested for their ... Table 1. Microbial contamination level of brand of intravenous fluids produced by some.

  12. Hyperammonemic Encephalopathy Resulting From Intravenous Valproate for Status Epilepticus

    National Research Council Canada - National Science Library

    Richards, Karen

    2004-01-01

    .... Intravenous vaiproate has been suggested as an alternative to phenytoin and/or phenobarbital in patients with hypersensitivity to or at high risk for the sedative or vasoactive effects of these drugs...

  13. 76 FR 43689 - Draft Guidance for Industry and Food and Drug Administration Staff; Mobile Medical Applications...

    Science.gov (United States)

    2011-07-21

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0530] Draft Guidance for Industry and Food and Drug Administration Staff; Mobile Medical Applications; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug...

  14. 42 CFR 2a.5 - Contents of application; research projects in which drugs will be administered.

    Science.gov (United States)

    2010-10-01

    ... application; research projects in which drugs will be administered. (a) In addition to the information... drug shall contain: (1) Identification of the drugs to be administered in the research project and a... project will be conducted. (b) An application for an authorization of confidentiality with respect to a...

  15. Applications for approval to market a new drug; complete response letter; amendments to unapproved applications. Final rule.

    Science.gov (United States)

    2008-07-10

    The Food and Drug Administration (FDA) is amending its regulations on new drug applications (NDAs) and abbreviated new drug applications (ANDAs) for approval to market new drugs and generic drugs (drugs for which approval is sought in an ANDA). The final rule discontinues FDA's use of approvable letters and not approvable letters when taking action on marketing applications. Instead, we will send applicants a complete response letter to indicate that the review cycle for an application is complete and that the application is not ready for approval. We are also revising the regulations on extending the review cycle due to the submission of an amendment to an unapproved application and starting a new review cycle after the resubmission of an application following receipt of a complete response letter. In addition, we are adding to the regulations on biologics license applications (BLAs) provisions on the issuance of complete response letters to BLA applicants. We are taking these actions to implement the user fee performance goals referenced in the Prescription Drug User Fee Amendments of 2002 (PDUFA III) that address procedures and establish target timeframes for reviewing human drug applications.

  16. The application of molecular topology for ulcerative colitis drug discovery.

    Science.gov (United States)

    Bellera, Carolina L; Di Ianni, Mauricio E; Talevi, Alan

    2018-01-01

    Although the therapeutic arsenal against ulcerative colitis has greatly expanded (including the revolutionary advent of biologics), there remain patients who are refractory to current medications while the safety of the available therapeutics could also be improved. Molecular topology provides a theoretic framework for the discovery of new therapeutic agents in a very efficient manner, and its applications in the field of ulcerative colitis have slowly begun to flourish. Areas covered: After discussing the basics of molecular topology, the authors review QSAR models focusing on validated targets for the treatment of ulcerative colitis, entirely or partially based on topological descriptors. Expert opinion: The application of molecular topology to ulcerative colitis drug discovery is still very limited, and many of the existing reports seem to be strictly theoretic, with no experimental validation or practical applications. Interestingly, mechanism-independent models based on phenotypic responses have recently been reported. Such models are in agreement with the recent interest raised by network pharmacology as a potential solution for complex disorders. These and other similar studies applying molecular topology suggest that some therapeutic categories may present a 'topological pattern' that goes beyond a specific mechanism of action.

  17. Capillary electrophoresis: principles and applications in illicit drug analysis.

    Science.gov (United States)

    Tagliaro, F; Turrina, S; Smith, F P

    1996-02-09

    Capillary electrophoresis, which appeared in the early 1980s, is now rapidly expanding into many scientific disciplines, including analytical chemistry, biotechnology and biomedical and pharmaceutical sciences. In capillary electrophoresis,electrokinetic separations are carried out in tiny capillaries at high voltages (10-30 kV), thus obtaining high efficiencies (N > 10(5)) and excellent mass sensitivities (down to 10(-18)-10(-20) moles). The main features of capillary electrophoresis are: versatility of application (from inorganic ions to large DNA fragments), use of different separation modes with different selectivity, extremely low demands on sample volume, negligible running costs, possibility of interfacing with different detection systems, ruggedness and simplicity of instrumentation. Capillary electrophoresis applications in forensic sciences have appeared only recently, but are now rapidly growing, particularly in forensic toxicology. The present paper briefly describes the basic principles of capillary electrophoresis, from both the instrumental and analytical points of view. Furthermore, the main applications in the analysis of illicit/controlled drugs in both illicit preparations and biological samples are presented and discussed (43 references). It is concluded that the particular separation mechanism and the high complementarity of this technique to chromatography makes capillary electrophoresis a new powerful tool of investigation in the hands of forensic toxicologists.

  18. Considerations for a Pediatric Biopharmaceutics Classification System (BCS): application to five drugs.

    Science.gov (United States)

    Gandhi, Shivani V; Rodriguez, William; Khan, Mansoor; Polli, James E

    2014-06-01

    It has been advocated that biopharmaceutic risk assessment should be conducted early in pediatric product development and synchronized with the adult product development program. However, we are unaware of efforts to classify drugs into a Biopharmaceutics Classification System (BCS) framework for pediatric patients. The objective was to classify five drugs into a potential BCS. These five drugs were selected since both oral and intravenous pharmacokinetic data were available for each drug, and covered the four BCS classes in adults. Literature searches for each drug were conducted using Medline and applied to classify drugs with respect to solubility and permeability in pediatric subpopulations. Four pediatric subpopulations were considered: neonates, infants, children, and adolescents. Regarding solubility, dose numbers were calculated using a volume for each subpopulation based on body surface area (BSA) relative to 250 ml for a 1.73 m(2) adult. Dose numbers spanned a range of values, depending upon the pediatric dose formula and subpopulation. Regarding permeability, pharmacokinetic literature data required assumptions and decisions about data collection. Using a devised pediatric BCS framework, there was agreement in adult and pediatric BCS class for two drugs, azithromycin (class 3) and ciprofloxacin (class 4). There was discordance for the three drugs that have high adult permeability since all pediatric permeabilities were low: dolasetron (class 3 in pediatric), ketoprofen (class 4 in pediatric), and voriconazole (class 4 in pediatric). A main contribution of this work is the identification of critical factors required for a pediatric BCS.

  19. Development of Applications about Hazards and Preventions of Drug Based On Android

    Science.gov (United States)

    Hartatik; Febriyanto, F.; Munawaroh, H.

    2018-03-01

    The number of drug abuse was increase among the younger generation, it caused younger generation fall into drug abuse, and it will lead to physical and mental damage. The lack of knowledge of drugs danger is one of the most potential problems, so in this study we made an application about the types, dangers, and how to avoid its abusement. The application built using PHP programming language with codeiniter framework on admin part, while the parsing data between mobile application server using Javascript Object Notation (JSON). This application has been tested and 85% respondents stated that this application provides positive benefits especially for the socialization of drug abuse.

  20. Screening applications in drug discovery based on microfluidic technology.

    Science.gov (United States)

    Eribol, P; Uguz, A K; Ulgen, K O

    2016-01-01

    Microfluidics has been the focus of interest for the last two decades for all the advantages such as low chemical consumption, reduced analysis time, high throughput, better control of mass and heat transfer, downsizing a bench-top laboratory to a chip, i.e., lab-on-a-chip, and many others it has offered. Microfluidic technology quickly found applications in the pharmaceutical industry, which demands working with leading edge scientific and technological breakthroughs, as drug screening and commercialization are very long and expensive processes and require many tests due to unpredictable results. This review paper is on drug candidate screening methods with microfluidic technology and focuses specifically on fabrication techniques and materials for the microchip, types of flow such as continuous or discrete and their advantages, determination of kinetic parameters and their comparison with conventional systems, assessment of toxicities and cytotoxicities, concentration generations for high throughput, and the computational methods that were employed. An important conclusion of this review is that even though microfluidic technology has been in this field for around 20 years there is still room for research and development, as this cutting edge technology requires ingenuity to design and find solutions for each individual case. Recent extensions of these microsystems are microengineered organs-on-chips and organ arrays.

  1. DFT application for chlorin derivatives photosensitizer drugs modeling

    Science.gov (United States)

    Machado, Neila; Carvalho, B. G.; Téllez Soto, C. A.; Martin, A. A.; Favero, P. P.

    2018-04-01

    Photodynamic therapy is an alternative form of cancer treatment that meets the desire for a less aggressive approach to the body. It is based on the interaction between a photosensitizer, activating light, and molecular oxygen. This interaction results in a cascade of reactions that leads to localized cell death. Many studies have been conducted to discover an ideal photosensitizer, which aggregates all the desirable characteristics of a potent cell killer and generates minimal side effects. Using Density Functional Theory (DFT) implemented in the program Vienna Ab-initio Simulation Package, new chlorin derivatives with different functional groups were simulated to evaluate the different absorption wavelengths to permit resonant absorption with the incident laser. Gaussian 09 program was used to determine vibrational wave numbers and Natural Bond Orbitals. The chosen drug with the best characteristics for the photosensitizer was a modified model of the original chlorin, which was called as Thiol chlorin. According to our calculations it is stable and is 19.6% more efficient at optical absorption in 708 nm in comparison to the conventional chlorin e6. Vibrational modes, optical and electronic properties were predicted. In conclusion, this study is an attempt to improve the development of new photosensitizer drugs through computational methods that save time and contribute to decrease the numbers of animals for model application.

  2. Screening applications in drug discovery based on microfluidic technology

    Science.gov (United States)

    Eribol, P.; Uguz, A. K.; Ulgen, K. O.

    2016-01-01

    Microfluidics has been the focus of interest for the last two decades for all the advantages such as low chemical consumption, reduced analysis time, high throughput, better control of mass and heat transfer, downsizing a bench-top laboratory to a chip, i.e., lab-on-a-chip, and many others it has offered. Microfluidic technology quickly found applications in the pharmaceutical industry, which demands working with leading edge scientific and technological breakthroughs, as drug screening and commercialization are very long and expensive processes and require many tests due to unpredictable results. This review paper is on drug candidate screening methods with microfluidic technology and focuses specifically on fabrication techniques and materials for the microchip, types of flow such as continuous or discrete and their advantages, determination of kinetic parameters and their comparison with conventional systems, assessment of toxicities and cytotoxicities, concentration generations for high throughput, and the computational methods that were employed. An important conclusion of this review is that even though microfluidic technology has been in this field for around 20 years there is still room for research and development, as this cutting edge technology requires ingenuity to design and find solutions for each individual case. Recent extensions of these microsystems are microengineered organs-on-chips and organ arrays. PMID:26865904

  3. Synthesis and applications of radiolabelled drugs in pharmaceutical development

    International Nuclear Information System (INIS)

    Landvatter, S.W.; Heys, J.R.; Garner, K.T.; Mack, J.F.; Senderoff, S.G.; Shu, A.Y.; Villani, A.J.; Saunders, D.

    1994-01-01

    Radiolabelled drugs play a vital role in the development of new pharmaceuticals including application in drug discovery, pre-clinical development and clinical development. The synthesis of these pharmaceuticals in tritium or carbon-14 labelled form poses many challenges for the synthetic organic chemist. The actual choice of synthetic route must take into account the small scale, limited choice and high cost of labelled precursors, and the positioning of the label into a metabolically stable position. There are, however, a number of synthetic strategies available for overcoming these constraints. Although in some C-14 syntheses the requisite labelled raw material can be purchased and the existing synthesis adapted for labelling, frequently the synthetic challenge is the synthesis of a structurally simple, yet commercially unavailable, labelled precursor (e.g., γ-butyrolactone-[2- 14 C], cyclohexanone-[ 3 H], CuCN-[ 14 C], 2-furancarboxaldehyde-[ 14 C]). Another useful strategy in C-14 synthesis is the conversion of an advanced intermediate, or perhaps the unlabelled product itself, into a precursor which can then be reconverted into the labelled version of the intermediate. Occasionally, a new total synthesis must be developed. In addition to these strategies, tritium labelling can uniquely take advantage of exchange labelling techniques, synthesis and reduction of unsaturated precursors, or tritium-halogen replacement reactions. Examples of these strategies and use of the labelled products are discussed

  4. Legal Responsibility of Doctor Regarding off-label Drug Applications

    Directory of Open Access Journals (Sweden)

    Erdal Yüzbaşıoğlu

    2012-03-01

    Full Text Available The use of off-label medication, which has been frequently applied in oncology, also started to be used in ophthalmology recently; thus, the legal problems that the doctors can encounter more often come up to be a topic of discussion. According to the drug administration guidelines released by the Ministry of Health, off-label medication depends on certain conditions, and applications other than these will be accepted as an experiment on humans according to the law No 5237 of the Turkish Criminal Code (TCC. The aim of this study was to clarify this issue in accordance with the justification of TCC/90. (Turk J Ophthalmol 2012; 42: 135-8

  5. Comparison between intravenous and intramuscular administration of ketamine in children sedation referred to emergency department

    Directory of Open Access Journals (Sweden)

    Behnaz Boroumand Rezazadeh

    2014-12-01

    Full Text Available Ketamine, among wide variety of sedative drugs, has shown beneficial effects when using during the procedural sedation, specifically in pediatrics. Various parameters should be considered in order to perform a safe and effective procedural sedation including optimum dosage of the sedative, administration methods of sedation, and need for applying any adjuvant drug. In this study, we aimed to review the studies, which have compared the efficacy of the different ways of the injection of ketamine such as intravenous or intramuscular ketamine application. Based on data obtained from the related articles, efficacy and safety of these two methods of ketamine usage in the pediatric procedural sedation were widely similar, but the intravenously administration of the ketamine can be proposed as the preferable mode.

  6. Risk Factors Associated with Unsafe Injection Practices at the First Injection Episode among Intravenous Drug Users in France: Results from PrimInject, an Internet Survey.

    Science.gov (United States)

    Guichard, Anne; Guignard, Romain; Lert, France; Roy, Elise

    2015-01-01

    Background. New drug use patterns may increase the risk of human immunodeficiency virus and hepatitis infections. In France, new injection patterns among youths with diverse social backgrounds have emerged, which may explain the persistently high rates of hepatitis C virus infection. This study explores factors associated with injection risk behaviours at first injection among users who began injecting in the post-2000 era. Methods. A cross-sectional study was conducted on the Internet from October 2010 to March 2011, through an online questionnaire. Multivariate logistic regression identified the independent correlates of needle sharing and equipment (cooker/cotton filter) sharing. Results. Among the 262 respondents (mean age 25 years), 65% were male. Both risk behaviours were positively associated with initiation before 18 years of age (aOR 3.7 CI 95% 1.3-10.6 and aOR 3.0 CI 95% 1.3-7.0) and being injected by another person (aOR 3.1 CI 95% 1.0-9.9 and aOR 3.0 CI 95% 1.3-7.1). Initiation at a party was an independent correlate of equipment sharing (aOR 2.6 95% CI 1.0-6.8). Results suggest a need for innovative harm reduction programmes targeting a variety of settings and populations, including youths and diverse party scenes. Education of current injectors to protect both themselves and those they might initiate into injection is critically important.

  7. Enhanced HIV-1 surveillance using molecular epidemiology to study and monitor HIV-1 outbreaks among intravenous drug users (IDUs) in Athens and Bucharest.

    Science.gov (United States)

    Paraskevis, Dimitrios; Paraschiv, Simona; Sypsa, Vana; Nikolopoulos, Georgios; Tsiara, Chryssa; Magiorkinis, Gkikas; Psichogiou, Mina; Flampouris, Andreas; Mardarescu, Mariana; Niculescu, Iulia; Batan, Ionelia; Malliori, Meni; Otelea, Dan; Hatzakis, Angelos

    2015-10-01

    A significant increase in HIV-1 diagnoses was reported among Injecting Drug Users (IDUs) in the Athens (17-fold) and Bucharest (9-fold) metropolitan areas starting 2011. Molecular analyses were conducted on HIV-1 sequences from IDUs comprising 51% and 20% of the diagnosed cases among IDUs during 2011-2013 for Greece and Romania, respectively. Phylodynamic analyses were performed using the newly developed birth-death serial skyline model which allows estimating of important epidemiological parameters, as implemented in BEAST programme. Most infections (>90%) occurred within four and three IDU local transmission networks in Athens and Bucharest, respectively. For all Romanian clusters, the viral strains originated from local circulating strains, whereas in Athens, the local strains seeded only two of the four sub-outbreaks. Birth-death skyline plots suggest a more explosive nature for sub-outbreaks in Bucharest than in Athens. In Athens, two sub-outbreaks had been controlled (Re1.0) and two had been controlled (Re<1.0). The lead times were shorter for the outbreak in Athens than in Bucharest. Enhanced molecular surveillance proved useful to gain information about the origin, causal pathways, dispersal patterns and transmission dynamics of the outbreaks that can be useful in a public health setting. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Risk Factors Associated with Unsafe Injection Practices at the First Injection Episode among Intravenous Drug Users in France: Results from PrimInject, an Internet Survey

    Directory of Open Access Journals (Sweden)

    Anne Guichard

    2015-01-01

    Full Text Available Background. New drug use patterns may increase the risk of human immunodeficiency virus and hepatitis infections. In France, new injection patterns among youths with diverse social backgrounds have emerged, which may explain the persistently high rates of hepatitis C virus infection. This study explores factors associated with injection risk behaviours at first injection among users who began injecting in the post-2000 era. Methods. A cross-sectional study was conducted on the Internet from October 2010 to March 2011, through an online questionnaire. Multivariate logistic regression identified the independent correlates of needle sharing and equipment (cooker/cotton filter sharing. Results. Among the 262 respondents (mean age 25 years, 65% were male. Both risk behaviours were positively associated with initiation before 18 years of age (aOR 3.7 CI 95% 1.3–10.6 and aOR 3.0 CI 95% 1.3–7.0 and being injected by another person (aOR 3.1 CI 95% 1.0–9.9 and aOR 3.0 CI 95% 1.3–7.1. Initiation at a party was an independent correlate of equipment sharing (aOR 2.6 95% CI 1.0–6.8. Conclusions. Results suggest a need for innovative harm reduction programmes targeting a variety of settings and populations, including youths and diverse party scenes. Education of current injectors to protect both themselves and those they might initiate into injection is critically important.

  9. Application of Model Animals in the Study of Drug Toxicology

    Science.gov (United States)

    Song, Yagang; Miao, Mingsan

    2018-01-01

    Drug safety is a key factor in drug research and development, Drug toxicology test is the main method to evaluate the safety of drugs, The body condition of an animal has important implications for the results of the study, Previous toxicological studies of drugs were carried out in normal animals in the past, There is a great deviation from the clinical practice.The purpose of this study is to investigate the necessity of model animals as a substitute for normal animals for toxicological studies, It is expected to provide exact guidance for future drug safety evaluation.

  10. Modelling Framework and Assistive Device for Peripheral Intravenous Injections

    Science.gov (United States)

    Kam, Kin F.; Robinson, Martin P.; Gilbert, Mathew A.; Pelah, Adar

    2016-02-01

    Intravenous access for blood sampling or drug administration that requires peripheral venepuncture is perhaps the most common invasive procedure practiced in hospitals, clinics and general practice surgeries.We describe an idealised mathematical framework for modelling the dynamics of the peripheral venepuncture process. Basic assumptions of the model are confirmed through motion analysis of needle trajectories during venepuncture, taken from video recordings of a skilled practitioner injecting into a practice kit. The framework is also applied to the design and construction of a proposed device for accurate needle guidance during venepuncture administration, assessed as consistent and repeatable in application and does not lead to over puncture. The study provides insights into the ubiquitous peripheral venepuncture process and may contribute to applications in training and in the design of new devices, including for use in robotic automation.

  11. Stable isotope-resolved metabolomics and applications for drug development

    Science.gov (United States)

    Fan, Teresa W-M.; Lorkiewicz, Pawel; Sellers, Katherine; Moseley, Hunter N.B.; Higashi, Richard M.; Lane, Andrew N.

    2012-01-01

    Advances in analytical methodologies, principally nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS), during the last decade have made large-scale analysis of the human metabolome a reality. This is leading to the reawakening of the importance of metabolism in human diseases, particularly cancer. The metabolome is the functional readout of the genome, functional genome, and proteome; it is also an integral partner in molecular regulations for homeostasis. The interrogation of the metabolome, or metabolomics, is now being applied to numerous diseases, largely by metabolite profiling for biomarker discovery, but also in pharmacology and therapeutics. Recent advances in stable isotope tracer-based metabolomic approaches enable unambiguous tracking of individual atoms through compartmentalized metabolic networks directly in human subjects, which promises to decipher the complexity of the human metabolome at an unprecedented pace. This knowledge will revolutionize our understanding of complex human diseases, clinical diagnostics, as well as individualized therapeutics and drug response. In this review, we focus on the use of stable isotope tracers with metabolomics technologies for understanding metabolic network dynamics in both model systems and in clinical applications. Atom-resolved isotope tracing via the two major analytical platforms, NMR and MS, has the power to determine novel metabolic reprogramming in diseases, discover new drug targets, and facilitates ADME studies. We also illustrate new metabolic tracer-based imaging technologies, which enable direct visualization of metabolic processes in vivo. We further outline current practices and future requirements for biochemoinformatics development, which is an integral part of translating stable isotope-resolved metabolomics into clinical reality. PMID:22212615

  12. Application of gold nanoparticles for improved drug efficiency

    Science.gov (United States)

    Shittu, K. O.; Bankole, M. T.; Abdulkareem, A. S.; Abubakre, O. K.; Ubaka, A. U.

    2017-09-01

    Due to increasing resistance of microorganisms towards current antibiotics, there is a need for new or enhanced antibiotics. Nanotechnology is a technology that enhances the use of gold nanoparticles (AuNP) in area of medical applications, especially as a drug carrier for targeted drug delivery. In this research, AuNPs was synthesized using biological method via bioreduction of Piper guineense aqueous leaf extract on tetra gold chloride, characterized using UV-Vis spectrophometer, DLS, TEM/EDS and FTIR. The synthesized AuNPs was covalently functionalized with polyethylene glycol and encapsulated with Lincomycin and in vitro dissolution methods was used to evaluate the potential performance of the formulated nanodrug. The nanodrug has highest release efficiency at the 9th minutes (23.4 mg ml-1 for 40 °C) and (29.5 mg ml-1 for 60 °C) compared with the non-nanodrug. The antibacterial potential of the nanodrug was seen on the gram-positive bacteria of Staphylococcus aureus and Streptococcus pyogenes with highest inhibitions of 18 mm (at 40 °C) and 16 mm (at 60 °C) for S. aureus, and 16 mm for S. pyogenes (both at 40 °C and 60 °C). The bacteria growth inhibition continued and lasted for 15 min, while that of non-nanodrug lasted for 9 min with lesser growth inhibition compared to the formulated nanodrug. This work shows that the presence of the AuNPs increased the release efficiency of lincomycin even at a lower concentration and also bacteria growth inhibition thereby suggesting the effectiveness of the nanodrug formulation.

  13. Repeated intravenous doxapram induces phrenic motor facilitation.

    Science.gov (United States)

    Sandhu, M S; Lee, K Z; Gonzalez-Rothi, E J; Fuller, D D

    2013-12-01

    Doxapram is a respiratory stimulant used to treat hypoventilation. Here we investigated whether doxapram could also trigger respiratory neuroplasticity. Specifically, we hypothesized that intermittent delivery of doxapram at low doses would lead to long-lasting increases (i.e., facilitation) of phrenic motor output in anesthetized, vagotomized, and mechanically-ventilated rats. Doxapram was delivered intravenously in a single bolus (2 or 6mg/kg) or as a series of 3 injections (2mg/kg) at 5min intervals. Control groups received pH-matched saline injections (vehicle) or no treatment (anesthesia time control). Doxapram evoked an immediate increase in phrenic output in all groups, but a persistent increase in burst amplitude only occurred after repeated dosing with 2mg/kg. At 60min following the last injection, phrenic burst amplitude was 168±24% of baseline (%BL) in the group receiving 3 injections (Pphrenic response to doxapram (2mg/kg) was reduced by 68% suggesting that at low doses the drug was acting primarily via the carotid chemoreceptors. We conclude that intermittent application of doxapram can trigger phrenic neuroplasticity, and this approach might be of use in the context of respiratory rehabilitation following neurologic injury. © 2013.

  14. Intravenous/oral ciprofloxacin therapy versus intravenous ceftazidime therapy for selected bacterial infections.

    Science.gov (United States)

    Gaut, P L; Carron, W C; Ching, W T; Meyer, R D

    1989-11-30

    The efficacy and toxicity of sequential intravenous and oral ciprofloxacin therapy was compared with intravenously administered ceftazidime in a prospective, randomized, controlled, non-blinded trial. Thirty-two patients (16 patients receiving ciprofloxacin and 16 patients receiving ceftazidime) with 38 infections caused by susceptible Pseudomonas aeruginosa, enteric gram-negative rods, Salmonella group B, Serratia marcescens, Pseudomonas cepacia, and Xanthomonas maltophilia at various sites were evaluable for determination of efficacy. Length of therapy varied from seven to 25 days. Concomitant antimicrobials included intravenously administered beta-lactams for gram-positive organisms, intravenous/oral metronidazole and clindamycin for anaerobes, and intravenous/local amphotericin B for Candida albicans. Intravenous administration of 200 mg ciprofloxacin every 12 hours to 11 patients produced peak serum levels between 1.15 and 3.12 micrograms/ml; trough levels ranged between 0.08 and 0.86 micrograms/ml. Overall response rates were similar for patients receiving ciprofloxacin and ceftazidime. Emergence of resistance was similar in both groups--one Enterobacter cloacae and two P. aeruginosa became resistant after ciprofloxacin therapy and two P. aeruginosa became resistant after ceftazidime therapy. The frequency of superinfection with a variety of organisms was also similar in both groups. Adverse events related to ciprofloxacin included transient pruritus at the infusion site and generalized rash leading to drug discontinuation (one patient each), and with ceftazidime adverse effects included pain at the site of infusion and the development of allergic interstitial nephritis (one patient each). Overall, intravenous/oral ciprofloxin therapy appears to be as safe and effective as intravenous ceftazidime therapy in the treatment of a variety of infections due to susceptible aerobic gram-negative organisms.

  15. Application for disability pension and change in use of prescribed drugs. A regional Danish cohort study.

    Science.gov (United States)

    Petersen, Thomas T; Fonager, Kirsten; Bøggild, Henrik; Pedersen, Lars; Mortensen, Jens T

    2009-06-01

    To investigate if a pending application for disability pension had an influence on the applicant's purchase of medical drugs, with a particular focus on musculoskeletal disorders and the use of painkillers. We performed a registry-based follow-up study including 12,020 applicants for disability pension in a Danish county from 1995 to 2000 and linked this information to a database of drug prescriptions. Purchase of drug was calculated for the 6-month period just before the decision and for the 6-month period 2 years later. Changes in a 2-year time period were estimated by differences in purchase rates. Furthermore, the proportion of applicants with an increased purchase of drugs and the proportion of applicants who ceased buying drugs were estimated. The results were stratified by diagnosis and result of application (awarded/rejected). The analyses were furthermore restricted to musculoskeletal disorders and the use of painkillers. At baseline 81% had a purchase and after the 2-year time period 11% ceased buying prescribed drugs. Half of all applicants increased the purchase of drugs. For musculoskeletal disorders one third had an increased purchase rate of painkillers while one fourth ceased purchase of drugs with variations in different diagnostic subgroups. The major changes of drug purchase after a pending application for disability pension are probably ascribed to characteristics of the diseases underlying the disability.

  16. Synthesis of an amphiphilic dendrimer-like block copolymer and its application on drug delivery

    KAUST Repository

    Wang, Shuaipeng; Song, Xiaowan; Feng, Xiaoshuang; Chen, Peng; Qian, Jiasheng; Xia, Ru; Miao, Jibin

    2014-01-01

    . The application on drug delivery of dendrimer-like diblock copolymer PEEGE-G2-b-PEO(OH)12 using DOX as a model drug was also studied. The drug loading content and encapsulation efficiency were found at 13.07% and 45.75%, respectively. In vitro release experiment

  17. Computed tomography intravenous cholangiography

    International Nuclear Information System (INIS)

    Nascimento, S.; Murray, W.; Wilson, P.

    1997-01-01

    Indications for direct visualization of the bile ducts include bile duct dilatation demonstrated by ultrasound or computed tomography (CT) scanning, where the cause of the bile duct dilatation is uncertain or where the anatomy of bile duct obstruction needs further clarification. Another indication is right upper quadrant pain, particularly in a post-cholecystectomy patient, where choledocholithiasis is suspected. A possible new indication is pre-operative evaluation prior to laparoscopic cholecystectomy. The bile ducts are usually studied by endoscopic retrograde cholangiopancreatography (ERCP), or, less commonly, trans-hepatic cholangiography. The old technique of intravenous cholangiography has fallen into disrepute because of inconsistent bile-duct opacification. The advent of spiral CT scanning has renewed interest in intravenous cholangiography. The CT technique is very sensitive to the contrast agent in the bile ducts, and angiographic and three-dimensional reconstructions of the biliary tree can readily be obtained using the CT intravenous cholangiogram technique (CT IVC). Seven patients have been studied using this CT IVC technique, between February 1995 and June 1996, and are the subject of the present report. Eight further studies have since been performed. The results suggest that CT IVC could replace ERCP as the primary means of direct cholangiography, where pancreatic duct visualization is not required. (authors)

  18. Chimeric mice with humanized liver: Application in drug metabolism and pharmacokinetics studies for drug discovery.

    Science.gov (United States)

    Naritomi, Yoichi; Sanoh, Seigo; Ohta, Shigeru

    2018-02-01

    Predicting human drug metabolism and pharmacokinetics (PK) is key to drug discovery. In particular, it is important to predict human PK, metabolite profiles and drug-drug interactions (DDIs). Various methods have been used for such predictions, including in vitro metabolic studies using human biological samples, such as hepatic microsomes and hepatocytes, and in vivo studies using experimental animals. However, prediction studies using these methods are often inconclusive due to discrepancies between in vitro and in vivo results, and interspecies differences in drug metabolism. Further, the prediction methods have changed from qualitative to quantitative to solve these issues. Chimeric mice with humanized liver have been developed, in which mouse liver cells are mostly replaced with human hepatocytes. Since human drug metabolizing enzymes are expressed in the liver of these mice, they are regarded as suitable models for mimicking the drug metabolism and PK observed in humans; therefore, these mice are useful for predicting human drug metabolism and PK. In this review, we discuss the current state, issues, and future directions of predicting human drug metabolism and PK using chimeric mice with humanized liver in drug discovery. Copyright © 2017 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

  19. 77 FR 65198 - Generic Drug User Fee-Abbreviated New Drug Application, Prior Approval Supplement, and Drug...

    Science.gov (United States)

    2012-10-25

    ..., U.S. postal money order, or wire transfer. FDA has partnered with the U.S. Department of the... money order and make payable to the order of the Food and Drug Administration. Your payment can be mailed to: Food and Drug Administration, P.O. Box 979108, St. Louis, MO 63197-9000. If checks are to be...

  20. In Vitro Drug Transfer Due to Drug Retention in Human Epidermis Pretreated with Application of Marketed Estradiol Transdermal Systems.

    Science.gov (United States)

    Krishnaiah, Yellela S R; Pavurala, Naresh; Yang, Yang; Manda, Prashanth; Katragadda, Usha; Yang, Yongsheng; Shah, Rakhi; Fang, Guodong; Khan, Mansoor A

    2017-08-01

    Study objective was to assess skin-to-skin drug transfer potential that may occur due to drug retention in human epidermis (DRE) pretreated with application of estradiol transdermal drug delivery systems (TDDS) and other estradiol transdermal dosage forms (gels and sprays). TDDS (products-A, B, and C) with varying formulation design and composition, and other estradiol transdermal products (gel and spray) were applied to heat separated human epidermis (HSE) and subjected to in vitro drug permeation study. Amounts of DRE were quantified after 24 h. The DRE with product-B was significantly (P  0.05) amounts of DRE. A separate in vitro permeation study was carried out to determine amounts of drug transferred from drug-retaining epidermis to untreated HSE. The amounts of drug transferred, due to DRE after 8 h, with product-C were significantly (P drug transfer due to the DRE after labeled period of using estradiol TDDS, though the clinical relevance of these findings is yet to be determined.

  1. Genetic Characterization of a Novel HIV-1 Circulating Recombinant Form (CRF74_01B) Identified among Intravenous Drug Users in Malaysia: Recombination History and Phylogenetic Linkage with Previously Defined Recombinant Lineages.

    Science.gov (United States)

    Cheong, Hui Ting; Chow, Wei Zhen; Takebe, Yutaka; Chook, Jack Bee; Chan, Kok Gan; Al-Darraji, Haider Abdulrazzaq Abed; Koh, Clayton; Kamarulzaman, Adeeba; Tee, Kok Keng

    2015-01-01

    In many parts of Southeast Asia, the HIV-1 epidemic has been driven by the sharing of needles and equipment among intravenous drug users (IDUs). Over the last few decades, many studies have proven time and again that the diversity of HIV-1 epidemics can often be linked to the route of infection transmission. That said, the diversity and complexity of HIV-1 molecular epidemics in the region have been increasing at an alarming rate, due in part to the high tendency of the viral RNA to recombine. This scenario was exemplified by the discovery of numerous circulating recombinant forms (CRFs), especially in Thailand and Malaysia. In this study, we characterized a novel CRF designated CRF74_01B, which was identified in six epidemiologically unlinked IDUs in Kuala Lumpur, Malaysia. The near-full length genomes were composed of CRF01_AE and subtype B', with eight breakpoints dispersed in the gag-pol and nef regions. Remarkably, this CRF shared four and two recombination hotspots with the previously described CRF33_01B and the less prevalent CRF53_01B, respectively. Genealogy-based Bayesian phylogenetic analysis of CRF74_01B genomic regions showed that it is closely related to both CRF33_01B and CRF53_01B. This observation suggests that CRF74_01B was probably a direct descendent from specific lineages of CRF33_01B, CRF53_01B and subtype B' that could have emerged in the mid-1990s. Additionally, it illustrated the active recombination processes between prevalent HIV-1 subtypes and recombinants in Malaysia. In summary, we report a novel HIV-1 genotype designated CRF74_01B among IDUs in Kuala Lumpur, Malaysia. The characterization of the novel CRF74_01B is of considerable significance towards the understanding of the genetic diversity and population dynamics of HIV-1 circulating in the region.

  2. Genetic Characterization of a Novel HIV-1 Circulating Recombinant Form (CRF74_01B Identified among Intravenous Drug Users in Malaysia: Recombination History and Phylogenetic Linkage with Previously Defined Recombinant Lineages.

    Directory of Open Access Journals (Sweden)

    Hui Ting Cheong

    Full Text Available In many parts of Southeast Asia, the HIV-1 epidemic has been driven by the sharing of needles and equipment among intravenous drug users (IDUs. Over the last few decades, many studies have proven time and again that the diversity of HIV-1 epidemics can often be linked to the route of infection transmission. That said, the diversity and complexity of HIV-1 molecular epidemics in the region have been increasing at an alarming rate, due in part to the high tendency of the viral RNA to recombine. This scenario was exemplified by the discovery of numerous circulating recombinant forms (CRFs, especially in Thailand and Malaysia. In this study, we characterized a novel CRF designated CRF74_01B, which was identified in six epidemiologically unlinked IDUs in Kuala Lumpur, Malaysia. The near-full length genomes were composed of CRF01_AE and subtype B', with eight breakpoints dispersed in the gag-pol and nef regions. Remarkably, this CRF shared four and two recombination hotspots with the previously described CRF33_01B and the less prevalent CRF53_01B, respectively. Genealogy-based Bayesian phylogenetic analysis of CRF74_01B genomic regions showed that it is closely related to both CRF33_01B and CRF53_01B. This observation suggests that CRF74_01B was probably a direct descendent from specific lineages of CRF33_01B, CRF53_01B and subtype B' that could have emerged in the mid-1990s. Additionally, it illustrated the active recombination processes between prevalent HIV-1 subtypes and recombinants in Malaysia. In summary, we report a novel HIV-1 genotype designated CRF74_01B among IDUs in Kuala Lumpur, Malaysia. The characterization of the novel CRF74_01B is of considerable significance towards the understanding of the genetic diversity and population dynamics of HIV-1 circulating in the region.

  3. Microencapsulation of indocyanine green for potential applications in image-guided drug delivery.

    Science.gov (United States)

    Zhu, Zhiqiang; Si, Ting; Xu, Ronald X

    2015-02-07

    We present a novel process to encapsulate indocyanine green (ICG) in liposomal droplets at high concentration for potential applications in image-guided drug delivery. The microencapsulation process follows two consecutive steps of droplet formation by liquid-driven coaxial flow focusing (LDCFF) and solvent removal by oil phase dewetting. These biocompatible lipid vesicles may have important applications in drug delivery and fluorescence imaging.

  4. 77 FR 50121 - Hospira, Inc.; Withdrawal of Approval of a New Drug Application for DEXTRAN 70

    Science.gov (United States)

    2012-08-20

    ...] Hospira, Inc.; Withdrawal of Approval of a New Drug Application for DEXTRAN 70 AGENCY: Food and Drug... new drug application (NDA) for DEXTRAN 70 (6% Dextran 70 and 0.9% NaCl or/5% Dextrose 500 mL Glass... that FDA withdraw approval of NDA 080-819, DEXTRAN 70 (6% Dextran 70 and 0.9% NaCl or/5% Dextrose 500 m...

  5. Application of ion mobility spectrometer for rapid drug detection

    Energy Technology Data Exchange (ETDEWEB)

    Xuemei, Zhu; Jian, Zheng [The Third Research Inst. of Ministry of Public Security, Shanghai (China); Yongjie, Lv; Yangqin, Chen [Department of Physics, Key Laboratory of Optical and Magnetic Resonance Spectroscopy, East China Normal Univ., Shanghai (China)

    2007-10-15

    A {sup 63}Ni source-based high resolution ion mobility spectrometer (IMS) was developed and applied to drug detection. The drugs included opium, morphine, heroin, methamphetamine, MDMA, MDEA, ketamine and cannabis. Their ion mobility spectra were acquired, ion types were derived and reduced mobilities were calculated, which are in good agreement with the data reported in literatures. The results indicate that the IMS can detect effectively a variety of drugs, especially for the amphetamine derivatives. And the reduced mobility standard database of drugs was established. (authors)

  6. Application of ion mobility spectrometer for rapid drug detection

    International Nuclear Information System (INIS)

    Zhu Xuemei; Zheng Jian; Lv Yongjie; Chen Yangqin

    2007-01-01

    A 63 Ni source-based high resolution ion mobility spectrometer (IMS) was developed and applied to drug detection. The drugs included opium, morphine, heroin, methamphetamine, MDMA, MDEA, ketamine and cannabis. Their ion mobility spectra were acquired, ion types were derived and reduced mobilities were calculated, which are in good agreement with the data reported in literatures. The results indicate that the IMS can detect effectively a variety of drugs, especially for the amphetamine derivatives. And the reduced mobility standard database of drugs was established. (authors)

  7. AIDS: sexual behavior and intravenous drug use

    National Research Council Canada - National Science Library

    Turner, Charles F; Miller, Heather G; Moses, Lincoln E

    1989-01-01

    ..., SOCIAL, AND STATISTICAL SCIENCES COMMISSION ON BEHAVIORAL AND SOCIAL SCIENCES AND EDUCATION NATIONAL RESEARCH COUNCIL NATIONAL ACADEMY PRESS WASHINGTON, D.C. 1989 Copyrightoriginal retained, the be not from cannot book, paper original however, for version formatting, authoritative the typesetting-specific created from the as publi...

  8. [Intravenous ethyl alcohol in metabolic resuscitation].

    Science.gov (United States)

    Agolini, G; Lipartiti, T; Zaffiri, O; Musso, L; Belloni, G P

    1980-11-01

    Intravenously administered ethyl alcohol may be effective as analgesic and hypotensive peripheric vasoactive drug. In the Intensive Care Departments parenteral ethanol administration is infrequent because no "sure dosage" can be suggested in adults and children. Liver, kidney and C.N.S. diseases can worsen; foetopathy can follow. Drug-ethanol interaction may be particularly important for some patients admitted in Intensive Care Departments. Often the potential caloric support cannot be fully utilized ("empty" calories) and seldom hyperventilation, hyperlactacidemia and impaired protein synthesis can follow.

  9. The application of machine learning techniques in the clinical drug therapy.

    Science.gov (United States)

    Meng, Huan-Yu; Jin, Wan-Lin; Yan, Cheng-Kai; Yang, Huan

    2018-05-25

    The development of a novel drug is an extremely complicated process that includes the target identification, design and manufacture, and proper therapy of the novel drug, as well as drug dose selection, drug efficacy evaluation, and adverse drug reaction control. Due to the limited resources, high costs, long duration, and low hit-to-lead ratio in the development of pharmacogenetics and computer technology, machine learning techniques have assisted novel drug development and have gradually received more attention by researchers. According to current research, machine learning techniques are widely applied in the process of the discovery of new drugs and novel drug targets, the decision surrounding proper therapy and drug dose, and the prediction of drug efficacy and adverse drug reactions. In this article, we discussed the history, workflow, and advantages and disadvantages of machine learning techniques in the processes mentioned above. Although the advantages of machine learning techniques are fairly obvious, the application of machine learning techniques is currently limited. With further research, the application of machine techniques in drug development could be much more widespread and could potentially be one of the major methods used in drug development. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Collagen like peptide bioconjugates for targeted drug delivery applications

    Science.gov (United States)

    Luo, Tianzhi

    , suggesting that the nanoparticles do not initiate inflammatory response. Endowed with specific collagen binding, controlled thermoresponsiveness, excellent cytocompatibility, and non-immune responsiveness, we believe the ELP-CLP nanoparticles are promising candidates as drug delivery vehicles for targeting collagen containing matrices. Considering the critical role of collagens in extracellular matrix and the unique ability of the CLP to target native collagens, our work offers significant opportunities for the design of collagen-like peptides and their bioconjugates for targeted application in the biomedical arena.

  11. Targeted drug delivery to magnetic implants for therapeutic applications

    International Nuclear Information System (INIS)

    Yellen, Benjamin B.; Forbes, Zachary G.; Halverson, Derek S.; Fridman, Gregory; Barbee, Kenneth A.; Chorny, Michael; Levy, Robert; Friedman, Gary

    2005-01-01

    A new method for locally targeted drug delivery is proposed that employs magnetic implants placed directly in the cardiovascular system to attract injected magnetic carriers. Theoretical simulations and experimental results support the assumption that using magnetic implants in combination with externally applied magnetic field will optimize the delivery of magnetic drug to selected sites within a subject

  12. Advances in the synthesis and application of nanoparticles for drug delivery.

    Science.gov (United States)

    Park, Wooram; Na, Kun

    2015-01-01

    The continuous development of drug delivery systems (DDSs) has been extensively researched by the need to maximize therapeutic efficacy while minimizing undesirable side effects. Nanoparticle technology was recently shown to hold great promise for drug delivery applications in nanomedicine due to its beneficial properties, such as better encapsulation, bioavailability, control release, and lower toxic effect. Despite the great progress in nanomedicine, there remain many limitations for clinical application. To overcome these limitations, advanced nanoparticles for drug delivery have been developed to enable the spatially and temporally controlled release of drugs in response to specific stimuli at disease sites. Furthermore, the controlled self-assembly of organic and inorganic materials may enable their use in theranostic applications. This review presents an overview of a recent advanced nanoparticulate system that can be used as a potential drug delivery carrier and focuses on the potential applications of nanoparticles in various biomedical fields for human health care. © 2015 Wiley Periodicals, Inc.

  13. Advances in the Applications of Polyhydroxyalkanoate Nanoparticles for Novel Drug Delivery System

    Directory of Open Access Journals (Sweden)

    Anupama Shrivastav

    2013-01-01

    Full Text Available Drug delivery technology is emerging as an interdisciplinary science aimed at improving human health. The controlled delivery of pharmacologically active agents to the specific site of action at the therapeutically optimal rate and dose regimen has been a major goal in designing drug delivery systems. Over the past few decades, there has been considerable interest in developing biodegradable drug carriers as effective drug delivery systems. Polymeric materials from natural sources play an important role in controlled release of drug at a particular site. Polyhydroxyalkanoates, due to their origin from natural sources, are given attention as candidates for drug delivery materials. Biodegradable and biocompatible polyhydroxyalkanoates are linear polyesters produced by microorganisms under unbalanced growth conditions, which have emerged as potential polymers for use as biomedical materials for drug delivery due to their unique physiochemical and mechanical properties. This review summarizes many of the key findings in the applications of polyhydroxyalkanoates and polyhydroxyalkanoate nanoparticles for drug delivery system.

  14. Applications of nanodiamonds in drug delivery and catalysis

    KAUST Repository

    Moosa, Basem; Fhayli, Karim; Li, Song; Julfakyan, Khachatur; Ezzeddine, Alaa; Khashab, Niveen M.

    2014-01-01

    The interest of researchers in utilizing nanomaterials as carriers for a wide spectrum of molecules has exploded in the last two decades. Nanodiamonds are one class of carbon-based nanomaterials that have emerged as promising drug delivery vehicles

  15. Applications of nanoparticle systems in drug delivery technology

    Directory of Open Access Journals (Sweden)

    Syed A.A. Rizvi

    2018-01-01

    Full Text Available The development of nanoparticle-based drug formulations has yielded the opportunities to address and treat challenging diseases. Nanoparticles vary in size but are generally ranging from 100 to 500 nm. Through the manipulation of size, surface characteristics and material used, the nanoparticles can be developed into smart systems, encasing therapeutic and imaging agents as well as bearing stealth property. Further, these systems can deliver drug to specific tissues and provide controlled release therapy. This targeted and sustained drug delivery decreases the drug related toxicity and increase patient’s compliance with less frequent dosing. Nanotechnology has proven beneficial in the treatment of cancer, AIDS and many other disease, also providing advancement in diagnostic testing.

  16. Erythrocytes for Drug Delivery and their Applications: A Review ...

    African Journals Online (AJOL)

    , dogs, rabbits, rats and mice. Encapsulation in erythrocytes drastically changes the pharmacokinetic properties of drugs in both animals and humans, enhancing liver and spleen uptake and targeting the reticulo-endothelial system (RES).

  17. 75 FR 73108 - Guidance for Industry on Abbreviated New Drug Applications: Impurities in Drug Products...

    Science.gov (United States)

    2010-11-29

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0584... Products.'' This guidance updates recommendations regarding degradation products and updates the draft... information on listing of degradation products, setting acceptance criteria, and qualifying degradation...

  18. 78 FR 37231 - Guidance for Industry; Guidance on Abbreviated New Drug Applications: Stability Testing of Drug...

    Science.gov (United States)

    2013-06-20

    .... 2201, Silver Spring, MD 20993-0002. Send one self-addressed adhesive label to assist the office in... comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane...

  19. Novel liquid application systems for poorly soluble drugs

    OpenAIRE

    Luschmann, Christoph Roman

    2015-01-01

    This thesis was focused on the development of efficient novel liquid formulations for poorly water soluble drugs for the treatment of inflammatory ophthalmic diseases. With Restasis® there is currently only one drug product approved by the FDA, in the US only, for the treatment of dry eye syndrome. It still suffers from low bioavailability, bad biocompatibility and thus a low patient compliance, as well as cumbersome manufacturing. Hence, there is a tremendous lack in the options for a causal...

  20. The application of halloysite tubule nanoclay in drug delivery.

    Science.gov (United States)

    Lvov, Yuri M; DeVilliers, Melgardt M; Fakhrullin, Rawil F

    2016-07-01

    Natural and biocompatible clay nanotubes are among the best inorganic materials for drug nanoformulations. These halloysite tubes with SiO2 on the outermost surface have diameter of ca. 50 nm, length around 1 micrometer and may be loaded with drugs at 10-30 wt. %. Narrow tube openings allow for controllable sustained drug release for hours, days or even weeks. Physical-chemical properties of these nanotubes are described followed by examples of drug-loading capabilities, release characteristics, and control of duration of release through the end tube capping with polymers. Development of halloysite-polymer composites such as tissue scaffolds and bone cement/dentist resin formulations with enhanced mechanical properties and extension of the drug release to 2-3 weeks are described. Examples of the compression properties of halloysite in tablets and capsules are also shown. We expect that clay nanotubes will be used primarily for non-injectable drug formulations, such as topical and oral dosage forms, cosmetics, as well as for composite materials with enhanced therapeutic effects. These include tissue scaffolds, bone cement and dentist resins with sustained release of antimicrobial and cell growth-promoting medicines (including proteins and DNA) as well as other formulations such as compounds for antiseptic treatment of hospitals.

  1. Deep Learning Applications for Predicting Pharmacological Properties of Drugs and Drug Repurposing Using Transcriptomic Data.

    Science.gov (United States)

    Aliper, Alexander; Plis, Sergey; Artemov, Artem; Ulloa, Alvaro; Mamoshina, Polina; Zhavoronkov, Alex

    2016-07-05

    Deep learning is rapidly advancing many areas of science and technology with multiple success stories in image, text, voice and video recognition, robotics, and autonomous driving. In this paper we demonstrate how deep neural networks (DNN) trained on large transcriptional response data sets can classify various drugs to therapeutic categories solely based on their transcriptional profiles. We used the perturbation samples of 678 drugs across A549, MCF-7, and PC-3 cell lines from the LINCS Project and linked those to 12 therapeutic use categories derived from MeSH. To train the DNN, we utilized both gene level transcriptomic data and transcriptomic data processed using a pathway activation scoring algorithm, for a pooled data set of samples perturbed with different concentrations of the drug for 6 and 24 hours. In both pathway and gene level classification, DNN achieved high classification accuracy and convincingly outperformed the support vector machine (SVM) model on every multiclass classification problem, however, models based on pathway level data performed significantly better. For the first time we demonstrate a deep learning neural net trained on transcriptomic data to recognize pharmacological properties of multiple drugs across different biological systems and conditions. We also propose using deep neural net confusion matrices for drug repositioning. This work is a proof of principle for applying deep learning to drug discovery and development.

  2. Recent progress on fabrication and drug delivery applications of nanostructured hydroxyapatite.

    Science.gov (United States)

    Mondal, Sudip; Dorozhkin, Sergy V; Pal, Umapada

    2018-07-01

    Through this brief review, we provide a comprehensive historical background of the development of nanostructured hydroxyapatite (nHAp), and its application potentials for controlled drug delivery, drug conjugation, and other biomedical treatments. Aspects associated with efficient utilization of hydroxyapatite (HAp) nanostructures such as their synthesis, interaction with drug molecules, and other concerns, which need to be resolved before they could be used as a potential drug carrier in body system, are discussed. This review focuses on the evolution of perceptions, practices, and accomplishments in providing improved delivery systems for drugs until date. The pioneering developments that have presaged today's fascinating state of the art drug delivery systems based on HAp and HAp-based composite nanostructures are also discussed. Special emphasis has been given to describe the application and effectiveness of modified HAp as drug carrier agent for different diseases such as bone-related disorders, carriers for antibiotics, anti-inflammatory, carcinogenic drugs, medical imaging, and protein delivery agents. As only a very few published works made comprehensive evaluation of HAp nanostructures for drug delivery applications, we try to cover the three major areas: concepts, practices and achievements, and applications, which have been consolidated and patented for their practical usage. The review covers a broad spectrum of nHAp and HAp modified inorganic drug carriers, emphasizing some of their specific aspects those needed to be considered for future drug delivery applications. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants Therapeutic Approaches and Drug Discovery > Nanomedicine for Respiratory Disease Nanotechnology Approaches to Biology > Cells at the Nanoscale. © 2017 Wiley Periodicals, Inc.

  3. A 125I-radiolabelled probe for vinblastine and vindesine radioimmunoassays: applications to measurements of vindesine plasma levels in man after intravenous injections and long-term infusions

    International Nuclear Information System (INIS)

    Rahmani, R.; Barbet, J.; Cano, J.-P.

    1983-01-01

    The transformation of vinblastine into a reactive acid azide was used for the preparation of a vindesine-glycyl-tyrosine conjugate. This conjugate was radiolabelled [ 125 I] and used as a tracer for the radioimmunoassay of vinblastine and vindesine with antisera developed by the Eli Lilly Research Laboratories and by the authors. Its higher specific activity as compared to tritiated vinblastine significantly increases the sensitivity of the assay (0.05 μg/l as compared to 0.6 μg/l). It was then possible to monitor vindesine plasma levels for more than 60 h after intravenous bolus injection and to evaluate the elimination rates more accurately. When plasma levels were also measurable using tritiated vinblastine a satisfactory agreement was observed with determinations performed with radioiodinated vindesine-glycyl-tyrosine. Furthermore, the use of a #betta#-emitting probe simplifies the radioimmunoassay procedure and accordingly increases its reproducibility. A few examples of vindesine level measurements in human plasma collected after bolus intravenous injection and during long-term infusion are given. (Auth.)

  4. An analytical solution for percutaneous drug absorption: application and removal of the vehicle.

    Science.gov (United States)

    Simon, L; Loney, N W

    2005-10-01

    The methods of Laplace transform were used to solve a mathematical model developed for percutaneous drug absorption. This model includes application and removal of the vehicle from the skin. A system of two linear partial differential equations was solved for the application period. The concentration of the medicinal agent in the skin at the end of the application period was used as the initial condition to determine the distribution of the drug in the skin following instantaneous removal of the vehicle. The influences of the diffusion and partition coefficients, clearance factor and vehicle layer thickness on the amount of drug in the vehicle and the skin were discussed.

  5. Drug delivery systems and materials for wound healing applications.

    Science.gov (United States)

    Saghazadeh, Saghi; Rinoldi, Chiara; Schot, Maik; Kashaf, Sara Saheb; Sharifi, Fatemeh; Jalilian, Elmira; Nuutila, Kristo; Giatsidis, Giorgio; Mostafalu, Pooria; Derakhshandeh, Hossein; Yue, Kan; Swieszkowski, Wojciech; Memic, Adnan; Tamayol, Ali; Khademhosseini, Ali

    2018-04-05

    Chronic, non-healing wounds place a significant burden on patients and healthcare systems, resulting in impaired mobility, limb amputation, or even death. Chronic wounds result from a disruption in the highly orchestrated cascade of events involved in wound closure. Significant advances in our understanding of the pathophysiology of chronic wounds have resulted in the development of drugs designed to target different aspects of the impaired processes. However, the hostility of the wound environment rich in degradative enzymes and its elevated pH, combined with differences in the time scales of different physiological processes involved in tissue regeneration require the use of effective drug delivery systems. In this review, we will first discuss the pathophysiology of chronic wounds and then the materials used for engineering drug delivery systems. Different passive and active drug delivery systems used in wound care will be reviewed. In addition, the architecture of the delivery platform and its ability to modulate drug delivery are discussed. Emerging technologies and the opportunities for engineering more effective wound care devices are also highlighted. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Intravenous versus oral etoposide

    DEFF Research Database (Denmark)

    Ali, Abir Salwa; Grönberg, Malin; Langer, Seppo W.

    2018-01-01

    High-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs, G3) are aggressive cancers of the digestive system with poor prognosis and survival. Platinum-based chemotherapy (cisplatin/carboplatin + etoposide) is considered the first-line palliative treatment. Etoposide is frequently...... administered intravenously; however, oral etoposide may be used as an alternative. Concerns for oral etoposide include decreased bioavailability, inter- and intra-patient variability and patient compliance. We aimed to evaluate possible differences in progression-free survival (PFS) and overall survival (OS......) in patients treated with oral etoposide compared to etoposide given as infusion. Patients (n = 236) from the Nordic NEC study were divided into three groups receiving etoposide as a long infusion (24 h, n = 170), short infusion (≤ 5 h, n = 33) or oral etoposide (n = 33) according to hospital tradition. PFS...

  7. Applications of nanodiamonds in drug delivery and catalysis.

    Science.gov (United States)

    Moosa, Basem; Fhayli, Karim; Li, Song; Julfakyan, Khatchatur; Ezzeddine, Alaa; Khashab, Niveen M

    2014-01-01

    The interest of researchers in utilizing nanomaterials as carriers for a wide spectrum of molecules has exploded in the last two decades. Nanodiamonds are one class of carbon-based nanomaterials that have emerged as promising drug delivery vehicles and imaging probes. Their ease of functionalization also led to the generation of stimuli-responsive nanodiamonds that deliver drugs on demand in a controlled manner. The ample surface area of NDs allowed for a higher loading of not only small molecules but also macromolecules like genes and proteins. Recently, the unique surface of NDs has attracted more attention as catalyst support in a huge range of organic modification and C-C bond formation reactions. Herein, recent advances in the utilization of nanodiamonds as a drug delivery vehicle and catalytical support are highlighted and summarized to illustrate the potential and versatility of this cheap and commercially available nanomaterial.

  8. Applications of nanodiamonds in drug delivery and catalysis

    KAUST Repository

    Moosa, Basem

    2014-01-01

    The interest of researchers in utilizing nanomaterials as carriers for a wide spectrum of molecules has exploded in the last two decades. Nanodiamonds are one class of carbon-based nanomaterials that have emerged as promising drug delivery vehicles and imaging probes. Their ease of functionalization also led to the generation of stimuli-responsive nanodiamonds that deliver drugs on demand in a controlled manner. The ample surface area of NDs allowed for a higher loading of not only small molecules but also macromolecules like genes and proteins. Recently, the unique surface of NDs has attracted more attention as catalyst support in a huge range of organic modification and C-C bond formation reactions. Herein, recent advances in the utilization of nanodiamonds as a drug delivery vehicle and catalytical support are highlighted and summarized to illustrate the potential and versatility of this cheap and commercially available nanomaterial. Copyright © 2014 American Scientific Publishers All rights reserved.

  9. Automated applications of sandwich-cultured hepatocytes in the evaluation of hepatic drug transport.

    Science.gov (United States)

    Perry, Cassandra H; Smith, William R; St Claire, Robert L; Brouwer, Kenneth R

    2011-04-01

    Predictions of the absorption, distribution, metabolism, excretion, and toxicity of compounds in pharmaceutical development are essential aspects of the drug discovery process. B-CLEAR is an in vitro system that uses sandwich-cultured hepatocytes to evaluate and predict in vivo hepatobiliary disposition (hepatic uptake, biliary excretion, and biliary clearance), transporter-based hepatic drug-drug interactions, and potential drug-induced hepatotoxicity. Automation of predictive technologies is an advantageous and preferred format in drug discovery. In this study, manual and automated studies are investigated and equivalence is demonstrated. In addition, automated applications using model probe substrates and inhibitors to assess the cholestatic potential of drugs and evaluate hepatic drug transport are examined. The successful automation of this technology provides a more reproducible and less labor-intensive approach, reducing potential operator error in complex studies and facilitating technology transfer.

  10. Application of Conformational Space Search in Drug Action | Adikwu ...

    African Journals Online (AJOL)

    The role of conformational space in drug action is presented. Two examples of molecules in different therapeutic groups are presented. Conformational space search will lead to isolating the exact conformation with the desired medicinal properties. Many conformations of a plant isolate may exist which are active, weakly ...

  11. Application of drug selective electrode in the drug release study of pH-responsive microgels.

    Science.gov (United States)

    Tan, Jeremy P K; Tam, Kam C

    2007-03-12

    The colloidal phenomenon of soft particles is becoming an important field of research due to the growing interest in using polymeric system in drug delivery. Previous studies have focused on techniques that require intermediate process step such as dialysis or centrifugation, which introduces additional errors in obtaining the diffusion kinetic data. In this study, a drug selective electrode was used to directly measure the concentration of procaine hydrochloride (PrHy) released from methacrylic acid-ethyl acrylate (MAA-EA) microgel, thereby eliminating the intermediate process step. PrHy selective membrane constructed using a modified poly (vinyl chloride) (PVC) membrane and poly (ethylene-co-vinyl acetate-co-carbon monoxide) as plasticizer exhibited excellent reproducibility and stability. The response was reproducible at pH of between 3 to 8.5 and the selectivity coefficients against various organic and inorganic cations were evaluated. Drug release was conducted using the drug electrode under different pHs and the release rate increased with pH. The release behavior of the system under different pH exhibited obvious gradient release characteristics.

  12. Fragment-based drug discovery and its application to challenging drug targets.

    Science.gov (United States)

    Price, Amanda J; Howard, Steven; Cons, Benjamin D

    2017-11-08

    Fragment-based drug discovery (FBDD) is a technique for identifying low molecular weight chemical starting points for drug discovery. Since its inception 20 years ago, FBDD has grown in popularity to the point where it is now an established technique in industry and academia. The approach involves the biophysical screening of proteins against collections of low molecular weight compounds (fragments). Although fragments bind to proteins with relatively low affinity, they form efficient, high quality binding interactions with the protein architecture as they have to overcome a significant entropy barrier to bind. Of the biophysical methods available for fragment screening, X-ray protein crystallography is one of the most sensitive and least prone to false positives. It also provides detailed structural information of the protein-fragment complex at the atomic level. Fragment-based screening using X-ray crystallography is therefore an efficient method for identifying binding hotspots on proteins, which can then be exploited by chemists and biologists for the discovery of new drugs. The use of FBDD is illustrated here with a recently published case study of a drug discovery programme targeting the challenging protein-protein interaction Kelch-like ECH-associated protein 1:nuclear factor erythroid 2-related factor 2. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  13. Superparamagnetic nanoparticles for biomedical applications: Possibilities and limitations of a new drug delivery system

    Energy Technology Data Exchange (ETDEWEB)

    Neuberger, Tobias [Musculoskeletal Research Unit, Equine Hospital, Vetsuisse Faculty Zurich, University of Zurich, Winterthurerstr. 260, 8057 Zurich (Switzerland); Schoepf, Bernhard [Musculoskeletal Research Unit, Equine Hospital, Vetsuisse Faculty Zurich, University of Zurich, Winterthurerstr. 260, 8057 Zurich (Switzerland); Hofmann, Heinrich [Laboratory of Powder Technology, Institute of Materials, Swiss Federal Institute of Technology, EPFL, 1015 Lausanne (Switzerland); Hofmann, Margarete [MatSearch Pully, Chemin Jean Pavillard, 14, CH-1009 Pully (Switzerland); Rechenberg, Brigitte von [Musculoskeletal Research Unit, Equine Hospital, Vetsuisse Faculty Zurich, University of Zurich, Winterthurerstr. 260, 8057 Zurich (Switzerland)]. E-mail: bvonrechenberg@vetclinics.unizh.ch

    2005-05-15

    Nanoparticles can be used in biomedical applications, where they facilitate laboratory diagnostics, or in medical drug targeting. They are used for in vivo applications such as contrast agent for magnetic resonance imaging (MRI), for tumor therapy or cardiovascular disease. Very promising nanoparticles for these applications are superparamagnetic nanoparticles based on a core consisting of iron oxides (SPION) that can be targeted through external magnets. SPION are coated with biocompatible materials and can be functionalized with drugs, proteins or plasmids. In this review, the characteristics and applications of SPION in the biomedical sector are introduced and discussed.

  14. Superparamagnetic nanoparticles for biomedical applications: Possibilities and limitations of a new drug delivery system

    International Nuclear Information System (INIS)

    Neuberger, Tobias; Schoepf, Bernhard; Hofmann, Heinrich; Hofmann, Margarete; Rechenberg, Brigitte von

    2005-01-01

    Nanoparticles can be used in biomedical applications, where they facilitate laboratory diagnostics, or in medical drug targeting. They are used for in vivo applications such as contrast agent for magnetic resonance imaging (MRI), for tumor therapy or cardiovascular disease. Very promising nanoparticles for these applications are superparamagnetic nanoparticles based on a core consisting of iron oxides (SPION) that can be targeted through external magnets. SPION are coated with biocompatible materials and can be functionalized with drugs, proteins or plasmids. In this review, the characteristics and applications of SPION in the biomedical sector are introduced and discussed

  15. Application of ion chromatography in pharmaceutical and drug analysis.

    Science.gov (United States)

    Jenke, Dennis

    2011-08-01

    Ion chromatography (IC) has developed and matured into an important analytical methodology in a number of diverse applications and industries, including pharmaceuticals. This manuscript provides a review of IC applications for the determinations of active and inactive ingredients, excipients, degradation products, and impurities relevant to pharmaceutical analyses and thus serves as a resource for investigators looking for insights into the use of the IC methodology in this field of application.

  16. Elucidating antimalarial drug targets/mode-of-action by application of system biology technologies

    CSIR Research Space (South Africa)

    Becker, J

    2008-11-01

    Full Text Available targets/mode-of-action by application of systems biology technologies J BECKER, L MTWISHA, B CRAMPTON AND D MANCAMA CSIR Biosciences, PO Box 395, Pretoria, 0001, South Africa Email: JBecker@csir.co.za – www.csir.co.za INTRODUCTION Malaria is one... The objective of this study was to use systems biology tools to unravel the drug target/mode-of-action (MoA) of an antimalarial drug (cyclohexylamine) with a known drug target/MoA, by analysing differential expression profiles of drug treated vs untreated...

  17. Intravenous Carbamazepine for Adults With Seizures.

    Science.gov (United States)

    Vickery, P Brittany; Tillery, Erika E; DeFalco, Alicia Potter

    2018-03-01

    To review the pharmacology, pharmacokinetics, efficacy, safety, dosage and administration, potential drug-drug interactions, and place in therapy of the intravenous (IV) formulation of carbamazepine (Carnexiv) for the treatment of seizures in adult patients. A comprehensive PubMed and EBSCOhost search (1945 to August 2017) was performed utilizing the keywords carbamazepine, Carnexiv, carbamazepine intravenous, IV carbamazepine, seizures, epilepsy, and seizure disorder. Additional data were obtained from literature review citations, manufacturer's product labeling, and Lundbeck website as well as Clinicaltrials.gov and governmental sources. All English-language trials evaluating IV carbamazepine were analyzed for this review. IV carbamazepine is FDA approved as temporary replacement therapy for treatment of adult seizures. Based on a phase I trial and pooled data from 2 open-label bioavailability studies comparing oral with IV dosing, there was no noted indication of loss of seizure control in patients switched to short-term replacement antiepileptic drug therapy with IV carbamazepine. The recommended dose of IV carbamazepine is 70% of the patient's oral dose, given every 6 hours via 30-minute infusions. The adverse effect profile of IV carbamazepine is similar to that of the oral formulation, with the exception of added infusion-site reactions. IV carbamazepine is a reasonable option for adults with generalized tonic-clonic or focal seizures, previously stabilized on oral carbamazepine, who are unable to tolerate oral medications for up to 7 days. Unknown acquisition cost and lack of availability in the United States limit its use currently.

  18. Fluorescence lifetime assays: current advances and applications in drug discovery.

    Science.gov (United States)

    Pritz, Stephan; Doering, Klaus; Woelcke, Julian; Hassiepen, Ulrich

    2011-06-01

    Fluorescence lifetime assays complement the portfolio of established assay formats available in drug discovery, particularly with the recent advances in microplate readers and the commercial availability of novel fluorescent labels. Fluorescence lifetime assists in lowering complexity of compound screening assays, affording a modular, toolbox-like approach to assay development and yielding robust homogeneous assays. To date, materials and procedures have been reported for biochemical assays on proteases, as well as on protein kinases and phosphatases. This article gives an overview of two assay families, distinguished by the origin of the fluorescence signal modulation. The pharmaceutical industry demands techniques with a robust, integrated compound profiling process and short turnaround times. Fluorescence lifetime assays have already helped the drug discovery field, in this sense, by enhancing productivity during the hit-to-lead and lead optimization phases. Future work will focus on covering other biochemical molecular modifications by investigating the detailed photo-physical mechanisms underlying the fluorescence signal.

  19. Synthesis of Nano Hydroxyapatite: Application in Drug Delivery of Sulfasalazine

    Directory of Open Access Journals (Sweden)

    D. Moslemi

    2015-10-01

    Full Text Available In this work we synthesized Nano hydroxyapatite (HAp  by Sol-gel method, Then we functionalized hydroxyapatite nanoparticle by use of  3-Aminopropyl trimethoxysilane (APTMS , to improve the loading and control release of sulfasalazine drug bonded to APTMS. The drug release patterns from Sulfasalazine loaded HAp nanoparticles at pH value 8 For 6h, Sulfasalazine loaded functionalized HAp nanoparticles (Sulfasalazine loaded HAp-APTMS at pH value 8 as in the intestine for 48h. Moreover, the functionalized HAp showed relatively slower release rate of sulfasalazine compare with non functionalized HAp. because the strong ionic interaction between NH2 group in sulfasalazine in HAp-APTMS. On other side, the functionalized HAp loaded more drug than pure HAp. The synthesized nanoparticles and functionalized HAp characterized by Scanning Electron Microscopy (SEM, X-ray Diffraction (XRD, Fourier transform infrared (FT-IR and  UV/Vis analysis techniques. Then the obtained material was studied in the simulated body fluid (SBF to this investigated storage and release properties.

  20. PEG-based degradable networks for drug delivery applications

    Science.gov (United States)

    Ostroha, Jamie L.

    The controlled delivery of therapeutic agents by biodegradable hydrogels has become a popular mechanism for drug administration in recent years. Hydrogels are three-dimensional networks of polymer chains held together by crosslinks. Although the changes which the hydrogel undergoes in solution are important to a wide range of experimental studies, they have not been investigated systematically and the factors which influence the degree of swelling have not been adequately described. Hydrogels made of poly(ethylene glycol) (PEG) will generally resist degradation in aqueous conditions, while a hydrogel made from a copolymer of poly(lactic acid) (PLA) and PEG will degrade via hydrolysis of the lactic acid group. This ability to degrade makes these hydrogels promising candidates for controlled release drug delivery systems. The goal of this research was to characterize the swelling and degradation of both degradable and non-degradable gels and to evaluate the release of different drugs from these hydrogels, where the key variable is the molecular weight of the PEG segment. These hydrogels were formed by the addition and subsequent chemically crosslinking of methacrylate end groups. During crosslinking, both PEG and LA-PEG-LA hydrogels of varied PEG molecular weight were loaded with Vitamin B12, Insulin, Haloperidol, and Dextran. It was shown that increasing PEG molecular weight produces a hydrogel with larger pores, thus increasing water uptake and degradation rate. While many environmental factors do not affect the swelling behavior, they do significantly impact the degradation of the hydrogel, and thus the release of incorporated therapeutic agents.

  1. Influences on physicians' choices of intravenous colloids.

    Science.gov (United States)

    Miletin, Michael S; Stewart, Thomas E; Norton, Peter G

    2002-07-01

    Controversy over the optimal intravenous fluid for volume resuscitation continues unabated. Our objectives were to characterize the demographics of physicians who prescribe intravenous colloids and determine factors that enter into their decision to choose a colloid. Questionnaire with 61 items. Ten percent ( n = 364) of frequent intravenous fluid prescribers in the province of Ontario, Canada. The response rate was 74%. Colloid use in the past year was reported by 79% of the responding physicians. Important reasons for choosing a colloid included blood loss and manipulation of oncotic pressure. Physicians tended to prefer either albumin or pentastarch, but no important reasons were found for choosing between the two. Albumin with or without crystalloid was preferred in 5/13 scenarios by more than 50% of the respondents, whereas pentastarch was not favored by more than 50% of respondents in any scenario. Physicians practising in critical care areas and teaching hospitals generally preferred pentastarch to albumin. Physicians reporting pentastarch as representing greater than 90% of total colloid use were more likely to have been visited by a drug detailer for pentastarch than those who used less synthetic colloid (54 vs 22%, p distribution. Although albumin appeared to be preferred in more clinical niches, most physicians did not state reasons for choosing between products. Marketing, specialty, location of practice and clinical scenario appear to play significant roles in the utilization of colloid products.

  2. Synthesis and characterization of novel dual-responsive nanogels and their application as drug delivery systems

    Science.gov (United States)

    Peng, Jinrong; Qi, Tingting; Liao, Jinfeng; Fan, Min; Luo, Feng; Li, He; Qian, Zhiyong

    2012-03-01

    In this study, a temperature/pH dual-response nanogel based on NIPAm, MAA, and PEGMA was synthesized via emulsion polymerization and characterized by 1H-NMR, FT-IR, TEM and DLS. By introducing a novel initiator, through which PEG-AIBN-PEG was synthesized, it was revealed that the PEG segments from PEG-AIBN-PEG with a dosage of initiator had a significant influence over the macro-state and stability of the nanogels. In order to optimize the feeding prescription for better application as a drug delivery system, the effect of the co-monomer contents on the response to stimuli (temperature and pH value) and cytotoxicity of the nanogels has been studied in detail. The results demonstrated that the responsiveness, reversibility and volume phase transition critical value of the nanogels could be controlled by adjusting the feeding ratio of the co-monomers in the synthesis process. MTT assay results revealed that nanogels with appropriate compositions showed good biocompatibility and relatively low toxicity. Most importantly, by studying the drug loading behavior, it was found that the dimensions of the drug molecules had a considerable influence on the drug loading efficiency and loading capacity of the nanogels, and that the mechanism by which drug molecule sizes influence the drug loading behavior of nanogels needs further investigation. The results indicated that such PNMP nanogels might have potential applications in drug delivery and other medical applications, but that the drug loading mechanism must be further developed.

  3. SynergyFinder: a web application for analyzing drug combination dose-response matrix data.

    Science.gov (United States)

    Ianevski, Aleksandr; He, Liye; Aittokallio, Tero; Tang, Jing

    2017-08-01

    Rational design of drug combinations has become a promising strategy to tackle the drug sensitivity and resistance problem in cancer treatment. To systematically evaluate the pre-clinical significance of pairwise drug combinations, functional screening assays that probe combination effects in a dose-response matrix assay are commonly used. To facilitate the analysis of such drug combination experiments, we implemented a web application that uses key functions of R-package SynergyFinder, and provides not only the flexibility of using multiple synergy scoring models, but also a user-friendly interface for visualizing the drug combination landscapes in an interactive manner. The SynergyFinder web application is freely accessible at https://synergyfinder.fimm.fi ; The R-package and its source-code are freely available at http://bioconductor.org/packages/release/bioc/html/synergyfinder.html . jing.tang@helsinki.fi. © The Author(s) 2017. Published by Oxford University Press.

  4. The application of nanomaterials in controlled drug delivery for bone regeneration.

    Science.gov (United States)

    Shi, Shuo; Jiang, Wenbao; Zhao, Tianxiao; Aifantis, Katerina E; Wang, Hui; Lin, Lei; Fan, Yubo; Feng, Qingling; Cui, Fu-zhai; Li, Xiaoming

    2015-12-01

    Bone regeneration is a complicated process that involves a series of biological events, such as cellular recruitment, proliferation and differentiation, and so forth, which have been found to be significantly affected by controlled drug delivery. Recently, a lot of research studies have been launched on the application of nanomaterials in controlled drug delivery for bone regeneration. In this article, the latest research progress in this area regarding the use of bioceramics-based, polymer-based, metallic oxide-based and other types of nanomaterials in controlled drug delivery for bone regeneration are reviewed and discussed, which indicates that the controlling drug delivery with nanomaterials should be a very promising treatment in orthopedics. Furthermore, some new challenges about the future research on the application of nanomaterials in controlled drug delivery for bone regeneration are described in the conclusion and perspectives part. Copyright © 2015 Wiley Periodicals, Inc.

  5. Application of RNAi to Genomic Drug Target Validation in Schistosomes.

    Directory of Open Access Journals (Sweden)

    Alessandra Guidi

    2015-05-01

    Full Text Available Concerns over the possibility of resistance developing to praziquantel (PZQ, has stimulated efforts to develop new drugs for schistosomiasis. In addition to the development of improved whole organism screens, the success of RNA interference (RNAi in schistosomes offers great promise for the identification of potential drug targets to initiate drug discovery. In this study we set out to contribute to RNAi based validation of putative drug targets. Initially a list of 24 target candidates was compiled based on the identification of putative essential genes in schistosomes orthologous of C. elegans essential genes. Knockdown of Calmodulin (Smp_026560.2 (Sm-Calm, that topped this list, produced a phenotype characterised by waves of contraction in adult worms but no phenotype in schistosomula. Knockdown of the atypical Protein Kinase C (Smp_096310 (Sm-aPKC resulted in loss of viability in both schistosomula and adults and led us to focus our attention on other kinase genes that were identified in the above list and through whole organism screening of known kinase inhibitor sets followed by chemogenomic evaluation. RNAi knockdown of these kinase genes failed to affect adult worm viability but, like Sm-aPKC, knockdown of Polo-like kinase 1, Sm-PLK1 (Smp_009600 and p38-MAPK, Sm-MAPK p38 (Smp_133020 resulted in an increased mortality of schistosomula after 2-3 weeks, an effect more marked in the presence of human red blood cells (hRBC. For Sm-PLK-1 the same effects were seen with the specific inhibitor, BI2536, which also affected viable egg production in adult worms. For Sm-PLK-1 and Sm-aPKC the in vitro effects were reflected in lower recoveries in vivo. We conclude that the use of RNAi combined with culture with hRBC is a reliable method for evaluating genes important for larval development. However, in view of the slow manifestation of the effects of Sm-aPKC knockdown in adults and the lack of effects of Sm-PLK-1 and Sm-MAPK p38 on adult viability

  6. Ultrasonography versus intravenous urography

    International Nuclear Information System (INIS)

    Aslaksen, A.

    1991-01-01

    The present study was performed to compare the clinical value of urography and ultrasonography in a non-selected group of patients referred for urography to a university hospital. The conslusions and clinical implications of the study are as follows: Intravenous urography remains the cornerstone imaging examination in the evaluation of ureteral calculi. Ultrasonography is a valuable adjunct in cases of non- visualization of the kidneys, in distal obstruction and known contrast media allergy. When women with recurrent urinary tract infection are referred for imaging of the urinary tract, ultrasonography should be used. Ultrasonography should replace urography for screening of non-acute hydronephrosis like in female genital cancer and benign prostate hyperplasia. There is good correlation between urography and ultrasonography in assessing the degree of hydronephrosis. However, more researh on the relationship between hydronephrosis and obstruction is necessary. Ultrasonography should be used as the only imaging method of the upper urinary tract in patients with microscopic hematuria. In patients less than 50 years with macroscopic hematuria, ultrasonography should be used as the only imaging of the upper urinary tract, and an examination of the urinary bladder should be included. In patients over 50 years, urography supplied with ultrasonography should be used, but more research is necessary on the subject of imaging method and age. 158 refs

  7. Application of Fused Deposition Modelling (FDM) Method of 3D Printing in Drug Delivery.

    Science.gov (United States)

    Long, Jingjunjiao; Gholizadeh, Hamideh; Lu, Jun; Bunt, Craig; Seyfoddin, Ali

    2017-01-01

    Three-dimensional (3D) printing is an emerging manufacturing technology for biomedical and pharmaceutical applications. Fused deposition modelling (FDM) is a low cost extrusion-based 3D printing technique that can deposit materials layer-by-layer to create solid geometries. This review article aims to provide an overview of FDM based 3D printing application in developing new drug delivery systems. The principle methodology, suitable polymers and important parameters in FDM technology and its applications in fabrication of personalised tablets and drug delivery devices are discussed in this review. FDM based 3D printing is a novel and versatile manufacturing technique for creating customised drug delivery devices that contain accurate dose of medicine( s) and provide controlled drug released profiles. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Use of general practice by intravenous heroin users on a methadone programme.

    OpenAIRE

    Leaver, E J; Elford, J; Morris, J K; Cohen, J

    1992-01-01

    Users of intravenous heroin represent a major challenge for general practice. A study was undertaken in a general practice in central London in 1990 to investigate the use of general practice made by intravenous heroin users who were on a methadone programme. Using information recorded in the patients' notes, 29 intravenous heroin users on a methadone programme were identified; 58 non-drug users (two controls per case) were matched for age, sex and general practitioner. A study of the number ...

  9. Cell-specific prediction and application of drug-induced gene expression profiles.

    Science.gov (United States)

    Hodos, Rachel; Zhang, Ping; Lee, Hao-Chih; Duan, Qiaonan; Wang, Zichen; Clark, Neil R; Ma'ayan, Avi; Wang, Fei; Kidd, Brian; Hu, Jianying; Sontag, David; Dudley, Joel

    2018-01-01

    Gene expression profiling of in vitro drug perturbations is useful for many biomedical discovery applications including drug repurposing and elucidation of drug mechanisms. However, limited data availability across cell types has hindered our capacity to leverage or explore the cell-specificity of these perturbations. While recent efforts have generated a large number of drug perturbation profiles across a variety of human cell types, many gaps remain in this combinatorial drug-cell space. Hence, we asked whether it is possible to fill these gaps by predicting cell-specific drug perturbation profiles using available expression data from related conditions--i.e. from other drugs and cell types. We developed a computational framework that first arranges existing profiles into a three-dimensional array (or tensor) indexed by drugs, genes, and cell types, and then uses either local (nearest-neighbors) or global (tensor completion) information to predict unmeasured profiles. We evaluate prediction accuracy using a variety of metrics, and find that the two methods have complementary performance, each superior in different regions in the drug-cell space. Predictions achieve correlations of 0.68 with true values, and maintain accurate differentially expressed genes (AUC 0.81). Finally, we demonstrate that the predicted profiles add value for making downstream associations with drug targets and therapeutic classes.

  10. Acute Toxicity of Intravenously Administered Titanium Dioxide Nanoparticles in Mice

    OpenAIRE

    Xu, Jiaying; Shi, Hongbo; Ruth, Magaye; Yu, Hongsheng; Lazar, Lissy; Zou, Baobo; Yang, Cui; Wu, Aiguo; Zhao, Jinshun

    2013-01-01

    BACKGROUND: With a wide range of applications, titanium dioxide (TiO₂) nanoparticles (NPs) are manufactured worldwide in large quantities. Recently, in the field of nanomedicine, intravenous injection of TiO₂ nanoparticulate carriers directly into the bloodstream has raised public concerns on their toxicity to humans. METHODS: In this study, mice were injected intravenously with a single dose of TiO₂ NPs at varying dose levels (0, 140, 300, 645, or 1387 mg/kg). Animal mortality, blood biochem...

  11. 78 FR 59038 - Mobile Medical Applications; Guidance for Industry and Food and Drug Administration Staff...

    Science.gov (United States)

    2013-09-25

    ... FDA intends to apply its regulatory oversight to only those mobile apps that are medical devices and...] Mobile Medical Applications; Guidance for Industry and Food and Drug Administration Staff; Availability...) is announcing the availability of the guidance entitled ``Mobile Medical Applications.'' The FDA is...

  12. Self-emulsifying drug delivery systems (SEDDS): formulation development, characterization, and applications.

    Science.gov (United States)

    Singh, Bhupinder; Bandopadhyay, Shantanu; Kapil, Rishi; Singh, Ramandeep; Katare, O

    2009-01-01

    Self-emulsifying drug delivery systems (SEDDS) possess unparalleled potential in improving oral bioavailability of poorly water-soluble drugs. Following their oral administration, these systems rapidly disperse in gastrointestinal fluids, yielding micro- or nanoemulsions containing the solubilized drug. Owing to its miniscule globule size, the micro/nanoemulsifed drug can easily be absorbed through lymphatic pathways, bypassing the hepatic first-pass effect. We present an exhaustive and updated account of numerous literature reports and patents on diverse types of self-emulsifying drug formulations, with emphasis on their formulation, characterization, and systematic optimization strategies. Recent advancements in various methodologies employed to characterize their globule size and shape, ability to encapsulate the drug, gastrointestinal and thermodynamic stability, rheological characteristics, and so forth, are discussed comprehensively to guide the formula-tor in preparing an effective and robust SEDDS formulation. Also, this exhaustive review offers an explicit discussion on vital applications of the SEDDS in bioavailability enhancement of various drugs, outlining an overview on myriad in vitro, in situ, and ex vivo techniques to assess the absorption and/ or permeation potential of drugs incorporated in the SEDDS in animal and cell line models, and the subsequent absorption pathways followed by them. In short, the current article furnishes an updated compilation of wide-ranging information on all the requisite vistas of the self-emulsifying formulations, thus paving the way for accelerated progress into the SEDDS application in pharmaceutical research.

  13. 78 FR 33426 - Eli Lilly and Co.; Withdrawal of Approval of a New Drug Application for ORAFLEX

    Science.gov (United States)

    2013-06-04

    ...] Eli Lilly and Co.; Withdrawal of Approval of a New Drug Application for ORAFLEX AGENCY: Food and Drug... new drug application (NDA) for ORAFLEX (benoxaprofen) Tablets, held by Eli Lilly and Co. (Lilly), Lilly Corporate Center, Indianapolis, IN 46285. Lilly has voluntarily requested that approval of this...

  14. Application of Novel Drugs for Corneal Cell Regeneration

    Directory of Open Access Journals (Sweden)

    Sang Beom Han

    2018-01-01

    Full Text Available Corneal transplantation has been the only treatment method for corneal blindness, which is the major cause of reversible blindness. However, despite the advancement of surgical techniques for corneal transplantation, demand for the surgery can never be met due to a global shortage of donor cornea. The development of bioengineering and pharmaceutical technology provided us with novel drugs and biomaterials that can be used for innovative treatment methods for corneal diseases. In this review, the authors will discuss the efficacy and safety of pharmacologic therapies, such as Rho-kinase (ROCK inhibitors, blood-derived products, growth factors, and regenerating agent on corneal cell regeneration. The promising results of these agents suggest that these can be viable options for corneal reconstruction and visual rehabilitation.

  15. Nano Sponges for Drug Delivery and Medicinal Applications

    Science.gov (United States)

    Tour, James M.; Lucente-Schultz, Rebecca; Leonard, Ashley; Kosynkin, Dimitry V.; Price, Brandi Katherine; Hudson, Jared L.; Conyers, Jodie L., Jr.; Moore, Valerie C.; Casscells, S. Ward; Myers, Jeffrey N.; hide

    2012-01-01

    This invention is a means of delivering a drug, or payload, to cells using non-covalent associations of the payload with nano-engineered scaffolds; specifically, functionalized single-walled carbon nanotubes (SWNTs) and their derivatives where the payload is effectively sequestered by the nanotube's addends and then delivered to the site (often interior of a cell) of interest. Polyethylene glycol (PEG) and other water-soluble organic molecules have been shown to greatly enhance the solubility of SWNTs in water. PEG groups and other water-solubilizing addends can act to sequester (sponge) molecules and deliver them into cells. Using PEG that, when attached to the SWNTs, the SWNT/PEG matrix will enter cells has been demonstrated. This was visualized by the addition of fluorescein isothiocyanate (FITC) to the SWNT/PEG matrix. Control studies showed that both FITC alone and FITC/PEG did not enter the cells. These observations suggest that the FITC is highly associated with the SWNT/PEG matrix that brings the FITC into the cells, allowing visualization of SWNTs in cells. The FITC is not covalently attached, because extended dialysis in hot DMF will remove all fluorescence quickly (one week). However, prolonged dialysis in water (1-2 months) will only slowly diminish the fluorescence. This demonstrates that the SWNT/PEG matrix solubilizes the FITC by sequestering it from the surrounding water and into the more solubilizing organic environment of the SWNT/PEG matrix of this type. This can be extended for the sequestering of other molecules such as drugs with PEG and other surfactants.

  16. Saccharomyces cerevisiae boulardii transient fungemia after intravenous self-inoculation

    OpenAIRE

    Cohen, Lola; Ranque, Stéphane; Raoult, Didier

    2013-01-01

    We report the case of a young psychotic intravenous drug user injecting herself with Saccharomyces cervisiae (boulardii). She experienced a 24 h fever, resolving spontaneously confirming, quasi experimentally, the inocuity of this yeast in a non-immunocompromised host.

  17. Pharmacokinetics and pharmacodynamics of eltanolone (pregnanolone), a new steroid intravenous anaesthetic, in humans

    DEFF Research Database (Denmark)

    Carl, Peder; Høgskilde, S; Lang-Jensen, T

    1994-01-01

    Eltanolone, a new intravenous steroid anaesthetic agent was administered intravenously in a dose of 0.6 mg.kg-1 over 45 s to eight healthy male volunteers to evaluate some of its pharmacokinetic and pharmacodynamic effects. Drug concentration-time data were analysed by PCNONLIN, a non...

  18. Application of the Pareto principle to identify and address drug-therapy safety issues.

    Science.gov (United States)

    Müller, Fabian; Dormann, Harald; Pfistermeister, Barbara; Sonst, Anja; Patapovas, Andrius; Vogler, Renate; Hartmann, Nina; Plank-Kiegele, Bettina; Kirchner, Melanie; Bürkle, Thomas; Maas, Renke

    2014-06-01

    Adverse drug events (ADE) and medication errors (ME) are common causes of morbidity in patients presenting at emergency departments (ED). Recognition of ADE as being drug related and prevention of ME are key to enhancing pharmacotherapy safety in ED. We assessed the applicability of the Pareto principle (~80 % of effects result from 20 % of causes) to address locally relevant problems of drug therapy. In 752 cases consecutively admitted to the nontraumatic ED of a major regional hospital, ADE, ME, contributing drugs, preventability, and detection rates of ADE by ED staff were investigated. Symptoms, errors, and drugs were sorted by frequency in order to apply the Pareto principle. In total, 242 ADE were observed, and 148 (61.2 %) were assessed as preventable. ADE contributed to 110 inpatient hospitalizations. The ten most frequent symptoms were causally involved in 88 (80.0 %) inpatient hospitalizations. Only 45 (18.6 %) ADE were recognized as drug-related problems until discharge from the ED. A limited set of 33 drugs accounted for 184 (76.0 %) ADE; ME contributed to 57 ADE. Frequency-based listing of ADE, ME, and drugs involved allowed identification of the most relevant problems and development of easily to implement safety measures, such as wall and pocket charts. The Pareto principle provides a method for identifying the locally most relevant ADE, ME, and involved drugs. This permits subsequent development of interventions to increase patient safety in the ED admission process that best suit local needs.

  19. Application of lean manufacturing concepts to drug discovery: rapid analogue library synthesis.

    Science.gov (United States)

    Weller, Harold N; Nirschl, David S; Petrillo, Edward W; Poss, Michael A; Andres, Charles J; Cavallaro, Cullen L; Echols, Martin M; Grant-Young, Katherine A; Houston, John G; Miller, Arthur V; Swann, R Thomas

    2006-01-01

    The application of parallel synthesis to lead optimization programs in drug discovery has been an ongoing challenge since the first reports of library synthesis. A number of approaches to the application of parallel array synthesis to lead optimization have been attempted over the years, ranging from widespread deployment by (and support of) individual medicinal chemists to centralization as a service by an expert core team. This manuscript describes our experience with the latter approach, which was undertaken as part of a larger initiative to optimize drug discovery. In particular, we highlight how concepts taken from the manufacturing sector can be applied to drug discovery and parallel synthesis to improve the timeliness and thus the impact of arrays on drug discovery.

  20. Data-intensive drug development in the information age: applications of Systems Biology/Pharmacology/Toxicology.

    Science.gov (United States)

    Kiyosawa, Naoki; Manabe, Sunao

    2016-01-01

    Pharmaceutical companies continuously face challenges to deliver new drugs with true medical value. R&D productivity of drug development projects depends on 1) the value of the drug concept and 2) data and in-depth knowledge that are used rationally to evaluate the drug concept's validity. A model-based data-intensive drug development approach is a key competitive factor used by innovative pharmaceutical companies to reduce information bias and rationally demonstrate the value of drug concepts. Owing to the accumulation of publicly available biomedical information, our understanding of the pathophysiological mechanisms of diseases has developed considerably; it is the basis for identifying the right drug target and creating a drug concept with true medical value. Our understanding of the pathophysiological mechanisms of disease animal models can also be improved; it can thus support rational extrapolation of animal experiment results to clinical settings. The Systems Biology approach, which leverages publicly available transcriptome data, is useful for these purposes. Furthermore, applying Systems Pharmacology enables dynamic simulation of drug responses, from which key research questions to be addressed in the subsequent studies can be adequately informed. Application of Systems Biology/Pharmacology to toxicology research, namely Systems Toxicology, should considerably improve the predictability of drug-induced toxicities in clinical situations that are difficult to predict from conventional preclinical toxicology studies. Systems Biology/Pharmacology/Toxicology models can be continuously improved using iterative learn-confirm processes throughout preclinical and clinical drug discovery and development processes. Successful implementation of data-intensive drug development approaches requires cultivation of an adequate R&D culture to appreciate this approach.

  1. Ultrasonography-guided peripheral intravenous access versus traditional approaches in patients with difficult intravenous access.

    Science.gov (United States)

    Costantino, Thomas G; Parikh, Aman K; Satz, Wayne A; Fojtik, John P

    2005-11-01

    We assess the success rate of emergency physicians in placing peripheral intravenous catheters in difficult-access patients who were unsuccessfully cannulated by emergency nurses. A technique using real-time ultrasonographic guidance by 2 physicians was compared with traditional approaches using palpation and landmark guidance. This was a prospective, systematically allocated study of all patients requiring intravenous access who presented to 2 university hospitals between October 2003 and March 2004. Inclusion criterion was the inability of any available nurse to obtain intravenous access after at least 3 attempts on a subgroup of patients who had a history of difficult intravenous access because of obesity, history of intravenous drug abuse, or chronic medical problems. Exclusion criterion was the need for central venous access. Patients presenting on odd days were allocated to the ultrasonographic-guided group, and those presenting on even days were allocated to the traditional-approach group. Endpoints were successful cannulation, number of sticks, time, and patient satisfaction. Sixty patients were enrolled, 39 on odd days and 21 on even days. Success rate was greater for the ultrasonographic group (97%) versus control (33%), difference in proportions of 64% (95% confidence interval [CI] 39% to 71%). The ultrasonographic group required less overall time (13 minutes versus 30 minutes, for a difference of 17 [95% CI 0.8 to 25.6]), less time to successful cannulation from first percutaneous puncture (4 minutes versus 15 minutes, for a difference of 11 [95% CI 8.2 to 19.4]), and fewer percutaneous punctures (1.7 versus 3.7, for a difference of 2.0 [95% CI 1.27 to 2.82]) and had greater patient satisfaction (8.7 versus 5.7, for a difference of 3.0 [95% CI 1.82 to 4.29]) than the traditional landmark approach. Ultrasonographic-guided peripheral intravenous access is more successful than traditional "blind" techniques, requires less time, decreases the number of

  2. Photopatternable Magnetic Hollowbots by Nd-Fe-B Nanocomposite for Potential Targeted Drug Delivery Applications

    Directory of Open Access Journals (Sweden)

    Hui Li

    2018-04-01

    Full Text Available In contrast to traditional drug administration, targeted drug delivery can prolong, localize, target and have a protected drug interaction with the diseased tissue. Drug delivery carriers, such as polymeric micelles, liposomes, dendrimers, nanotubes, and so on, are hard to scale-up, costly, and have short shelf life. Here we show the novel fabrication and characterization of photopatternable magnetic hollow microrobots that can potentially be utilized in microfluidics and drug delivery applications. These magnetic hollowbots can be fabricated using standard ultraviolet (UV lithography with low cost and easily accessible equipment, which results in them being easy to scale up, and inexpensive to fabricate. Contact-free actuation of freestanding magnetic hollowbots were demonstrated by using an applied 900 G external magnetic field to achieve the movement control in an aqueous environment. According to the movement clip, the average speed of the magnetic hollowbots was estimated to be 1.9 mm/s.

  3. Strontium doped injectable bone cement for potential drug delivery applications.

    Science.gov (United States)

    Taha, Ali; Akram, Muhammad; Jawad, Zaidoon; Alshemary, Ammar Z; Hussain, Rafaqat

    2017-11-01

    Microwave assisted wet precipitation method was used to synthesize calcium deficient strontium doped β-tricalcium phosphate (Sr-βTCP) with a chemical formula of Ca 2.96-x Sr x (PO 4 ) 2 . Sr-βTCP was reacted with monocalcium phosphate monohydrate [Ca(H 2 PO 4 ) 2 .H 2 O, MCPM] in presence of water to furnish corresponding Sr containing brushite cement (Sr-Brc). The samples were characterized by using X-ray diffractometry (XRD), Fourier transform infrared spectroscopy (FTIR) and field emission scanning electron microscopy (FESEM). Strontium content in the prepared samples was determined by using inductively coupled plasma optical emission spectrometry (ICP-OES). The effect of Sr 2+ ions on the structural, mechanical, setting properties and drug release of the cement is reported. Incorporation of Sr 2+ ions improved the injectability, setting time and mechanical properties of the Brc. The release profiles of antibiotics incorporated in Brc and Sr-Brc confirmed that the Sr incorporation into the Brc results in the efficient release of the antibiotics from the cement. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Packaging protein drugs as bacterial inclusion bodies for therapeutic applications

    Directory of Open Access Journals (Sweden)

    Villaverde Antonio

    2012-06-01

    Full Text Available Abstract A growing number of insights on the biology of bacterial inclusion bodies (IBs have revealed intriguing utilities of these protein particles. Since they combine mechanical stability and protein functionality, IBs have been already exploited in biocatalysis and explored for bottom-up topographical modification in tissue engineering. Being fully biocompatible and with tuneable bio-physical properties, IBs are currently emerging as agents for protein delivery into mammalian cells in protein-replacement cell therapies. So far, IBs formed by chaperones (heat shock protein 70, Hsp70, enzymes (catalase and dihydrofolate reductase, grow factors (leukemia inhibitory factor, LIF and structural proteins (the cytoskeleton keratin 14 have been shown to rescue exposed cells from a spectrum of stresses and restore cell functions in absence of cytotoxicity. The natural penetrability of IBs into mammalian cells (reaching both cytoplasm and nucleus empowers them as an unexpected platform for the controlled delivery of essentially any therapeutic polypeptide. Production of protein drugs by biopharma has been traditionally challenged by IB formation. However, a time might have arrived in which recombinant bacteria are to be engineered for the controlled packaging of therapeutic proteins as nanoparticulate materials (nanopills, for their extra- or intra-cellular release in medicine and cosmetics.

  5. Biodegradable PLGA-b-PEG polymeric nanoparticles: synthesis, properties, and nanomedical applications as drug delivery system

    Energy Technology Data Exchange (ETDEWEB)

    Locatelli, Erica; Comes Franchini, Mauro, E-mail: mauro.comesfranchini@unibo.it [University of Bologna, Dipartimento di Chimica Industriale Toso Montanari (Italy)

    2012-12-15

    During the past decades many synthetic polymers have been studied for nanomedicine applications and in particular as drug delivery systems. For this purpose, polymers must be non-toxic, biodegradable, and biocompatible. Polylactic-co-glycolic acid (PLGA) is one of the most studied polymers due to its complete biodegradability and ability to self-assemble into nanometric micelles that are able to entrap small molecules like drugs and to release them into body in a time-dependent manner. Despite fine qualities, using PLGA polymeric nanoparticles for in vivo applications still remains an open challenge due to many factors such as poor stability in water, big diameter (150-200 nm), and the removal of these nanocarriers from the blood stream by the liver and spleen thus reducing the concentration of drugs drastically in tumor tissue. Polyethylene glycol (PEG) is the most used polymers for drug delivery applications and the first PEGylated product is already on the market for over 20 years. This is due to its stealth behavior that inhibits the fast recognition by the immune system (opsonization) and generally leads to a reduced blood clearance of nanocarriers increasing blood circulation time. Furthermore, PEG is hydrophilic and able to stabilize nanoparticles by steric and not ionic effects especially in water. PLGA-PEG block copolymer is an emergent system because it can be easily synthesized and it possesses all good qualities of PLGA and also PEG capability so in the last decade it arose as one of the most promising systems for nanoparticles formation, drug loading, and in vivo drug delivery applications. This review will discuss briefly on PLGA-b-PEG synthesis and physicochemical properties, together with its improved qualities with respect to the single PLGA and PEG polymers. Moreover, we will focus on but in particular will treat nanoparticles formation and uses as new drug delivery system for nanomedical applications.

  6. Construction and characterization of a pure protein hydrogel for drug delivery application.

    Science.gov (United States)

    Xu, Xu; Xu, ZhaoKang; Yang, XiaoFeng; He, YanHao; Lin, Rong

    2017-02-01

    Injectable hydrogels have a variety of applications, including regenerative medicine, tissue engineering and controlled drug delivery. In this paper, we reported on a pure protein hydrogel based on tetrameric recombinant proteins for the potential drug delivery application. This protein hydrogel was formed instantly by simply mixing two recombinant proteins (ULD-TIP1 and ULD-GGGWRESAI) through the specific protein-peptide interaction. The protein hydrogel was characterized by rheology and scanning electron microscopy (SEM). In vitro cytotoxicity test indicated that the developed protein hydrogel had no apparent cytotoxicity against L-929 cells and HCEC cells after 48h incubation. The formed protein hydrogels was gradually degraded after incubation in phosphate buffered solution (PBS, pH=7.4) for a period of 144h study, as indicated by in vitro degradation test. Encapsulation of model drug (sodium diclofenac; DIC) were achieved by simple mixing of drugs with hydrogelator and the entrapped drugs was almost completely released from hydrogels within 24h via a diffusion manner. As a conclusion, the simple and mild preparation procedure and good biocompatibility of protein hydrogel would render its good promising candidate for drug delivery applications. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Advances in the use of intravenous techniques in ambulatory anesthesia

    Directory of Open Access Journals (Sweden)

    Eng MR

    2015-07-01

    Full Text Available Matthew R Eng,1 Paul F White1,2 1Department of Anesthesiology, Cedars-Sinai Medical Center, Los Angeles, CA, USA; 2White Mountain Institute, The Sea Ranch, CA, USA Summary statement: Advances in the use of intravenous techniques in ambulatory anesthesia has become important for the anesthesiologist as the key perioperative physician in outpatient surgery. Key techniques and choices of anesthetics are important in accomplishing fast track goals of ambulatory surgery. Purpose of review: The anesthesiologist in the outpatient environment must focus on improving perioperative efficiency and reducing recovery times while accounting for patients' well-being and safety. This review article focuses on recent intravenous anesthetic techniques to accomplish these goals. Recent findings: This review is an overview of techniques in intravenous anesthesia for ambulatory anesthesia. Intravenous techniques may be tailored to accomplish outpatient surgery goals for the type of surgical procedure and individual patient needs. Careful anesthetic planning and the application of the plans are critical to an anesthesiologist's success with fast-track ambulatory surgery. Conclusion: Careful planning and application of intravenous techniques are critical to an anesthesiologist's success with fast-track ambulatory surgery. Keywords: intravenous anesthesia, outpatient anesthesia, fast-track surgery

  8. An Overview of Chitosan Nanoparticles and Its Application in Non-Parenteral Drug Delivery

    Directory of Open Access Journals (Sweden)

    Munawar A. Mohammed

    2017-11-01

    Full Text Available The focus of this review is to provide an overview of the chitosan based nanoparticles for various non-parenteral applications and also to put a spotlight on current research including sustained release and mucoadhesive chitosan dosage forms. Chitosan is a biodegradable, biocompatible polymer regarded as safe for human dietary use and approved for wound dressing applications. Chitosan has been used as a carrier in polymeric nanoparticles for drug delivery through various routes of administration. Chitosan has chemical functional groups that can be modified to achieve specific goals, making it a polymer with a tremendous range of potential applications. Nanoparticles (NP prepared with chitosan and chitosan derivatives typically possess a positive surface charge and mucoadhesive properties such that can adhere to mucus membranes and release the drug payload in a sustained release manner. Chitosan-based NP have various applications in non-parenteral drug delivery for the treatment of cancer, gastrointestinal diseases, pulmonary diseases, drug delivery to the brain and ocular infections which will be exemplified in this review. Chitosan shows low toxicity both in vitro and some in vivo models. This review explores recent research on chitosan based NP for non-parenteral drug delivery, chitosan properties, modification, toxicity, pharmacokinetics and preclinical studies.

  9. Self-Assembled Nanocarriers Based on Amphiphilic Natural Polymers for Anti- Cancer Drug Delivery Applications.

    Science.gov (United States)

    Sabra, Sally; Abdelmoneem, Mona; Abdelwakil, Mahmoud; Mabrouk, Moustafa Taha; Anwar, Doaa; Mohamed, Rania; Khattab, Sherine; Bekhit, Adnan; Elkhodairy, Kadria; Freag, May; Elzoghby, Ahmed

    2017-01-01

    Micellization provides numerous merits for the delivery of water insoluble anti-cancer therapeutic agents including a nanosized 'core-shell' drug delivery system. Recently, hydrophobically-modified polysaccharides and proteins are attracting much attention as micelle forming polymers to entrap poorly soluble anti-cancer drugs. By virtue of their small size, the self-assembled micelles can passively target tumor tissues via enhanced permeation and retention effect (EPR). Moreover, the amphiphilic micelles can be exploited for active-targeted drug delivery by attaching specific targeting ligands to the outer micellar hydrophilic surface. Here, we review the conjugation techniques, drug loading methods, physicochemical characteristics of the most important amphiphilic polysaccharides and proteins used as anti-cancer drug delivery systems. Attention focuses on the mechanisms of tumor-targeting and enhanced anti-tumor efficacy of the encapsulated drugs. This review will highlight the remarkable advances of hydrophobized polysaccharide and protein micelles and their potential applications as anti-cancer drug delivery nanosystems. Micellar nanocarriers fabricated from amphiphilic natural polymers hold great promise as vehicles for anti-cancer drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Application of three-dimensional printing for colon targeted drug delivery systems.

    Science.gov (United States)

    Charbe, Nitin B; McCarron, Paul A; Lane, Majella E; Tambuwala, Murtaza M

    2017-01-01

    Orally administered solid dosage forms currently dominate over all other dosage forms and routes of administrations. However, human gastrointestinal tract (GIT) poses a number of obstacles to delivery of the drugs to the site of interest and absorption in the GIT. Pharmaceutical scientists worldwide have been interested in colon drug delivery for several decades, not only for the delivery of the drugs for the treatment of colonic diseases such as ulcerative colitis and colon cancer but also for delivery of therapeutic proteins and peptides for systemic absorption. Despite extensive research in the area of colon targeted drug delivery, we have not been able to come up with an effective way of delivering drugs to the colon. The current tablets designed for colon drug release depend on either pH-dependent or time-delayed release formulations. During ulcerative colitis the gastric transit time and colon pH-levels is constantly changing depending on whether the patient is having a relapse or under remission. Hence, the current drug delivery system to the colon is based on one-size-fits-all. Fails to effectively deliver the drugs locally to the colon for colonic diseases and delivery of therapeutic proteins and peptides for systemic absorption from the colon. Hence, to overcome the current issues associated with colon drug delivery, we need to provide the patients with personalized tablets which are specifically designed to match the individual's gastric transit time depending on the disease state. Three-dimensional (3D) printing (3DP) technology is getting cheaper by the day and bespoke manufacturing of 3D-printed tablets could provide the solutions in the form of personalized colon drug delivery system. This review provides a bird's eye view of applications and current advances in pharmaceutical 3DP with emphasis on the development of colon targeted drug delivery systems.

  11. [Universal ethical principles and their application in clinical drug trials].

    Science.gov (United States)

    Gonorazky, Sergio Eduardo

    2015-03-01

    Since 1931, and especially since the Nuremberg Code of 1947, an increasing number of declarations, regulations, norms, guidelines, laws, resolutions, and rules intended to create conditions for better protection of subjects participating in research studies have been published, although some have meant setbacks in the human rights of vulnerable populations. As such, violations of the dignity of experimental subjects in clinical trials continue. What researchers investigate and how the research is done, the quality and transparency of the data, and the analysis and the publication of results (of both raw and processed data) respond to the financial interests of the pharmaceutical companies, coming into permanent tension with bioethical principles and the needs of society. The active participation of civil society is necessary to make it so that pharmaceutical research, results and applications subordinate economic benefits to the protection of human rights.

  12. Anaphylaxis following intravenous paracetamol: the problem is the solution.

    Science.gov (United States)

    Jain, S S; Green, S; Rose, M

    2015-11-01

    Paracetamol is a ubiquitous analgesic and antipyretic that is widely administered, including by anaesthetists. Immediate hypersensitivity reactions to intravenous paracetamol are particularly rare. We report two cases involving four separate episodes of anaphylaxis to intravenous paracetamol in different perioperative settings without a past history of intolerance to the oral form. The allergological investigations are described, during which it became evident that both patients were allergic to an excipient (mannitol) present in the formulation and that neither was allergic to the principal agent (paracetamol). The importance of referral and investigation of perioperative drug reactions is underscored by these two cases.

  13. Recurrence of Intravenous Talc Granulomatosis following Single Lung Transplantation

    Directory of Open Access Journals (Sweden)

    Richard C Cook

    1998-01-01

    Full Text Available Advanced pulmonary disease is an unusual consequence of the intravenous injection of oral medications, usually developing over a period of several years. A number of patients with this condition have undergone lung transplantation for respiratory failure. However, a history of drug abuse is often considered to be a contraindication to transplantation in the context of limited donor resources. A patient with pulmonary talc granulomatosis secondary to intravenous methylphenidate injection who underwent successful lung transplantation and subsequently presented with recurrence of the underlying disease in the transplanted lung 18 months after transplantation is reported.

  14. Seaweed Polysaccharide-Based Nanoparticles: Preparation and Applications for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Jayachandran Venkatesan

    2016-01-01

    Full Text Available In recent years, there have been major advances and increasing amounts of research on the utilization of natural polymeric materials as drug delivery vehicles due to their biocompatibility and biodegradability. Seaweed polysaccharides are abundant resources and have been extensively studied for several biological, biomedical, and functional food applications. The exploration of seaweed polysaccharides for drug delivery applications is still in its infancy. Alginate, carrageenan, fucoidan, ulvan, and laminarin are polysaccharides commonly isolated from seaweed. These natural polymers can be converted into nanoparticles (NPs by different types of methods, such as ionic gelation, emulsion, and polyelectrolyte complexing. Ionic gelation and polyelectrolyte complexing are commonly employed by adding cationic molecules to these anionic polymers to produce NPs of a desired shape, size, and charge. In the present review, we have discussed the preparation of seaweed polysaccharide-based NPs using different types of methods as well as their usage as carriers for the delivery of various therapeutic molecules (e.g., proteins, peptides, anti-cancer drugs, and antibiotics. Seaweed polysaccharide-based NPs exhibit suitable particle size, high drug encapsulation, and sustained drug release with high biocompatibility, thereby demonstrating their high potential for safe and efficient drug delivery.

  15. Recent Advances in the Application of Vitamin E TPGS for Drug Delivery

    Science.gov (United States)

    Yang, Conglian; Wu, Tingting; Qi, Yan; Zhang, Zhiping

    2018-01-01

    D-ɑ-tocopheryl polyethylene glycol succinate (Vitamin E TPGS or TPGS) has been approved by FDA as a safe adjuvant and widely used in drug delivery systems. The biological and physicochemical properties of TPGS provide multiple advantages for its applications in drug delivery like high biocompatibility, enhancement of drug solubility, improvement of drug permeation and selective antitumor activity. Notably, TPGS can inhibit the activity of ATP dependent P-glycoprotein and act as a potent excipient for overcoming multi-drug resistance (MDR) in tumor. In this review, we aim to discuss the recent advances of TPGS in drug delivery including TPGS based prodrugs, nitric oxide donor and polymers, and unmodified TPGS based formulations. These potential applications are focused on enhancing delivery efficiency as well as the therapeutic effect of agents, especially on overcoming MDR of tumors. It also demonstrates that the clinical translation of TPGS based nanomedicines is still faced with many challenges, which requires more detailed study on TPGS properties and based delivery system in the future. PMID:29290821

  16. Porous silicon-cyclodextrin based polymer composites for drug delivery applications.

    Science.gov (United States)

    Hernandez-Montelongo, J; Naveas, N; Degoutin, S; Tabary, N; Chai, F; Spampinato, V; Ceccone, G; Rossi, F; Torres-Costa, V; Manso-Silvan, M; Martel, B

    2014-09-22

    One of the main applications of porous silicon (PSi) in biomedicine is drug release, either as a single material or as a part of a composite. PSi composites are attractive candidates for drug delivery systems because they can display new chemical and physical characteristics, which are not exhibited by the individual constituents alone. Since cyclodextrin-based polymers have been proven efficient materials for drug delivery, in this work β-cyclodextrin-citric acid in-situ polymerization was used to functionalize two kinds of PSi (nanoporous and macroporous). The synthesized composites were characterized by microscopy techniques (SEM and AFM), physicochemical methods (ATR-FTIR, XPS, water contact angle, TGA and TBO titration) and a preliminary biological assay was performed. Both systems were tested as drug delivery platforms with two different model drugs, namely, ciprofloxacin (an antibiotic) and prednisolone (an anti-inflammatory), in two different media: pure water and PBS solution. Results show that both kinds of PSi/β-cyclodextrin-citric acid polymer composites, nano- and macro-, provide enhanced release control for drug delivery applications than non-functionalized PSi samples. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. The application of carbon nanotubes in target drug delivery systems for cancer therapies

    Science.gov (United States)

    Zhang, Wuxu; Zhang, Zhenzhong; Zhang, Yingge

    2011-10-01

    Among all cancer treatment options, chemotherapy continues to play a major role in killing free cancer cells and removing undetectable tumor micro-focuses. Although chemotherapies are successful in some cases, systemic toxicity may develop at the same time due to lack of selectivity of the drugs for cancer tissues and cells, which often leads to the failure of chemotherapies. Obviously, the therapeutic effects will be revolutionarily improved if human can deliver the anticancer drugs with high selectivity to cancer cells or cancer tissues. This selective delivery of the drugs has been called target treatment. To realize target treatment, the first step of the strategies is to build up effective target drug delivery systems. Generally speaking, such a system is often made up of the carriers and drugs, of which the carriers play the roles of target delivery. An ideal carrier for target drug delivery systems should have three pre-requisites for their functions: (1) they themselves have target effects; (2) they have sufficiently strong adsorptive effects for anticancer drugs to ensure they can transport the drugs to the effect-relevant sites; and (3) they can release the drugs from them in the effect-relevant sites, and only in this way can the treatment effects develop. The transporting capabilities of carbon nanotubes combined with appropriate surface modifications and their unique physicochemical properties show great promise to meet the three pre-requisites. Here, we review the progress in the study on the application of carbon nanotubes as target carriers in drug delivery systems for cancer therapies.

  18. Orthostatic stability with intravenous levodopa

    Directory of Open Access Journals (Sweden)

    Shan H. Siddiqi

    2015-08-01

    Full Text Available Intravenous levodopa has been used in a multitude of research studies due to its more predictable pharmacokinetics compared to the oral form, which is used frequently as a treatment for Parkinson’s disease (PD. Levodopa is the precursor for dopamine, and intravenous dopamine would strongly affect vascular tone, but peripheral decarboxylase inhibitors are intended to block such effects. Pulse and blood pressure, with orthostatic changes, were recorded before and after intravenous levodopa or placebo—after oral carbidopa—in 13 adults with a chronic tic disorder and 16 tic-free adult control subjects. Levodopa caused no statistically or clinically significant changes in blood pressure or pulse. These data add to previous data that support the safety of i.v. levodopa when given with adequate peripheral inhibition of DOPA decarboxylase.

  19. Drug Delivery and Cosmeceutical Applications of Poly- Lactic Acid Based Novel Constructs - A Review.

    Science.gov (United States)

    Ruiz-Ruiz, Federico; Mancera-Andrade, Elena Ivonne; Parra-Saldivar, Roberto; Keshavarz, Tajalli; Iqbal, Hafiz M N

    2017-01-01

    Poly (lactic acid) (PLA) based novel constructs have been engineered for targeted applications in various biomedical sectors of the modern world. In this context, a special focus has been given to pharmaceutical and cosmeceutical industries. In this review, we extensively reviewed, analyzed and compiled salient information from the authentic bibliographic sources including PubMed, Scopus, Elsevier, Springer, Bentham Science and other scientific databases. A focused review question and inclusion/exclusion criterion were adopted to appraise the quality of retrieved peer-reviewed research literature. Recently, bio-based constructs are being engineered for target applications in different bio- and non-bio sectors of the modern world to address the growing human health-related serious concerns. The utilization of properly designed and structured materials thus allows the creation of a well-defined environment that induces a series of directed measures, and so on. Over the last few years, PLA-based novel constructs have received exceptional attention as potential candidates for various biotechnological and biomedical applications at large and drug delivery in particular. Owing to their unique characteristics including biocompatibility, together with the adjustable thermomechanical and tunable control drug release, PLA has raised interesting applications in many sectors of the medical world. So far, many of such PLA-based bio-constructs have been exploited in drug delivery systems, cosmeceutical products, and therapeutic uses. In recent years, many new applications have been reported for PLA-based materials at the micro- and nano- level, resulting in novel requests for specific drug delivery and cosmeceutical sectors. In summary, this review summarizes recent research on different aspects of PLA and PLA-based novel constructs and their potential biomedical applications. Moreover, with the aid of nanotechnology, PLA has made a positive impact in emerging sectors such as

  20. Computational Fragment-Based Drug Design: Current Trends, Strategies, and Applications.

    Science.gov (United States)

    Bian, Yuemin; Xie, Xiang-Qun Sean

    2018-04-09

    Fragment-based drug design (FBDD) has become an effective methodology for drug development for decades. Successful applications of this strategy brought both opportunities and challenges to the field of Pharmaceutical Science. Recent progress in the computational fragment-based drug design provide an additional approach for future research in a time- and labor-efficient manner. Combining multiple in silico methodologies, computational FBDD possesses flexibilities on fragment library selection, protein model generation, and fragments/compounds docking mode prediction. These characteristics provide computational FBDD superiority in designing novel and potential compounds for a certain target. The purpose of this review is to discuss the latest advances, ranging from commonly used strategies to novel concepts and technologies in computational fragment-based drug design. Particularly, in this review, specifications and advantages are compared between experimental and computational FBDD, and additionally, limitations and future prospective are discussed and emphasized.

  1. Emerging technologies, recent developments, and novel applications for drug metabolite identification.

    Science.gov (United States)

    Lu, Wenjie; Xu, Youzhi; Zhao, Yinglan; Cen, Xiaobo

    2014-01-01

    Drug metabolite identification and metabolic characteristics analysis play a crucial role in new drug research and development, because they can lead to varied efficacy, severe adverse reactions, and even toxicity. Classical methodologies for metabolite identification have mainly been based on mass spectrometry (MS) coupled with gas chromatography (GC) or liquid chromatography (LC), and some other techniques are used as complementary approaches, such as nuclear magnetic resonance (NMR). Over the past decade, more and more newly emerging techniques or technologies have been applied to metabolite identification, and are making the procedure easier and more robust, such as LC-NMR-MS, ion mobility MS, ambient ionization techniques, and imaging MS. A novel application of drug metabolite identification based on "omics" known as pharmacometabonomics is discussed, which is an interdisciplinary field that combines pre-dose metabolite profiling and chemometrics methods for data analysis and modeling, aiming to predict the responses of individuals to drugs.

  2. Synthesis of an amphiphilic dendrimer-like block copolymer and its application on drug delivery

    KAUST Repository

    Wang, Shuaipeng

    2014-10-27

    Dendrimer-like amphiphilic copolymer is a kind of three-dimensional spherical structure polymer. An amphiphilic dendrimer-like diblock copolymer, PEEGE-G2-b-PEO(OH)12, constituted of a hydrophobic poly(ethoxyethyl glycidol ether) inner core and a hydrophilic poly(ethylene oxide) outer layer, has been successfully synthesized by the living anionic ring-opening polymerization method. The intermediates and targeted products were characterized with 1H NMR spectroscopy and gel permeation chromatography. The application on drug delivery of dendrimer-like diblock copolymer PEEGE-G2-b-PEO(OH)12 using DOX as a model drug was also studied. The drug loading content and encapsulation efficiency were found at 13.07% and 45.75%, respectively. In vitro release experiment results indicated that the drug-loaded micelles exhibited a sustained release behavior under acidic media.

  3. A review of integrating electroactive polymers as responsive systems for specialized drug delivery applications.

    Science.gov (United States)

    Pillay, Viness; Tsai, Tong-Sheng; Choonara, Yahya E; du Toit, Lisa C; Kumar, Pradeep; Modi, Girish; Naidoo, Dinesh; Tomar, Lomas K; Tyagi, Charu; Ndesendo, Valence M K

    2014-06-01

    Electroactive polymers (EAPs) are promising candidate materials for the design of drug delivery technologies, especially in conditions where an "on-off" drug release mechanism is required. To achieve this, EAPs such as polyaniline, polypyrrole, polythiophene, ethylene vinyl acetate, and polyethylene may be blended into responsive hydrogels in conjunction with the desired drug to obtain a patient-controlled drug release system. The "on-off" drug release mechanism can be achieved through the environmental-responsive nature of the interpenetrating hydrogel-EAP complex via (i) charged ions initiated diffusion of drug molecules; (ii) conformational changes that occur during redox switching of EAPs; or (iii) electroerosion. These release mechanisms are not exhaustive and new release mechanisms are still under investigation. Therefore, this review seeks to provide a concise incursion and critical overview of EAPs and responsive hydrogels as a strategy for advanced drug delivery, for example, controlled release of neurotransmitters, sulfosalicyclic acid from cross-linked hydrogel, and vaccine delivery. The review further discusses techniques such as linear sweep voltammetry, cyclic voltammetry, impedance spectroscopy, and chronoamperometry for the determination of the redox capability of EAPs. The future implications of the hydrogel-EAP composites include, but not limited to, application toward biosensors, DNA hybridizations, microsurgical tools, and miniature bioreactors and may be utilized to their full potential in the form of injectable devices as nanorobots or nanobiosensors. Copyright © 2013 Wiley Periodicals, Inc.

  4. Nanotechnology in Drug Delivery and Tissue Engineering: From Discovery to Applications

    OpenAIRE

    Shi, Jinjun; Votruba, Alexander R.; Farokhzad, Omid C.; Langer, Robert

    2010-01-01

    The application of nanotechnology in medicine, referred to as nanomedicine, is offering numerous exciting possibilities in healthcare. Herein, we discuss two important aspects of nanomedicine—drug delivery and tissue engineering—highlighting the advances we have recently experienced, the challenges we are currently facing, and what we are likely to witness in the near future.

  5. Nanotechnology in Drug Delivery and Tissue Engineering: From Discovery to Applications

    Science.gov (United States)

    Shi, Jinjun; Votruba, Alexander R.; Farokhzad, Omid C.; Langer, Robert

    2010-01-01

    The application of nanotechnology in medicine, referred to as nanomedicine, is offering numerous exciting possibilities in healthcare. Herein, we discuss two important aspects of nanomedicine—drug delivery and tissue engineering—highlighting the advances we have recently experienced, the challenges we are currently facing, and what we are likely to witness in the near future. PMID:20726522

  6. Nanotechnology in drug delivery and tissue engineering: from discovery to applications.

    Science.gov (United States)

    Shi, Jinjun; Votruba, Alexander R; Farokhzad, Omid C; Langer, Robert

    2010-09-08

    The application of nanotechnology in medicine, referred to as nanomedicine, is offering numerous exciting possibilities in healthcare. Herein, we discuss two important aspects of nanomedicine, drug delivery and tissue engineering, highlighting the advances we have recently experienced, the challenges we are currently facing, and what we are likely to witness in the near future.

  7. Medical applications of membranes: Drug delivery, artificial organs and tissue engineering

    NARCIS (Netherlands)

    Stamatialis, Dimitrios; Papenburg, B.J.; Girones nogue, Miriam; Saiful, S.; Bettahalli Narasimha, M.S.; Schmitmeier, Stephanie; Wessling, Matthias

    2008-01-01

    This paper covers the main medical applications of artificial membranes. Specific attention is given to drug delivery systems, artificial organs and tissue engineering which seem to dominate the interest of the membrane community this period. In all cases, the materials, methods and the current

  8. Prediction of Human Pharmacokinetic Profile After Transdermal Drug Application Using Excised Human Skin.

    Science.gov (United States)

    Yamamoto, Syunsuke; Karashima, Masatoshi; Arai, Yuta; Tohyama, Kimio; Amano, Nobuyuki

    2017-09-01

    Although several mathematical models have been reported for the estimation of human plasma concentration profiles of drug substances after dermal application, the successful cases that can predict human pharmacokinetic profiles are limited. Therefore, the aim of this study is to investigate the prediction of human plasma concentrations after dermal application using in vitro permeation parameters obtained from excised human skin. The in vitro skin permeability of 7 marketed drug products was evaluated. The plasma concentration-time profiles of the drug substances in humans after their dermal application were simulated using compartment models and the clinical pharmacokinetic parameters. The transdermal process was simulated using the in vitro skin permeation rate and lag time assuming a zero-order absorption. These simulated plasma concentration profiles were compared with the clinical data. The result revealed that the steady-state plasma concentration of diclofenac and the maximum concentrations of nicotine, bisoprolol, rivastigmine, and lidocaine after topical application were within 2-fold of the clinical data. Furthermore, the simulated concentration profiles of bisoprolol, nicotine, and rivastigmine reproduced the decrease in absorption due to drug depletion from the formulation. In conclusion, this simple compartment model using in vitro human skin permeation parameters as zero-order absorption predicted the human plasma concentrations accurately. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  9. Mass Spectrometry for Research and Application in Therapeutic Drug Monitoring or Clinical and Forensic Toxicology.

    Science.gov (United States)

    Maurer, Hans H

    2018-04-30

    This paper reviews current applications of various hyphenated low- and high-resolution mass spectrometry techniques in the field of therapeutic drug monitoring and clinical/forensic toxicology in both research and practice. They cover gas chromatography, liquid chromatography, matrix-assisted laser desorption ionization, or paper spray ionization coupled to quadrupole, ion trap, time-of-flight, or Orbitrap mass analyzers.

  10. 75 FR 80061 - Abbott Laboratories, Inc.; Withdrawal of Approval of a New Drug Application for MERIDIA

    Science.gov (United States)

    2010-12-21

    ... withdrawing approval of a new drug application (NDA) for MERIDIA (sibutramine hydrochloride (HCl)) oral... requested that Abbott voluntarily withdraw MERIDIA (sibutramine HCl) oral capsules from the market, based on FDA's recent analysis of clinical trial data from the Sibutramine Cardiovascular Outcomes Trial (SCOUT...

  11. Feature Issue Introduction: Bio-Optics in Clinical Applications, Nanotechnology, and Drug Discovery

    OpenAIRE

    Nordstrom, Robert J.; Almutairi, Adah; Hillman, Elizabeth M.C.

    2010-01-01

    The editors introduce the Biomedical Optics Express feature issue, “Bio-Optics in Clinical Applications, Nanotechnology, and Drug Discovery,” which combines three technical areas from the 2010 Optical Society of America (OSA), Biomedical Optics (BIOMED) Topical Meeting held on 11–14 April in Miami, FL and includes contributions from conference attendees.

  12. [Stabilizing the social and health status of drug dependent patients with methadone. Long-term maintainance therapy--Vienna results].

    Science.gov (United States)

    Loimer, N; Werner, E; Hollerer, E; Pfersmann, V; Schmid-Siegel, B; Presslich, O

    1991-01-01

    On September 25th, 1987 methadone was legalized in Austria for therapeutic use in drug addiction treatment in case of: 1. Long-term drug addiction with intravenous application of the drug, and several unsuccessful withdrawal therapies and/or 2. opiate addiction through intravenous application of the drug along with an existing HIV-1 infection. Since than, 291 patients were treated with methadone at the drug-dependency outpatient clinic of the Psychiatric Clinic of the University of Vienna. In 1990, 96 patients treated for more than one year were investigated using a standardized questionnaire. The image in which crime, prostitution, poverty, ill health all merge was broken by this decriminalization. Methadone treatment offers a first step toward social rehabilitation for drug addicts who have been living as criminals on the fringe of society.

  13. Application of electroretinography (ERG) in early drug development for assessing retinal toxicity in rats

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Wenhu, E-mail: wenhu.huang@pfizer.com; Collette, Walter; Twamley, Michelle; Aguirre, Shirley A.; Sacaan, Aida

    2015-12-15

    Retinal ocular toxicity is among the leading causes of drug development attrition in the pharmaceutical industry. Electroretinography (ERG) is a non-invasive functional assay used to assess neuro-retinal physiological integrity by measuring the electrical responses. To directly assess the utility of ERG, a series of studies was conducted following intravitreal and/or iv administration of pan-cyclin-dependent kinase inhibitors: AG-012,986 and AG-024,322 in rats. Both compounds have previously shown to induce retinal toxicity. Retinal injury was evaluated by ERG, histopathology and TUNEL staining. Intravitreal injection of AG-012,986 at ≥ 10 μg/eye resulted in decreases (60%) in ERG b-wave and microscopic changes of mild to moderate retinal degeneration, and at 30 μg/eye led to additional ophthalmic findings. Intravenous administration of AG-012,986 daily at ≥ 5 mg/kg resulted in dose-related decreases (25 to 40%) in b-wave and sporadic to intense positive TUNEL staining. Intravitreal injection of AG-024,322 at 30 μg/eye also resulted in decreases (50 to 60%) in b-wave, mild to marked retinal degeneration and mild vitreous debris. These experiments demonstrate that ERG can be used as a sensitive and reliable functional tool to evaluate retinal toxicity induced by test compounds in rats complementing other classical ocular safety measurements. - Highlights: • There were strong correlations of ERG readouts to in vivo ophthalmic exams, TUNEL assay, and histopathology. • ERG appears to be more sensitive and can detect retinal functional changes at a very early stage of pathogenesis. • ERG can be incorporated into routine exploratory toxicity study to identify compound ocular safety issues. • In drug discovery, ERG is a quick, non-invasive, sensitive and reliable tool in retinal toxicity de-risking.

  14. Application of electroretinography (ERG) in early drug development for assessing retinal toxicity in rats

    International Nuclear Information System (INIS)

    Huang, Wenhu; Collette, Walter; Twamley, Michelle; Aguirre, Shirley A.; Sacaan, Aida

    2015-01-01

    Retinal ocular toxicity is among the leading causes of drug development attrition in the pharmaceutical industry. Electroretinography (ERG) is a non-invasive functional assay used to assess neuro-retinal physiological integrity by measuring the electrical responses. To directly assess the utility of ERG, a series of studies was conducted following intravitreal and/or iv administration of pan-cyclin-dependent kinase inhibitors: AG-012,986 and AG-024,322 in rats. Both compounds have previously shown to induce retinal toxicity. Retinal injury was evaluated by ERG, histopathology and TUNEL staining. Intravitreal injection of AG-012,986 at ≥ 10 μg/eye resulted in decreases (60%) in ERG b-wave and microscopic changes of mild to moderate retinal degeneration, and at 30 μg/eye led to additional ophthalmic findings. Intravenous administration of AG-012,986 daily at ≥ 5 mg/kg resulted in dose-related decreases (25 to 40%) in b-wave and sporadic to intense positive TUNEL staining. Intravitreal injection of AG-024,322 at 30 μg/eye also resulted in decreases (50 to 60%) in b-wave, mild to marked retinal degeneration and mild vitreous debris. These experiments demonstrate that ERG can be used as a sensitive and reliable functional tool to evaluate retinal toxicity induced by test compounds in rats complementing other classical ocular safety measurements. - Highlights: • There were strong correlations of ERG readouts to in vivo ophthalmic exams, TUNEL assay, and histopathology. • ERG appears to be more sensitive and can detect retinal functional changes at a very early stage of pathogenesis. • ERG can be incorporated into routine exploratory toxicity study to identify compound ocular safety issues. • In drug discovery, ERG is a quick, non-invasive, sensitive and reliable tool in retinal toxicity de-risking.

  15. Panlobular emphysema in young intravenous Ritalin abusers

    International Nuclear Information System (INIS)

    Schmidt, R.A.; Glenny, R.W.; Godwin, J.D.; Hampson, N.B.; Cantino, M.E.; Reichenbach, D.D.

    1991-01-01

    We studied a distinctive group of young intravenous Ritalin abusers with profound obstructive lung disease. Clinically, they seemed to have severe emphysema, but the pathologic basis of their symptoms had not been investigated previously. Seven patients have died and been autopsied: in four, the lungs were fixed, inflated, dried, and examined in detail radiologically, grossly, microscopically, and by electron probe X-ray microanalysis. All seven patients had severe panlobular (panacinar) emphysema that tended to be more severe in the lower lung zones and that was associated with microscopic talc granulomas. Vascular involvement by talc granulomas was variable, but significant interstitial fibrosis was not present. Five patients were tested for alpha-1-antitrypsin deficiency and found to be normal, as were six similar living patients. These findings indicate that some intravenous drug abusers develop emphysema that clinically, radiologically, and pathologically resembles that caused by alpha-1-antitrypsin deficiency but which must have a different pathogenesis. Talc from the Ritalin tablets may be important, but the mechanism remains to be elucidated

  16. Intravenous ferric carboxymaltose for anaemia in pregnancy.

    Science.gov (United States)

    Froessler, Bernd; Collingwood, Joshua; Hodyl, Nicolette A; Dekker, Gustaaf

    2014-03-25

    Iron deficiency is a common nutritional deficiency amongst women of childbearing age. Peri-partum iron deficiency anaemia (IDA) is associated with significant maternal, fetal and infant morbidity. Current options for treatment are limited: these include oral iron supplementation, which can be ineffective and poorly tolerated, and red blood cell transfusions, which carry an inherent risk and should be avoided. Ferric carboxymaltose is a new treatment option that may be better tolerated.The study was designed to assess the safety and efficacy of iron deficiency anaemia (IDA) correction with intravenous ferric carboxymaltose in pregnant women with mild, moderate and severe anaemia in the second and third trimester. Prospective observational study; 65 anaemic pregnant women received ferric carboxymaltose up to 15 mg/kg between 24 and 40 weeks of pregnancy (median 35 weeks gestational age, SD 3.6). Treatment effectiveness was assessed by repeat haemoglobin (Hb) measurements and patient report of well-being in the postpartum period. Safety was assessed by analysis of adverse drug reactions and fetal heart rate monitoring during the infusion. Intravenous ferric carboxymaltose infusion significantly increased Hb values (p anaemia in pregnancy.

  17. 78 FR 48177 - Purdue Pharma L.P.; Withdrawal of Approval of a New Drug Application for Oxycontin

    Science.gov (United States)

    2013-08-07

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0883] Purdue Pharma L.P.; Withdrawal of Approval of a New Drug Application for Oxycontin AGENCY: Food and Drug... Purdue Pharma L.P. (Purdue), One Stamford Forum, Stamford, CT 06901-3431. Purdue has voluntarily...

  18. Bioaccumulation and Toxicity of Carbon Nanoparticles Suspension Injection in Intravenously Exposed Mice

    Directory of Open Access Journals (Sweden)

    Ping Xie

    2017-11-01

    Full Text Available Carbon nanoparticles suspension injection (CNSI has been widely used in tumor drainage lymph node mapping, and its new applications in drug delivery, photothermal therapy, and so on have been extensively investigated. To develop new clinical applications, the toxicity of CNSI after intravenous exposure should be thoroughly investigated to ensure its safe use. Herein, we studied the bioaccumulation of CNSI in reticuloendothelial system (RES organs and the corresponding toxicity to mice. After the intravenous injection of CNSI, no abnormal behavior of mice was observed during the 28-day observation period. The body weight increases were similar among the exposed groups and the control group. The parameters of hematology and serum biochemistry remained nearly unchanged, with very few of them showing significant changes. The low toxicity of CNSI was also reflected by the unchanged histopathological characteristics of these organs. The injection of CNSI did not induce higher apoptosis levels either. The slight oxidative stress was observed in RES organs at high dosages at day 7 post-exposure. The implication to the clinical applications and toxicological evaluations of carbon nanomaterials is discussed.

  19. intravenous infusion of chlorimipramine (anafranil)

    African Journals Online (AJOL)

    the already extensive outpatient facilities at Johannesburg. Hospital as well as the Tara Neuro-Psychiatric Hospital for long-term therapy. Technique of Chlorimipramine Infusion. Initially 1 ampoule of chlorimipramine 25 mg in 250 mg of 5°~ dextrose saline was administered intravenously at the rate of 60 drops per minute.

  20. Nanodiamonds as novel nanomaterials for biomedical applications: drug delivery and imaging systems

    Directory of Open Access Journals (Sweden)

    Kaur R

    2013-01-01

    Full Text Available Randeep Kaur, Ildiko BadeaDrug Design and Discovery Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, CanadaAbstract: Detonation nanodiamonds (NDs are emerging as delivery vehicles for small chemical drugs and macromolecular biotechnology products due to their primary particle size of 4 to 5 nm, stable inert core, reactive surface, and ability to form hydrogels. Nanoprobe technology capitalizes on the intrinsic fluorescence, high refractive index, and unique Raman signal of the NDs, rendering them attractive for in vitro and in vivo imaging applications. This review provides a brief introduction of the various types of NDs and describes the development of procedures that have led to stable single-digit-sized ND dispersions, a crucial feature for drug delivery systems and nanoprobes. Various approaches used for functionalizing the surface of NDs are highlighted, along with a discussion of their biocompatibility status. The utilization of NDs to provide sustained release and improve the dispersion of hydrophobic molecules, of which chemotherapeutic drugs are the most investigated, is described. The prospects of improving the intracellular delivery of nucleic acids by using NDs as a platform are exemplified. The photoluminescent and optical scattering properties of NDs, together with their applications in cellular labeling, are also reviewed. Considering the progress that has been made in understanding the properties of NDs, they can be envisioned as highly efficient drug delivery and imaging biomaterials for use in animals and humans.Keywords: dispersion, surface functionalization, toxicity, carriers, fluorescence, light scattering

  1. Stimulus-responsive liposomes as smart nanoplatforms for drug delivery applications.

    Science.gov (United States)

    Zangabad, Parham Sahandi; Mirkiani, Soroush; Shahsavari, Shayan; Masoudi, Behrad; Masroor, Maryam; Hamed, Hamid; Jafari, Zahra; Taghipour, Yasamin Davatgaran; Hashemi, Hura; Karimi, Mahdi; Hamblin, Michael R

    2018-02-01

    Liposomes are known to be promising nanoparticles (NPs) for drug delivery applications. Among different types of self-assembled NPs, liposomes stand out for their non-toxic nature, and their possession of dual hydrophilic-hydrophobic domains. Advantages of liposomes include the ability to solubilize hydrophobic drugs, the ability to incorporate different hydrophilic and lipophilic drugs at the same time, lessening the exposure of host organs to potentially toxic drugs and allowing modification of the surface by a variety of different chemical groups. This modification of the surface, or of the individual constituents, may be used to achieve two important goals. Firstly, ligands for active targeting can be attached that are recognized by cognate receptors over-expressed on the target cells of tissues. Secondly, modification can be used to impart a stimulus-responsive or "smart" character to the liposomes, whereby the cargo is released on demand only when certain internal stimuli (pH, reducing agents, specific enzymes) or external stimuli (light, magnetic field or ultrasound) are present. Here, we review the field of smart liposomes for drug delivery applications.

  2. Enhanced performance of magnesium alloy for drug-eluting vascular scaffold application

    Science.gov (United States)

    Dong, Hongzhou; Li, Daikun; Mao, Daoyong; Bai, Ningning; Chen, Yashi; Li, Qing

    2018-03-01

    Bio-absorbable magnesium alloys drug-eluting vascular scaffold was developed to resolve the defect of permanent metal and drug-eluting stents, most notably a chronic vessel wall inflammation and the risk of stent thrombosis. Nevertheless, violent chemical reaction and rapid degradation under physiological conditions limits their application. Furthermore, multifunctional drug-eluting stents which could reduce the formation of thrombus and repair the damaged vessels need more attention to fundamentally cure the coronary artery disease. Herein, a drug delivery system (Mg/MgO/PLA-FA) which can realize sustainable release of ferulaic acid was designed via anodic oxidation process and dip coating process. Electrochemical tests and immersion experiments showed that the superior anticorrosion behavior, it is due to the dense MgO-PLA composite layer. The released ferulaic acid can effectively decrease platelets adhesion and aggregation during the early stage of implantation. Besides, hemolysis tests showed that the composite coatings endowed the Mg alloy with a low hemolysis ratio. The Mg/MgO/PLA-FA composite materials may be appropriate for applications on biodegradable Mg alloys drug-eluting stents.

  3. Live Cell in Vitro and in Vivo Imaging Applications: Accelerating Drug Discovery

    Directory of Open Access Journals (Sweden)

    Neil O Carragher

    2011-04-01

    Full Text Available Dynamic regulation of specific molecular processes and cellular phenotypes in live cell systems reveal unique insights into cell fate and drug pharmacology that are not gained from traditional fixed endpoint assays. Recent advances in microscopic imaging platform technology combined with the development of novel optical biosensors and sophisticated image analysis solutions have increased the scope of live cell imaging applications in drug discovery. We highlight recent literature examples where live cell imaging has uncovered novel insight into biological mechanism or drug mode-of-action. We survey distinct types of optical biosensors and associated analytical methods for monitoring molecular dynamics, in vitro and in vivo. We describe the recent expansion of live cell imaging into automated target validation and drug screening activities through the development of dedicated brightfield and fluorescence kinetic imaging platforms. We provide specific examples of how temporal profiling of phenotypic response signatures using such kinetic imaging platforms can increase the value of in vitro high-content screening. Finally, we offer a prospective view of how further application and development of live cell imaging technology and reagents can accelerate preclinical lead optimization cycles and enhance the in vitro to in vivo translation of drug candidates.

  4. Mass Spectrometry in Clinical Laboratory: Applications in Therapeutic Drug Monitoring and Toxicology.

    Science.gov (United States)

    Garg, Uttam; Zhang, Yan Victoria

    2016-01-01

    Mass spectrometry (MS) has been used in research and specialized clinical laboratories for decades as a very powerful technology to identify and quantify compounds. In recent years, application of MS in routine clinical laboratories has increased significantly. This is mainly due to the ability of MS to provide very specific identification, high sensitivity, and simultaneous analysis of multiple analytes (>100). The coupling of tandem mass spectrometry with gas chromatography (GC) or liquid chromatography (LC) has enabled the rapid expansion of this technology. While applications of MS are used in many clinical areas, therapeutic drug monitoring, drugs of abuse, and clinical toxicology are still the primary focuses of the field. It is not uncommon to see mass spectrometry being used in routine clinical practices for those applications.

  5. Nanotechnology-based polymeric bio(muco)adhesive platforms for controlling drug delivery - properties, methodologies and applications

    International Nuclear Information System (INIS)

    Carvalho, Flavia Chiva; Chorilli, Marlus; Gremiao, Maria Palmira Daflon

    2014-01-01

    Studies using bio(muco)adhesive drug delivery systems have recently gained great interest, which can promote drug targeting and more specific contact of the drug delivery system with the various absorptive membranes of the body. This technological platform associated with nanotechnology offers potential for controlling drug delivery; therefore, they are excellent strategies to increase the bioavailability of drugs. The objective of this work was to study nanotechnology-based polymeric bio(muco)adhesive platforms for controlling drug delivery, highlighting their properties, how the bio(muco)adhesion can be measured and their potential applications for different routes of administration. (author)

  6. Anaphylaxis after intravenous infusion of dexketoprofen trometamol

    Directory of Open Access Journals (Sweden)

    Sertac Guler

    2016-09-01

    Full Text Available Dexketoprofen trometamol (DT, a nonsteroidal anti-inflammatory drug, is a highly water-soluble salt and active enantiomer of rac-ketoprofen. Its parenteral form is commonly used for acute pain management in emergency departments of our country. Side effects such as diarrhea, indigestion, nausea, stomach pain, and vomiting may be seen after the use of DT. Anaphylactic shock (AS secondary to infusion of DT is very rare and, to our knowledge, it is the first case report describing this side effect. This case report was presented to emphasize that AS may be seen after the use of DT. Keywords: Anaphylactic shock, Dexketoprofen trometamol, Intravenous infusion (MeSH database

  7. Switching between intravenous and subcutaneous trastuzumab

    DEFF Research Database (Denmark)

    Gligorov, Joseph; Curigliano, Giuseppe; Müller, Volkmar

    2017-01-01

    AIM: To assess the safety and tolerability of switching between subcutaneous (SC) and intravenous (IV) trastuzumab in the PrefHer study (NCT01401166). PATIENTS AND METHODS: Patients with HER2-positive early breast cancer completed (neo)adjuvant chemotherapy and were randomised to receive four...... cycles of SC trastuzumab, via single-use injection device (SID; Cohort 1) or hand-held syringe (Cohort 2), followed by four cycles of IV, or vice versa (the crossover period presented here) as part of their 18 standard cycles of adjuvant trastuzumab treatment. Adverse events (AEs) were reported using....... Rates of clinically important events, including grade ≥3 AEs, serious AEs, AEs leading to study drug discontinuation and cardiac AEs, were low and similar between treatment arms (trastuzumab were observed. CONCLUSIONS: PrefHer revealed...

  8. Application of PBPK modelling in drug discovery and development at Pfizer.

    Science.gov (United States)

    Jones, Hannah M; Dickins, Maurice; Youdim, Kuresh; Gosset, James R; Attkins, Neil J; Hay, Tanya L; Gurrell, Ian K; Logan, Y Raj; Bungay, Peter J; Jones, Barry C; Gardner, Iain B

    2012-01-01

    Early prediction of human pharmacokinetics (PK) and drug-drug interactions (DDI) in drug discovery and development allows for more informed decision making. Physiologically based pharmacokinetic (PBPK) modelling can be used to answer a number of questions throughout the process of drug discovery and development and is thus becoming a very popular tool. PBPK models provide the opportunity to integrate key input parameters from different sources to not only estimate PK parameters and plasma concentration-time profiles, but also to gain mechanistic insight into compound properties. Using examples from the literature and our own company, we have shown how PBPK techniques can be utilized through the stages of drug discovery and development to increase efficiency, reduce the need for animal studies, replace clinical trials and to increase PK understanding. Given the mechanistic nature of these models, the future use of PBPK modelling in drug discovery and development is promising, however, some limitations need to be addressed to realize its application and utility more broadly.

  9. [Application of ultrasound-enhanced gene and drug delivery to the ocular tissue].

    Science.gov (United States)

    Sonoda, Shozo; Yamashita, Toshifumi; Suzuki, Ryo; Maruyama, Kazuo; Sakamoto, Taiji

    2013-01-01

    Visual images provide an immensely rich source of information about the external world. Eye has characteristic structure sensory cells are arranged along the eye wall, and is filled inside with vitreous body. In recent years, intravitreal injection of anti-vascular endothelial growth factor (VEGF) agent had widely spread, and numerous number of patients who suffered ocular angiogenic disease such as diabetic retinopathy, age-related macular degeneration and retinal vascular occlusion for the disease, were treated and spared the blindness. Vitreous cavity was regarded as reservoir of drug, intravitreal injection is thought a sort of drug delivery. However, with regard to the administration of a selective drug deliver, it has not yet been solved. Our aim is to establish a new method of gene transfer, drug delivery using low-energy ultrasound to the eye, to date, we confirmed drug and gene deliver to the ocular tissue such as cornea, conjunctiva and retina with high efficiency. In addition, tissue damage was minimal. We have also shown that ultrasound irradiation with combination of a microbubbles or bubble liposome could be introduced drug and gene more effectively. Based on these knowledge, we will focus on development of a new device for intraocular ultrasound exposure and potential for therapeutic application of ultrasound to humans retinal disease such as retinal artery obstruction.

  10. Sonochemically synthesized biocompatible zirconium phosphate nanoparticles for pH sensitive drug delivery application

    Energy Technology Data Exchange (ETDEWEB)

    Kalita, Himani, E-mail: hkalita74@gmail.com [Department of Chemistry, Indian Institute of Technology Kharagpur, West Bengal 721302 (India); Prashanth Kumar, B.N., E-mail: prasanthkumar999@gmail.com [School of Medical Science and Technology, Indian Institute of Technology Kharagpur, West Bengal 721302 (India); Konar, Suraj, E-mail: suraj.konar@gmail.com [Department of Chemistry, Indian Institute of Technology Kharagpur, West Bengal 721302 (India); Tantubay, Sangeeta, E-mail: sang.chem2@gmail.com [Department of Chemistry, Indian Institute of Technology Kharagpur, West Bengal 721302 (India); Mahto, Madhusudan Kr., E-mail: mahtomk0@gmail.com [Department of Chemistry, Indian Institute of Technology Kharagpur, West Bengal 721302 (India); Mandal, Mahitosh, E-mail: mahitosh@smst.iitkgp.ernet.in [School of Medical Science and Technology, Indian Institute of Technology Kharagpur, West Bengal 721302 (India); Pathak, Amita, E-mail: ami@chem.iitkgp.ernet.in [Department of Chemistry, Indian Institute of Technology Kharagpur, West Bengal 721302 (India)

    2016-03-01

    The present work reports the synthesis of biocompatible zirconium phosphate (ZP) nanoparticles as nanocarrier for drug delivery application. The ZP nanoparticles were synthesized via a simple sonochemical method in the presence of cetyltrimethylammonium bromide and their efficacy for the delivery of drugs has been tested through various in-vitro experiments. The particle size and BET surface area of the nanoparticles were found to be ~ 48 nm and 206.51 m{sup 2}/g respectively. The conventional MTT assay and cellular localization studies of the particles, performed on MDA-MB-231 cell lines, demonstrate their excellent biocompatibility and cellular internalization behavior. The loading of curcumin, an antitumor drug, onto the ZP nanoparticles shows the rapid drug uptake ability of the particles, while the drug release study, performed at two different pH values (at 7.4 and 5) depicts pH sensitive release-profile. The MTT assay and cellular localization studies revealed higher cellular inhibition and better bioavailability of the nanoformulated curcumin compared to free curcumin. - Highlights: • Biocompatible zirconium phosphate nanoparticles were synthesized by a simple sonochemical approach. • Curcumin was rapidly loaded onto the particles by the aid by hydrogen bond formation. • The curcumin loaded zirconium phosphate nanoparticles depict pH triggered drug release phenomenon. • The nanoformulated curcumin showed enhanced anti-tumor activity as compared to the native curcumin.

  11. Sonochemically synthesized biocompatible zirconium phosphate nanoparticles for pH sensitive drug delivery application

    International Nuclear Information System (INIS)

    Kalita, Himani; Prashanth Kumar, B.N.; Konar, Suraj; Tantubay, Sangeeta; Mahto, Madhusudan Kr.; Mandal, Mahitosh; Pathak, Amita

    2016-01-01

    The present work reports the synthesis of biocompatible zirconium phosphate (ZP) nanoparticles as nanocarrier for drug delivery application. The ZP nanoparticles were synthesized via a simple sonochemical method in the presence of cetyltrimethylammonium bromide and their efficacy for the delivery of drugs has been tested through various in-vitro experiments. The particle size and BET surface area of the nanoparticles were found to be ~ 48 nm and 206.51 m"2/g respectively. The conventional MTT assay and cellular localization studies of the particles, performed on MDA-MB-231 cell lines, demonstrate their excellent biocompatibility and cellular internalization behavior. The loading of curcumin, an antitumor drug, onto the ZP nanoparticles shows the rapid drug uptake ability of the particles, while the drug release study, performed at two different pH values (at 7.4 and 5) depicts pH sensitive release-profile. The MTT assay and cellular localization studies revealed higher cellular inhibition and better bioavailability of the nanoformulated curcumin compared to free curcumin. - Highlights: • Biocompatible zirconium phosphate nanoparticles were synthesized by a simple sonochemical approach. • Curcumin was rapidly loaded onto the particles by the aid by hydrogen bond formation. • The curcumin loaded zirconium phosphate nanoparticles depict pH triggered drug release phenomenon. • The nanoformulated curcumin showed enhanced anti-tumor activity as compared to the native curcumin.

  12. Biocompatible fluorescent zein nanoparticles for simultaneous bioimaging and drug delivery application

    International Nuclear Information System (INIS)

    Girija Aswathy, Ravindran; Sivakumar, Balasubramanian; Brahatheeswaran, Dhandayudhapani; Fukuda, Takahiro; Yoshida, Yasuhiko; Maekawa, Toru; Sakthi Kumar, D

    2012-01-01

    We report the synthesis of 5-fluorouracil (5-FU) loaded biocompatible fluorescent zein nanoparticles. Zein is the storage protein in corn kernels that has a variety of unique characteristics and functionalities that makes zein valuable in various commercial applications. It is classified as generally recognized as safe (GRAS) by the Food and Drug Administration (FDA). We synthesized zein nanoparticles of around 800 nm in size and conjugated with quantum dot ZnS:Mn. The nanoparticle was in turn encapsulated with the drug 5-FU. The luminescent properties of these nanoparticles were studied by using fluorescence microscopy. The nanoparticles were characterized and the drug release profile was studied. The biocompatibility of zein nanoparticle and the cytotoxicity with drug-loaded nanoparticle was studied in L929 and MCF-7 cell lines. The nanoparticles were successfully employed for cellular imaging. In vitro drug release studies were also performed. The biocompatibility of the nanoparticle showed that nanoparticles at higher concentrations are compatible for cells and are expected to be promising agents for the targeted delivery of drugs in the near future

  13. Common characteristics of open source software development and applicability for drug discovery: a systematic review.

    Science.gov (United States)

    Ardal, Christine; Alstadsæter, Annette; Røttingen, John-Arne

    2011-09-28

    Innovation through an open source model has proven to be successful for software development. This success has led many to speculate if open source can be applied to other industries with similar success. We attempt to provide an understanding of open source software development characteristics for researchers, business leaders and government officials who may be interested in utilizing open source innovation in other contexts and with an emphasis on drug discovery. A systematic review was performed by searching relevant, multidisciplinary databases to extract empirical research regarding the common characteristics and barriers of initiating and maintaining an open source software development project. Common characteristics to open source software development pertinent to open source drug discovery were extracted. The characteristics were then grouped into the areas of participant attraction, management of volunteers, control mechanisms, legal framework and physical constraints. Lastly, their applicability to drug discovery was examined. We believe that the open source model is viable for drug discovery, although it is unlikely that it will exactly follow the form used in software development. Hybrids will likely develop that suit the unique characteristics of drug discovery. We suggest potential motivations for organizations to join an open source drug discovery project. We also examine specific differences between software and medicines, specifically how the need for laboratories and physical goods will impact the model as well as the effect of patents.

  14. [Efficacy of intravenous phenobarbital treatment for status epilepticus].

    Science.gov (United States)

    Muramoto, Emiko; Mizobuchi, Masahiro; Sumi, Yoshihiro; Sako, Kazuya; Nihira, Atsuko; Takeuchi, Akiko; Nakamura, Hirohiko

    2013-08-01

    Intravenous phenobarbital (IV-PB) therapy was launched in Japan in October 2008. We retrospectively investigated its efficacy and tolerability in patients with status epilepticus. Forty-three consecutive patients received IV-PB for status epilepticus between June 2009 and April 2011. Among them, 39 patients had underlying diseases, which included acute diseases in 19 patients and chronic conditions in 20 patients. Although 18 patients had been taking antiepileptic drugs (AEDs) before the occurrence of status epilepticus, the blood AED concentrations in 8 patients was below the therapeutic levels. Before the administration of IV-PB, 39 patients were treated with intravenous benzodiazepine, 17 patients were treated with intravenous phenytoin, and 15 patients with intravenous infusion of lidocaine. The initial doses of IV-PB ranged from 125 to 1,250 mg (1.9-20.0 mg/kg). Additional doses of IV-PB were required in 12 patients. Seizures were controlled in 35 patients (81%) after IV-PB administration. Cessation of status epilepticus was attained in 24 patients after the initial dose and in 11 patients after additional doses. There were no serious adverse effects, although respiratory suppression was observed in 3 patients and drug eruption was observed in 1 patient. IV-PB is relatively safe and effective for controlling status epilepticus. If the first dose is not effective, additional doses are required up to the recommended maximum dose.

  15. Magnetite Nanoparticles Coated with Rifampicin and Chlortetracycline for Drug Delivery Applications

    International Nuclear Information System (INIS)

    Nadejde, Claudia; Ciurlica, Ecaterina Foca-nici; Creanga, Dorina; Carlescu, Aurelian; Badescu, Vasile

    2010-01-01

    Four types of biocompatible magnetic fluids based on superparamagnetic nanoparticles with Fe 3 O 4 cores were functionalized with antibiotics (rifampicin or chlortetracycline) as potential candidates for in vivo biomedical applications, such as magnetically controlled drug delivery. The synthesis consisted in coprecipitation of iron oxide in basic, as well as in acid medium, followed by the dispersion of the resulted magnetite nanoparticles in aqueous solution containing the antibiotic. The chosen method to prepare the magnetite-core/drug-shell systems avoided intermediate organic coating of the magnetic nanoparticles. Comparative analysis of the rheological features of the aqueous magnetic fluid samples was performed. The structural features of the coated magnetic particles were investigated by X-Ray Diffraction (XRD), Transmission Electron Microscopy (TEM) and Vibrating Sample Magnetometry (VSM). Good crystallinity and adequate stability in time were evidenced. Drug delivery curves were spectrophotometrically provided.

  16. An albumin-oligonucleotide assembly for potential combinatorial drug delivery and half-life extension applications

    DEFF Research Database (Denmark)

    Kuhlmann, Matthias; Hamming, Jonas Bohn Refslund; Voldum, Anders

    2017-01-01

    The long blood circulatory property of human serum albumin, due to engagement with the cellular recycling neonatal Fc receptor (FcRn), is an attractive drug half-life extension enabling technology. This work describes a novel site-specific albumin double-stranded (ds) DNA assembly approach, in wh...... technology platform that offers potential combinatorial drug delivery and half-life extension applications.......The long blood circulatory property of human serum albumin, due to engagement with the cellular recycling neonatal Fc receptor (FcRn), is an attractive drug half-life extension enabling technology. This work describes a novel site-specific albumin double-stranded (ds) DNA assembly approach......, in which the 3' or 5' end maleimide-derivatized oligodeoxynucleotides are conjugated to albumin cysteine at position 34 (cys34) and annealed with complementary strands to allow single site-specific protein modification with functionalized ds oligodeoxynucleotides. Electrophoretic gel shift assays...

  17. Machine Learning-based Virtual Screening and Its Applications to Alzheimer's Drug Discovery: A Review.

    Science.gov (United States)

    Carpenter, Kristy A; Huang, Xudong

    2018-06-07

    Virtual Screening (VS) has emerged as an important tool in the drug development process, as it conducts efficient in silico searches over millions of compounds, ultimately increasing yields of potential drug leads. As a subset of Artificial Intelligence (AI), Machine Learning (ML) is a powerful way of conducting VS for drug leads. ML for VS generally involves assembling a filtered training set of compounds, comprised of known actives and inactives. After training the model, it is validated and, if sufficiently accurate, used on previously unseen databases to screen for novel compounds with desired drug target binding activity. The study aims to review ML-based methods used for VS and applications to Alzheimer's disease (AD) drug discovery. To update the current knowledge on ML for VS, we review thorough backgrounds, explanations, and VS applications of the following ML techniques: Naïve Bayes (NB), k-Nearest Neighbors (kNN), Support Vector Machines (SVM), Random Forests (RF), and Artificial Neural Networks (ANN). All techniques have found success in VS, but the future of VS is likely to lean more heavily toward the use of neural networks - and more specifically, Convolutional Neural Networks (CNN), which are a subset of ANN that utilize convolution. We additionally conceptualize a work flow for conducting ML-based VS for potential therapeutics of for AD, a complex neurodegenerative disease with no known cure and prevention. This both serves as an example of how to apply the concepts introduced earlier in the review and as a potential workflow for future implementation. Different ML techniques are powerful tools for VS, and they have advantages and disadvantages albeit. ML-based VS can be applied to AD drug development. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Theory and Applications of Covalent Docking in Drug Discovery: Merits and Pitfalls

    Directory of Open Access Journals (Sweden)

    Hezekiel Mathambo Kumalo

    2015-01-01

    Full Text Available he present art of drug discovery and design of new drugs is based on suicidal irreversible inhibitors. Covalent inhibition is the strategy that is used to achieve irreversible inhibition. Irreversible inhibitors interact with their targets in a time-dependent fashion, and the reaction proceeds to completion rather than to equilibrium. Covalent inhibitors possessed some significant advantages over non-covalent inhibitors such as covalent warheads can target rare, non-conserved residue of a particular target protein and thus led to development of highly selective inhibitors, covalent inhibitors can be effective in targeting proteins with shallow binding cleavage which will led to development of novel inhibitors with increased potency than non-covalent inhibitors. Several computational approaches have been developed to simulate covalent interactions; however, this is still a challenging area to explore. Covalent molecular docking has been recently implemented in the computer-aided drug design workflows to describe covalent interactions between inhibitors and biological targets. In this review we highlight: (i covalent interactions in biomolecular systems; (ii the mathematical framework of covalent molecular docking; (iii implementation of covalent docking protocol in drug design workflows; (iv applications covalent docking: case studies and (v shortcomings and future perspectives of covalent docking. To the best of our knowledge; this review is the first account that highlights different aspects of covalent docking with its merits and pitfalls. We believe that the method and applications highlighted in this study will help future efforts towards the design of irreversible inhibitors.

  19. Applications and limitations of lipid nanoparticles in dermal and transdermal drug delivery via the follicular route.

    Science.gov (United States)

    Lauterbach, Andreas; Müller-Goymann, Christel C

    2015-11-01

    Lipid nanoparticles (LN) such as solid lipid nanoparticles (SLN) and nanolipid carriers (NLC) feature several claimed benefits for topical drug therapy including biocompatible ingredients, drug release modification, adhesion to the skin, and film formation with subsequent hydration of the superficial skin layers. However, penetration and permeation into and across deeper skin layers are restricted due to the barrier function of the stratum corneum (SC). As different kinds of nanoparticles provide the potential for penetration into hair follicles (HF) LN are applicable drug delivery systems (DDS) for this route in order to enhance the dermal and transdermal bioavailability of active pharmaceutical ingredients (API). Therefore, this review addresses the HF as application site, published formulations of LN which showed follicular penetration (FP), and characterization methods in order to identify and quantify the accumulation of API delivered by the LN in the HF. Since LN are based on lipids that appear in human sebum which is the predominant medium in HF an increased localization of the colloidal carriers as well as a promoted drug release may be assumed. Therefore, sebum-like lipid material and a size of less or equal 640 nm are appropriate specifications for FP of particulate formulations. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Nanodiamonds as novel nanomaterials for biomedical applications: drug delivery and imaging systems.

    Science.gov (United States)

    Kaur, Randeep; Badea, Ildiko

    2013-01-01

    Detonation nanodiamonds (NDs) are emerging as delivery vehicles for small chemical drugs and macromolecular biotechnology products due to their primary particle size of 4 to 5 nm, stable inert core, reactive surface, and ability to form hydrogels. Nanoprobe technology capitalizes on the intrinsic fluorescence, high refractive index, and unique Raman signal of the NDs, rendering them attractive for in vitro and in vivo imaging applications. This review provides a brief introduction of the various types of NDs and describes the development of procedures that have led to stable single-digit-sized ND dispersions, a crucial feature for drug delivery systems and nanoprobes. Various approaches used for functionalizing the surface of NDs are highlighted, along with a discussion of their biocompatibility status. The utilization of NDs to provide sustained release and improve the dispersion of hydrophobic molecules, of which chemotherapeutic drugs are the most investigated, is described. The prospects of improving the intracellular delivery of nucleic acids by using NDs as a platform are exemplified. The photoluminescent and optical scattering properties of NDs, together with their applications in cellular labeling, are also reviewed. Considering the progress that has been made in understanding the properties of NDs, they can be envisioned as highly efficient drug delivery and imaging biomaterials for use in animals and humans.

  1. X-ray diagnostics. Oral and intravenous cholegraphy

    International Nuclear Information System (INIS)

    1981-04-01

    The standard deals with oral and intravenous cholegraphy. It includes information on indications, contraindications, prerequisites and preparations as well as on application and appropriate dosage of contrast media. Parameters on focussing, imaging conditions and on the program of taking radiographies are outlined. The necessity of special examinations according to findings as well as measures concerning radiation protection and hygiene are presented

  2. Species differences in drug glucuronidation: Humanized UDP-glucuronosyltransferase 1 mice and their application for predicting drug glucuronidation and drug-induced toxicity in humans.

    Science.gov (United States)

    Fujiwara, Ryoichi; Yoda, Emiko; Tukey, Robert H

    2018-02-01

    More than 20% of clinically used drugs are glucuronidated by a microsomal enzyme UDP-glucuronosyltransferase (UGT). Inhibition or induction of UGT can result in an increase or decrease in blood drug concentration. To avoid drug-drug interactions and adverse drug reactions in individuals, therefore, it is important to understand whether UGTs are involved in metabolism of drugs and drug candidates. While most of glucuronides are inactive metabolites, acyl-glucuronides that are formed from compounds with a carboxylic acid group can be highly toxic. Animals such as mice and rats are widely used to predict drug metabolism and drug-induced toxicity in humans. However, there are marked species differences in the expression and function of drug-metabolizing enzymes including UGTs. To overcome the species differences, mice in which certain drug-metabolizing enzymes are humanized have been recently developed. Humanized UGT1 (hUGT1) mice were created in 2010 by crossing Ugt1-null mice with human UGT1 transgenic mice in a C57BL/6 background. hUGT1 mice can be promising tools to predict human drug glucuronidation and acyl-glucuronide-associated toxicity. In this review article, studies of drug metabolism and toxicity in the hUGT1 mice are summarized. We further discuss research and strategic directions to advance the understanding of drug glucuronidation in humans. Copyright © 2017 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

  3. Applications of covalent organic frameworks (COFs): From gas storage and separation to drug delivery

    Institute of Scientific and Technical Information of China (English)

    Ming-Xue Wu; Ying-Wei Yang

    2017-01-01

    Covalent organic frameworks (COFs) are an emerging class of porous covalent organic structures whose backbones were composed of light elements (B,C,N,O,Si) and linked by robust covalent bonds to endow such material with desirable properties,i.e.,inherent porosity,well-defined pore aperture,ordered channel structure,large surface area,high stability,and multi-dimension.As expected,the abovementioned properties of COFs broaden the applications of this class of materials in various fields such as gas storage and separation,catalysis,optoelectronics,sensing,small molecules adsorption,and drug delivery.In this review,we outlined the synthesis of COFs and highlighted their applications ranging from the initial gas storage and separation to drug delivery.

  4. Sonochemically synthesized biocompatible zirconium phosphate nanoparticles for pH sensitive drug delivery application.

    Science.gov (United States)

    Kalita, Himani; Prashanth Kumar, B N; Konar, Suraj; Tantubay, Sangeeta; Kr Mahto, Madhusudan; Mandal, Mahitosh; Pathak, Amita

    2016-03-01

    The present work reports the synthesis of biocompatible zirconium phosphate (ZP) nanoparticles as nanocarrier for drug delivery application. The ZP nanoparticles were synthesized via a simple sonochemical method in the presence of cetyltrimethylammonium bromide and their efficacy for the delivery of drugs has been tested through various in-vitro experiments. The particle size and BET surface area of the nanoparticles were found to be ~48 nm and 206.51 m(2)/g respectively. The conventional MTT assay and cellular localization studies of the particles, performed on MDA-MB-231 cell lines, demonstrate their excellent biocompatibility and cellular internalization behavior. The loading of curcumin, an antitumor drug, onto the ZP nanoparticles shows the rapid drug uptake ability of the particles, while the drug release study, performed at two different pH values (at 7.4 and 5) depicts pH sensitive release-profile. The MTT assay and cellular localization studies revealed higher cellular inhibition and better bioavailability of the nanoformulated curcumin compared to free curcumin. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Current applications of miniaturized chromatographic and electrophoretic techniques in drug analysis.

    Science.gov (United States)

    Aturki, Zeineb; Rocco, Anna; Rocchi, Silvia; Fanali, Salvatore

    2014-12-01

    In the last decade, miniaturized separation techniques have become greatly popular in pharmaceutical analysis. Miniaturized separation methods are increasingly utilized in all processes of drug discovery as well as quality control of pharmaceutical preparation. The great advantages presented by the analytical miniaturized techniques, including high separation efficiency and resolution, rapid analysis and minimal consumption of reagents and samples, make them an attractive alternative to the conventional chromatographic methods for drug analysis. The purpose of this review is to give a general overview of the applicability of capillary electrophoresis (CE), capillary electrochromatography (CEC) and micro/capillary/nano-liquid chromatography (micro-LC/CLC/nano-LC) for the analysis of pharmaceutical formulations, active pharmaceutical ingredients (API), drug impurity testing, chiral drug separation, determination of drugs and metabolites in biological fluids. The results concerning the use of CEC, micro-LC, CLC, and nano-LC in the period 2009-2013, while for CE, those from 2012 up to the review draft are here summarized and some specific examples are discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Poly(amidoamine) (PAMAM) dendrimers: from biomimicry to drug delivery and biomedical applications.

    Science.gov (United States)

    Esfand, R; Tomalia, D A.

    2001-04-01

    Poly(amidoamine) (PAMAM) dendrimers are the first complete dendrimer family to be synthesized, characterized and commercialized. Based on this extensive activity, they are recognized as a unique new class of synthetic nanostructures. Dendrimers allow the precise control of size, shape and placement of functional groups that is desirable for many life science applications. From this perspective, this review focuses on crucial properties of biomimetic dendrimers that will broaden the potential for their use as macromolecular vectors in novel drug delivery and biomedical applications.

  7. Strategies of bringing drug product marketing applications to meet current regulatory standards.

    Science.gov (United States)

    Wu, Yan; Freed, Anita; Lavrich, David; Raghavachari, Ramesh; Huynh-Ba, Kim; Shah, Ketan; Alasandro, Mark

    2015-08-01

    In the past decade, many guidance documents have been issued through collaboration of global organizations and regulatory authorities. Most of these are applicable to new products, but there is a risk that currently marketed products will not meet the new compliance standards during audits and inspections while companies continue to make changes through the product life cycle for continuous improvement or market demands. This discussion presents different strategies to bringing drug product marketing applications to meet current and emerging standards. It also discusses stability and method designs to meet process validation and global development efforts.

  8. Near-infrared light-responsive liposomal contrast agent for photoacoustic imaging and drug release applications.

    Science.gov (United States)

    Sivasubramanian, Kathyayini; Mathiyazhakan, Malathi; Wiraja, Christian; Upputuri, Paul Kumar; Xu, Chenjie; Pramanik, Manojit

    2017-04-01

    Photoacoustic imaging has become an emerging tool for theranostic applications. Not only does it help in release and therapeutic applications. We explore near-infrared light-sensitive liposomes coated with gold nanostars (AuNSs) for both imaging and drug release applications using a photoacoustic imaging system. Being amphiphilic, the liposomes lipid bilayer and the aqueous core enable encapsulation of both hydrophobic and hydrophilic drugs. The AuNSs on the surface of the liposomes act as photon absorbers due to their intrinsic surface plasmon resonance. Upon excitation by laser light at specific wavelength, AuNSs facilitate rapid release of the contents encapsulated in the liposomes due to local heating and pressure wave formation (photoacoustic wave). Herein, we describe the design and optimization of the AuNSs-coated liposomes and demonstrate the release of both hydrophobic and hydrophilic model drugs (paclitaxel and calcein, respectively) through laser excitation at near-infrared wavelength. The use of AuNSs-coated liposomes as contrast agents for photoacoustic imaging is also explored with tissue phantom experiments. In comparison to blood, the AuNSs-coated liposomes have better contrast (approximately two times) at 2-cm imaging depth.

  9. A Performance/Cost Evaluation for a GPU-Based Drug Discovery Application on Volunteer Computing

    Science.gov (United States)

    Guerrero, Ginés D.; Imbernón, Baldomero; García, José M.

    2014-01-01

    Bioinformatics is an interdisciplinary research field that develops tools for the analysis of large biological databases, and, thus, the use of high performance computing (HPC) platforms is mandatory for the generation of useful biological knowledge. The latest generation of graphics processing units (GPUs) has democratized the use of HPC as they push desktop computers to cluster-level performance. Many applications within this field have been developed to leverage these powerful and low-cost architectures. However, these applications still need to scale to larger GPU-based systems to enable remarkable advances in the fields of healthcare, drug discovery, genome research, etc. The inclusion of GPUs in HPC systems exacerbates power and temperature issues, increasing the total cost of ownership (TCO). This paper explores the benefits of volunteer computing to scale bioinformatics applications as an alternative to own large GPU-based local infrastructures. We use as a benchmark a GPU-based drug discovery application called BINDSURF that their computational requirements go beyond a single desktop machine. Volunteer computing is presented as a cheap and valid HPC system for those bioinformatics applications that need to process huge amounts of data and where the response time is not a critical factor. PMID:25025055

  10. A Performance/Cost Evaluation for a GPU-Based Drug Discovery Application on Volunteer Computing

    Directory of Open Access Journals (Sweden)

    Ginés D. Guerrero

    2014-01-01

    Full Text Available Bioinformatics is an interdisciplinary research field that develops tools for the analysis of large biological databases, and, thus, the use of high performance computing (HPC platforms is mandatory for the generation of useful biological knowledge. The latest generation of graphics processing units (GPUs has democratized the use of HPC as they push desktop computers to cluster-level performance. Many applications within this field have been developed to leverage these powerful and low-cost architectures. However, these applications still need to scale to larger GPU-based systems to enable remarkable advances in the fields of healthcare, drug discovery, genome research, etc. The inclusion of GPUs in HPC systems exacerbates power and temperature issues, increasing the total cost of ownership (TCO. This paper explores the benefits of volunteer computing to scale bioinformatics applications as an alternative to own large GPU-based local infrastructures. We use as a benchmark a GPU-based drug discovery application called BINDSURF that their computational requirements go beyond a single desktop machine. Volunteer computing is presented as a cheap and valid HPC system for those bioinformatics applications that need to process huge amounts of data and where the response time is not a critical factor.

  11. Microneedles as Enhancer of Drug Absorption Through the Skin and Applications in Medicine and Cosmetology.

    Science.gov (United States)

    Serrano-Castañeda, Pablo; Escobar-Chavez, Jose Juan; Rodriguez-Cruz, Isabel Marlen; Melgoza, Luz Maria; Martinez-Hernandez, Jessica

    2018-01-01

    The microneedles technology has found applications in many health-related fields. For example, their application in drugs and vaccines delivery as well, as the determination of biomarkers, has been reported. They also have a place in the dermatology and cosmetic areas such as the treatment of wounds from burns, scars, acne, depigmentation, and alopecia will be shown. Microneedles are used in therapeutic applications and are manufactured using materials such as metal (steel, titanium, nickel), polymer (oly-glycolic acid (PGA), poly-lactide-co-glycolide acid (PLGA), poly-L-lactic acid (PLA), chitosan), glass, silicon, ceramic, carbohydrates (trehalose, sucrose, mannitol). Examples of application of microneedles and their advantages and disadvantages are discussed. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

  12. Evaluation of blood-brain barrier transport and CNS drug metabolism in diseased and control brain after intravenous L-DOPA in a unilateral rat model of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Ravenstijn Paulien GM

    2012-02-01

    Full Text Available Abstract Background Changes in blood-brain barrier (BBB functionality have been implicated in Parkinson's disease. This study aimed to investigate BBB transport of L-DOPA transport in conjunction with its intra-brain conversion, in both control and diseased cerebral hemispheres in the unilateral rat rotenone model of Parkinson's disease. Methods In Lewis rats, at 14 days after unilateral infusion of rotenone into the medial forebrain bundle, L-DOPA was administered intravenously (10, 25 or 50 mg/kg. Serial blood samples and brain striatal microdialysates were analysed for L-DOPA, and the dopamine metabolites DOPAC and HVA. Ex-vivo brain tissue was analyzed for changes in tyrosine hydroxylase staining as a biomarker for Parkinson's disease severity. Data were analysed by population pharmacokinetic analysis (NONMEM to compare BBB transport of L-DOPA in conjunction with the conversion of L-DOPA into DOPAC and HVA, in control and diseased cerebral hemisphere. Results Plasma pharmacokinetics of L-DOPA could be described by a 3-compartmental model. In rotenone responders (71%, no difference in L-DOPA BBB transport was found between diseased and control cerebral hemisphere. However, in the diseased compared with the control side, basal microdialysate levels of DOPAC and HVA were substantially lower, whereas following L-DOPA administration their elimination rates were higher. Conclusions Parkinson's disease-like pathology, indicated by a huge reduction of tyrosine hydroxylase as well as by substantially reduced levels and higher elimination rates of DOPAC and HVA, does not result in changes in BBB transport of L-DOPA. Taking the results of this study and that of previous ones, it can be concluded that changes in BBB functionality are not a specific characteristic of Parkinson's disease, and cannot account for the decreased benefit of L-DOPA at later stages of Parkinson's disease.

  13. Mesoporous Silica Nanomaterials for Applications in Catalysis, Sensing, Drug Delivery and Gene Transfection

    Energy Technology Data Exchange (ETDEWEB)

    Radu, Daniela Rodica [Iowa State Univ., Ames, IA (United States)

    2004-01-01

    The central theme of this dissertation is represented by the versatility of mesoporous silica nanomaterials in various applications such as catalysis and bio-applications, with main focus on biological applications of Mesoporous Silica Nanospheres (MSN). The metamorphosis that we impose to these materials from catalysis to sensing and to drug and gene delivery is detailed in this dissertation. First, we developed a synthetic method that can fine tune the amount of chemically accessible organic functional groups on the pores surface of MSN by exploiting electrostatic and size matching between the cationic alkylammonium head group of the cetyltrimethylammonium bromide (CTAB) surfactant and various anionic organoalkoxysilane precursors at the micelle-water interface in a base-catalyzed condensation reaction of silicate. Aiming nature imitation, we demonstrated the catalytic abilities of the MSNs, We utilized an ethylenediamine functional group for chelating Cu2+ as a catalytic functional group anchored inside the mesopores. Thus, a polyalkynylene-based conducting polymer (molecular wire) was synthesized within the Cu-functionalized MSNs silica catalyst. For sensing applications, we have synthesized a poly(lactic acid) coated mesoporous silica nanosphere (PLA-MSN) material that serves as a fluorescence sensor system for detection of amino-containing neurotransmitters in neutral aqueous buffer. We exploited the mesoporosity of MSNs for encapsulating pharmaceutical drugs. We examined bio-friendly capping molecules such as polyamidoamine dendrimers of generations G2 to G4, to prevent the drug leaching. Next, the drug delivery system employed MSNs loaded with Doxorubicin, an anticancer drug. The results demonstrated that these nano-Trojan horses have ability to deliver Doxorubicin to cancer cells and induce their death. Finally, to demonstrate the potential of MSN as an universal cellular transmembrane nanovehicle, we anchored positively charged dendrimers on

  14. Novel approach for a PTX/VEGF dual drug delivery system in cardiovascular applications-an innovative bulk and surface drug immobilization.

    Science.gov (United States)

    Wulf, Katharina; Teske, Michael; Matschegewski, Claudia; Arbeiter, Daniela; Bajer, Dalibor; Eickner, Thomas; Schmitz, Klaus-Peter; Grabow, Niels

    2018-06-01

    The successive incorporation of several drugs into the polymeric bulk of implants mostly results in loss of considerable quantity of one drug, and/or the loss in quality of the coating and also in changes of drug release time points. A dual drug delivery system (DDDS) based on poly-L-lactide (PLLA) copolymers combining the effective inhibition of smooth muscle cell proliferation while simultaneously promoting re-endothelialization was successfully developed. To overcome possible antagonistic drug interactions and the limitation of the polymeric bulk material as release system for dual drugs, a novel concept which combines the bulk and surface drug immobilization for a DDDS was investigated. The advantage of this DDDS is that the bulk incorporation of fluorescein diacetate (FDAc) (model drug for paclitaxel (PTX)) via spray coating enhanced the subsequent cleavable surface coupling of vascular endothelial growth factor (VEGF) via the crosslinker bissulfosuccinimidyl suberate (BS 3 ). In the presence of the embedded FDAc, the VEGF loading and release are about twice times higher than in absence. Furthermore, the DDDS combines the diffusion drug delivery (FDAc or PTX) and the chemical controlled drug release, VEGF via hydrolysable ester bonds, without loss in quantity and quality of the drug release curves. Additionally, the performed in vitro biocompatibility study showed the bimodal influences of PTX and VEGF on human endothelial EA.hy926 cells. In conclusion, it was possible to show the feasibility to develop a novel DDDS which has a high potential for the medical application due to the possible easy and short modification of a polymer-based PTX delivery system.

  15. Mathematical Model to Predict Skin Concentration after Topical Application of Drugs

    Directory of Open Access Journals (Sweden)

    Hiroaki Todo

    2013-12-01

    Full Text Available Skin permeation experiments have been broadly done since 1970s to 1980s as an evaluation method for transdermal drug delivery systems. In topically applied drug and cosmetic formulations, skin concentration of chemical compounds is more important than their skin permeations, because primary target site of the chemical compounds is skin surface or skin tissues. Furthermore, the direct pharmacological reaction of a metabolically stable drug that binds with specific receptors of known expression levels in an organ can be determined by Hill’s equation. Nevertheless, little investigation was carried out on the test method of skin concentration after topically application of chemical compounds. Recently we investigated an estimating method of skin concentration of the chemical compounds from their skin permeation profiles. In the study, we took care of “3Rs” issues for animal experiments. We have proposed an equation which was capable to estimate animal skin concentration from permeation profile through the artificial membrane (silicone membrane and animal skin. This new approach may allow the skin concentration of a drug to be predicted using Fick’s second law of diffusion. The silicone membrane was found to be useful as an alternative membrane to animal skin for predicting skin concentration of chemical compounds, because an extremely excellent extrapolation to animal skin concentration was attained by calculation using the silicone membrane permeation data. In this chapter, we aimed to establish an accurate and convenient method for predicting the concentration profiles of drugs in the skin based on the skin permeation parameters of topically active drugs derived from steady-state skin permeation experiments.

  16. A close collaboration of chitosan with lipid colloidal carriers for drug delivery applications.

    Science.gov (United States)

    Bugnicourt, Loïc; Ladavière, Catherine

    2017-06-28

    Chitosan and lipid colloids have separately shown a growing interest in the field of drug delivery applications. Their success is mainly due to their interesting physicochemical behaviors, as well as their biological properties such as bioactivity and biocompatibility. While chitosan is a well-known cationic polysaccharide with the ability to strongly interact with drugs and biological matrices through mainly electrostatic interactions, lipid colloids are carriers particularly recognized for the drug vectorization. In recent years, the combination of both entities has been considered because it offers new systems which gather the advantages of each of them to efficiently deliver various types of bioactive species. The purpose of this review is to describe these associations between chemically-unmodified chitosan chains (solubilized or dispersed) and lipid colloids (as nanoparticles or organized in lipid layers), as well as their potential in the drug delivery area so far. Three assemblies have mainly been reported in the literature: i) lipid nanoparticles (solid lipid nanoparticles or nanostructured lipid carriers) coated with chitosan chains, ii) lipid vesicles covered with chitosan chains, and iii) chitosan chains structured in nanoparticles with a lipid coating. Their elaboration processes, their physicochemical characterization, and their biological studies are detailed and discussed herein. The different bioactive species (drugs and bio(macro)molecules) incorporated in these assemblies, their maximal incorporation efficiency, and their loading capacity are also presented. This review reveals the versatility of these assemblies. Depending on the organization of lipids (i.e., nanoparticles or vesicles) and the state of polymer chains (i.e., solubilized or dispersed under the form of nanoparticles), a large variety of drugs can be successfully incorporated, and various routes of administration can be considered. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. HDL as a drug and nucleic acid delivery vehicle

    Directory of Open Access Journals (Sweden)

    Andras G Lacko

    2015-10-01

    Full Text Available This review is intended to evaluate the research findings and potential clinical applications of drug transport systems, developed based on the concepts of the structure/function and physiological role(s of high density lipoprotein=type nanoparticles. These macromolecules provide targeted transport of cholesteryl esters (a highly lipophilic payload in their natural/physiological environment. The property of accommodating highly water insoluble constituents in their core region enables HDL type nanoparticles to effectively transport hydrophobic drugs upon intravenous administration. Even though the application of reconstituted HDL in the treatment of a number of diseases is reviewed, the primary focus is on the application of HDL type drug delivery agents in cancer chemotherapy. The use of both native and synthetic HDL as drug delivery agents are compared to evaluate their respective potentials for commercial and clinical development. The current status and future perspectives for HDL type nanoparticles are discussed, including current obstacles and future applications in therapeutics.

  18. Comparison of analgesic efficacy of intravenous Paracetamol and intravenous dexketoprofen trometamol in multimodal analgesia after hysterectomy.

    Science.gov (United States)

    Unal, Ciğdem; Cakan, Türkay; Baltaci, Bülent; Başar, Hülya

    2013-10-01

    [corrected] We aimed to evaluate analgesic efficacy, opioid-sparing, and opioid-related adverse effects of intravenous paracetamol and intravenous dexketoprofen trometamol in combination with iv morphine after total abdominal hysterectomy. Sixty American Society of Anesthesiologist Physical Status Classification I-II patients scheduled for total abdominal hysterectomy were enrolled to this double-blinded, randomized, placebo controlled, and prospective study. Patients were divided into three groups as paracetamol, dexketoprofen trometamol, and placebo (0.9% NaCl) due to their post-operative analgesic usage. Intravenous patient controlled analgesia morphine was used as a rescue analgesic in all groups. Pain scores, hemodynamic parameters, morphine consumption, patient satisfaction, and side-effects were evaluated. Visual Analog Scale (VAS) scores were not statistically significantly different among the groups in all evaluation times, but decrease in VAS scores was statistically significant after the evaluation at 12(th) h in all groups. Total morphine consumption (morphine concentration = 0.2 mg/ml) in group paracetamol (72.3 ± 38.0 ml) and dexketoprofen trometamol (69.3 ± 24.1 ml) was significantly lower than group placebo (129.3 ± 22.6 ml) (P dexketoprofen trometamol after surgery and the increase in global satisfaction score was significant only in group placebo. Dexketoprofen trometamol and Paracetamol didn't cause significant change on pain scores, but increased patients' comfort. Although total morphine consumption was significantly decreased by both drugs, the incidence of nausea and vomiting were similar among the groups. According to results of the present study routine addition of dexketoprofen trometamol and paracetamol to patient controlled analgesia morphine after hysterectomies is not recommended.

  19. Comparison of analgesic efficacy of intravenous Paracetamol and intravenous dexketoprofen trometamol in multimodal analgesia after hysterectomy

    Directory of Open Access Journals (Sweden)

    Çiğdem Ünal

    2013-01-01

    Full Text Available Backround: We aimed to evaluate analgesic efficacy, opioid-sparing, and opioid-related adverse effects of intravenous paracetamol and intravenous dexketoprofen trometamol in combination with iv morphine after total abdominal hysterectomy. Materials and Methods: Sixty American Society of Anesthesiologist Physical Status Classification I-II patients scheduled for total abdominal hysterectomy were enrolled to this double-blinded, randomized, placebo controlled, and prospective study. Patients were divided into three groups as paracetamol, dexketoprofen trometamol, and placebo (0.9% NaCl due to their post-operative analgesic usage. Intravenous patient controlled analgesia morphine was used as a rescue analgesic in all groups. Pain scores, hemodynamic parameters, morphine consumption, patient satisfaction, and side-effects were evaluated. Results: Visual Analog Scale (VAS scores were not statistically significantly different among the groups in all evaluation times, but decrease in VAS scores was statistically significant after the evaluation at 12 th h in all groups. Total morphine consumption (morphine concentration = 0.2 mg/ml in group paracetamol (72.3 ± 38.0 ml and dexketoprofen trometamol (69.3 ± 24.1 ml was significantly lower than group placebo (129.3 ± 22.6 ml (P < 0.001. Global satisfaction scores of the patients in group placebo was significantly lower than group dexketoprofen trometamol after surgery and the increase in global satisfaction score was significant only in group placebo. Conclusion: Dexketoprofen trometamol and Paracetamol didn′t cause significant change on pain scores, but increased patients′ comfort. Although total morphine consumption was significantly decreased by both drugs, the incidence of nausea and vomiting were similar among the groups. According to results of the present study routine addition of dexketoprofen trometamol and paracetamol to patient controlled analgesia morphine after hysterectomies is not

  20. Ultrastructural Changes in the Liver of Intravenous Heroin Addicts

    Directory of Open Access Journals (Sweden)

    Goran Ilić

    2010-02-01

    Full Text Available The ultrastructural research has a decisive role in gathering the knowledge on the liver’s response to the influence of some drugs. The aim of the study was to perform an ultrastructurai analysis of the liver in chronic intravenous heroin addicts.The study involved the autopsy conducted on 40 bodies of intravenous heroin addicts and 10 control autopsies. The liver tissue was fixed in glutaraldehyde and moulded with epon for investigation purposes of ultrastructural changes. The analysis was performed using the method of transmission electron microscopy.In the group of intravenous heroin addicts, the liver autopsy samples showed degenerative vesicular and fat changes, chronic active and persistent hepatitis, cirrhosis, reduction in the amount of glycogen in hepatocytes, as well as the Kupffer cell’s dominant hypertrophy. Various changes occur in organelles, plasma membrane of hepatocytes and biliary channels as well as in the nucleus.The most important ultrastructural findings include: hyperplasia and hypertrophy of the smooth endoplasmic reticulum, which is histologically proven vesicular degeneration of hepatocyte occurring as a result of the increased synthesis of enzymes of smooth endoplasmic reticulum due to chronic intravenous heroin intake, and the presence of continuous basal membrane followed by transformation of the sinusoids into capillaries (in the cases of chronic active hepatitis and cirrhosis which leads to a disorder of microcirculation and further progress of cirrhosis.

  1. Electrospun Fibers as a Dressing Material for Drug and Biological Agent Delivery in Wound Healing Applications

    Science.gov (United States)

    Gizaw, Mulugeta; Thompson, Jeffrey; Faglie, Addison; Lee, Shih-Yu; Neuenschwander, Pierre; Chou, Shih-Feng

    2018-01-01

    Wound healing is a complex tissue regeneration process that promotes the growth of new tissue to provide the body with the necessary barrier from the outside environment. In the class of non-healing wounds, diabetic wounds, and ulcers, dressing materials that are available clinically (e.g., gels and creams) have demonstrated only a slow improvement with current available technologies. Among all available current technologies, electrospun fibers exhibit several characteristics that may provide novel replacement dressing materials for the above-mentioned wounds. Therefore, in this review, we focus on recent achievements in electrospun drug-eluting fibers for wound healing applications. In particular, we review drug release, including small molecule drugs, proteins and peptides, and gene vectors from electrospun fibers with respect to wound healing. Furthermore, we provide an overview on multifunctional dressing materials based on electrospun fibers, including those that are capable of achieving wound debridement and wound healing simultaneously as well as multi-drugs loading/types suitable for various stages of the healing process. Our review provides important and sufficient information to inform the field in development of fiber-based dressing materials for clinical treatment of non-healing wounds. PMID:29382065

  2. Microengineering methods for cell-based microarrays and high-throughput drug-screening applications

    International Nuclear Information System (INIS)

    Xu Feng; Wu Jinhui; Wang Shuqi; Gurkan, Umut Atakan; Demirci, Utkan; Durmus, Naside Gozde

    2011-01-01

    Screening for effective therapeutic agents from millions of drug candidates is costly, time consuming, and often faces concerns due to the extensive use of animals. To improve cost effectiveness, and to minimize animal testing in pharmaceutical research, in vitro monolayer cell microarrays with multiwell plate assays have been developed. Integration of cell microarrays with microfluidic systems has facilitated automated and controlled component loading, significantly reducing the consumption of the candidate compounds and the target cells. Even though these methods significantly increased the throughput compared to conventional in vitro testing systems and in vivo animal models, the cost associated with these platforms remains prohibitively high. Besides, there is a need for three-dimensional (3D) cell-based drug-screening models which can mimic the in vivo microenvironment and the functionality of the native tissues. Here, we present the state-of-the-art microengineering approaches that can be used to develop 3D cell-based drug-screening assays. We highlight the 3D in vitro cell culture systems with live cell-based arrays, microfluidic cell culture systems, and their application to high-throughput drug screening. We conclude that among the emerging microengineering approaches, bioprinting holds great potential to provide repeatable 3D cell-based constructs with high temporal, spatial control and versatility.

  3. Microengineering methods for cell-based microarrays and high-throughput drug-screening applications

    Energy Technology Data Exchange (ETDEWEB)

    Xu Feng; Wu Jinhui; Wang Shuqi; Gurkan, Umut Atakan; Demirci, Utkan [Department of Medicine, Demirci Bio-Acoustic-MEMS in Medicine (BAMM) Laboratory, Center for Biomedical Engineering, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA (United States); Durmus, Naside Gozde, E-mail: udemirci@rics.bwh.harvard.edu [School of Engineering and Division of Biology and Medicine, Brown University, Providence, RI (United States)

    2011-09-15

    Screening for effective therapeutic agents from millions of drug candidates is costly, time consuming, and often faces concerns due to the extensive use of animals. To improve cost effectiveness, and to minimize animal testing in pharmaceutical research, in vitro monolayer cell microarrays with multiwell plate assays have been developed. Integration of cell microarrays with microfluidic systems has facilitated automated and controlled component loading, significantly reducing the consumption of the candidate compounds and the target cells. Even though these methods significantly increased the throughput compared to conventional in vitro testing systems and in vivo animal models, the cost associated with these platforms remains prohibitively high. Besides, there is a need for three-dimensional (3D) cell-based drug-screening models which can mimic the in vivo microenvironment and the functionality of the native tissues. Here, we present the state-of-the-art microengineering approaches that can be used to develop 3D cell-based drug-screening assays. We highlight the 3D in vitro cell culture systems with live cell-based arrays, microfluidic cell culture systems, and their application to high-throughput drug screening. We conclude that among the emerging microengineering approaches, bioprinting holds great potential to provide repeatable 3D cell-based constructs with high temporal, spatial control and versatility.

  4. Application of PK/PD Modeling in Veterinary Field: Dose Optimization and Drug Resistance Prediction

    Directory of Open Access Journals (Sweden)

    Ijaz Ahmad

    2016-01-01

    Full Text Available Among veterinary drugs, antibiotics are frequently used. The true mean of antibiotic treatment is to administer dose of drug that will have enough high possibility of attaining the preferred curative effect, with adequately low chance of concentration associated toxicity. Rising of antibacterial resistance and lack of novel antibiotic is a global crisis; therefore there is an urgent need to overcome this problem. Inappropriate antibiotic selection, group treatment, and suboptimal dosing are mostly responsible for the mentioned problem. One approach to minimizing the antibacterial resistance is to optimize the dosage regimen. PK/PD model is important realm to be used for that purpose from several years. PK/PD model describes the relationship between drug potency, microorganism exposed to drug, and the effect observed. Proper use of the most modern PK/PD modeling approaches in veterinary medicine can optimize the dosage for patient, which in turn reduce toxicity and reduce the emergence of resistance. The aim of this review is to look at the existing state and application of PK/PD in veterinary medicine based on in vitro, in vivo, healthy, and disease model.

  5. Application of drug delivery system for boron neutron capture therapy. Basic research toward clinical application

    International Nuclear Information System (INIS)

    Yanagie, Hironobu; Takahashi, Hiroyuki

    2010-01-01

    Tumour cell destruction in boron neutron-capture therapy (BNCT) is due to the nuclear reaction between 10 B and thermal neutrons ( 10 B+ 1 n → 7 Li+ 4 He (α) +2.31 MeV (93.7%)/2.79 MeV (6.3%)). The resulting lithium ions and αparticles are high linear energy transfer (LET) particles which give high biological effect. Their short range in tissue (5-9 μm) restricts radiation damage to those cells in which boron atoms are located at the time of neutron irradiation. BNCT has been applied clinically for the treatment of malignant brain tumors, malignant melanoma, head and neck cancer and hepatoma etc, recently. Sodium borocaptate (Na 2 10 B 12 H 11 SH; BSH) and borono-phenylalanine ( 10 BPA) are currently being used in clinical treatments. To achieve the selective delivery of boron atoms to cancer cells, drug delivery system (DDS) becomes an attractive intelligent technology as targeting and controlled release of drugs. We have firstly reported that 10 B atoms delivered by immunoliposomes are cytotoxic to human pancreatic carcinoma cells (AsPC-1) after thermal neutron irradiation in vitro. The intra-tumoural injection of boronated immunoliposomes can increase the retention of 10 B atoms in tumour cells, causing suppression of tumour growth in vivo following thermal neutron irradiation. We prepared polyethylene-glycol binding liposomes (PEG-liposomes) as an effective 10 B carrier to obviate phagocytosis by reticuloendotherial systems. We had prepared 10 BSH entrapped Water-in-Oil-in-Water (WOW) emulsion. The 10 B concentration in VX-2 tumour after intra-arterial injection of 10 BSH entrapped WOW emulsion was superior to the groups of 10 BSH entrapped conventional Lipiodol mix emulsion. 10 Boron entrapped WOW emulsion is one of the most useful for intra-arterial boron delivery carrier on BNCT to hepatocellular carcinoma. (author)

  6. Structural and biological properties of thermosensitive chitosan-graphene hybrid hydrogels for sustained drug delivery applications.

    Science.gov (United States)

    Saeednia, Leyla; Yao, Li; Berndt, Marcus; Cluff, Kim; Asmatulu, Ramazan

    2017-09-01

    Chitosan has the ability to make injectable thermosensitive hydrogels which has been highly investigated for drug delivery applications. The addition of nanoparticles is one way to increase the mechanical strength of thermosensitive chitosan hydrogel and subsequently and control the burst release of drug. Graphene nanoparticles have shown unique mechanical, optical and electrical properties which can be exploited for biomedical applications, especially in drug delivery. This study, have focused on the mechanical properties of a thermosensitive and injectable hybrid chitosan hydrogel incorporated with graphene nanoparticles. Scanning electron microscope (SEM), Fourier transform infrared (FTIR) spectroscopy, Raman spectroscopy, and X-ray diffraction (XRD) have been used for morphological and chemical characterization of graphene infused chitosan hydrogels. The cell viability and cytotoxicity of graphene-contained hydrogels were analyzed using the alamarBlue ® technique. In-vitro methotrexate (MTX) release was investigated from MTX-loaded hybrid hydrogels as well. As a last step, to evaluate their efficiency as a cancer treatment delivery system, an in vitro anti-tumor test was also carried out using MCF-7 breast cancer cell lines. Results confirmed that a thermosensitive chitosan-graphene hybrid hydrogel can be used as a potential breast cancer therapy system for controlled delivery of methotrexate. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2381-2390, 2017. © 2017 Wiley Periodicals, Inc.

  7. High intensity focused ultrasound technology, its scope and applications in therapy and drug delivery.

    Science.gov (United States)

    Phenix, Christopher Peter; Togtema, Melissa; Pichardo, Samuel; Zehbe, Ingeborg; Curiel, Laura

    2014-01-01

    Ultrasonography is a safe, inexpensive and wide-spread diagnostic tool capable of producing real-time non-invasive images without significant biological effects. However, the propagation of higher energy, intensity and frequency ultrasound waves through living tissues can induce thermal, mechanical and chemical effects useful for a variety of therapeutic applications. With the recent development of clinically approved High Intensity Focused Ultrasound (HIFU) systems, therapeutic ultrasound is now a medical reality. Indeed, HIFU has been used for the thermal ablation of pathological lesions; localized, minimally invasive ultrasound-mediated drug delivery through the transient formation of pores on cell membranes; the temporary disruption of skin and the blood brain barrier; the ultrasound induced break-down of blood clots; and the targeted release of drugs using ultrasound and temperature sensitive drug carriers. This review seeks to engage the pharmaceutical research community by providing an overview on the biological effects of ultrasound as well as highlighting important therapeutic applications, current deficiencies and future directions.

  8. Application of Absorption Modeling in Rational Design of Drug Product Under Quality-by-Design Paradigm.

    Science.gov (United States)

    Kesisoglou, Filippos; Mitra, Amitava

    2015-09-01

    Physiologically based absorption models can be an important tool in understanding product performance and hence implementation of Quality by Design (QbD) in drug product development. In this report, we show several case studies to demonstrate the potential application of absorption modeling in rational design of drug product under the QbD paradigm. The examples include application of absorption modeling—(1) prior to first-in-human studies to guide development of a formulation with minimal sensitivity to higher gastric pH and hence reduced interaction when co-administered with PPIs and/or H2RAs, (2) design of a controlled release formulation with optimal release rate to meet trough plasma concentrations and enable QD dosing, (3) understanding the impact of API particle size distribution on tablet bioavailability and guide formulation design in late-stage development, (4) assess impact of API phase change on product performance to guide specification setting, and (5) investigate the effect of dissolution rate changes on formulation bioperformance and enable appropriate specification setting. These case studies are meant to highlight the utility of physiologically based absorption modeling in gaining a thorough understanding of the product performance and the critical factors impacting performance to drive design of a robust drug product that would deliver the optimal benefit to the patients.

  9. Are postoperative intravenous antibiotics necessary after bimaxillary orthognathic surgery? A prospective, randomized, double-blind, placebo-controlled clinical trial.

    Science.gov (United States)

    Tan, S K; Lo, J; Zwahlen, R A

    2011-12-01

    Postoperative antibiotic prophylaxis is often administered intravenously, despite an increased morbidity rate compared with oral application. This study investigates whether a postoperative oral antibiotic regimen is as effective as incorporation of intravenous antibiotics after bimaxillary orthognathic surgery. 42 patients who underwent bimaxillary orthognathic surgery between December 2008 and May 2010 were randomly allocated to 2 placebo-controlled postoperative antibiotic prophylaxis groups. Group 1 received oral amoxicillin 500mg three times daily; group 2 received intravenous ampicillin 1g four times daily, during the first two postoperative days. Both groups subsequently took oral amoxicillin for three more days. Clinically, the infection rate was assessed in both study groups for a period of 6 weeks after the surgery. 9 patients (21.4%) developed infection. No adverse drug event was detected. No significant difference (p=0.45) was detected in the infection rate between group 1 (3/21) and group 2 (6/21). Age, type of surgical procedures, duration of the operative procedure, surgical procedure-related events, blood loss, and blood transfusion were all found not related to infection (p>0.05). Administration of more cost-effective oral antibiotic prophylaxis, which causes less comorbidity, can be considered to be safe in bimaxillary orthognathic surgery with segmentalizations. Copyright © 2011 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  10. Study on the Application of Chinese Patent Drug and Chinese Formula of Rabdosia Rubescens

    Science.gov (United States)

    Peng, Mengfan; Liu, Baosong; Mao, Mingsan

    2018-01-01

    Rabdosia rubescens contais many active ingredients such as terpenoids, flavonoids, polysaccharides and organic acids. Modern research has proved that Rabdosia rubescens has the effect of heat-clearing and detoxicating, antibacterial and anticancer, promoting blood circulation to arrest pain and anti-tumor. It is used in the treatment of sore throat, rheumatoid arthritis and various kinds of cancer. The clinical application of Rabdosia rubescens is restricted in the fat-soluble components, and the solubility of water solubility is ignored. The application of prescriptions, Chinese patent drug and food therapy of Rabdosia rubescens are less and fragmented. This paper inquires relevant literature, the application of Rabdosia rubescens in prescription, Chinese patent medicine and food therapy was reviewed, in order to make Rabdosiae rubescens play a greater role in the relevant area. On the basis of make the best use of everything, to promote the innovation and development of Chinese medicine and services to the people in our country.

  11. 75 FR 55676 - Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of New Animal Drug Applications...

    Science.gov (United States)

    2010-09-14

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 510, 520, and...; International Nutrition, Inc., 7706 ``I'' Plaza, Omaha, NE 68127; and Feed Service Co., Inc., 303 Lundin Blvd... 520--ORAL DOSAGE FORM NEW ANIMAL DRUGS 0 3. The authority citation for 21 CFR part 520 continues to...

  12. 21 CFR 310.201 - Exemption for certain drugs limited by new-drug applications to prescription sale.

    Science.gov (United States)

    2010-04-01

    ... children under 6 years of age, except as directed by a physician, and against driving a car or operating... other drugs, in an aqueous vehicle suitable for administration in self-medication as nose drops, and..., and against driving a car or operating machinery while using the drug, since it may cause drowsiness...

  13. 76 FR 17776 - Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of New Animal Drug Applications...

    Science.gov (United States)

    2011-03-31

    ...'s Sponsor (established name of drug) drug labeler code) Roche Vitamins, Inc., 45 Waterview Blvd.... Medicator TS-40 Premix (tylosin phosphate/ sulfamethazine). Pegasus Laboratories, Inc., 8809 Ely Rd., NADA... Laboratories, Inc., 100 Nancy Dr., NADA 108-487, DEC Tabs 520.622a (015579). Belle Plaine, MN 56011...

  14. 78 FR 66748 - Smith Miller and Patch Inc. et al.; Proposal to Withdraw Approval of 14 New Drug Applications...

    Science.gov (United States)

    2013-11-06

    ... Ave., Glendale, CA 91201. NDA 017861 Acthar Gel Synthetic Armour (seractide acetate) Pharmaceutical Co... the Center for Drug Evaluation and Research proposes to issue an order under section 505(e) of the..., all issues relating to the legal status of the drug products covered by these applications. An...

  15. Dendrimers as tunable vectors of drug delivery systems and biomedical and ocular applications

    Science.gov (United States)

    Kalomiraki, Marina; Thermos, Kyriaki; Chaniotakis, Nikos A

    2016-01-01

    Dendrimers are large polymeric structures with nanosize dimensions (1–10 nm) and unique physicochemical properties. The major advantage of dendrimers compared with linear polymers is their spherical-shaped structure. During synthesis, the size and shape of the dendrimer can be customized and controlled, so the finished macromolecule will have a specific “architecture” and terminal groups. These characteristics will determine its suitability for drug delivery, diagnostic imaging, and as a genetic material carrier. This review will focus initially on the unique properties of dendrimers and their use in biomedical applications, as antibacterial, antitumor, and diagnostic agents. Subsequently, emphasis will be given to their use in drug delivery for ocular diseases. PMID:26730187

  16. Dendrimers as tunable vectors of drug delivery systems and biomedical and ocular applications

    Directory of Open Access Journals (Sweden)

    Kalomiraki M

    2015-12-01

    Full Text Available Marina Kalomiraki,1 Kyriaki Thermos,2 Nikos A Chaniotakis1 1Laboratory of Analytical Chemistry, Department of Chemistry, 2Department of Pharmacology, School of Medicine, University of Crete Voutes, Heraklion, Greece Abstract: Dendrimers are large polymeric structures with nanosize dimensions (1–10 nm and unique physicochemical properties. The major advantage of dendrimers compared with linear polymers is their spherical-shaped structure. During synthesis, the size and shape of the dendrimer can be customized and controlled, so the finished macromolecule will have a specific “architecture” and terminal groups. These characteristics will determine its suitability for drug delivery, diagnostic imaging, and as a genetic material carrier. This review will focus initially on the unique properties of dendrimers and their use in biomedical applications, as antibacterial, antitumor, and diagnostic agents. Subsequently, emphasis will be given to their use in drug delivery for ocular diseases. Keywords: nanoparticles, ocular diseases, encapsulation, macromolecule, diagnostic agent

  17. Assessing Miniaturized Sensor Performance using Supervised Learning, with Application to Drug and Explosive Detection

    DEFF Research Database (Denmark)

    Alstrøm, Tommy Sonne

    of sensors, as the sensors are designed to provide robust and reliable measurements. That means, the sensors are designed to have repeated measurement clusters. Sensor fusion is presented for the sensor based on chemoselective compounds. An array of color changing compounds are handled and in unity they make......This Ph.D. thesis titled “Assessing Miniaturized Sensor Performance using Supervised Learning, with Application to Drug and Explosive Detection” is a part of the strategic research project “Miniaturized sensors for explosives detection in air” funded by the Danish Agency for Science and Technology...... emanated by explosives and drugs, similar to an electronic nose. To evaluate sensor responses a data processing and evaluation pipeline is required. The work presented herein focuses on the feature extraction, feature representation and sensor accuracy. Thus the primary aim of this thesis is twofold...

  18. Core-shell designs of photoluminescent nanodiamonds with porous silica coatings for bioimaging and drug delivery, II : Application

    NARCIS (Netherlands)

    Prabhakar, N.; Näreoja, T.; Haartman, Von E.; Karaman, D.S.; Jiang, H.; Koho, S.; Dolenko, T.A.; Hänninen, P.E.; Vlasov, D.I.; Ralchenko, V.G.; Hosomi, S.; Vlasov, I.I.; Sahlgren, C.M.; Rosenholm, J.M.

    2013-01-01

    Recent advances within materials science and its interdisciplinary applications in biomedicine have emphasized the potential of using a single multifunctional composite material for concurrent drug delivery and biomedical imaging. Here we present a novel composite material consisting of a

  19. Projecting ADME Behavior and Drug-Drug Interactions in Early Discovery and Development: Application of the Extended Clearance Classification System.

    Science.gov (United States)

    El-Kattan, Ayman F; Varma, Manthena V; Steyn, Stefan J; Scott, Dennis O; Maurer, Tristan S; Bergman, Arthur

    2016-12-01

    To assess the utility of Extended Clearance Classification System (ECCS) in understanding absorption, distribution, metabolism, and elimination (ADME) attributes and enabling victim drug-drug interaction (DDI) predictions. A database of 368 drugs with relevant ADME parameters, main metabolizing enzymes, uptake transporters, efflux transporters, and highest change in exposure (%AUC) in presence of inhibitors was developed using published literature. Drugs were characterized according to ECCS using ionization, molecular weight and estimated permeability. Analyses suggested that ECCS class 1A drugs are well absorbed and systemic clearance is determined by metabolism mediated by CYP2C, esterases, and UGTs. For class 1B drugs, oral absorption is high and the predominant clearance mechanism is hepatic uptake mediated by OATP transporters. High permeability neutral/basic drugs (class 2) showed high oral absorption, with metabolism mediated generally by CYP3A, CYP2D6 and UGTs as the predominant clearance mechanism. Class 3A/4 drugs showed moderate absorption with dominant renal clearance involving OAT/OCT2 transporters. Class 3B drugs showed low to moderate absorption with hepatic uptake (OATPs) and/or renal clearance as primary clearance mechanisms. The highest DDI risk is typically seen with class 2/1B/3B compounds manifested by inhibition of either CYP metabolism or active hepatic uptake. Class 2 showed a wider range in AUC change likely due to a variety of enzymes involved. DDI risk for class 3A/4 is small and associated with inhibition of renal transporters. ECCS provides a framework to project ADME profiles and further enables prediction of victim DDI liabilities in drug discovery and development.

  20. Liposomal Drug Product Development and Quality: Current US Experience and Perspective.

    Science.gov (United States)

    Kapoor, Mamta; Lee, Sau L; Tyner, Katherine M

    2017-05-01

    Research in the area of liposomes has grown substantially in the past few decades. Liposomes are lipid bilayer structures that can incorporate drug substances to modify the drug's pharmacokinetic profile thereby improving drug delivery. The agency has received over 400 liposomal drug product submissions (excluding combination therapies), and there are currently eight approved liposomal drug products on the US market. In order to identify the pain points in development and manufacturing of liposomal drug products, a retrospective analysis was performed from a quality perspective on submissions for new and generic liposomal drug products. General analysis on liposomal drug product submissions was also performed. Results indicated that 96% of the submissions were Investigational New Drug (IND) applications, 3% were New Drug Applications (NDAs), and the remaining 1% was Abbreviated New Drug Applications (ANDAs). Doxorubicin hydrochloride was the most commonly used drug substance incorporated into the liposomes (31%). The majority of the liposomal products were administered via intravenous route (84%) with cancer (various types) being the most common indication (63%). From a quality perspective, major challenges during the development of liposomal drug products included identification and (appropriate) characterization of critical quality attributes of liposomal drug products and suitable control strategies during product development. By focusing on these areas, a faster and more efficient development of liposomal drug products may be achieved. Additionally, in this way, the drug review process for such products can be streamlined.

  1. Bioactivity of Hybrid Polymeric Magnetic Nanoparticles and Their Applications in Drug Delivery.

    Science.gov (United States)

    Mohammed, Leena; Ragab, Doaa; Gomaa, Hassan

    2016-01-01

    Engineered magnetic nanoparticles (MNPs) possess unique properties and hold great potential in biomedicine and clinical applications. With their magnetic properties and their ability to work at cellular and molecular level, MNP have been applied both in-vitro and in-vivo in targeted drug delivery and imaging. Focusing on Iron Oxide Superparamagnetic nanoparticles (SPIONs), this paper elaborates on the recent advances in development of hybrid polymeric-magnetic nanoparticles. Their main applications in drug delivery include Chemotherapeutics, Hyperthermia treatment, Radio-therapeutics, Gene delivary, and Biotheraputics. Physiochemical properties such as size, shape, surface and magnetic properties are key factors in determining their behavior. Additionally tailoring SPIONs surface is often vital for desired cell targetting and improved efficiency. Polymer coating is specifically reviewed with brief discussion of SPIONs administration routes. Commonly used drug release models for describing release mechanisms and the nanotoxicity aspects are also discussed. This review focus on superparamagnetic nanoparticles coated with different types of polymers starting with the key physiochemical features that dominate their behavior. The importance of surface modification is addressed. Subsequently, the major classes of polymer modified iron oxide nanoparticles is demonstrated according to their clinical use and application. Clinically approved nanoparticles are then addressed and the different routes of administration are mentioned. Lastly, mathematical models of drug release profile of the common used nanoparticles are addressed. MNPs emerging in recent medicine are remarkable for both imaging and therapeutics, particularly, as drug carriers for their great potential in targeted delivery and cancer treatment. Targeting ability and biocompatibility can be improved though surface coating which provides a mean to alter the surface features including physical characteristics and

  2. Adverse drug reactions after intravenous rituximab infusion are more common in hematologic malignancies than in autoimmune disorders and can be predicted by the combination of few clinical and laboratory parameters: results from a retrospective, multicenter study of 374 patients.

    Science.gov (United States)

    D'Arena, Giovanni; Simeon, Vittorio; Laurenti, Luca; Cimminiello, Michele; Innocenti, Idanna; Gilio, Michele; Padula, Angela; Vigliotti, Maria Luigia; De Lorenzo, Sonya; Loseto, Giacomo; Passarelli, Anna; Di Minno, Matteo Nicola Dario; Tucci, Marco; De Feo, Vincenzo; D'Auria, Fiorella; Silvestris, Francesco; Di Minno, Giovanni; Musto, Pellegrino

    2017-11-01

    Rituximab is an effective treatment for CD20 + B-cell malignancies and autoimmune disorders. However, adverse drug reactions (ADRs) may occur after rituximab infusion, causing, in rare cases, its discontinuation. In this multicenter, retrospective study, among 374 patients treated with rituximab i.v., 23.5% experienced ADRs. Mean follow-up was 20.6 months (range 8-135). Overall, ADRs were significantly more frequent in non-Hodgkin lymphomas (NHL) and chronic lymphocytic leukemias (25-35.9%), than in autoimmune diseases (9.4-17.5%) (p < .0001). Grade 3-4 toxicity was observed in eight patients (2.1%), and in four of them (1% of all patients) definitive drug discontinuation was necessary. Interestingly, three groups of patients with different risk of developing ADR were identified, according to a predictive heat-map developed combining four parameters (splenomegaly, history of allergy, hemoglobin levels and gender) selected by multivariate analysis. This model may be useful in identifying patients at higher risk of ADRs, needing appropriate preventing therapies.

  3. Application of rotational atherectomy in the drug-eluting stent era

    Science.gov (United States)

    Chen, Chun-Chi; Hsieh, I-Chang

    2013-01-01

    Rotational atherectomy (RA) was introduced in the interventional arena in 1988 as a dedicated device for calcified lesions. Due to the complexity of the technique, the development of alternative methods such as the cutting balloon procedure, and the high restenosis rate of subsequent bare metal stenting in long lesions, its use had later declined. However, with the increasing use of drug-eluting stents (DES) and the aggressive treatment of longer lesions, the number of procedure performed with RA has increased significantly again in recent years. In this article, we reviewed the application of RA in DES era. PMID:24133506

  4. Synthesis of click-reactive HPMA copolymers using RAFT polymerization for drug delivery applications

    DEFF Research Database (Denmark)

    Ebbesen, Morten F; Schaffert, D.H.; Crowley, Michael L

    2013-01-01

    This study describes a versatile strategy combining reversible addition fragmentation transfer (RAFT) polymerization and click chemistry to synthesize well-defined, reactive copolymers of N-(2-hydroxypropyl)methacrylamide (HPMA) for drug delivery applications. A novel azide containing monomer N-(3......-azidopropyl)methacrylamide (AzMA) was synthesized and copolymerized with HPMA using RAFT polymerization to provide p(HPMA-co-AzMA) copolymers with high control of molecular weight (∼10–54 kDa) and polydispersity (≤1.06). The utility of the side-chain azide functionality by Cu(I)-catalyzed azide...

  5. Supply and demand: application of Lean Six Sigma methods to improve drug round efficiency and release nursing time.

    Science.gov (United States)

    Kieran, Maríosa; Cleary, Mary; De Brún, Aoife; Igoe, Aileen

    2017-10-01

    To improve efficiency, reduce interruptions and reduce the time taken to complete oral drug rounds. Lean Six Sigma methods were applied to improve drug round efficiency using a pre- and post-intervention design. A 20-bed orthopaedic ward in a large teaching hospital in Ireland. Pharmacy, nursing and quality improvement staff. A multifaceted intervention was designed which included changes in processes related to drug trolley organization and drug supply planning. A communications campaign aimed at reducing interruptions during nurse-led during rounds was also developed and implemented. Average number of interruptions, average drug round time and variation in time taken to complete drug round. At baseline, the oral drug round took an average of 125 min. Following application of Lean Six Sigma methods, the average drug round time decreased by 51 min. The average number of interruptions per drug round reduced from an average of 12 at baseline to 11 following intervention, with a 75% reduction in drug supply interruptions. Lean Six Sigma methodology was successfully employed to reduce interruptions and to reduce time taken to complete the oral drug round. © The Author 2017. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  6. Intravenous paracetamol and patent ductus arteriosus closure in preterm infants

    Directory of Open Access Journals (Sweden)

    Rizky Adriansyah

    2017-08-01

    Full Text Available Background Indomethacin and ibuprofen are the drugs of choice for closure of patent ductus arteriosus (PDA in preterm infants. However, intravenous preparations are of limited availability in Indonesia. Circumstantial evidence has shown that intravenous paracetamol may be an alternative therapy for PDA closure in premature infants. Objective To evaluate the effect of intravenous paracetamol on PDA closure in preterm infants. Methods A before-and-after study was conducted between May and August 2014 in Cipto Mangunkusumo General Hospital, Jakarta in preterm infants with hemodynamically significant PDAs, as established by echocardiography using the following criteria: duct diameter >1.4 mm/kg, left atrium to aorta ratio >1.4, and mean velocity in the left pulmonary artery >0.42 m/s or mean diastolic velocity in the left pulmonary artery >0.2 m/s. Subjects, aged 2 and 7 days, received intravenous paracetamol (15 mg/kg every six hours for 3 days. Paired T-test was used to compare pre-intervention PDA diameter to those assessed at 24 hours after the intervention and at 14 days of life. Results Twenty-nine subjects had a mean gestational age of 30.8 weeks and mean birth weight of 1,347 grams. Nineteen (65.5% patients had closed PDAs at the day 14 evaluation, 1 experienced PDA reopening, and 9 had failed PDA closure. No liver toxicity was identified. Mean duct diameters before, 24 hours after the intervention, and at 14 days of life were 3.0, 0.9, and 0.6 mm, respectively (P<0.0001. Conclusion Intravenous paracetamol seems to be reasonably effective for PDA closure in preterm infants.

  7. Quantification of drug-loaded magnetic nanoparticles in rabbit liver and tumor after in vivo administration

    Energy Technology Data Exchange (ETDEWEB)

    Tietze, Rainer; Jurgons, Roland; Lyer, Stefan; Schreiber, Eveline [Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander-University Erlangen-Nuernberg, Waldstr. 1, 91054 Erlangen (Germany); Wiekhorst, Frank; Eberbeck, Dietmar; Richter, Heike; Steinhoff, Uwe; Trahms, Lutz [Physikalisch-Technische Bundesanstalt, Berlin (Germany); Alexiou, Christoph [Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander-University Erlangen-Nuernberg, Waldstr. 1, 91054 Erlangen (Germany)], E-mail: C.Alexiou@web.de

    2009-05-15

    Magnetic nanoparticles have been investigated for biomedical applications for more than 30 years. The development of biocompatible nanosized drug delivery systems for specific targeting of therapeutics is imminent in medical research, especially for treating cancer and vascular diseases. We used drug-labeled magnetic iron oxide nanoparticles, which were attracted to an experimental tumor in rabbits with an external magnetic field (magnetic drug targeting, MDT). Aim of this study was to detect and quantify the biodistribution of the magnetic nanoparticles by magnetorelaxometry. The study shows higher amount of nanoparticles in the tumor after intraarterial application and MDT compared to intravenous administration.

  8. Molecular characterization of hepatitis C virus for determination of subtypes and detection of resistance mutations to protease inhibitors in a group of intravenous drug users co-infected with HIV.

    Science.gov (United States)

    Silva, Tânia; Cortes Martins, Helena; Coutinho, Rodrigo; Leitão, Emília; Silva, Rui; Pádua, Elizabeth

    2015-09-01

    Modifications in therapeutic regimens for the treatment of hepatitis C virus (HCV) have been observed since the approval of viral protease inhibitors (PI), and the selection of natural drug-resistant variants has been also reported. Thus, it becomes crucial to be aware of consequences of new therapeutic approaches and make available tools for monitoring the infection. The study aimed to apply an "in-house" method for amplification and sequencing of the NS3 region which is the target of PI, and allowing simultaneously the classification of viral subtypes and identification of resistance mutations. Forty-seven samples collected from HIV injecting drug users and drug naive for HCV protease inhibitors were tested for anti-HCV antibodies, 93.6% of them had a positive result and in 70.5% was determined HCV active infection. High frequency of subtype 1a (46.2%), followed by an equal proportion of subtypes 3a, 4a, and 4d (15.4%) was obtained. Two potential recombinants, RF1_2k/1b (3.8%) and 2q/2k (3.8%) were identified. Substitutions V36L/P, T54A, I72L/N/T/V, Q80K/G, S122R/T, D168Q, and I170L/V were observed in 65.4% of the samples. The T54A and Q80K mutations, and the combination V36L + T54A were also identified. Polymorphisms were observed exclusively associated with specific genotypes, particularly, I72L and D168Q with genotype 3, and S122T with genotype 4. The V36L substitution was identified in 92.8% of sequences of non-genotype 1 denoting that this amino acid substitution is a natural polymorphism associated with non-genotype 1 strains. Although no major PI resistance mutations were detected, a more extensive study is needed to evaluate the impact of mutations identified in efficacy of PI treatment. © 2015 Wiley Periodicals, Inc.

  9. Development of description framework of pharmacodynamics ontology and its application to possible drug-drug interaction reasoning.

    Science.gov (United States)

    Imai, Takeshi; Hayakawa, Masayo; Ohe, Kazuhiko

    2013-01-01

    Prediction of synergistic or antagonistic effects of drug-drug interaction (DDI) in vivo has been of considerable interest over the years. Formal representation of pharmacological knowledge such as ontology is indispensable for machine reasoning of possible DDIs. However, current pharmacology knowledge bases are not sufficient to provide formal representation of DDI information. With this background, this paper presents: (1) a description framework of pharmacodynamics ontology; and (2) a methodology to utilize pharmacodynamics ontology to detect different types of possible DDI pairs with supporting information such as underlying pharmacodynamics mechanisms. We also evaluated our methodology in the field of drugs related to noradrenaline signal transduction process and 11 different types of possible DDI pairs were detected. The main features of our methodology are the explanation capability of the reason for possible DDIs and the distinguishability of different types of DDIs. These features will not only be useful for providing supporting information to prescribers, but also for large-scale monitoring of drug safety.

  10. Differential effect of intravenous S-ketamine and fentanyl on atypical odontalgia and capsaicin-evoked pain

    DEFF Research Database (Denmark)

    Baad-Hansen, Lene; Juhl, Gitte Irene; Jensen, Troels Staehelin

    2007-01-01

    temporal summation were compared between groups and sides. Both drugs failed to produce an analgesic effect on spontaneous AO pain, but fentanyl effectively reduced capsaicin-evoked pain. AO patients showed increased sensitivity to capsaicin and heat pain, but no significant differences in cold......Atypical odontalgia (AO) is an intraoral pain condition of currently unknown mechanisms. In 10 AO patients and 10 matched healthy controls, we examined the effect of intravenous infusion of an N-methyl-D-aspartate (NMDA) receptor antagonist S-ketamine and a mu-opioid agonist fentanyl on spontaneous...... AO pain and on an acute intraoral nociceptive input evoked by topical application of capsaicin. The drugs were administered in a randomized, placebo-controlled, cross-over manner. Furthermore, measures of intraoral sensitivity to mechanical and thermal quantitative sensory testing (QST) including...

  11. Intravenous lignocaine infusion for intractable pain in Ewing's sarcoma

    Directory of Open Access Journals (Sweden)

    Nivedita Page

    2018-01-01

    Full Text Available A 23-year-old female presented to our palliative care center with Ewing's sarcoma of the humerus with lung metastases. Pain in her arm was unrelieved by nonsteroidal anti-inflammatory drugs, neuropathic medication as well as morphine. She could not tolerate any further increase in opioid dose but was so distraught due to the pain that she wanted to die. An intravenous lignocaine infusion in a dose of 2 mg/kg was given over an hour for three successive days. This successfully relieved her pain after which she was settled with her original medication. We feel that in palliative care settings, where intractable pain and tolerance to morphine are so common, intravenous lignocaine infusions could provide a safe and effective tool for pain relief.

  12. Conversion from intravenous to oral medications: assessment of a computerized intervention for hospitalized patients.

    Science.gov (United States)

    Fischer, Michael A; Solomon, Daniel H; Teich, Jonathan M; Avorn, Jerry

    2003-11-24

    Many hospitalized patients continue to receive intravenous medications longer than necessary. Earlier conversion from the intravenous to the oral route could increase patient safety and comfort, reduce costs, and facilitate earlier discharge from the hospital without compromising clinical care. We examined the effect of a computer-based intervention to prompt physicians to switch appropriate patients from intravenous to oral medications. This study was performed at Brigham and Women's Hospital, an academic tertiary care hospital at which all medications are ordered online. We targeted 5 medications with equal oral and intravenous bioavailability: fluconazole, levofloxacin, metronidazole, ranitidine, and amiodarone. We used the hospital's computerized order entry system to prompt physicians to convert appropriate intravenous medications to the oral route. We measured the total use of the targeted medications via each route in the 4 months before and after the implementation of the intervention. We also measured the rate at which physicians responded to the intervention when prompted. The average intravenous defined daily dose declined by 11.1% (P =.002) from the preintervention to the postintervention period, while the average oral defined daily dose increased by 3.7% (P =.002). Length of stay, case-mix index, and total drug use at the hospital increased during the study period. The average total monthly use of the intravenous preparation of all of the targeted medications declined in the 4 months after the intervention began, compared with the 4 months before. In 35.6% of 1045 orders for which a prompt was generated, the physician either made a conversion from the intravenous to the oral version or canceled the order altogether. Computer-generated reminders can produce a substantial reduction in excessive use of targeted intravenous medications. As online prescribing becomes more common, this approach can be used to reduce excess use of intravenous medications

  13. Increases in Intravenous Magnesium Use among Hospitalized Patients: An Institution Cross-Sectional Experience

    Directory of Open Access Journals (Sweden)

    Bryce A. Kiberd

    2015-06-01

    Full Text Available Background: Among hospitalized patients, indications for the measurement of magnesium levels and treatment of hypomagnesemia with intravenous magnesium are not well defined. Recently, there have been reports of worldwide shortages of intravenous magnesium sulphate. Objective: To examine secular trends in the administration of intravenous magnesium on hospital wards at a tertiary care institution. The secondary objective is to identify factors associated with magnesium use among admitted patients. Methods: Retrospective cross-section review of hospitalized patients at a single Canadian tertiary care center. Utilization of non-parental nutrition intravenous magnesium from 2003 to 2013 stratified by hospital ward was examined. In addition, patient level data from select wards (including medical and surgical services was examined at early and more recent time period (4/2006 versus 4/2013. Results: Among the 248,329 hospitalized patients, intravenous magnesium use increased by 2.86 fold from 2003 to 2013. Not all wards had an increase whereas some had nearly a 10 fold increase in use. In the sample ( n = 769, (adjusting for admission magnesium level, presence of an indication for intravenous magnesium, ward location, comorbidity and demographics intravenous magnesium administration was higher (25.8 % versus 5.5 % in 2013 versus 2006 (OR 13.91 (95 % CI, 6.21–31.17, p < 0.001. Despite this increase in intravenous magnesium administration, <3 % of patients were admitted on oral magnesium in 2006 and 2013. For patients receiving intravenous magnesium only a minority were discharged on oral therapy despite low levels. Conclusions: This center has witnessed a considerable increase in the use of in-hospital intravenous magnesium over the last 6 years that cannot be explained for by medical indications. The risks and benefits of this therapy deserve further study. If this change in practice is representative of other North American hospitals, it may be

  14. Nanomedicine: towards development of patient-friendly drug-delivery systems for oncological applications

    Directory of Open Access Journals (Sweden)

    Ranganathan R

    2012-02-01

    Full Text Available Ramya Ranganathan1,*, Shruthilaya Madanmohan1,*, Akila Kesavan1, Ganga Baskar1, Yoganathan Ramia Krishnamoorthy2, Roy Santosham3, D Ponraju4, Suresh Kumar Rayala2, Ganesh Venkatraman1 1Department of Human Genetics, Sri Ramachandra University, Porur, 2Department of Biotechnology, Indian Institute of Technology, Madras, 3Department of Radiology and Imaging Sciences, Sri Ramachandra University, Porur, Chennai, 4Safety Engineering Division, Nuclear and Engineering Safety Group, Indira Gandhi Center for Atomic Research, Kalpakkam, India*Authors contributed equally to this workAbstract: The focus on nanotechnology in cancer treatment and diagnosis has intensified due to the serious side effects caused by anticancer agents as a result of their cytotoxic actions on normal cells. This nonspecific action of chemotherapy has awakened a need for formulations capable of definitive targeting with enhanced tumor-killing. Nanooncology, the application of nanobiotechnology to the management of cancer, is currently the most important area of nanomedicine. Currently several nanomaterial-based drug-delivery systems are in vogue and several others are in various stages of development. Tumor-targeted drug-delivery systems are envisioned as magic bullets for cancer therapy and several groups are working globally for development of robust systems.Keywords: patient-friendly, drug-delivery systems, cancer, nanomedicine

  15. Controlled adsorption and release onto calcium phosphates materials and drug delivery applications

    Directory of Open Access Journals (Sweden)

    Barroug A.

    2013-11-01

    Full Text Available The adsorptive properties of synthetic calcium phosphates analogous to bone mineral were examined with respect to cisplatin and risedronate, two biological active drugs; the uptake and release experiments were carried out under various conditions in order to understand the basic mechanism of interaction. The effect of temperature and solution composition were highlighted and discussed. The adsorption results obtained for the therapeutic agents demonstrated that, depending on the conditions investigated (nature of the sorbent, concentration range, ionic composition, temperature…, the shape of the isotherms is of Freundlich or Langmuir type. The adsorption is described as an ion-exchange process in dilute solutions, while the interaction appears to be reactive for concentrated solutions (dissolution of mineral ions from the apatite substrate and formation of soluble calcium complex and/or precipitation of calcium salts involving sorbate molecules. The information gained on the surface reactivity of calcium phosphate were exploited to associate an antibiotic to calcium phosphate cements for drug delivery applications. The specimens were obtained by combination of calcium phosphate and calcium carbonate powders upon mixing with water. The physicochemical properties of the paste were altered by the drug loading method (in the liquid or solid phase. Thus, a dose-dependent effect was noticed for the paste setting time, hardening and the release process.

  16. Applicator for in-vitro ultrasound-activated targeted drug delivery

    Science.gov (United States)

    Gerold, B.; Gourevich, D.; Volovick, A.; Xu, D.; Arditti, F.; Prentice, P.; Cochran, S.; Gnaim, J.; Medan, Y.; Wang, L.; Melzer, A.

    2012-10-01

    Reducing toxicity and improving uptake of cancer drugs in tumors are important goals of targeted drug delivery (TDD). Ultrasonic drug release from various encapsulants has been a focus of many research groups. However, a single standard ultrasonic device, viable for use by biologists, is not currently present in the market. The device reported here is designed to allow investigation of the impact of ultrasound on cellular uptake and cell viability in-vitro. In it, single-element transducers with different operating frequencies are mounted below a standard 96-well plate. The plate is moved above the transducers, such that each line of wells can be sonicated at a different frequency. To assess the device, 96-well plates were seeded with cells and sonicated using different ultrasonic parameters, with and without doxorubicin. Cell viability was measured by colorimetric MTT assay and the uptake of doxorubicin by cells was also determined. The device proved to be highly viable in preliminary tests; it demonstrated that change in ultrasonic parameters produces different effect on cells. For example, increase in uptake of doxorubicin was demonstrated following ultrasound application. The growing interest in ultrasound-activated TDD emphasizes the need for standardization of the ultrasound device and the one reported here may offer some indications of how that may be achieved. It is planned to further improve the prototype by increasing the number of ultrasonic frequencies and degrees of freedom for each transducer.

  17. Text Mining for Drugs and Chemical Compounds: Methods, Tools and Applications.

    Science.gov (United States)

    Vazquez, Miguel; Krallinger, Martin; Leitner, Florian; Valencia, Alfonso

    2011-06-01

    Providing prior knowledge about biological properties of chemicals, such as kinetic values, protein targets, or toxic effects, can facilitate many aspects of drug development. Chemical information is rapidly accumulating in all sorts of free text documents like patents, industry reports, or scientific articles, which has motivated the development of specifically tailored text mining applications. Despite the potential gains, chemical text mining still faces significant challenges. One of the most salient is the recognition of chemical entities mentioned in text. To help practitioners contribute to this area, a good portion of this review is devoted to this issue, and presents the basic concepts and principles underlying the main strategies. The technical details are introduced and accompanied by relevant bibliographic references. Other tasks discussed are retrieving relevant articles, identifying relationships between chemicals and other entities, or determining the chemical structures of chemicals mentioned in text. This review also introduces a number of published applications that can be used to build pipelines in topics like drug side effects, toxicity, and protein-disease-compound network analysis. We conclude the review with an outlook on how we expect the field to evolve, discussing its possibilities and its current limitations. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Synthesis and evaluation of functional alginate hydrogels based on click chemistry for drug delivery applications.

    Science.gov (United States)

    García-Astrain, Clara; Avérous, Luc

    2018-06-15

    Environment-sensitive alginate-based hydrogels for drug delivery applications are receiving increasing attention. However, most work in this field involves traditional cross-linking strategies which led to hydrogels with poor long-term stability. Herein, a series of chemically cross-linked alginate hydrogels was synthesized via click chemistry using Diels-Alder reaction by reacting furan-modified alginate and bifunctional cross-linkers. Alginate was successfully functionalized with furfurylamine. Then, 3D architectures were synthesized with water-soluble bismaleimides. Different substitution degrees were achieved in order to study the effect of alginate modification and the cross-linking extent over the behaviour of the hydrogels. The ensuing hydrogels were analysed in terms of microstructure, swelling, structure modification and rheological behaviour. The materials response to external stimuli such as pH was also investigated, revealing a pulsatile behaviour in a large pH range (1-13) and a clear pH-dependent swelling. Finally, vanillin release studies were conducted to demonstrate the potential of these biobased materials for drug delivery applications. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. COMPARATIVE STUDY OF EFFECT OF INTRAVENOUS MAGNESIUM SULPHATE AND INTRAVENOUS FENTANYL IN ATTENUATING THE HAEMODYNAMIC RESPONSES TO LARYNGOSCOPY AND INTUBATION

    Directory of Open Access Journals (Sweden)

    Patta

    2016-07-01

    Full Text Available AIM To compare the haemodynamic response to laryngoscopy and intubation with intravenous MgSO4 and intravenous fentanyl. METHODS Fifty adult patients were divided into two groups randomly into group M and group F. Patients of group M received 30 mg/kg body weight of IV MgSO4 and group F received IV fentanyl 1.5 µg/kg 5 minutes before intubation. RESULTS IV Fentanyl showed greater degree of haemodynamic stability i.e. rise in heart rate, mean arterial pressure during laryngoscopy and intubation compared to IV MgSO4. IV fentanyl showed side effects like respiratory depression, nausea and vomiting. CONCLUSION IV fentanyl is a better drug in controlling haemodynamic response to laryngoscopy and intubation.

  20. Polyethyleneimine-modified iron oxide nanoparticles for brain tumor drug delivery using magnetic targeting and intra-carotid administration

    OpenAIRE

    Chertok, Beata; David, Allan E.; Yang, Victor C.

    2010-01-01

    This study aimed to examine the applicability of polyethyleneimine (PEI)-modified magnetic nanoparticles (GPEI) as a potential vascular drug/gene carrier to brain tumors. In vitro, GPEI exhibited high cell association and low cell toxicity – properties which are highly desirable for intracellular drug/gene delivery. In addition, a high saturation magnetization of 93 emu/g Fe was expected to facilitate magnetic targeting of GPEI to brain tumor lesions. However, following intravenous administra...

  1. Intentional intravenous mercury injection | Yudelowitz | South African ...

    African Journals Online (AJOL)

    Intravenous mercury injection is rarely seen, with few documented cases. Treatment strategies are not clearly defined for such cases, although a few options do show benefit. This case report describes a 29-year-old man suffering from bipolar disorder, who presented following self-inflicted intravenous injection of mercury.

  2. Today and tomorrow of intravenous coronary angiography programme in Japan

    International Nuclear Information System (INIS)

    Ando, Masami; Hyodo, Kazuyuki

    1994-01-01

    Development of an intravenous coronary angiography system using monochromated synchrotron radiation at the Photon Factory is described. This comprises an asymmetric cut silicon monochromator crystal to get a larger exposure area, a two dimensional imaging system using an imaging intensifier coupled to a CCD TV camera and a fast video data acquisition system. The whole system is under development using alive dogs. A future system including a dedicated insertion device applicable to alive humans is also proposed. (author)

  3. Intravenous elimination and percutaneous absorption of topically applied melphalan-14C (NSC-8806) in Yorkshire white pigs. Final report, 17 August-1 December 1977

    International Nuclear Information System (INIS)

    Skierkowski, P.; Murphy, J.C.; Watson, E.S.; Folk, R.M.; Pavkov, K.L.

    1978-01-01

    The distribution and elimination of intravenously administered Melphalan-14C (NSC-8806) was studied in female, weanling Yorkshire white pigs. A three compartment pharmacokinetic model is indicated with a very slow elimination phase (half life = 214 hours). Assay of tissue samples indicate bone and fat may be acting as depots for the drug. After 8 days an average of 70% was eliminated via the urine. Percutaneous studies showed an average of 4.02% of the applied dose was absorbed after 14 days. Significant levels of radioactivity were also detected in skin surrounding the site of application

  4. Catheter indwell time and phlebitis development during peripheral intravenous catheter administration.

    Science.gov (United States)

    Pasalioglu, Kadriye Burcu; Kaya, Hatice

    2014-07-01

    Intravenous catheters have been indispensable tools of modern medicine. Although intravenous applications can be used for a multitude of purposes, these applications may cause complications, some of which have serious effects. Of these complications, the most commonly observed is phlebitis. This study was conducted to determine the effect of catheter indwell time on phlebitis development during peripheral intravenous catheter administration. This study determined the effect of catheter indwell time on phlebitis development during peripheral intravenous catheter administration. The study included a total of 103 individuals who were administered 439 catheters and satisfied the study enrollment criteria at one infectious diseases clinic in Istanbul/Turkey. Data were compiled from Patient Information Forms, Peripheral Intravenous Catheter and Therapy Information Forms, reported grades based on the Visual Infusion Phlebitis Assessment Scale, and Peripheral Intravenous Catheter Nurse Observation Forms. The data were analyzed using SPSS. Results : The mean patient age was 53.75±15.54 (standard deviation) years, and 59.2% of the study participants were men. Phlebitis was detected in 41.2% of peripheral intravenous catheters, and the rate decreased with increased catheter indwell time. Analyses showed that catheter indwell time, antibiotic usage, sex, and catheterization sites were significantly associated with development of phlebitis. The results of this study show that catheters can be used for longer periods of time when administered under optimal conditions and with appropriate surveillance.

  5. Nanotechnology applications and approaches for neuroregeneration and drug delivery to the central nervous system.

    Science.gov (United States)

    Silva, Gabriel A

    2010-06-01

    Nanotechnology is the science and engineering concerned with the design, synthesis, and characterization of materials and devices that have a functional organization in at least one dimension on the nanometer (i.e., one billionth of a meter) scale. The potential impact of bottom up self-assembling nanotechnology, custom made molecules that self-assemble or self-organize into higher ordered structures in response to a defined chemical or physical cue, and top down lithographic type technologies where detail is engineered at smaller scales starting from bulk materials, stems from the fact that these nanoengineered materials and devices exhibit emergent mesocale and macroscale chemical and physical properties that are often different than their constituent nanoscale building block molecules or materials. As such, applications of nanotechnology to medicine and biology allow the interaction and integration of cells and tissues with nanoengineered substrates at a molecular (i.e., subcellular) level with a very high degree of functional specificity and control. This review considers applications of nanotechnology aimed at the neuroprotection and functional regeneration of the central nervous system (CNS) following traumatic or degenerative insults, and nanotechnology approaches for delivering drugs and other small molecules across the blood-brain barrier. It also discusses developing platform technologies that may prove to have broad applications to medicine and physiology, including some being developed for rescuing or replacing anatomical and/or functional CNS structures.

  6. physico-chemical studies on DNA-drugs interaction and their analytical applications

    International Nuclear Information System (INIS)

    Kandil, S.A

    2003-01-01

    The present thesis is devoted to study the interaction of some antibacterial agents i.e. fluoroquinolones . these agents include ciprofloxacin, norfloxacin , ofloxacin , pefloxacin and levofloxacin with DNA. voltammetric and spectrophotometric methods were used to carry out this study. Also the interaction of the suggested drugs with DNA at the surface of carbon electrode by cyclic voltammetry and differential pulse techniques is examined. The work comprises three chapters: (1) includes an introduction of voltammetry , differential pulse, drug-DNA interaction and fluoroquinoline- DNA interaction and literature survey on fluoroquinolones.Chapter (II) includes preparation of the solutions and instruments which were used for the measurements using the different techniques.Chapter(III) comprises three parts; (1) deals with the interaction of fluoroquinolones (ciprofloxacin, norfloxacin, ofloxacin, pefloxacin and levofloxacin) with DNA in solution have been investigated by means of voltammetry and spectroscopy . the results show that the values of binding constant of fluoroquinolne drugs with DNA obtained through the changes of the anodic peak current, and their values are, 30900,31000,32300,32000 and 32500 M -1 respectively. or changes of absorption and values are, 36000,30200.38300,36500 and 34400 M -1 receptively.(II) includes voltammetric behavior of fluoroquinolones on DNA-modified carbon paste electrode. (III)includes analytical application for proposed method for the determination of levofloxacin as a typical example for fluoroquinolones. Concentration in the range 5.0x10 -7 ∼ 5.0x10 -6 mol/L , with a detection limit of 1.0x10 -7 mol/L. direct and simple determination of levofloxacin in urine was established with no manipulation of urine sample other than dilution 1:10

  7. Malária em usuários de drogas de administração endovenosa associada à soropositividade para HIV The association of malaria, HIV seropositivity and intravenous administration in drug users

    Directory of Open Access Journals (Sweden)

    Shin Shiang Lo

    1991-02-01

    not been to any possible transmission area of malaria. All of them had, however, taken cocaine, sharing the same contaminated needle and syringe. Previously, one person with imported malaria was detected, who had transmitted the disease to the first case in 1988 and also to a further group of 3 people in 1989. One of these three latter cases then transmitted the disease to two other people. As the group of people continued to use the drug among themselve, 2 new cases arose. Afterwards, they re-infected themselves again (one of the was re-infected twice. The test for Humam Immunodeficiency Vírus was positive for 5 individuals, of whom one had a negative result and 2 others did not undergo the test. This information is discussed within the present context.

  8. Postoperative analgesic efficacy of intravenous dexketoprofen in lumbar disc surgery.

    Science.gov (United States)

    Yazar, Mehmet Akif; Inan, Nurten; Ceyhan, Aysegul; Sut, Esra; Dikmen, Bayazit

    2011-07-01

    We investigated the postoperative analgesic efficacy and effect on total tramadol consumption of intravenous dexketoprofen trometamol, a new nonsteroidal anti-inflammatory drug, in patients that had undergone lumbar disc surgery. Sixty patients were included in this placebo-controlled, randomized, double-blind study. General anesthesia was applied to both groups. Group D (n=30) received dexketoprofen (50 mg) intravenously 30 minutes before the end of surgery and at the postoperative 12th hour, whereas group C (n=30) received 2 mL of 0.9% NaCL intravenously at the same time points. All patients received a patient controlled analgesia device with a tramadol, 25 mg bolus, 15 minutes lockout protocol, and were followed with visual analog scale, verbal rating scale, modified Aldrete recovery scoring system, and Ramsay sedation scale in the postoperative period. There was no significant difference between the groups for demographic data, duration of surgery, mean arterial pressure, and heart rate. The time to first postoperative analgesic requirement was significantly longer in group D (151.33±81.98 min) than group C (19±5.78 min) (Pdexketoprofen was an effective analgesic for postdiscectomy pain when used alone or in addition to opioids. It is easy to administer and decreases tramadol consumption and opioid-related side effects.

  9. Peripheral Applications of Drug-Coated Balloons: Past, Present and Future

    Energy Technology Data Exchange (ETDEWEB)

    Krokidis, Miltiadis, E-mail: mkrokidis@hotmail.com; Spiliopoulos, Stavros, E-mail: stavspiliop@upatras.gr; Katsanos, Konstantinos, E-mail: katsanos@med.upatras.gr; Sabharwal, Tarun, E-mail: tarun_sabharwal@yahoo.co.uk [Guy' s and St. Thomas' Hospitals, NHS Foundation Trust, Department of Radiology (United Kingdom)

    2013-04-15

    Drug-coated balloon (DCB) technologies represent the latest and hottest development in the field of endovascular treatment of peripheral arterial disease. Initial experience with paclitaxel-coated balloon use in the femoral artery has demonstrated lower mid-term restenosis and superior mid-term clinical outcomes in terms of improved wound healing and reduced repeat angioplasty rates compared with standard balloon angioplasty. Many companies are presently developing and/or improving DCB catheters and therefore ongoing, technical improvements of the already existing platforms, new drugs, and innovative carriers are expected. The ongoing basic research studies and various multicenter randomized, controlled trials that are currently in progress will offer valuable scientific insights regarding the long-term effectiveness and other crucial issues, such as efficacy in various vascular beds, optimal balloon dosage, and post angioplasty antiplatelet therapy. Future applications of these devices also could include in-stent restenosis, anastomotic stenosis of surgical bypass, and benign stenoses of the central venous system. The authors envision that DCB angioplasty will evolve to a major paradigm shift in the endovascular treatment of occlusive vascular diseases.

  10. Peripheral Applications of Drug-Coated Balloons: Past, Present and Future

    International Nuclear Information System (INIS)

    Krokidis, Miltiadis; Spiliopoulos, Stavros; Katsanos, Konstantinos; Sabharwal, Tarun

    2013-01-01

    Drug-coated balloon (DCB) technologies represent the latest and hottest development in the field of endovascular treatment of peripheral arterial disease. Initial experience with paclitaxel-coated balloon use in the femoral artery has demonstrated lower mid-term restenosis and superior mid-term clinical outcomes in terms of improved wound healing and reduced repeat angioplasty rates compared with standard balloon angioplasty. Many companies are presently developing and/or improving DCB catheters and therefore ongoing, technical improvements of the already existing platforms, new drugs, and innovative carriers are expected. The ongoing basic research studies and various multicenter randomized, controlled trials that are currently in progress will offer valuable scientific insights regarding the long-term effectiveness and other crucial issues, such as efficacy in various vascular beds, optimal balloon dosage, and post angioplasty antiplatelet therapy. Future applications of these devices also could include in-stent restenosis, anastomotic stenosis of surgical bypass, and benign stenoses of the central venous system. The authors envision that DCB angioplasty will evolve to a major paradigm shift in the endovascular treatment of occlusive vascular diseases.

  11. Frequency-controlled wireless shape memory polymer microactuator for drug delivery application.

    Science.gov (United States)

    Zainal, M A; Ahmad, A; Mohamed Ali, M S

    2017-03-01

    This paper reports the wireless Shape-Memory-Polymer actuator operated by external radio frequency magnetic fields and its application in a drug delivery device. The actuator is driven by a frequency-sensitive wireless resonant heater which is bonded directly to the Shape-Memory-Polymer and is activated only when the field frequency is tuned to the resonant frequency of heater. The heater is fabricated using a double-sided Cu-clad Polyimide with much simpler fabrication steps compared to previously reported methods. The actuation range of 140 μm as the tip opening distance is achieved at device temperature 44 °C in 30 s using 0.05 W RF power. A repeatability test shows that the actuator's average maximum displacement is 110 μm and standard deviation of 12 μm. An experiment is conducted to demonstrate drug release with 5 μL of an acidic solution loaded in the reservoir and the device is immersed in DI water. The actuator is successfully operated in water through wireless activation. The acidic solution is released and diffused in water with an average release rate of 0.172 μL/min.

  12. Magnetic microgels for drug targeting applications: Physical–chemical properties and cytotoxicity evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Turcu, Rodica, E-mail: rodica.turcu@itim-cj.ro [National Institute for Research and Development of Isotopic and Molecular Technologies, 65-103 Donath Street, 400293 Cluj-Napoca (Romania); Craciunescu, Izabell [National Institute for Research and Development of Isotopic and Molecular Technologies, 65-103 Donath Street, 400293 Cluj-Napoca (Romania); Garamus, Vasil M. [Helmholtz-Zentrum Geesthacht, Zentrum für Material- und Küstenforschung GmbH, 21502 Geesthacht (Germany); Janko, Christina; Lyer, Stefan; Tietze, Rainer; Alexiou, Christoph [ENT-Department, Else Kröner-Fresenius Stiftung-Professorship, Section for Experimental Oncology and Nanomedicine (SEON), University Hospital Erlangen (Germany); Vekas, Ladislau, E-mail: vekas@acad-tim.tm.edu.ro [Romanian Academy-Timisoara Branch, CFATR, Laboratory of Magnetic Fluids, Mihai Viteazul Street 24, 300223 Timisoara (Romania)

    2015-04-15

    Magnetoresponsive microgels with high saturation magnetization values have been obtained by a strategy based on the miniemulsion method using high colloidal stability organic carrier ferrofluid as primary material. Hydrophobic nanoparticles Fe{sub 3}O{sub 4}/oleic acid are densely packed into well-defined spherical nanoparticle clusters coated with polymers with sizes in the range 40–350 nm. Physical–chemical characteristics of magnetic microgels were investigated by TEM, SAXS, XPS and VSM measurements with the focus on the structure–properties relationship. The impact of magnetic microgels loaded with anticancer drug mitoxantrone (MTO) on the non-adherent human T cell leukemia line Jurkat was investigated in multiparameter flow cytometry. We showed that both MTO and microgel-loaded MTO penetrate into cells and both induce apoptosis and later secondary necrosis in a time- and dose dependent manner. In contrast, microgels without MTO are not cytotoxic in the corresponding concentrations. Our results show that MTO-loaded microgels are promising structures for application in magnetic drug targeting. - Highlights: • Densely packed spherical clusters of magnetic nanoparticles were obtained. • High magnetization microgels with superparamagnetic behavior are reported. • The facile and reproducible synthesis procedure applied is easy to be up-scaled. • The toxicity tests show that magnetic microgels are not cytotoxic. • We show that mitoxantrone loaded microgels induce death of Jurkat cells.

  13. A pilot study of a smartphone application supporting recovery from drug addiction.

    Science.gov (United States)

    Liang, Di; Han, Hui; Du, Jiang; Zhao, Min; Hser, Yih-Ing

    2018-05-01

    Mobile health (mHealth) technologies have the potential to facilitate self-monitoring and self-management for individuals with substance use disorders (SUD). S-Health is a bilingual smartphone application based on cognitive behavioral principles and is designed to support recovery from drug addiction by trigger recognition so as to allow practice in-the-moment coping to prevent relapse. For this pilot randomized controlled study, 75 participants were recruited from methadone maintenance treatment clinics and the social worker consortium in Shanghai, China. Participants in the control group (N=25) received text messages from S-Health (e.g., HIV prevention and other educational materials). Participants in the intervention group (N=50) received both text messages and daily surveys on cravings, affects, triggers, responses to triggers, and social contexts. At the end of the 1-month study trial, 26.2% of the intervention group and 50% of the control group had positive urine test results (p=0.06). Also, the number of days using drug in the past week was significantly lower among participants in the intervention group (Mean=0.71, SD=1.87) relative to the control group (Mean=2.20, SD=3.06) (paddiction. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Production methodologies of polymeric and hydrogel particles for drug delivery applications.

    Science.gov (United States)

    Lima, Ana Catarina; Sher, Praveen; Mano, João F

    2012-02-01

    Polymeric particles are ideal vehicles for controlled delivery applications due to their ability to encapsulate a variety of substances, namely low- and high-molecular mass therapeutics, antigens or DNA. Micro and nano scale spherical materials have been developed as carriers for therapies, using appropriated methodologies, in order to achieve a prolonged and controlled drug administration. This paper reviews the methodologies used for the production of polymeric micro/nanoparticles. Emulsions, phase separation, spray drying, ionic gelation, polyelectrolyte complexation and supercritical fluids precipitation are all widely used processes for polymeric micro/nanoencapsulation. This paper also discusses the recent developments and patents reported in this field. Other less conventional methodologies are also described, such as the use of superhydrophobic substrates to produce hydrogel and polymeric particulate biomaterials. Polymeric drug delivery systems have gained increased importance due to the need for improving the efficiency and versatility of existing therapies. This allows the development of innovative concepts that could create more efficient systems, which in turn may address many healthcare needs worldwide. The existing methods to produce polymeric release systems have some critical drawbacks, which compromise the efficiency of these techniques. Improvements and development of new methodologies could be achieved by using multidisciplinary approaches and tools taken from other subjects, including nanotechnologies, biomimetics, tissue engineering, polymer science or microfluidics.

  15. The application of drug delivery system about nanoparticles in nuclear medicine

    International Nuclear Information System (INIS)

    Yao Ning; Wang Rongfu

    2013-01-01

    The development of nuclear medicine relies on the advancement of precise probes at the cellular and molecular levels. Nanoparticle as a new molecular probe, is mainly consists of the targeting groups, imaging groups, the superb biocompatible 'shells' and the modify groups. These nanoparticles have the better image contrast by targeting positioning in the target tissues and cells. At the same time, because of the diversity of the materials and the uniqueness of the structures, the nanoparticles can realize multimodal imaging at molecular level, which complement each other's advantages of different imaging modals. If the treatment groups are joined into the nanoparticles, a new nanoparticles are formed-the theranosis nanoparticles, which have realized the diagnosis and therapy at the molecular level synchronously. In addition, the application of intelligent nanoprobes can achieve the smart control of drug release and reduce the side effects of cancer treatment. Anyhow, the development of this new drug delivery system about nanoparticles has brought about a new breakthrough on the nuclear medicine. (authors)

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

    Science.gov (United States)

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

    2015-06-01

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

  17. Design of Hybrid Gels Based on Gellan-Cholesterol Derivative and P90G Liposomes for Drug Depot Applications

    Directory of Open Access Journals (Sweden)

    Nicole Zoratto

    2017-05-01

    Full Text Available Gels are extensively studied in the drug delivery field because of their potential benefits in therapeutics. Depot gel systems fall in this area, and the interest in their development has been focused on long-lasting, biocompatible, and resorbable delivery devices. The present work describes a new class of hybrid gels that stem from the interaction between liposomes based on P90G phospholipid and the cholesterol derivative of the polysaccharide gellan. The mechanical properties of these gels and the delivery profiles of the anti-inflammatory model drug diclofenac embedded in such systems confirmed the suitability of these hybrid gels as a good candidate for drug depot applications.

  18. Preparation of magnetic nanoparticles and their application to magnetic targeting drug delivery

    International Nuclear Information System (INIS)

    Li Guiping; Wang Yongxian

    2006-01-01

    Magnetic nanoparticles barrier is a novel kind of drug delivery system for magnetic targeting drugs, which can effectively deliver the drug to a tumor target site and increase therapeutic benefit, with the side effects minimized. This article summarizes the most outstanding papers on the of magnetic nanoparticles used as the targeting drug's delivery systems. (authors)

  19. A Review of the Effect of Processing Variables on the Fabrication of Electrospun Nanofibers for Drug Delivery Applications

    Directory of Open Access Journals (Sweden)

    Viness Pillay

    2013-01-01

    Full Text Available Electrospinning is a fast emerging technique for producing ultrafine fibers by utilizing electrostatic repulsive forces. The technique has gathered much attention due to the emergence of nanotechnology that sparked worldwide research interest in nanomaterials for their preparation and application in biomedicine and drug delivery. Electrospinning is a simple, adaptable, cost-effective, and versatile technique for producing nanofibers. For effective and efficient use of the technique, several processing parameters need to be optimized for fabricating polymeric nanofibers. The nanofiber morphology, size, porosity, surface area, and topography can be refined by varying these parameters. Such flexibility and diversity in nanofiber fabrication by electrospinning has broadened the horizons for widespread application of nanofibers in the areas of drug and gene delivery, wound dressing, and tissue engineering. Drug-loaded electrospun nanofibers have been used in implants, transdermal systems, wound dressings, and as devices for aiding the prevention of postsurgical abdominal adhesions and infection. They show great promise for use in drug delivery provided that one can confidently control the processing variables during fabrication. This paper provides a concise incursion into the application of electrospun nanofibers in drug delivery and cites pertinent processing parameters that may influence the performance of the nanofibers when applied to drug delivery.

  20. A Review of the Effect of Processing Variables on the Fabrication of Electro spun Nano fibers for Drug Delivery Applications

    International Nuclear Information System (INIS)

    Pillay, V.; Dott, C.; Choonara, Y.E.; Tyagi, Ch.; Tomar, L.; Kumar, P.; Toit, L.C.D.; Ndesendo, V.M.K.

    2013-01-01

    Electro spinning is a fast emerging technique for producing ultrafine fibers by utilizing electrostatic repulsive forces. The technique has gathered much attention due to the emergence of nano technology that sparked worldwide research interest in nano materials for their preparation and application in biomedicine and drug delivery. Electro spinning is a simple, adaptable, cost-effective, and versatile technique for producing nano fibers. For effective and efficient use of the technique, several processing parameters need to be optimized for fabricating polymeric nano fibers. The nano fiber morphology, size, porosity, surface area, and topography can be refined by varying these parameters. Such flexibility and diversity in nano fiber fabrication by electro spinning has broadened the horizons for widespread application of nano fibers in the areas of drug and gene delivery, wound dressing, and tissue engineering. Drug-loaded electro spun nano fibers have been used in implants, transdermal systems, wound dressings, and as devices for aiding the prevention of post surgical abdominal adhesions and infection. They show great promise for use in drug delivery provided that one can confidently control the processing variables during fabrication. This paper provides a concise incursion into the application of electro spun nano fibers in drug delivery and cites pertinent processing parameters that may influence the performance of the nano fibers when applied to drug delivery.

  1. Copper-gold nanoparticles: Fabrication, characteristic and application as drug carriers

    Energy Technology Data Exchange (ETDEWEB)

    Woźniak-Budych, Marta J., E-mail: marta.budych@amu.edu.pl; Langer, Krzysztof; Peplińska, Barbara; Przysiecka, Łucja; Jarek, Marcin; Jarzębski, Maciej; Jurga, Stefan

    2016-08-15

    In this investigation, the fabrication of porous core/shell nanostructures consisting of copper (core) and copper-gold nanoalloy (shell) for medical applications is presented. As a core triangular-shaped copper nanoparticles were used. The porous bimetallic nanoshell was prepared via galvanic reaction in the presence of oil-in water emulsion. It was proved that porous nanoalloy layer can be prepared at pH 7 and in the presence 0.1% and 0.5% oil-in water emulsion. The porous structure fabrication was mainly determined by volume fraction of hexadecane to acetone in the oil-in water emulsion and Zeta-potential of emulsion droplets (pH of emulsion). The influence of emulsion droplets size before galvanic reaction on porous structure preparation was negligible. It was found that doxorubicin could be easily introduced and released from porous core/shell nanostructures, due to spontaneous adsorption on the copper-gold nanoporous surface. The in vitro test showed that cytotoxic effect was more prominent once the doxorubicin was adsorbed on the porous copper-gold nanocarriers. It was demonstrated, that doxorubicin-loaded copper-gold nanostructures caused inhibition cell proliferation and viability of cancer cells, in a concentration-dependent manner. The results indicates that presented coper-gold nanocarrier have potential to be used in targeted cancer therapy, due to its porous structure and cytotoxic effect in cancer cells. - Highlights: • Porous copper-gold nanostructure as a cytostatic drug carrier was prepared. • Kinetics and thermodynamics of drug adsorption were studied. • DOX-loaded copper-gold nanoparticles showed a pH-controlled release rate. • DOX-loaded copper-gold NPs caused inhibition cell proliferation of cancer cells. • The Cu-Au NPs could serve as a theranostic platform for biomedical applications.

  2. Improving pharmacokinetic-pharmacodynamic modeling to investigate anti-infective chemotherapy with application to the current generation of antimalarial drugs.

    Directory of Open Access Journals (Sweden)

    Katherine Kay

    Full Text Available Mechanism-based pharmacokinetic-pharmacodynamic (PK/PD modelling is the standard computational technique for simulating drug treatment of infectious diseases with the potential to enhance our understanding of drug treatment outcomes, drug deployment strategies, and dosing regimens. Standard methodologies assume only a single drug is used, it acts only in its unconverted form, and that oral drugs are instantaneously absorbed across the gut wall to their site of action. For drugs with short half-lives, this absorption period accounts for a significant period of their time in the body. Treatment of infectious diseases often uses combination therapies, so we refined and substantially extended the PK/PD methodologies to incorporate (i time lags and drug concentration profiles resulting from absorption across the gut wall and, if required, conversion to another active form; (ii multiple drugs within a treatment combination; (iii differing modes of action of drugs in the combination: additive, synergistic, antagonistic; (iv drugs converted to an active metabolite with a similar mode of action. This methodology was applied to a case study of two first-line malaria treatments based on artemisinin combination therapies (ACTs, artemether-lumefantrine and artesunate-mefloquine where the likelihood of increased artemisinin tolerance/resistance has led to speculation on their continued long-term effectiveness. We note previous estimates of artemisinin kill rate were underestimated by a factor of seven, both the unconverted and converted form of the artemisinins kill parasites and the extended PK/PD methodology produced results consistent with field observations. The simulations predict that a potentially rapid decline in ACT effectiveness is likely to occur as artemisinin resistance spreads, emphasising the importance of containing the spread of artemisinin resistance before it results in widespread drug failure. We found that PK/PD data is generally very

  3. Convective transport of highly plasma protein bound drugs facilitates direct penetration into deep tissues after topical application

    Science.gov (United States)

    Dancik, Yuri; Anissimov, Yuri G; Jepps, Owen G; Roberts, Michael S

    2012-01-01

    AIMS To relate the varying dermal, subcutaneous and muscle microdialysate concentrations found in man after topical application to the nature of the drug applied and to the underlying physiology. METHODS We developed a physiologically based pharmacokinetic model in which transport to deeper tissues was determined by tissue diffusion, blood, lymphatic and intersitial flow transport and drug properties. The model was applied to interpret published human microdialysis data, estimated in vitro dermal diffusion and protein binding affinity of drugs that have been previously applied topically in vivo and measured in deep cutaneous tissues over time. RESULTS Deeper tissue microdialysis concentrations for various drugs in vivo vary widely. Here, we show that carriage by the blood to the deeper tissues below topical application sites facilitates the transport of highly plasma protein bound drugs that penetrate the skin, leading to rapid and significant concentrations in those tissues. Hence, the fractional concentration for the highly plasma protein bound diclofenac in deeper tissues is 0.79 times that in a probe 4.5 mm below a superficial probe whereas the corresponding fractional concentration for the poorly protein bound nicotine is 0.02. Their corresponding estimated in vivo lag times for appearance of the drugs in the deeper probes were 1.1 min for diclofenac and 30 min for nicotine. CONCLUSIONS Poorly plasma protein bound drugs are mainly transported to deeper tissues after topical application by tissue diffusion whereas the transport of highly plasma protein bound drugs is additionally facilitated by convective blood, lymphatic and interstitial transport to deep tissues. PMID:21999217

  4. Can surveillance systems identify and avert adverse drug events? A prospective evaluation of a commercial application.

    Science.gov (United States)

    Jha, Ashish K; Laguette, Julia; Seger, Andrew; Bates, David W

    2008-01-01

    Computerized monitors can effectively detect and potentially prevent adverse drug events (ADEs). Most monitors have been developed in large academic hospitals and are not readily usable in other settings. We assessed the ability of a commercial program to identify and prevent ADEs in a community hospital. and Measurement We prospectively evaluated the commercial application in a community-based hospital. We examined the frequency and types of alerts produced, how often they were associated with ADEs and potential ADEs, and the potential financial impact of monitoring for ADEs. Among 2,407 patients screened, the application generated 516 high priority alerts. We were able to review 266 alerts at the time they were generated and among these, 30 (11.3%) were considered substantially important to warrant contacting the physician caring for the patient. These 30 alerts were associated with 4 ADEs and 11 potential ADEs. In all 15 cases, the responsible physician was unaware of the event, leading to a change in clinical care in 14 cases. Overall, 23% of high priority alerts were associated with an ADE (95% confidence interval [CI] 12% to 34%) and another 15% were associated with a potential ADE (95% CI 6% to 24%). Active surveillance used approximately 1.5 hours of pharmacist time daily. A commercially available, computer-based ADE detection tool was effective at identifying ADEs. When used as part of an active surveillance program, it can have an impact on preventing or ameliorating ADEs.

  5. A convenient method to prepare emulsified polyacrylate nanoparticles from powders [corrected] for drug delivery applications.

    Science.gov (United States)

    Garay-Jimenez, Julio C; Turos, Edward

    2011-08-01

    We describe a method to obtain purified, polyacrylate nanoparticles in a homogeneous powdered form that can be readily reconstituted in aqueous media for in vivo applications. Polyacrylate-based nanoparticles can be easily prepared by emulsion polymerization using a 7:3 mixture of butyl acrylate and styrene in water containing sodium dodecyl sulfate as a surfactant and potassium persulfate as a water-soluble radical initiator. The resulting emulsions contain nanoparticles measuring 40-50 nm in diameter with uniform morphology, and can be purified by centrifugation and dialysis to remove larger coagulants as well as residual surfactant and monomers associated with toxicity. These purified emulsions can be lyophilized in the presence of maltose (a non-toxic cryoprotectant) to provide a homogeneous dried powder, which can be reconstituted as an emulsion by addition of an aqueous diluent. Dynamic light scattering and microbiological experiments were carried out on the reconstituted nanoparticles. This procedure allows for ready preparation of nanoparticle emulsions for drug delivery applications. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Receptor-based 3D-QSAR in Drug Design: Methods and Applications in Kinase Studies.

    Science.gov (United States)

    Fang, Cheng; Xiao, Zhiyan

    2016-01-01

    Receptor-based 3D-QSAR strategy represents a superior integration of structure-based drug design (SBDD) and three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis. It combines the accurate prediction of ligand poses by the SBDD approach with the good predictability and interpretability of statistical models derived from the 3D-QSAR approach. Extensive efforts have been devoted to the development of receptor-based 3D-QSAR methods and two alternative approaches have been exploited. One associates with computing the binding interactions between a receptor and a ligand to generate structure-based descriptors for QSAR analyses. The other concerns the application of various docking protocols to generate optimal ligand poses so as to provide reliable molecular alignments for the conventional 3D-QSAR operations. This review highlights new concepts and methodologies recently developed in the field of receptorbased 3D-QSAR, and in particular, covers its application in kinase studies.

  7. Phytosome and Liposome: The Beneficial Encapsulation Systems in Drug Delivery and Food Application

    Directory of Open Access Journals (Sweden)

    Nayyer Karimi

    2015-06-01

    Full Text Available Due to poor solubility in lipids, many of bioactive components (Nutraceutical materials show less bioactivity than optimal state in water solution. Phytosomes improve absorption and bioavailability of biomaterials. Liposomes, spherical shaped nanocarriers, were discovered in the 1960s by bangham. Due to their composition, variability and structural properties, liposomes and phytosomes are extremely versatile, leading to a large number of applications including pharmaceutical, cosmetics and food industrial fields. They are advanced forms of herbal formulations containing the bioactive phytoconstituents of herb extracts such as flavonoids, glycosides and terpenoids, which have good ability to transit from a hydrophilic environment into the lipid friendly environment of the outer cell membrane. They have better bioavailability and actions than the conventional herbal extracts containing dosage. Phytosome technology has increasing effect on the bioavailability of herbal extracts including ginkgo biloba, grape seed, green tea, milk thistle, ginseng, etc., and can be developed for various therapeutic uses or dietary supplements. Liposomes are composed of bilayer membranes, which are made of lipid molecules. They form when phospholipids are dispersed in aqueous media and exposed to high shear rates by using micro-fluidization or colloid mill. The mechanism for formation of liposomes is mainly the hydrophilic–hydrophobic interactions between phospholipids and water molecules. Here, we attempt to review the features of phytosomes and liposomes as well as their preparation methods and capacity in food and drug applications. Generally, it is believed that phytosomes and liposomes are suitable delivery systems for nutraceuticals, and can be widely used in food industry.

  8. Illicit drugs and pharmaceuticals in the environment - Forensic applications of environmental data. Part 1: Estimation of the usage of drugs in local communities

    Energy Technology Data Exchange (ETDEWEB)

    Kasprzyk-Hordern, Barbara, E-mail: b.kasprzyk-hordern@hud.ac.u [University of Huddersfield, Department of Chemical and Biological Sciences, Queensgate, Huddersfield HD1 3DH (United Kingdom); University of Glamorgan, Sustainable Environment Research Centre, Faculty of Health, Sport and Science, Pontypridd CF37 1DL (United Kingdom); Dinsdale, Richard M.; Guwy, Alan J. [University of Glamorgan, Sustainable Environment Research Centre, Faculty of Health, Sport and Science, Pontypridd CF37 1DL (United Kingdom)

    2009-06-15

    Pharmaceuticals and recently also illicit drugs have been recognised as emerging environmental contaminants due to their potential environmental impact: frequent occurrence, persistence and risk to aquatic life and humans. This manuscript is part one of the two-part study aiming to provide a better understanding and application of environmental data not only for environmental aims but also to meet forensic objectives. An attempt to use wastewater data is made in order to verify patterns of the usage of drugs (in particular illicit) in local communities. The average usage of cocaine in South Wales was estimated at 0.9 g day{sup -1} 1000 people{sup -1}, which equals 1 tonne of this drug used or disposed of to sewage annually in Wales. The calculated usage of amphetamine denoted 2.5 g day{sup -1} 1000 people{sup -1} and is suspected to be an overestimate. Because no analysis of enantiomers of amphetamine was undertaken, no distinction between amphetamine's legal and illicit usage could be made. - Wastewater as an indicative source of information can be used in forensic applications.

  9. Illicit drugs and pharmaceuticals in the environment - Forensic applications of environmental data. Part 1: Estimation of the usage of drugs in local communities

    International Nuclear Information System (INIS)

    Kasprzyk-Hordern, Barbara; Dinsdale, Richard M.; Guwy, Alan J.

    2009-01-01

    Pharmaceuticals and recently also illicit drugs have been recognised as emerging environmental contaminants due to their potential environmental impact: frequent occurrence, persistence and risk to aquatic life and humans. This manuscript is part one of the two-part study aiming to provide a better understanding and application of environmental data not only for environmental aims but also to meet forensic objectives. An attempt to use wastewater data is made in order to verify patterns of the usage of drugs (in particular illicit) in local communities. The average usage of cocaine in South Wales was estimated at 0.9 g day -1 1000 people -1 , which equals 1 tonne of this drug used or disposed of to sewage annually in Wales. The calculated usage of amphetamine denoted 2.5 g day -1 1000 people -1 and is suspected to be an overestimate. Because no analysis of enantiomers of amphetamine was undertaken, no distinction between amphetamine's legal and illicit usage could be made. - Wastewater as an indicative source of information can be used in forensic applications.

  10. Rectal dihydroartemisinin versus intravenous quinine in the ...

    African Journals Online (AJOL)

    Rectal dihydroartemisinin versus intravenous quinine in the treatment of severe malaria: A randomised clinical trial. F Esamai, P Ayuo, W Owino-Ongor, J Rotich, A Ngindu, A Obala, F Ogaro, L Quoqiao, G Xingbo, L Guangqian ...

  11. Intravenous iron-containing products: EMA procrastination.

    Science.gov (United States)

    2014-07-01

    A European reassessment has led to identical changes in the summaries of product characteristics (SPCs) for all intravenous iron-containing products: the risk of serious adverse effects is now highlighted, underlining the fact that intravenous iron-containing products should only be used when the benefits clearly outweigh the harms. Unfortunately, iron dextran still remains on the market despite a higher risk of hypersensitivity reactions than with iron sucrose.

  12. Fabrication of Calcium Phosphate-Based Nanocomposites Incorporating DNA Origami, Gold Nanorods, and Anticancer Drugs for Biomedical Applications.

    Science.gov (United States)

    Zhang, Hongbo; Qu, Xiangmeng; Chen, Hong; Kong, Haixin; Ding, Ruihua; Chen, Dong; Zhang, Xu; Pei, Hao; Santos, Hélder A; Hai, Mingtan; Weitz, David A

    2017-10-01

    DNA origami is designed by folding DNA strands at the nanoscale with arbitrary control. Due to its inherent biological nature, DNA origami is used in drug delivery for enhancement of synergism and multidrug resistance inhibition, cancer diagnosis, and many other biomedical applications, where it shows great potential. However, the inherent instability and low payload capacity of DNA origami restrict its biomedical applications. Here, this paper reports the fabrication of an advanced biocompatible nano-in-nanocomposite, which protects DNA origami from degradation and facilities drug loading. The DNA origami, gold nanorods, and molecular targeted drugs are co-incorporated into pH responsive calcium phosphate [Ca 3 (PO 4 ) 2 ] nanoparticles. Subsequently, a thin layer of phospholipid is coated onto the Ca 3 (PO 4 ) 2 nanoparticle to offer better biocompatibility. The fabricated nanocomposite shows high drug loading capacity, good biocompatibility, and a photothermal and pH-responsive payload release profile and it fully protects DNA origami from degradation. The codelivery of DNA origami with cancer drugs synergistically induces cancer cell apoptosis, reduces the multidrug resistance, and enhances the targeted killing efficiency toward human epidermal growth factor receptor 2 positive cells. This nanocomposite is foreseen to open new horizons for a variety of clinical and biomedical applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Efficacy and pharmacokinetics of intravenous paracetamol in the critically ill patient

    NARCIS (Netherlands)

    Samson, A.D.; Hunfeld, N.G.; Touw, D.J.; Melief, P.H.

    2009-01-01

    Introduction: Paracetamol (PCM) is a drug with analgesic and antipyretic properties. Despite its frequent use, little is known about its efficacy and pharmacokinetics (PK) when intravenously administered in the critically ill patient. A previous study suggests that therapeutic concentrations are not

  14. Intravenous flurbiprofen axetil can increase analgesic effect in refractory cancer pain

    Directory of Open Access Journals (Sweden)

    Hao Jiqing

    2009-03-01

    Full Text Available Abstract Background The aim of this study was to investigate the analgesic effects of intravenous flurbiprofen axetil for the refractory pain in cancer patients. Methods 2109 patients were screened from the department of medical oncology, the first affiliated hospital of Anhui medical university in China between October of 2007 and October of 2008. Thirty-seven cases of cancer patients who had bad effect from anaesthetic drugs were received administration of intravenous flurbiprofen axetil with dose of 50 mg/5 ml/day. The pain score was evaluated for pre- and post- treatment by Pain Faces Scale criteria, and the side effects were also observed. Results Intravenous flurbiprofen axetil increased the analgesic effects. The total effective rate was 92%. The side effects, such as abdominal pain, alimentary tract bleeding which were found in using NSAIDs or constipation, nausea, vomit, sleepiness which were found in using opioid drugs did not be found. Conclusion Intravenous flurbiprofen axetil could provide better analgesia effects and few side effects to patients with refractory cancer pain. It could also increase analgesia effects when combining with anesthetic drugs in treatment of moderate or severe pain, especially breakthrough pain, and suit to patients who can not take oral drugs for the reason of constipation and psychosomatic symptoms.

  15. Intravenous flurbiprofen axetil can increase analgesic effect in refractory cancer pain

    Science.gov (United States)

    Wu, Hongyang; Chen, Zhendong; Sun, Guoping; Gu, Kangsheng; Pan, Yueyin; Hao, Jiqing; Du, Yingying; Ning, Jie

    2009-01-01

    Background The aim of this study was to investigate the analgesic effects of intravenous flurbiprofen axetil for the refractory pain in cancer patients. Methods 2109 patients were screened from the department of medical oncology, the first affiliated hospital of Anhui medical university in China between October of 2007 and October of 2008. Thirty-seven cases of cancer patients who had bad effect from anaesthetic drugs were received administration of intravenous flurbiprofen axetil with dose of 50 mg/5 ml/day. The pain score was evaluated for pre- and post- treatment by Pain Faces Scale criteria, and the side effects were also observed. Results Intravenous flurbiprofen axetil increased the analgesic effects. The total effective rate was 92%. The side effects, such as abdominal pain, alimentary tract bleeding which were found in using NSAIDs or constipation, nausea, vomit, sleepiness which were found in using opioid drugs did not be found. Conclusion Intravenous flurbiprofen axetil could provide better analgesia effects and few side effects to patients with refractory cancer pain. It could also increase analgesia effects when combining with anesthetic drugs in treatment of moderate or severe pain, especially breakthrough pain, and suit to patients who can not take oral drugs for the reason of constipation and psychosomatic symptoms. PMID:19267934

  16. Intravenøs administration af lipid ved forgiftning med lipofilt laegemiddel

    DEFF Research Database (Denmark)

    Skjønnemand, Martin; Damgaard-Jensen, Jens; Gottschau, Bo

    2011-01-01

    OBJECTIVE: To draw attention to the use of intravenous lipids in the treatment of cardiac arrests caused by overdosage of lipophilic drugs. Case reports and animal studies have shown beneficial use of lipids in severe intoxication. The literature is reviewed. CONCLUSION: Lipids have a place in th...

  17. Randomised controlled trial comparing oral and intravenous paracetamol (acetaminophen) plasma levels when given as preoperative analgesia.

    Science.gov (United States)

    van der Westhuizen, J; Kuo, P Y; Reed, P W; Holder, K

    2011-03-01

    Gastric absorption of oral paracetamol (acetaminophen) may be unreliable perioperatively in the starved and stressed patient. We compared plasma concentrations of parenteral paracetamol given preoperatively and oral paracetamol when given as premedication. Patients scheduled for elective ear; nose and throat surgery or orthopaedic surgery were randomised to receive either oral or intravenous paracetamol as preoperative medication. The oral dose was given 30 minutes before induction of anaesthesia and the intravenous dose given pre-induction. All patients were given a standardised anaesthetic by the same specialist anaesthetist who took blood for paracetamol concentrations 30 minutes after the first dose and then at 30 minute intervals for 240 minutes. Therapeutic concentrations of paracetamol were reached in 96% of patients who had received the drug parenterally, and 67% of patients who had received it orally. Maximum median plasma concentrations were 19 mg.l(-1) (interquartile range 15 to 23 mg.l(-1)) and 13 mg.l(-1) (interquartile range 0 to 18 mg.l(-1)) for the intravenous and oral group respectively. The difference between intravenous and oral groups was less marked after 150 minutes but the intravenous preparation gave higher plasma concentrations throughout the study period. It can be concluded that paracetamol gives more reliable therapeutic plasma concentrations when given intravenously.

  18. Patient-Centered Tablet Application for Improving Medication Adherence after a Drug-Eluting Stent.

    Science.gov (United States)

    Shah, Vicki; Dileep, Anandu; Dickens, Carolyn; Groo, Vicki; Welland, Betty; Field, Jerry; Baumann, Matthew; Flores, Jose D; Shroff, Adhir; Zhao, Zhongsheng; Yao, Yingwei; Wilkie, Diana J; Boyd, Andrew D

    2016-01-01

    This study's objective was to evaluate a patient-centered educational electronic tablet application, "My Interventional Drug-Eluting Stent Educational App" (MyIDEA) to see if there was an increase in patient knowledge about dual antiplatelet therapy (DAPT) and medication possession ratio (MPR) compared to treatment as usual. In a pilot project, 24 elderly (≥50 years old) research participants were recruited after a drug-eluting stent. Eleven were randomized to the control arm and 13 to the interventional arm. All the participants completed psychological and knowledge questionnaires. Adherence was assessed through MPR, which was calculated at 3 months for all participants who were scheduled for second and third follow-up visits. Relative to control, the interventional group had a 10% average increase in MPR. As compared to the interventional group, more patients in the control group had poor adherence (<80% MPR). The psychological data revealed a single imbalance in anxiety between the control and interventional groups. On average, interventional participants spent 21 min using MyIDEA. Consumer health informatics has enabled us to engage patients with their health data using novel methods. Consumer health technology needs to focus more on patient knowledge and engagement to improve long-term health. MyIDEA takes a unique approach in targeting DAPT from the onset. MyIDEA leverages patient-centered information with clinical care and the electronic health record highlighting the patients' role as a team member in their own health care. The patients think critically about adverse events and how to solve issues before leaving the hospital.

  19. Patient Centered Tablet Application for improving medication adherence after a Drug Eluting Stent

    Directory of Open Access Journals (Sweden)

    Vicki Shah

    2016-12-01

    Full Text Available Background/Aims: This study’s objective was to evaluate a patient-centered educational electronic tablet application, My Interventional Drug-Eluting Stent Educational App (MyIDEA to see if there was an increase in patient knowledge about dual antiplatelet therapy (DAPT and medication possession ratio (MPR compared to treatment as usual. Methods: In a pilot project, 24 elderly (≥50 years-old research participants were recruited after a Drug Eluting Stent. 11 were randomized to the control arm and 13 to the interventional arm. All participants completed psychological and knowledge questionnaires. Adherence was assessed through MPR, which was calculated at three months for all participants who were scheduled for a second and third follow-up visit.Results: Relative to control, the interventional group had a 10% average increase in MPR. As compared to the interventional group, more patients in the control group had poor adherence (<80% MPR. The psychological data revealed a single imbalance in anxiety between the control and interventional groups. On average interventional participants spent 21 minutes using MyIDEA. Discussion: Consumer health informatics has enabled us to engage patients with their health data using novel methods. Consumer health technology needs to focus more on patient knowledge and engagement to improve long term health. MyIDEA takes a unique approach in targeting DAPT from the onset.Conclusion: MyIDEA leverages patient centered information with clinical care and the electronic health record highlighting the patients’ role as a team member in their own healthcare. The patients think critically about adverse events and how to solve issues before leaving the hospital.

  20. Magnetic manipulation of superparamagnetic nanoparticles in a microfluidic system for drug delivery applications

    International Nuclear Information System (INIS)

    Agiotis, L.; Theodorakos, I.; Samothrakitis, S.; Papazoglou, S.; Zergioti, I.; Raptis, Y.S.

    2016-01-01

    Magnetic nanoparticles (MNPs), such as superparamagnetic iron oxide nanoparticles (SPIONS), have attracted major interest, due to their small size and unique magnetic properties, for drug delivery applications. In this context, iron oxide nanoparticles of magnetite (Fe 3 O 4 ) (150 nm magnetic core diameter), were used as drug carriers, aiming to form a magnetically controlled nano-platform. The navigation capabilities of the iron oxide nanoparticles in a microfluidic channel were investigated by simulating the magnetic field and the magnetic force applied on the magnetic nanoparticles inside a microfluidic chip. The simulations have been performed using finite element method (ANSY’S software). The optimum setup which intends to simulate the magnetic navigation of the nanoparticles, by the use of MRI-type fields, in the human circulatory system, consists of two parallel permanent magnets to produce a homogeneous magnetic field, in order to ensure the maximum magnetization of the magnetic nanoparticles, an electromagnet for the induction of the magnetic gradients and the creation of the magnetic force and a microfluidic setup so as to simulate the blood flow inside the human blood vessels. The magnetization of the superparamagnetic nanoparticles and the consequent magnetic torque developed by the two permanent magnets, together with the mutual interactions between the magnetized nanoparticles lead to the creation of rhabdoid aggregates in the direction of the homogeneous field. Additionally, the magnetic gradients introduced by the operation of the electromagnet are capable of directing the aggregates, as a whole, to the desired direction. By removing the magnetic fields, the aggregates are disrupted, due to the super paramagnetic nature of the nanoparticles, avoiding thus the formation of undesired thrombosis. - Highlights: • Homogeneous field yields an aggregation of particles along the lines of the field. • Additional electromagnet field rotates the

  1. Magnetic manipulation of superparamagnetic nanoparticles in a microfluidic system for drug delivery applications

    Energy Technology Data Exchange (ETDEWEB)

    Agiotis, L.; Theodorakos, I.; Samothrakitis, S.; Papazoglou, S.; Zergioti, I.; Raptis, Y.S.

    2016-03-01

    Magnetic nanoparticles (MNPs), such as superparamagnetic iron oxide nanoparticles (SPIONS), have attracted major interest, due to their small size and unique magnetic properties, for drug delivery applications. In this context, iron oxide nanoparticles of magnetite (Fe{sub 3}O{sub 4}) (150 nm magnetic core diameter), were used as drug carriers, aiming to form a magnetically controlled nano-platform. The navigation capabilities of the iron oxide nanoparticles in a microfluidic channel were investigated by simulating the magnetic field and the magnetic force applied on the magnetic nanoparticles inside a microfluidic chip. The simulations have been performed using finite element method (ANSY’S software). The optimum setup which intends to simulate the magnetic navigation of the nanoparticles, by the use of MRI-type fields, in the human circulatory system, consists of two parallel permanent magnets to produce a homogeneous magnetic field, in order to ensure the maximum magnetization of the magnetic nanoparticles, an electromagnet for the induction of the magnetic gradients and the creation of the magnetic force and a microfluidic setup so as to simulate the blood flow inside the human blood vessels. The magnetization of the superparamagnetic nanoparticles and the consequent magnetic torque developed by the two permanent magnets, together with the mutual interactions between the magnetized nanoparticles lead to the creation of rhabdoid aggregates in the direction of the homogeneous field. Additionally, the magnetic gradients introduced by the operation of the electromagnet are capable of directing the aggregates, as a whole, to the desired direction. By removing the magnetic fields, the aggregates are disrupted, due to the super paramagnetic nature of the nanoparticles, avoiding thus the formation of undesired thrombosis. - Highlights: • Homogeneous field yields an aggregation of particles along the lines of the field. • Additional electromagnet field rotates the

  2. Long-circulating Janus nanoparticles made by electrohydrodynamic co-jetting for systemic drug delivery applications

    Science.gov (United States)

    Rahmani, Sahar; Villa, Carlos H.; Dishman, Acacia F.; Grabowski, Marika E.; Pan, Daniel C.; Durmaz, Hakan; Misra, Asish C; Colón-Meléndez, Laura; Solomon, Michael J.; Muzykantov, Vladimir R.; Lahann, Joerg

    2016-01-01

    Background Nanoparticles with controlled physical properties have been widely used for controlled release applications. In addition to shape, the anisotropic nature of the particles can be an important design criterion to ensure selective surface modification or independent release of combinations of drugs. Purpose Electrohydrodynamic (EHD) co-jetting is used for the fabrication of uniform anisotropic nanoparticles with individual compartments and initial physicochemical and biological characterization is reported. Methods EHD co-jetting is used to create nanoparticles, which are characterized at each stage with scanning electron microscopy (SEM), structured illumination microscopy (SIM), dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA). Surface immobilization techniques are used to incorporate polyethylene glycol (PEG) and I125 radiolabels into the nanoparticles. Particles are injected in mice and the particle distribution after 1, 4 and 24 hours is assessed. Results and discussion Nanoparticles with an average diameter of 105.7 nm are prepared by EHD co-jetting. The particles contain functional chemical groups for further surface modification and radiolabeling. The density of PEG molecules attached to the surface of nanoparticles is determined to range between 0.02 and 6.04 ligands per square nanometer. A significant fraction of the nanoparticles (1.2% injected dose per mass of organ) circulates in the blood after 24 h. Conclusion EHD co-jetting is a versatile method for the fabrication of nanoparticles for drug delivery. Circulation of the nanoparticles for 24 h is a pre-requisite for subsequent studies to explore defined targeting of the nanoparticles to a specific anatomic site. PMID:26453170

  3. 76 FR 60504 - Guidance for Industry on Time and Extent Applications for Nonprescription Drug Products...

    Science.gov (United States)

    2011-09-29

    ... monograph need not obtain FDA approval before marketing if their drug product meets the conditions in part... introduce into the United States an OTC drug product that had been marketed solely in a foreign country...

  4. Application of spray-drying and electrospraying/electospinning for poorly water-soluble drugs

    DEFF Research Database (Denmark)

    Bohr, Adam; Boetker, Johan P; Rades, Thomas

    2014-01-01

    Solid dispersions have been widely studied as an attractive formulation strategy for the increasingly prevalent poorly water-soluble drug compounds, including herbal medicines, often leading to improvements in drug dissolution rate and bioavailability. However, several challenges are encountered...

  5. Drugs@FDA: FDA Approved Drug Products

    Science.gov (United States)

    ... Cosmetics Tobacco Products Home Drug Databases Drugs@FDA Drugs@FDA: FDA Approved Drug Products Share Tweet Linkedin Pin it More sharing ... Download Drugs@FDA Express for free Search by Drug Name, Active Ingredient, or Application Number Enter at ...

  6. Physiologically Based Pharmacokinetic Modeling: Methodology, Applications, and Limitations with a Focus on Its Role in Pediatric Drug Development

    Directory of Open Access Journals (Sweden)

    Feras Khalil

    2011-01-01

    Full Text Available The concept of physiologically based pharmacokinetic (PBPK modeling was introduced years ago, but it has not been practiced significantly. However, interest in and implementation of this modeling technique have grown, as evidenced by the increased number of publications in this field. This paper demonstrates briefly the methodology, applications, and limitations of PBPK modeling with special attention given to discuss the use of PBPK models in pediatric drug development and some examples described in detail. Although PBPK models do have some limitations, the potential benefit from PBPK modeling technique is huge. PBPK models can be applied to investigate drug pharmacokinetics under different physiological and pathological conditions or in different age groups, to support decision-making during drug discovery, to provide, perhaps most important, data that can save time and resources, especially in early drug development phases and in pediatric clinical trials, and potentially to help clinical trials become more “confirmatory” rather than “exploratory”.

  7. The first object oriented monitor for intravenous anesthesia.

    Science.gov (United States)

    Cantraine, F R; Coussaert, E J

    2000-01-01

    To describe the design and implementation of "INFUSION TOOLBOX," a software tool to control and monitor multiple intravenous drug infusions simultaneously using pharmacokinetic and pharmacodynamic principles. INFUSION TOOLBOX has been designed to present a graphical interface. Object Oriented design was used and the software was implemented using Smalltalk, to run on a PC. Basic tools are available to manage patient, drugs, pumps and reports. These tools are the PatientPanel, the DrugPanel, the PumpPanel and the HistoryPanel. The screen is built dynamically. The panels may be collapsed or closed to avoid a crowded display. We also built control panels such as the Target ControlPanel which calculates the best infusion sequence to bring the drug concentration in the plasma compartment to a preset value. Before drug delivery, the user enters the patient's data, selects a drug, enters its dilution factor and chooses a pharmacokinetic model. The calculated plasma concentration is continually displayed and updated. The anesthetist may ask for the history of the delivery to obtain a graphic report or to add events to the logbook. A panel targeting the effect is used when a pharmacodynamic model is known. Data files for drugs, pumps and surgery are upgradable. By creating a resizeable ControlPanel we enable the anesthetist to display the information he wishes, when he wishes it. The available panels are diverse enough to meet the anesthetist needs; they may be adapted to the drug used, pumps used and surgery. It is the anesthetist who builds dynamically its different control screens. By adopting an evolutionary solution model we have achieved considerable success in building our drug delivery monitor. In addition we have gained valuable insight into the anesthesia information domain that will allow us to further enhance and expand the system.

  8. Development of membranes containing a controlled drug release system for ophthalmological applications

    OpenAIRE

    Pinão, Sílvia Raquel das Neves

    2016-01-01

    The effectiveness of drug administration strongly depends on attainment of an effective drug concentration in the area to be treated, for a sufficient period of time. Nowadays, the most used drug administration method for many eye diseases is delivery through eye drops, although it is very inefficient and can lead to negative side effects. The use of soft contact lenses as drug delivery systems appeared as a promising alternative, due to the prolonged contact with the eye surface, high degree...

  9. The Therapeutic Utility of Employment in Treating Drug Addiction: Science to Application

    OpenAIRE

    Silverman, Kenneth; Holtyn, August F.; Morrison, Reed

    2016-01-01

    Research on a model Therapeutic Workplace has allowed for evaluation of the use of employment in the treatment of drug addiction. Under the Therapeutic Workplace intervention, adults with histories of drug addiction are hired and paid to work. To promote drug abstinence or adherence to addiction medications, participants are required to provide drug-free urine samples or take prescribed addiction medications, respectively, to gain access to the workplace and/or to maintain their maximum rate ...

  10. Chitosan and its derivatives for application in mucoadhesive drug delivery systems

    OpenAIRE

    Ways, Twana Mohammed M.; Lau, Wing Man; Khutoryanskiy, Vitaliy V.

    2018-01-01

    Mucoadhesive drug delivery systems are desirable as they can increase the residence time of drugs at the site of absorption/action, provide sustained drug release and minimize the degradation of drugs in various body sites. Chitosan is a cationic polysaccharide that exhibits mucoadhesive properties and it has been widely used in the design of mucoadhesive dosage forms. However, its limited mucoadhesive strength and limited water-solubility at neutral and basic pHs are considered as two major ...

  11. Chitosan and Its Derivatives for Application in Mucoadhesive Drug Delivery Systems

    OpenAIRE

    Twana Mohammed M. Ways; Wing Man Lau; Vitaliy V. Khutoryanskiy

    2018-01-01

    Mucoadhesive drug delivery systems are desirable as they can increase the residence time of drugs at the site of absorption/action, provide sustained drug release and minimize the degradation of drugs in various body sites. Chitosan is a cationic polysaccharide that exhibits mucoadhesive properties and it has been widely used in the design of mucoadhesive dosage forms. However, its limited mucoadhesive strength and limited water-solubility at neutral and basic pHs are considered as two major ...

  12. Supramolecular Nanostructures Based on Cyclodextrin and Poly(ethylene oxide: Syntheses, Structural Characterizations and Applications for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Yue Zheng

    2016-05-01

    Full Text Available Cyclodextrins (CDs have been extensively studied as drug delivery carriers through host–guest interactions. CD-based poly(pseudorotaxanes, which are composed of one or more CD rings threading on the polymer chain with or without bulky groups (or stoppers, have attracted great interest in the development of supramolecular biomaterials. Poly(ethylene oxide (PEO is a water-soluble, biocompatible polymer. Depending on the molecular weight, PEO can be used as a plasticizer or as a toughening agent. Moreover, the hydrogels of PEO are also extensively studied because of their outstanding characteristics in biological drug delivery systems. These biomaterials based on CD and PEO for controlled drug delivery have received increasing attention in recent years. In this review, we summarize the recent progress in supramolecular architectures, focusing on poly(pseudorotaxanes, vesicles and supramolecular hydrogels based on CDs and PEO for drug delivery. Particular focus will be devoted to the structures and properties of supramolecular copolymers based on these materials as well as their use for the design and synthesis of supramolecular hydrogels. Moreover, the various applications of drug delivery techniques such as drug absorption, controlled release and drug targeting based CD/PEO supramolecular complexes, are also discussed.

  13. Application of receiver operating characteristic analysis to refine the prediction of potential digoxin drug interactionss

    NARCIS (Netherlands)

    Ellens, H.; Deng, S.; Coleman, J.; Bentz, J.; Taub, M.E.; Ragueneau-Majlessi, I.; Chung, S.P.; Herédi-Szabó, K.; Neuhoff, S.; Palm, J.; Balimane, P.; Zhang, L.; Jamei, M.; Hanna, I.; O'connor, M.; Bednarczyk, D.; Forsgard, M.; Chu, X.; Funk, C.; Guo, A.; Hillgren, K.M.; Li, L.; Pak, A.Y.; Perloff, E.S.; Rajaraman, G.; Salphati, L.; Taur, J.-S.; Weitz, D.; Wortelboer, H.M.; Xia, C.Q.; Xiao, G.; Yamagata, T.; Lee, C.A.

    2013-01-01

    In the 2012 Food and Drug Administration (FDA) draft guidance on drug-drug interactions (DDIs), a new molecular entity that inhibits Pglycoprotein (P-gp) may need a clinical DDI study with a P-gp substrate such as digoxin when themaximumconcentration of inhibitor at steady state divided by IC50

  14. Complexity of intravenous iron nanoparticle formulations: implications for bioequivalence evaluation.

    Science.gov (United States)

    Pai, Amy Barton

    2017-11-01

    Intravenous iron formulations are a class of complex drugs that are commonly used to treat a wide variety of disease states associated with iron deficiency and anemia. Venofer® (iron-sucrose) is one of the most frequently used formulations, with more than 90% of dialysis patients in the United States receiving this formulation. Emerging data from global markets outside the United States, where many iron-sucrose similars or copies are available, have shown that these formulations may have safety and efficacy profiles that differ from the reference listed drug. This may be attributable to uncharacterized differences in physicochemical characteristics and/or differences in labile iron release. As bioequivalence evaluation guidance evolves, clinicians should be educated on these potential clinical issues before a switch to the generic formulation is made in the clinical setting. © 2017 New York Academy of Sciences.

  15. 75 FR 35044 - Notice of Approval of a Supplemental New Animal Drug Application; Penicillin G Procaine Suspension

    Science.gov (United States)

    2010-06-21

    ...] Notice of Approval of a Supplemental New Animal Drug Application; Penicillin G Procaine Suspension AGENCY... Laboratories, Ltd. The supplemental NADA provides for a revised formulation of penicillin G procaine injectable... of NOROCILLIN (penicillin G procaine) Injectable Suspension by intramuscular injection in cattle...

  16. 77 FR 16039 - Abbott Laboratories et al.; Withdrawal of Approval of 35 New Drug Applications and 64 Abbreviated...

    Science.gov (United States)

    2012-03-19

    ...] Abbott Laboratories et al.; Withdrawal of Approval of 35 New Drug Applications and 64 Abbreviated New... Tablets... Abbott Laboratories, PA77/Bldg. AP30-1E, 200 Abbott Park Rd., Abbott Park, IL 60064-6157. NDA... (diphenhydramine Healthcare. HCl)) Injection Preservative Free. NDA 010021 Placidyl Abbott Laboratories...

  17. Protein cages and synthetic polymers: a fruitful symbiosis for drug delivery applications, bionanotechnology and materials science.

    Science.gov (United States)

    Rother, Martin; Nussbaumer, Martin G; Renggli, Kasper; Bruns, Nico

    2016-11-07

    Protein cages are hollow protein nanoparticles, such as viral capsids, virus-like particles, ferritin, heat-shock proteins and chaperonins. They have well-defined capsule-like structures with a monodisperse size. Their protein subunits can be modified by genetic engineering at predetermined positions, allowing for example site-selective introduction of attachment points for functional groups, catalysts or targeting ligands on their outer surface, in their interior and between subunits. Therefore, protein cages have been extensively explored as functional entities in bionanotechnology, as drug-delivery or gene-delivery vehicles, as nanoreactors or as templates for the synthesis of organic and inorganic nanomaterials. The scope of functionalities and applications of protein cages can be significantly broadened if they are combined with synthetic polymers on their surface or within their interior. For example, PEGylation reduces the immunogenicity of protein cage-based delivery systems and active targeting ligands can be attached via polymer chains to favour their accumulation in diseased tissue. Polymers within protein cages offer the possibility of increasing the loading density of drug molecules, nucleic acids, magnetic resonance imaging contrast agents or catalysts. Moreover, the interaction of protein cages and polymers can be used to modulate the size and shape of some viral capsids to generate structures that do not occur with native viruses. Another possibility is to use the interior of polymer cages as a confined reaction space for polymerization reactions such as atom transfer radical polymerization or rhodium-catalysed polymerization of phenylacetylene. The protein nanoreactors facilitate a higher degree of control over polymer synthesis. This review will summarize the hybrid structures that have been synthesized by polymerizing from protein cage-bound initiators, by conjugating polymers to protein cages, by embedding protein cages into bulk polymeric

  18. Assessing sample representativeness in randomized controlled trials: application to the National Institute of Drug Abuse Clinical Trials Network.

    Science.gov (United States)

    Susukida, Ryoko; Crum, Rosa M; Stuart, Elizabeth A; Ebnesajjad, Cyrus; Mojtabai, Ramin

    2016-07-01

    To compare the characteristics of individuals participating in randomized controlled trials (RCTs) of treatments of substance use disorder (SUD) with individuals receiving treatment in usual care settings, and to provide a summary quantitative measure of differences between characteristics of these two groups of individuals using propensity score methods. Design Analyses using data from RCT samples from the National Institute of Drug Abuse Clinical Trials Network (CTN) and target populations of patients drawn from the Treatment Episodes Data Set-Admissions (TEDS-A). Settings Multiple clinical trial sites and nation-wide usual SUD treatment settings in the United States. A total of 3592 individuals from 10 CTN samples and 1 602 226 individuals selected from TEDS-A between 2001 and 2009. Measurements The propensity scores for enrolling in the RCTs were computed based on the following nine observable characteristics: sex, race/ethnicity, age, education, employment status, marital status, admission to treatment through criminal justice, intravenous drug use and the number of prior treatments. Findings The proportion of those with ≥ 12 years of education and the proportion of those who had full-time jobs were significantly higher among RCT samples than among target populations (in seven and nine trials, respectively, at P difference in the mean propensity scores between the RCTs and the target population was 1.54 standard deviations and was statistically significant at P different from individuals receiving treatment in usual care settings. Notably, RCT participants tend to have more years of education and a greater likelihood of full-time work compared with people receiving care in usual care settings. © 2016 Society for the Study of Addiction.

  19. User profiles of a smartphone application to support drug adherence--experiences from the iNephro project.

    Directory of Open Access Journals (Sweden)

    Stefan Becker

    Full Text Available PURPOSE: One of the key problems in the drug therapy of patients with chronic conditions is drug adherence. In 2010 the initiative iNephro was launched (www.inephro.de. A software to support regular and correct drug intake was developed for a smartphone platform (iOS. The study investigated whether and how smartphone users deployed such an application. METHODS: Together with cooperating partners the mobile application "Medikamentenplan" ("Medication Plan" was developed. Users are able to keep and alter a list of their regular medication. A memory function supports regular intake. The application can be downloaded free of charge from the App Store™ by Apple™. After individual consent of users from December 2010 to April 2012 2042338 actions were recorded and analysed from the downloaded applications. Demographic data were collected from 2279 users with a questionnaire. RESULTS: Overall the application was used by 11688 smartphone users. 29% (3406/11688 used it at least once a week for at least four weeks. 27% (3209/11688 used the application for at least 84 days. 68% (1554/2279 of users surveyed were male, the stated age of all users was between 6-87 years (mean 44. 74% of individuals (1697 declared to be suffering from cardiovascular disease, 13% (292 had a previous history of transplantation, 9% (205 were suffering from cancer, 7% (168 reported an impaired renal function and 7% (161 suffered from diabetes mellitus. 69% (1568 of users were on <6 different medications, 9% (201 on 6 - 10 and 1% (26 on more than 10. CONCLUSION: A new smartphone application, which supports drug adherence, was used regularly by chronically ill users with a wide range of diseases over a longer period of time. The majority of users so far were middle-aged and male.

  20. Risk-taking related to drug use: an application of the shift-to-risk design.

    Science.gov (United States)

    Deren, S; Des Jarlais, D C

    1977-01-01

    The utility of the shift-to-risk design for studying the influence of peer groups on drug taking was investigated. Two studies using this design with drug content were conducted, varying the level of information provided about a drug. Subjects were from two college classes consisting of 26 and 28 students. Results indicated that the specification of possible harmful drug effects which are somewhat minimal lead to a significantly greater willingness to recommend trying the drug. In addition, a tendency for a shift-to-caution was found. It was concluded that the shift-to-risk designwas useful for studying decision-making regarding drug use, and that both users and nonusers of drugs should be included in future research.

  1. UV SPECTROPHOTOMETRY APPLICATION FOR QUANTITATIVE DETERMINATION OF VINPOCETINE IN DRUG FORMULATIONS

    Directory of Open Access Journals (Sweden)

    J. V. Monaykina

    2014-12-01

    procedure was successfully applied for the analysis of two new pharmaceutical formulations. The results obtained by applying the proposed procedure were statistically analyzed. Validation studies of the methods confirmed their proper precision and recovery (for cream: 99,73%, RSD% = 0.924, n = 9; for suppositories: 100,3, RSD% = 0,378, n = 9, linearity (for cream: r =0,9999, n=6; for suppositories: r =0,9998, n=6 The received parameters enable the use of developed methods in quantitative pharmaceutical analysis. Conclusions. The applicability of the new procedure is well established by vinpocetine assay in the new drug formulations, namely 0,01 suppositories and 0,5% nasal cream. The developed UV spectrophotometric methods are potentially useful because of their simplicity, rapidity and accuracy. The methods are valid according to the validation requirements of Ukrainian Pharmacopeia.

  2. Quantum-Mechanics Methodologies in Drug Discovery: Applications of Docking and Scoring in Lead Optimization.

    Science.gov (United States)

    Crespo, Alejandro; Rodriguez-Granillo, Agustina; Lim, Victoria T

    2017-01-01

    The development and application of quantum mechanics (QM) methodologies in computer- aided drug design have flourished in the last 10 years. Despite the natural advantage of QM methods to predict binding affinities with a higher level of theory than those methods based on molecular mechanics (MM), there are only a few examples where diverse sets of protein-ligand targets have been evaluated simultaneously. In this work, we review recent advances in QM docking and scoring for those cases in which a systematic analysis has been performed. In addition, we introduce and validate a simplified QM/MM expression to compute protein-ligand binding energies. Overall, QMbased scoring functions are generally better to predict ligand affinities than those based on classical mechanics. However, the agreement between experimental activities and calculated binding energies is highly dependent on the specific chemical series considered. The advantage of more accurate QM methods is evident in cases where charge transfer and polarization effects are important, for example when metals are involved in the binding process or when dispersion forces play a significant role as in the case of hydrophobic or stacking interactions. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. From innovation to application: social-ecological context, diagnostics, drugs and integrated control of schistosomiasis.

    Science.gov (United States)

    Utzinger, Jürg; N'goran, Eliézer K; Caffrey, Conor R; Keiser, Jennifer

    2011-09-01

    Compared to malaria, tuberculosis and HIV/AIDS, schistosomiasis remains a truly neglected tropical disease. Schistosomiasis, perhaps more than any other disease, is entrenched in prevailing social-ecological systems, since transmission is governed by human behaviour (e.g. open defecation and patterns of unprotected surface water contacts) and ecological features (e.g. living in close proximity to suitable freshwater bodies in which intermediate host snails proliferate). Moreover, schistosomiasis is intimately linked with poverty and the disease has spread to previously non-endemic areas as a result of demographic, ecological and engineering transformations. Importantly though, thanks to increased advocacy there is growing awareness, financial and technical support to control and eventually eliminate schistosomiasis as a public health problem at local, regional and global scales. The purpose of this review is to highlight recent progress made in innovation, validation and application of new tools and strategies for research and integrated control of schistosomiasis. First, we explain that schistosomiasis is deeply embedded in social-ecological systems and explore linkages with poverty. We then summarize and challenge global statistics, risk maps and burden estimates of human schistosomiasis. Discovery and development research pertaining to novel diagnostics and drugs forms the centrepiece of our review. We discuss unresolved issues and emerging opportunities for integrated and sustainable control of schistosomiasis and conclude with a series of research needs. Copyright © 2010 Elsevier B.V. All rights reserved.

  4. Improvement of interaction between PVA and chitosan via magnetite nanoparticles for drug delivery application.

    Science.gov (United States)

    Shagholani, Hamidreza; Ghoreishi, Sayed Mehdi; Mousazadeh, Mohammad

    2015-01-01

    Magnetite nanoparticles were synthesized by coprecipitation under ultrasonication followed by coating with chitosan. Polyvinyl alcohol (PVA) is then combined with the chitosan that coated the magnetite nanoparticles. The combination occurs by hydrogen binding and ionic cross-linking of the amino and hydroxyl groups of chitosan and PVA respectively. The magnetite nanoparticles have an average size of 10.62 nm that was confirmed by TEM. The VSM measurements showed that nanoparticles were superparamagnetic. The coatings on the core nanoparticles were estimated by AAS and the attachments of coating to the nanoparticles were confirmed by FT-IR analysis. Physicochemical properties of nanoparticles were measured by DLS and zeta potential. Naked magnetite, chitosan and PVA coating have zeta potential of +36.4, +48.1 and -12.5 mV respectively. The unspecific adsorption and interaction between nanoparticles and bovine serum albumin (BSA) were investigated systematically by UV-vis spectroscopy method. The nanoparticles that were modified by PVA present low protein adsorption, which makes them a practical choice for preventing opsonization in clinical application and drug delivery. Copyright © 2015. Published by Elsevier B.V.

  5. Functional genetic research for radiation and drug resistant adenocarcinoma and its application

    Energy Technology Data Exchange (ETDEWEB)

    Kim, In Gyu; Kim, Kug Chan; Jung, Il Lae; Chul, Shin Byung; Kook, Park Hyo; Lee, Hee Min

    2012-01-15

    The work scope of 'Functional genetic research for radiation and drug resistant adenocarcinoma and its application' had contained the research about effect of transgelin(SM22a), neurotensin, metallothionein-1G transgelin-2 genes on the cell death triggered ionizing radiation, cisplatin, MMS, luteolin and H{sub 2}O{sub 2}(toxic agents), which are highly expressed in radiation-induced mutant cells. In this study, to elucidate the role of these proteins in the ionizing radiation (toxic chemicals)-induced cell death, we utilized sensed (or antisense, small interference RNA) cells, which overexpress (or down-regulate) RNAs associated with these proteins biosynthesis, and investigated the effects of these genes on the cytotoxicity caused by ionizing radiation, H{sub 2}O{sub 2} and toxic chemicals. We also investigated the functions of downstream target genes of transgelin such as IGF-1Rβ/PI3K/AKT pathway and transgelin/metallothioneine in A-549 and HepG2 cells because such target genes are able to potentiate the cell-killing or cell protecting effects against radiation.

  6. Functional genetic research for radiation and drug resistant adenocarcinoma and its application

    International Nuclear Information System (INIS)

    Kim, In Gyu; Kim, Kug Chan; Jung, Il Lae; Chul, Shin Byung; Kook, Park Hyo; Lee, Hee Min

    2012-01-01

    The work scope of 'Functional genetic research for radiation and drug resistant adenocarcinoma and its application' had contained the research about effect of transgelin(SM22a), neurotensin, metallothionein-1G transgelin-2 genes on the cell death triggered ionizing radiation, cisplatin, MMS, luteolin and H 2 O 2 (toxic agents), which are highly expressed in radiation-induced mutant cells. In this study, to elucidate the role of these proteins in the ionizing radiation (toxic chemicals)-induced cell death, we utilized sensed (or antisense, small interference RNA) cells, which overexpress (or down-regulate) RNAs associated with these proteins biosynthesis, and investigated the effects of these genes on the cytotoxicity caused by ionizing radiation, H 2 O 2 and toxic chemicals. We also investigated the functions of downstream target genes of transgelin such as IGF-1Rβ/PI3K/AKT pathway and transgelin/metallothioneine in A-549 and HepG2 cells because such target genes are able to potentiate the cell-killing or cell protecting effects against radiation

  7. Magnetic field pattern synthesis and its application in targeted drug delivery: Design and implementation.

    Science.gov (United States)

    Hajiaghajani, Amirhossein; Abdolali, Ali

    2018-05-01

    In cancer therapy, magnetic drug targeting is considered as an effective treatment to reduce chemotherapy's side effects. The accurate design and shaping of magnetic fields are crucial for healthy cells to be immune from chemotherapeutics. In this paper, arbitrary 2-dimensional spatial patterns of magnetic fields from DC to megahertz are represented in terms of spatial Fourier spectra with sinusoidal eigenfunctions. Realization of each spatial frequency was investigated by a set of elliptical coils. Therefore, it is shown that the desired pattern was synthesized by simultaneous use of coil sets. Currents running on each set were obtained via fast and straightforward analytical Fourier series calculation. Experimentally scanned sample patterns were in close agreement with full wave analysis. Discussions include the evaluation of the Fourier series approximation error and cross-polarization of produced magnetic fields. It was observed that by employing the controlled magnetic field produced by the proposed setup, we were able to steer therapeutic particles toward the right or left half-spheres of the breast, with an efficiency of 90%. Such a pattern synthesizer may be employed in numerous human arteries as well as other bioelectromagnetic patterning applications, e.g., wireless power transfer, magnetic innervation, and tomography. Bioelectromagnetics. 39:325-338, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

  8. A review of geographic variation and Geographic Information Systems (GIS) applications in prescription drug use research.

    Science.gov (United States)

    Wangia, Victoria; Shireman, Theresa I

    2013-01-01

    While understanding geography's role in healthcare has been an area of research for over 40 years, the application of geography-based analyses to prescription medication use is limited. The body of literature was reviewed to assess the current state of such studies to demonstrate the scale and scope of projects in order to highlight potential research opportunities. To review systematically how researchers have applied geography-based analyses to medication use data. Empiric, English language research articles were identified through PubMed and bibliographies. Original research articles were independently reviewed as to the medications or classes studied, data sources, measures of medication exposure, geographic units of analysis, geospatial measures, and statistical approaches. From 145 publications matching key search terms, forty publications met the inclusion criteria. Cardiovascular and psychotropic classes accounted for the largest proportion of studies. Prescription drug claims were the primary source, and medication exposure was frequently captured as period prevalence. Medication exposure was documented across a variety of geopolitical units such as countries, provinces, regions, states, and postal codes. Most results were descriptive and formal statistical modeling capitalizing on geospatial techniques was rare. Despite the extensive research on small area variation analysis in healthcare, there are a limited number of studies that have examined geographic variation in medication use. Clearly, there is opportunity to collaborate with geographers and GIS professionals to harness the power of GIS technologies and to strengthen future medication studies by applying more robust geospatial statistical methods. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Single Intravenous Dose of Novel Flurbiprofen-Loaded Proniosome Formulations Provides Prolonged Systemic Exposure and Anti-inflammatory Effect.

    Science.gov (United States)

    Verma, Preeti; Prajapati, Sunil K; Yadav, Rajbharan; Senyschyn, Danielle; Shea, Peter R; Trevaskis, Natalie L

    2016-11-07

    hydrated proniosomes can prolong systemic drug exposure over 3 days and provide a sustained therapeutic effect. The developed proniosomes represent a novel approach to treat acute pain and inflammation with the potential to be administered as a single intravenous dose by a clinician at the time of injury or surgery that provides adequate relief for several days and reduces fluctuations in therapy. Similar systems loaded with different drugs have potential for broader application in anesthesia, anti-infective, antiemetic, and cancer therapy.

  10. Application of methyl methacrylate copolymers to the development of transdermal or loco-regional drug delivery systems.

    Science.gov (United States)

    Cilurzo, Francesco; Selmin, Francesca; Gennari, Chiara G M; Montanari, Luisa; Minghetti, Paola

    2014-07-01

    Methyl methacrylate copolymers (Eudragit®) have been exploited to develop transdermal patches, medicated plasters (hereinafter patches) and, more recently, film-forming sprays, microsponges and nanoparticles intended to be applied on the skin. The article reviews the information regarding the application of Eudragits in the design and development of these dosage forms focusing on the impact of formulative variables on the skin drug penetration and the patch adhesive properties. Eudragits combined with a large amount of plasticizers are used to design the pressure-sensitive adhesives, specialized materials used in the patch development. They have to assure the drug skin penetration and the contact with the skin. Most of the studies mainly deal with the former aspect. The authors used a Eudragit type opportunely plasticized to merely investigate the in vitro or in vivo skin permeability of a loaded drug. However, the summa of these data evidenced that a strict connection between the matrix hydrophilicity and drug penetration probably exists. The criticisms of adhesion are addressed in a limited number of papers reporting data on technological properties, namely tack, shear adhesion and peel adhesion, while the structural data of the Eudragit adhesives, rheology and surface free energy are not described, excepting the case of Eudragit E. Among other applications, micro- and nanosystems exploiting the ionizable nature of some Eudragits can offer novel opportunities to develop pH-sensitive drug delivery systems suitable for triggering its release onto the skin.

  11. Thermo-acoustical analysis of sodium dodecyl sulfate: Fluconazole (antifungal drug) based micellar system in hydro-ethanol solutions for potential drug topical application

    International Nuclear Information System (INIS)

    Bhardwaj, Tarun; Bhardwaj, Varun; Sharma, Kundan; Gupta, Abhishek; Cameotra, Swaranjit Singh; Sharma, Poonam

    2014-01-01

    Highlights: • The mixed micellar system was analyzed for sodium dodecyl sulfate and fluconazole. • Early micellization was found with CMC shift towards lower surfactant concentration. • Negative ΔG m o values suggested that the micelle formation is spontaneous and feasible. • Thermo-acoustical parameters revealed the existence of intermolecular interactions within the molecules. - Abstract: Micellar systems hold excellent drug delivery applications due to their capability to solubilize a large number of hydrophobic and hydrophilic molecules. In this present work, the mixed micelle formation between the anionic surfactant sodium dodecyl sulfate (SDS) and the ‘Azole’ derivative antifungal drug fluconazole (FLZ) have been studied at four temperatures in different hydro-ethanolic solutions. The critical micelle concentration (CMC) was determined by specific conductance techniques and the experimental data was used to calculate several useful thermodynamic parameters, like standard free energy, enthalpy and entropy of micelle formation. Early micellization was found with critical micelle concentration shifting towards lower concentration (CMC) than the standard concentration of SDS in water at 25 °C suggesting that drug and the solvent system facilitates the micellization process. In addition, the transport properties were examined by employing controlled approaches likely, apparent molar volume (ϕ v ), apparent molar adiabatic compression (ϕ k ), and isentropic compression (κ s ) of SDS in presence of FLZ. These parameters revealed the existence of intermolecular interactions within the molecules. Therefore, this study would cast light on utilizing surfactant immobilized FLZ system for better topical biological action

  12. Illicit drugs and pharmaceuticals in the environment--forensic applications of environmental data. Part 1: Estimation of the usage of drugs in local communities.

    Science.gov (United States)

    Kasprzyk-Hordern, Barbara; Dinsdale, Richard M; Guwy, Alan J

    2009-06-01

    Pharmaceuticals and recently also illicit drugs have been recognised as emerging environmental contaminants due to their potential environmental impact: frequent occurrence, persistence and risk to aquatic life and humans. This manuscript is part one of the two-part study aiming to provide a better understanding and application of environmental data not only for environmental aims but also to meet forensic objectives. An attempt to use wastewater data is made in order to verify patterns of the usage of drugs (in particular illicit) in local communities. The average usage of cocaine in South Wales was estimated at 0.9 g day(-1) 1000 people(-1), which equals 1 tonne of this drug used or disposed of to sewage annually in Wales. The calculated usage of amphetamine denoted 2.5 g day(-1) 1000 people(-1) and is suspected to be an overestimate. Because no analysis of enantiomers of amphetamine was undertaken, no distinction between amphetamine's legal and illicit usage could be made.

  13. [Development and effectiveness of a drug dosage calculation training program using cognitive loading theory based on smartphone application].

    Science.gov (United States)

    Kim, Myoung Soo; Park, Jung Ha; Park, Kyung Yeon

    2012-10-01

    This study was done to develop and evaluate a drug dosage calculation training program using cognitive loading theory based on a smartphone application. Calculation ability, dosage calculation related self-efficacy and anxiety were measured. A nonequivalent control group design was used. Smartphone application and a handout for self-study were developed and administered to the experimental group and only a handout was provided for control group. Intervention period was 4 weeks. Data were analyzed using descriptive analysis, χ²-test, t-test, and ANCOVA with the SPSS 18.0. The experimental group showed more 'self-efficacy for drug dosage calculation' than the control group (t=3.82, psmartphone application is effective in improving dosage calculation related self-efficacy and calculation ability. Further study should be done to develop additional interventions for reducing anxiety.

  14. Clinical applications of fast liquid chromatography: a review on the analysis of cardiovascular drugs and their metabolites.

    Science.gov (United States)

    Baranowska, Irena; Magiera, Sylwia; Baranowski, Jacek

    2013-05-15

    One of the major challenges facing the medicine today is developing new therapies that enhance human health. To help address these challenges the utilization of analytical technologies and high-throughput automated platforms has been employed; in order to perform more experiments in a shorter time frame with increased data quality. In the last decade various analytical strategies have been established to enhance separation speed and efficiency in liquid chromatography applications. Liquid chromatography is an increasingly important tool for monitoring drugs and their metabolites. Furthermore, liquid chromatography has played an important role in pharmacokinetics and metabolism studies at these drug development stages since its introduction. This paper provides an overview of current trends in fast chromatography for the analysis of cardiovascular drugs and their metabolites in clinical applications. Current trends in fast liquid chromatographic separations involve monolith technologies, fused-core columns, high-temperature liquid chromatography (HTLC) and ultra-high performance liquid chromatography (UHPLC). The high specificity in combination with high sensitivity makes it an attractive complementary method to traditional methodology used for routine applications. The practical aspects of, recent developments in and the present status of fast chromatography for the analysis of biological fluids for therapeutic drug and metabolite monitoring, pharmacokinetic studies and bioequivalence studies are presented. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Applicability of bioanalysis of multiple analytes in drug discovery and development: review of select case studies including assay development considerations.

    Science.gov (United States)

    Srinivas, Nuggehally R

    2006-05-01

    The development of sound bioanalytical method(s) is of paramount importance during the process of drug discovery and development culminating in a marketing approval. Although the bioanalytical procedure(s) originally developed during the discovery stage may not necessarily be fit to support the drug development scenario, they may be suitably modified and validated, as deemed necessary. Several reviews have appeared over the years describing analytical approaches including various techniques, detection systems, automation tools that are available for an effective separation, enhanced selectivity and sensitivity for quantitation of many analytes. The intention of this review is to cover various key areas where analytical method development becomes necessary during different stages of drug discovery research and development process. The key areas covered in this article with relevant case studies include: (a) simultaneous assay for parent compound and metabolites that are purported to display pharmacological activity; (b) bioanalytical procedures for determination of multiple drugs in combating a disease; (c) analytical measurement of chirality aspects in the pharmacokinetics, metabolism and biotransformation investigations; (d) drug monitoring for therapeutic benefits and/or occupational hazard; (e) analysis of drugs from complex and/or less frequently used matrices; (f) analytical determination during in vitro experiments (metabolism and permeability related) and in situ intestinal perfusion experiments; (g) determination of a major metabolite as a surrogate for the parent molecule; (h) analytical approaches for universal determination of CYP450 probe substrates and metabolites; (i) analytical applicability to prodrug evaluations-simultaneous determination of prodrug, parent and metabolites; (j) quantitative determination of parent compound and/or phase II metabolite(s) via direct or indirect approaches; (k) applicability in analysis of multiple compounds in select

  16. Network-based discovery through mechanistic systems biology. Implications for applications--SMEs and drug discovery: where the action is.

    Science.gov (United States)

    Benson, Neil

    2015-08-01

    Phase II attrition remains the most important challenge for drug discovery. Tackling the problem requires improved understanding of the complexity of disease biology. Systems biology approaches to this problem can, in principle, deliver this. This article reviews the reports of the application of mechanistic systems models to drug discovery questions and discusses the added value. Although we are on the journey to the virtual human, the length, path and rate of learning from this remain an open question. Success will be dependent on the will to invest and make the most of the insight generated along the way. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Theoretical study on the cage-like nanostructures formed by amino acids and their potential applications as drug carriers

    Science.gov (United States)

    Weng, Pei Pei; Fan, Jian Fen; Lin, Hui Fang; Zhao, Xin; Si, Xia Lan

    2017-12-01

    The cage-like octamer, decamer and dodecamer constructed from aspartic acid monomers have been studied to explore their potential applications as drug carriers using the density functional theory. The calculation results indicate that these stable cage-like oligomers are mainly connected by the -C=O…HOOC- and -HN…HOOC- H-bonds and still keep stability and good drum-shaped topologies after the incorporation of 5-fluorouracil, paraldehyde and C24, respectively. The self-assembled cage-like oligomers may be applied to the preparation of new biological materials and the design of drug delivery systems.

  18. Preparation and characterization of polymer nanocomposites coated magnetic nanoparticles for drug delivery applications

    International Nuclear Information System (INIS)

    Prabha, G.; Raj, V.

    2016-01-01

    In the present research work, the anticancer drug ‘curcumin’ is loaded with Chitosan (CS)-polyethylene glycol (PEG)-polyvinylpyrrolidone (PVP) (CS-PEG-PVP) polymer nanocomposites coated with superparamagnetic iron oxide (Fe 3 O 4 ) nanoparticles. The system can be used for targeted and controlled drug delivery of anticancer drugs with reduced side effects and greater efficiency. The prepared nanoparticles were characterized by Fourier transmission infrared spectroscopy (FTIR), vibrating sample magnetometry (VSM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Curcumin drug loaded Fe 3 O 4 -CS, Fe 3 O 4 -CS-PEG and Fe 3 O 4 -CS-PEG-PVP nanoparticles exhibited the mean particle size in the range of 183–390 nm with a zeta potential value of 26–41 mV as measured using Malvern Zetasizer. The encapsulation efficiency, loading capacity and in-vitro drug release behavior of curcumin drug loaded Fe 3 O 4 -CS, Fe 3 O 4 -CS-PEG and Fe 3 O 4 -CS-PEG-PVP nanoparticles were studied using UV spectrophotometer. Besides, the cytotoxicity of the prepared nanoparticles using MTT assay was also studied. The curcumin drug release was examined at different pH medium and it was proved that the drug release depends upon the pH medium in addition to the nature of matrix. - Highlights: • The considered drug carrier Fe 3 O 4 -CS-PEG-PVP nanoparticles were prepared and entrapping (Curcumin). • The amount of the drug had great effect on the drug LC and EE and zeta potential Nanocomposites. • The Curcumin- loaded Fe 3 O 4 -CS, Fe 3 O 4 -CS-PEG and Fe 3 O 4 -CS-PEG-PVP nanocomposites showed pH responsive drug release.

  19. Novel micellar systems for the formulation of poorly water soluble drugs : biocompatibility aspects and pharmaceutical applications

    OpenAIRE

    Dumontet Mondon, Karine

    2010-01-01

    Amongst the large number of novel drugs, 95% are lipophilic and poorly water soluble. Particularly, this renders their aqueous formulation very difficult. In this regard this thesis focused on polymeric micelles based on novel MPEG-hexPLA copolymers forming a hydrophilic shell and a very hydrophobic core that favors the incorporation of poorly water soluble drugs. Although the drug hydrophobicity and water solubility are the main parameters in respect to their incorporation efficiency, struct...

  20. Application of in situ polymerization for design and development of oral drug delivery systems.

    Science.gov (United States)

    Ngwuluka, Ndidi

    2010-12-01

    Although preformed polymers are commercially available for use in the design and development of drug delivery systems, in situ polymerization has also been employed. In situ polymerization affords the platform to tailor and optimize the drug delivery properties of polymers. This review brings to light the benefits of in situ polymerization for oral drug delivery and the possibilities it provides to overcome the challenges of oral route of administration.

  1. Application of In Situ Polymerization for Design and Development of Oral Drug Delivery Systems

    OpenAIRE

    Ngwuluka, Ndidi

    2010-01-01

    Although preformed polymers are commercially available for use in the design and development of drug delivery systems, in situ polymerization has also been employed. In situ polymerization affords the platform to tailor and optimize the drug delivery properties of polymers. This review brings to light the benefits of in situ polymerization for oral drug delivery and the possibilities it provides to overcome the challenges of oral route of administration.

  2. Direct encapsulation of water-soluble drug into silica microcapsules for sustained release applications

    International Nuclear Information System (INIS)

    Wang Jiexin; Wang Zhihui; Chen Jianfeng; Yun, Jimmy

    2008-01-01

    Direct encapsulation of water-soluble drug into silica microcapsules was facilely achieved by a sol-gel process of tetraethoxysilane (TEOS) in W/O emulsion with hydrochloric acid (HCl) aqueous solution containing Tween 80 and drug as well as cyclohexane solution containing Span 80. Two water-soluble drugs of gentamicin sulphate (GS) and salbutamol sulphate (SS) were chosen as model drugs. The characterization of drug encapsulated silica microcapsules by scanning electronic microscopy (SEM), FTIR, thermogravimetry (TG) and N 2 adsorption-desorption analyses indicated that drug was successfully entrapped into silica microcapsules. The as-prepared silica microcapsules were uniform spherical particles with hollow structure, good dispersion and a size of 5-10 μm, and had a specific surface area of about 306 m 2 /g. UV-vis and thermogravimetry (TG) analyses were performed to determine the amount of drug encapsulated in the microcapsules. The BJH pore size distribution (PSD) of silica microcapsules before and after removing drug was examined. In vitro release behavior of drug in simulated body fluid (SBF) revealed that such system exhibited excellent sustained release properties

  3. Physically Targeted Intravenous Polyurethane Nanoparticles for Controlled Release of Atorvastatin Calcium

    Science.gov (United States)

    Eftekhari, Behnaz Sadat; Karkhaneh, Akbar; Alizadeh, Ali

    2017-01-01

    Background: Intravenous drug delivery is an advantageous choice for rapid administration, immediate drug effect, and avoidance of first-pass metabolism in oral drug delivery. In this study, the synthesis, formulation, and characterization of atorvastatin-loaded polyurethane (PU) nanoparticles were investigated for intravenous route of administration. Method: First, PU was synthesized and characterized. Second, nanoparticles were prepared in four different ratios of drug to polymer through two different techniques, including emulsion-diffusion and single-emulsion. Finally, particle size and polydispersity index, shape and surface morphology, drug entrapment efficiency (EE), drug loading, and in vitro release were evaluated by dynamics light scattering, scanning electron microscopy, and UV visible spectroscopy, respectively. Results: Within two methods, the prepared nanoparticles had a spherical shape and a smooth surface with a diversity of size ranged from 174.04 nm to 277.24 nm in emulsion-diffusion and from 306.5 nm to 393.12 in the single-emulsion method. The highest EE was 84.76%, for (1:4) sample in the emulsion-diffusion method. It has also been shown that in vitro release of nanoparticles, using the emulsion-diffusion method, was sustained up to eight days by two mechanisms: drug diffusion and polymer relaxation. Conclusion: PU nanoparticles, that were prepared by the emulsion-diffusion method, could be used as effective carriers for the controlled drug delivery of poorly water soluble drugs such as atorvastatin calcium. PMID:28532144

  4. APPLICATION OF UV-SPECTROPHOTOMETRY FOR THE QUANTITATIVE DETERMINATION OF CAPTOPRIL IN DRUG

    Directory of Open Access Journals (Sweden)

    Yu. V. Monaykina

    2015-04-01

    formulations. The results obtained by applying the proposed method were statistically analyzed. Validation of the method confirmed its proper precision and recovery (for gel: 100,2%, RSD% = 0,572, n = 9; for suppositories: 99,87%, RSD% = 0,420, n = 9, linearity (for gel: r =0,9978, n=6; for suppositories: r =0,9982, n=6 The received parameters enable the developed procedure to be used in quantitative pharmaceutical analysis. Conclusions. The applicability of the new procedure is well established by the assay the new drug formulations of captopril – 0,05 suppositories and 2,5% nasal gel. The developed UV spectrophotometric method is potentially useful because of its simplicity, rapidity and accuracy. The procedure is valid according to the validation requirements of Ukrainian Pharmacopeia

  5. Layer-by-layer assembled multilayers and polymeric nanoparticles for drug delivery in tissue engineering applications

    Science.gov (United States)

    Mehrotra, Sumit

    Tissues and organs in vivo are structured in three dimensional (3-D) ordered assemblies to maintain their metabolic functions. In the case of an injury, certain tissues lack the regenerative abilities without an external supportive environment. In order to regenerate the natural in vivo environment post-injury, there is a need to design three-dimensional (3-D) tissue engineered constructs of appropriate dimensions along with strategies that can deliver growth factors or drugs at a controlled rate from such constructs. This thesis focuses on the applications of hydrogen bonded (H-bonded) nanoscale layer-by-layer (LbL) assembled multilayers for time controlled drug delivery, fabrication of polymeric nanoparticles as drug delivery carriers, and engineering 3-D cellular constructs. Axonal regeneration in the central nervous system after spinal cord injury is often disorganized and random. To support linear axonal growth into spinal cord lesion sites, certain growth factors, such as brain-derived neurotrophic factor (BDNF), needs to be delivered at a controlled rate from an array of uniaxial channels patterned in a scaffold. In this study, we demonstrate for the first time that H-bonded LbL assembled degradable thin films prepared over agarose hydrogel, whereby the protein was loaded separately from the agarose fabrication, provided sustained release of protein under physiological conditions for more than four weeks. Further, patterned agarose scaffolds implanted at the site of a spinal cord injury forms a reactive cell layer of leptomeningeal fibroblasts in and around the scaffold. This limits the ability of axons to reinnervate the spinal cord. To address this challenge, we demonstrate the time controlled release of an anti-mitotic agent from agarose hydrdgel to control the growth of the reactive cell layer of fibroblasts. Challenges in tissue engineering can also be addressed using gene therapy approaches. Certain growth factors in the body are known to inhibit

  6. Higher lung accumulation of intravenously injected organic nanotubes

    Directory of Open Access Journals (Sweden)

    Maitani Y

    2013-01-01

    Full Text Available Yoshie Maitani,1 Yuri Nakamura,1 Masao Kon,1 Emi Sanada,1 Kae Sumiyoshi,1 Natsuki Fujine,1 Masumi Asakawa,2 Masaki Kogiso,2 Toshimi Shimizu21Institute of Medicinal Chemistry, Hoshi University, Tokyo, Japan; 2Nanotube Research Center (NTRC, National Institute of Advanced Industrial Science and Technology (AIST, Tsukuba, JapanAbstract: The size and shape of intravenously injected particles can affect their biodistribution and is of importance for the development of particulated drug carrier systems. In this study, organic nanotubes (ONTs with a carboxyl group at the surface, a length of approximately 2 µm and outer diameter of 70–90 nm, were injected intravenously into tumor-bearing mice. To use ONTs as drug carriers, the biodistribution in selected organs of ONTs postinjection was examined using irinotecan, as an entrapped water-soluble marker inside ONTs, and gadolinium-chelated ONT, as an ONT marker, and compared with that of a 3 µm fluorescently labeled spherical microparticle which was similar size to the length of ONTs. It was found that for irinotecan, its active metabolite and gadolinium-chelated ONTs were highly accumulated in the lung, but to a lower level in the liver and spleen. On the other hand, microparticles deposited less in the lung and more highly in the liver. Moreover, histologic examination showed ONTs distributed more in lung tissues in part, whereas microparticles were present in blood vessels postinjection. These preliminary results support the notion of using negatively charged ONTs as intravascular carriers to maximize accumulation in the lung whilst reducing sequestration by the liver and spleen. This finding suggested that ONTs are potential carriers for lung-targeting drug delivery.Keywords: organic nanotube, lung, biodistribution, microparticle, particle shape

  7. [Peripheral intravenous catheter-related phlebitis].

    Science.gov (United States)

    van der Sar-van der Brugge, Simone; Posthuma, E F M Ward

    2011-01-01

    Phlebitis is a very common complication of the use of intravenous catheters. Two patients with an i.v. catheter complicated by thrombophlebitis are described. Patient A was immunocompromised due to chronic lymphatic leukaemia and developed septic thrombophlebitis with positive blood cultures for S. Aureus. Patient B was being treated with flucloxacillin because of an S. Aureus infection and developed chemical phlebitis. Septic phlebitis is rare, but potentially serious. Chemical or mechanical types of thrombophlebitis are usually less severe, but happen very frequently. Risk factors include: female sex, previous episode of phlebitis, insertion at (ventral) forearm, emergency placement and administration of antibiotics. Until recently, routine replacement of peripheral intravenous catheters after 72-96 h was recommended, but randomised controlled trials have not shown any benefit of this routine. A recent Cochrane Review recommends replacement of peripheral intravenous catheters when clinically indicated only.

  8. Research on Optimization of Pooling System and Its Application in Drug Supply Chain Based on Big Data Analysis.

    Science.gov (United States)

    Wu, DengFeng; Mao, Hongyi

    2017-01-01

    Reform of drug procurement is being extensively implemented and expanded in China, especially in today's big data environment. However, the pattern of supply mode innovation lags behind procurement improvement. Problems in financial strain and supply break frequently occur, which affect the stability of drug supply. Drug Pooling System is proposed and applied in a few pilot cities to resolve these problems. From the perspective of supply chain, this study analyzes the process of setting important parameters and sets out the tasks of involved parties in a pooling system according to the issues identified in the pilot run. The approach is based on big data analysis and simulation using system dynamic theory and modeling of Vensim software to optimize system performance. This study proposes a theoretical framework to resolve problems and attempts to provide a valuable reference for future application of pooling systems.

  9. Distribution of blood derivatives by registered blood establishments that qualify as health care entities; Prescription Drug Marketing Act of 1987; Prescription Drug Amendments of 1992; delay of applicability date. Final rule; delay of applicability date.

    Science.gov (United States)

    2006-11-13

    The Food and Drug Administration (FDA) is further delaying, until December 1, 2008, the applicability date of a certain requirement of a final rule published in the Federal Register of December 3, 1999 (64 FR 67720) (the final rule). The final rule implements the Prescription Drug Marketing Act of 1987 (PDMA), as modified by the Prescription Drug Amendments of 1992 (PDA), and the Food and Drug Administration Modernization Act of 1997 (the Modernization Act). The provisions of the final rule became effective on December 4, 2000, except for certain provisions whose effective or applicability dates were delayed in five subsequent Federal Register notices, until December 1, 2006. The provision with the delayed applicability date would prohibit wholesale distribution of blood derivatives by registered blood establishments that meet the definition of a "health care entity." In the Federal Register of February 1, 2006 (71 FR 5200), FDA published a proposed rule specific to the distribution of blood derivatives by registered blood establishments that qualify as health care entities (the proposed rule). The proposed rule would amend certain limited provisions of the final rule to allow certain registered blood establishments that qualify as health care entities to distribute blood derivatives. In response to the proposed rule, FDA received substantive comments. As explained in the SUPPLEMENTARY INFORMATION section of this document, further delaying the applicability of Sec. 203.3(q) (21 CFR 203.3(q)) to the wholesale distribution of blood derivatives by health care entities is necessary to give the agency additional time to address comments on the proposed rule, consider whether regulatory changes are appropriate, and, if so, to initiate such changes.

  10. The application of hematopoietic growth factors in drug-induced agranulocytosis: a review of 70 cases

    NARCIS (Netherlands)

    Sprikkelman, A.; de Wolf, J. T.; Vellenga, E.

    1994-01-01

    Since 1989, granulocyte-macrophage and granulocyte colony-stimulating factors (GM-CSF, G-CSF) have been increasingly applied in the treatment of drug-induced agranulocytosis. In order to evaluate the effectiveness of GM-CSF and G-CSF in the treatment of drug-induced agranulocytosis, we have studied

  11. 77 FR 22789 - Withdrawal of Approval of Part of a New Animal Drug Application; Tiamulin

    Science.gov (United States)

    2012-04-17

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0262... Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is withdrawing approval of... to the production indications for use of increased rate of weight gain and improved feed efficiency...

  12. 78 FR 14667 - New Animal Drug Applications; Alfaprostol; Bicyclohexylammonium Fumagillin; N

    Science.gov (United States)

    2013-03-07

    ... Part 558 Animal drugs, Animal feeds. Therefore, under the Federal Food, Drug, and Cosmetic Act and...-, 884-, or 1,768-milligram, or 4.42-gram capsules. (3) Conditions of use in dogs--(i) Amount. Administered capsules orally. Capsules containing 221 milligrams of n-butyl chloride are administered to dogs...

  13. The application of skin metabolomics in the context of transdermal drug delivery.

    Science.gov (United States)

    Li, Jinling; Xu, Weitong; Liang, Yibiao; Wang, Hui

    2017-04-01

    Metabolomics is a powerful emerging tool for the identification of biomarkers and the exploration of metabolic pathways in a high-throughput manner. As an administration site for percutaneous absorption, the skin has a variety of metabolic enzymes, except other than hepar. However, technologies to fully detect dermal metabolites remain lacking. Skin metabolomics studies have mainly focused on the regulation of dermal metabolites by drugs or on the metabolism of drugs themselves. Skin metabolomics techniques include collection and preparation of skin samples, data collection, data processing and analysis. Furthermore, studying dermal metabolic effects via metabolomics can provide novel explanations for the pathogenesis of some dermatoses and unique insights for designing targeted prodrugs, promoting drug absorption and controlling drug concentration. This paper reviews current progress in the field of skin metabolomics, with a specific focus on dermal drug delivery systems and dermatosis. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

  14. Understanding release kinetics of biopolymer drug delivery microcapsules for biomedical applications

    International Nuclear Information System (INIS)

    Desai, Salil; Perkins, Jessica; Harrison, Benjamin S.; Sankar, Jag

    2010-01-01

    Drug delivery and dosage concentrations are considered as major focal points in conventional as well as battlefield emergency medicine. The concept of localizing drug delivery via microcapsules is an evolving field to confine the adverse side effects of high concentration drug doses. This paper focuses on understanding release kinetics through biopolymer microcapsules for time-dependent drug release. Calcium alginate microcapsules were manufactured using a direct-write inkjet technique. Rhodamine 6G was used as the release agent to observe the release kinetics from calcium alginate beads in distilled water. A design of experiments was constructed to compare the effect of the microcapsule diameter and different concentrations of calcium chloride (M) and sodium alginate (%, w/v) solutions on the release kinetics profiles of the microcapsules. This research gives insight to identify favorable sizes of microcapsules and concentrations of sodium alginate and calcium chloride solutions for controlled release behavior of drug delivery microcapsules.

  15. The application of ATR-FTIR spectroscopy and multivariate data analysis to study drug crystallisation in the stratum corneum.

    Science.gov (United States)

    Goh, Choon Fu; Craig, Duncan Q M; Hadgraft, Jonathan; Lane, Majella E

    2017-02-01

    Drug permeation through the intercellular lipids, which pack around and between corneocytes, may be enhanced by increasing the thermodynamic activity of the active in a formulation. However, this may also result in unwanted drug crystallisation on and in the skin. In this work, we explore the combination of ATR-FTIR spectroscopy and multivariate data analysis to study drug crystallisation in the skin. Ex vivo permeation studies of saturated solutions of diclofenac sodium (DF Na) in two vehicles, propylene glycol (PG) and dimethyl sulphoxide (DMSO), were carried out in porcine ear skin. Tape stripping and ATR-FTIR spectroscopy were conducted simultaneously to collect spectral data as a function of skin depth. Multivariate data analysis was applied to visualise and categorise the spectral data in the region of interest (1700-1500cm -1 ) containing the carboxylate (COO - ) asymmetric stretching vibrations of DF Na. Spectral data showed the redshifts of the COO - asymmetric stretching vibrations for DF Na in the solution compared with solid drug. Similar shifts were evident following application of saturated solutions of DF Na to porcine skin samples. Multivariate data analysis categorised the spectral data based on the spectral differences and drug crystallisation was found to be confined to the upper layers of the skin. This proof-of-concept study highlights the utility of ATR-FTIR spectroscopy in combination with multivariate data analysis as a simple and rapid approach in the investigation of drug deposition in the skin. The approach described here will be extended to the study of other actives for topical application to the skin. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Mathematical description of drug-target interactions: application to biologics that bind to targets with two binding sites.

    Science.gov (United States)

    Gibiansky, Leonid; Gibiansky, Ekaterina

    2018-02-01

    The emerging discipline of mathematical pharmacology occupies the space between advanced pharmacometrics and systems biology. A characteristic feature of the approach is application of advance mathematical methods to study the behavior of biological systems as described by mathematical (most often differential) equations. One of the early application of mathematical pharmacology (that was not called this name at the time) was formulation and investigation of the target-mediated drug disposition (TMDD) model and its approximations. The model was shown to be remarkably successful, not only in describing the observed data for drug-target interactions, but also in advancing the qualitative and quantitative understanding of those interactions and their role in pharmacokinetic and pharmacodynamic properties of biologics. The TMDD model in its original formulation describes the interaction of the drug that has one binding site with the target that also has only one binding site. Following the framework developed earlier for drugs with one-to-one binding, this work aims to describe a rigorous approach for working with similar systems and to apply it to drugs that bind to targets with two binding sites. The quasi-steady-state, quasi-equilibrium, irreversible binding, and Michaelis-Menten approximations of the model are also derived. These equations can be used, in particular, to predict concentrations of the partially bound target (RC). This could be clinically important if RC remains active and has slow internalization rate. In this case, introduction of the drug aimed to suppress target activity may lead to the opposite effect due to RC accumulation.

  17. Membrane Interactions of Phytochemicals as Their Molecular Mechanism Applicable to the Discovery of Drug Leads from Plants

    Directory of Open Access Journals (Sweden)

    Hironori Tsuchiya

    2015-10-01

    Full Text Available In addition to interacting with functional proteins such as receptors, ion channels, and enzymes, a variety of drugs mechanistically act on membrane lipids to change the physicochemical properties of biomembranes as reported for anesthetic, adrenergic, cholinergic, non-steroidal anti-inflammatory, analgesic, antitumor, antiplatelet, antimicrobial, and antioxidant drugs. As well as these membrane-acting drugs, bioactive plant components, phytochemicals, with amphiphilic or hydrophobic structures, are presumed to interact with biological membranes and biomimetic membranes prepared with phospholipids and cholesterol, resulting in the modification of membrane fluidity, microviscosity, order, elasticity, and permeability with the potencies being consistent with their pharmacological effects. A novel mechanistic point of view of phytochemicals would lead to a better understanding of their bioactivities, an insight into their medicinal benefits, and a strategic implication for discovering drug leads from plants. This article reviews the membrane interactions of different classes of phytochemicals by highlighting their induced changes in membrane property. The phytochemicals to be reviewed include membrane-interactive flavonoids, terpenoids, stilbenoids, capsaicinoids, phloroglucinols, naphthodianthrones, organosulfur compounds, alkaloids, anthraquinonoids, ginsenosides, pentacyclic triterpene acids, and curcuminoids. The membrane interaction’s applicability to the discovery of phytochemical drug leads is also discussed while referring to previous screening and isolating studies.

  18. From Protein Structure to Small-Molecules: Recent Advances and Applications to Fragment-Based Drug Discovery.

    Science.gov (United States)

    Ferreira, Leonardo G; Andricopulo, Adriano D

    2017-01-01

    Fragment-based drug discovery (FBDD) is a broadly used strategy in structure-guided ligand design, whereby low-molecular weight hits move from lead-like to drug-like compounds. Over the past 15 years, an increasingly important role of the integration of these strategies into industrial and academic research platforms has been successfully established, allowing outstanding contributions to drug discovery. One important factor for the current prominence of FBDD is the better coverage of the chemical space provided by fragment-like libraries. The development of the field relies on two features: (i) the growing number of structurally characterized drug targets and (ii) the enormous chemical diversity available for experimental and virtual screenings. Indeed, fragment-based campaigns have contributed to address major challenges in lead optimization, such as the appropriate physicochemical profile of clinical candidates. This perspective paper outlines the usefulness and applications of FBDD approaches in medicinal chemistry and drug design. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Cloxacillin distribution in the rabbit eye after intravenous injection

    International Nuclear Information System (INIS)

    Salminen, L.

    1978-01-01

    Distribution of isotopically labelled and intravenously injected cloxacillin was studied in the rabbit eye. The antibiotic concentration determined by liquid scintillation counting proved to be a reliable measure of the total antibiotic concentration when controlled by microbiological assay. In the rabbit eye after an intravenous injection of 50 mg/kg of cloxacillin sodium, longlasting antibiotic concentration regarded as therapeutic against penicillinase producing staphylococci was obtained in all vascularized ocular structures and in the cornea. The antibiotic present in the iris and ciliary body, and in the retina and choroid preparations, proved to be partly intravascular, whereas it penetrated better into the extravascular tissue compartment of the sclera and limbal area. Cloxacillin failed to achieve a therapeutic antibiotic concentration in the vitreous body and in the lens. Administration of probenecid had an enhancing effect on ocular cloxacillin concentration allowing improved drug diffusion into the eye by means of an elevated plasma concentration. No specific ocular effect of probenecid was noticed. Therapeutic concentration of cloxacillin in the aqueous humour, otherwise barely achieved, was more satisfactorily obtained with a previous injection of probenecid. (author)

  20. The in silico drug discovery toolbox: applications in lead discovery and optimization.

    Science.gov (United States)

    Bruno, Agostino; Costantino, Gabriele; Sartori, Luca; Radi, Marco

    2017-11-06

    Discovery and development of a new drug is a long lasting and expensive journey that takes around 15 years from starting idea to approval and marketing of new medication. Despite the R&D expenditures have been constantly increasing in the last few years, number of new drugs introduced into market has been steadily declining. This is mainly due to preclinical and clinical safety issues, which still represent about 40% of drug discontinuation. From this point of view, it is clear that if we want to increase drug-discovery success rate and reduce costs associated with development of a new drug, a comprehensive evaluation/prediction of potential safety issues should be conducted as soon as possible during early drug discovery phase. In the present review, we will analyse the early steps of drug-discovery pipeline, describing the sequence of steps from disease selection to lead optimization and focusing on the most common in silico tools used to assess attrition risks and build a mitigation plan. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Photo-synthesis of protein-based nanoparticles and the application in drug delivery

    International Nuclear Information System (INIS)

    Xie, Jinbing; Wang, Hongyang; Cao, Yi; Qin, Meng; Wang, Wei

    2015-01-01

    Recently, protein-based nanoparticles as drug delivery systems have attracted great interests due to the excellent behavior of high biocompatibility and biodegradability, and low toxicity. However, the synthesis techniques are generally costly, chemical reagents introduced, and especially present difficulties in producing homogeneous monodispersed nanoparticles. Here, we introduce a novel physical method to synthesize protein nanoparticles which can be accomplished under physiological condition only through ultraviolet (UV) illumination. By accurately adjusting the intensity and illumination time of UV light, disulfide bonds in proteins can be selectively reduced and the subsequent self-assembly process can be well controlled. Importantly, the co-assembly can also be dominated when the proteins mixed with either anti-cancer drugs, siRNA, or active targeting molecules. Both in vitro and in vivo experiments indicate that our synthesized protein–drug nanoparticles (drug-loading content and encapsulation efficiency being ca. 8.2% and 70%, respectively) not only possess the capability of traditional drug delivery systems (DDS), but also have a greater drug delivery efficiency to the tumor sites and a better inhibition of tumor growth (only 35% of volume comparing to the natural growing state), indicating it being a novel drug delivery system in tumor therapy

  2. The synthesis and application involving regulation of the insoluble drug release from mesoporous silica nanotubes

    International Nuclear Information System (INIS)

    Li, Jia; Wang, Yan; Zheng, Xin; Zhang, Ying; Sun, Changshan; Gao, Yikun; Jiang, Tongying; Wang, Siling

    2015-01-01

    Highlights: • Mesoporous silica nanotubes (SNT) were synthesized by using CNT as hard template, and the formation of the SNT shows that CTAB played a significant effect on the coating process. • The tube mesoporous silica materials which were seldom reported were applied in the drug delivery system to improve the loading amount and the drug dissolution. • The release rate could be controlled by the gelatin layer on the silica surface and the mechanism was illustrated. - Abstract: Mesoporous silica nanotubes (SNT) were synthesized using hard template carbon nanotubes (CNT) with the aid of cetyltrimethyl ammonium bromide (CTAB) in a method, which was simple and inexpensive. Scanning electron microscopy, transmission electron microscopy and specific surface area analysis were employed to characterize the morphology and structure of SNT, and the formation mechanism of SNT was also examined by Fourier transform infrared spectroscopy. There are few published reports of the mesoporous SNT with large specific surface area applied in the drug delivery systems to improve the amount of drug loading. In addition, the structure of SNT allows investigators to control the drug particle size in the pore channels and significantly increase the drug dissolution rate. The insoluble drug, cilostazol, was chosen as a model drug to be loaded into SNT and we developed a simple and efficient method for regulating the drug release by using a gelatin coating with different thicknesses around the SNT. The release rate was adjusted by the amount of gelatin surrounding the SNT, with an increased barrier leading to a reduction in the release rate. A model developed on the basis of the Weibull modulus was established to fit the release results

  3. Preparation and characterization of polymer nanocomposites coated magnetic nanoparticles for drug delivery applications

    Energy Technology Data Exchange (ETDEWEB)

    Prabha, G., E-mail: gprabhagovinn@gmail.com; Raj, V., E-mail: alaguraj2@rediffmail.com

    2016-06-15

    In the present research work, the anticancer drug ‘curcumin’ is loaded with Chitosan (CS)-polyethylene glycol (PEG)-polyvinylpyrrolidone (PVP) (CS-PEG-PVP) polymer nanocomposites coated with superparamagnetic iron oxide (Fe{sub 3}O{sub 4}) nanoparticles. The system can be used for targeted and controlled drug delivery of anticancer drugs with reduced side effects and greater efficiency. The prepared nanoparticles were characterized by Fourier transmission infrared spectroscopy (FTIR), vibrating sample magnetometry (VSM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Curcumin drug loaded Fe{sub 3}O{sub 4}-CS, Fe{sub 3}O{sub 4}-CS-PEG and Fe{sub 3}O{sub 4}-CS-PEG-PVP nanoparticles exhibited the mean particle size in the range of 183–390 nm with a zeta potential value of 26–41 mV as measured using Malvern Zetasizer. The encapsulation efficiency, loading capacity and in-vitro drug release behavior of curcumin drug loaded Fe{sub 3}O{sub 4}-CS, Fe{sub 3}O{sub 4}-CS-PEG and Fe{sub 3}O{sub 4}-CS-PEG-PVP nanoparticles were studied using UV spectrophotometer. Besides, the cytotoxicity of the prepared nanoparticles using MTT assay was also studied. The curcumin drug release was examined at different pH medium and it was proved that the drug release depends upon the pH medium in addition to the nature of matrix. - Highlights: • The considered drug carrier Fe{sub 3}O{sub 4}-CS-PEG-PVP nanoparticles were prepared and entrapping (Curcumin). • The amount of the drug had great effect on the drug LC and EE and zeta potential Nanocomposites. • The Curcumin- loaded Fe{sub 3}O{sub 4}-CS, Fe{sub 3}O{sub 4}-CS-PEG and Fe{sub 3}O{sub 4}-CS-PEG-PVP nanocomposites showed pH responsive drug release.

  4. Pharmaceutical cocrystals as an opportunity to modify drug properties: From the idea to application. A review.

    Science.gov (United States)

    Sokal, Agnieszka; Pindelska, Edyta

    2017-12-26

    The properties of many drugs which have been available on the pharmaceutical market for a long time still need to be improved. Cocrystals are the solid state drug modification which can improve such properties as low solubility, stability and mechanical properties (e.g. compressibility). In this paper examples how to use cocrystals to modify properties of API (Active Pharmaceutical Ingredient) will be reported. Additionally, in this review the way from an idea of the new cocrystal to drug dosage form registration will be shortly described. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. 78 FR 35117 - Orphan Drug Regulations

    Science.gov (United States)

    2013-06-12

    ..., ``This [framework] affects the plasma protein therapeutics industry significantly because various drugs... orphan designated.'' Because many plasma protein therapies lack orphan-drug designation, they are... change in delivery system from intravenous (IV) to oral may, in some cases and for some drugs, constitute...

  6. Recent progress in the synthesis of poly(organo)phosphazenes and their applications in tissue engineering and drug delivery

    Science.gov (United States)

    Khan, R. U.; Wang, L.; Yu, H.; Zain-ul-Abdin; Akram, M.; Wu, J.; Haroon, M.; Ullah, R. S.; Deng, Zh; Xia, X.

    2018-02-01

    It is a highly desirable goal of researchers to develop effective biomaterials with minimum recovery time and affordable treatment expense for tissue engineering and drug delivery. In this scenario, numerous synthetic and natural polymers have been used. Among those synthetic polymers, polyorganophosphazenes (POPs) have got much attention as highly promising candidates for applications in tissue engineering and drug delivery. Polyorganophosphazenes are hybrid polymers containing inorganic backbone consisting of alternating nitrogen and phosphorus atoms with two organic side groups. POPs possess a wide range of unique properties, i.e., synthetic flexibility, biocompatibility, osteocompatibility, osteoinductivity, sustainability and degradability into harmless end products with predictable degradation rate and adjustable mechanical strength. Moreover, their tunable hydrophilic/hydrophobic and stimuli responsive properties add extra points to their use in biomedical applications. In addition, their various polymeric forms, i.e., microspheres, nano/microfibres, micelles, membranes, polymersomes, hydrogels and nano-conjugate linear polymers provide different carriers to efficiently deliver various hydrophilic/hydrophobic therapeutic agents both in vitro and in vivo. This review focuses on the most recent progress that has been made in the synthesis and applications of POPs in tissue engineering and their different polymeric forms used for drug delivery. Moreover, we have also summarized the effect of different side groups on the overall efficiency of POPs. The bibliography includes 239 references.

  7. Clinical Evaluation of Ciprofloxacin Intravenous Preparation ...

    African Journals Online (AJOL)

    The most common site of bacteria infection in humans is the urinary tract. For nosocomial infections it is the catheterized urinary tract. Compromised immune responses in hospitalized patients contribute to the difficulties encountered in treating their infections. In these patients, administration of intravenous antibiotic is ...

  8. The adverse effects of inadvertent intraoperative intravenous ...

    African Journals Online (AJOL)

    Inadvertent intravenous injection of 1% phenylephrine (10 mg) induced severe hypertension and tachycardia in a previously healthy female patient undergoing elective gynaecological surgery. This medical error was investigated using the criticalincident technique that is available in our department. This case report ...

  9. Intravenous iron supplementation in children on hemodialysis.

    NARCIS (Netherlands)

    Leijn, E.; Monnens, L.A.H.; Cornelissen, E.A.M.

    2004-01-01

    BACKGROUND: Children with end-stage renal disease (ESRD) on hemodialysis (HD) are often absolute or functional iron deficient. There is little experience in treating these children with intravenous (i.v.) iron-sucrose. In this prospective study, different i.v. iron-sucrose doses were tested in

  10. Campaign best practice in intravenous therapy.

    Science.gov (United States)

    Baldwin, Wayne; Murphy, Jayne; Shakespeare, David; Kelly, Chris; Fox, Louise; Kelly, Matthew

    Intravenous therapy is an integral part of nursing care but is associated with a high risk of infection. This article outlines a campaign that aimed to increase awareness of best practice for IV therapy and reduce the risks of healthcare-associated IV infections in hospital and community settings.

  11. Intravenous voriconazole after toxic oral administration

    NARCIS (Netherlands)

    Alffenaar, J.W.C.; Van Assen, S.; De Monchy, J.G.R.; Uges, D.R.A.; Kosterink, J.G.W.; Van Der Werf, T.S.

    In a male patient with rhinocerebral invasive aspergillosis, prolonged high-dosage oral administration of voriconazole led to hepatotoxicity combined with a severe cutaneous reaction while intravenous administration in the same patient did not. High concentrations in the portal blood precipitate

  12. Complex intravenous anesthesia in interventional procedures

    International Nuclear Information System (INIS)

    Xie Zonggui; Hu Yuanming; Huang Yunlong; You Yong; Wu Juan; Huang Zengping; Li Jian

    2006-01-01

    Objective: To evaluate the value and safety of Diprivan and Fentany intravenous administration of analgesia in interventional procedures. Methods: Diprivan with Fentany intravenous administration for analgesia was used in eighty interventional procedures of sixty-five patients, without tracheal tube insertion. Vital signs including HR, BP, arterial oxygen saturation (SpO 2 ) and patients' reaction to operating were recorded. Results: Intravenous anesthesia was cared out successfully in eighty interventional procedures, with patients under sleeping condition during the operation, together with no pain and no agony memory of the procedure. The amount of Diprivan was 500±100 mg and Fentany was 0.2±0.025 mg. Mean arterial pressure and SpO 2 were 11.4±2.2 kPa, 10.6±2.1 kPa and 98±1.0, 96±1.5 respectively before and after ten minutes of the operation, with no significant difference. Conclusions: Diprivan with Fentany intravenous administration for interventional procedure analgesia possess good safety, painless and no agony memory of the procedure; therefor ought to be recommended. (authors)

  13. Facilitating adverse drug event detection in pharmacovigilance databases using molecular structure similarity: application to rhabdomyolysis

    Science.gov (United States)

    Vilar, Santiago; Harpaz, Rave; Chase, Herbert S; Costanzi, Stefano; Rabadan, Raul

    2011-01-01

    Background Adverse drug events (ADE) cause considerable harm to patients, and consequently their detection is critical for patient safety. The US Food and Drug Administration maintains an adverse event reporting system (AERS) to facilitate the detection of ADE in drugs. Various data mining approaches have been developed that use AERS to detect signals identifying associations between drugs and ADE. The signals must then be monitored further by domain experts, which is a time-consuming task. Objective To develop a new methodology that combines existing data mining algorithms with chemical information by analysis of molecular fingerprints to enhance initial ADE signals generated from AERS, and to provide a decision support mechanism to facilitate the identification of novel adverse events. Results The method achieved a significant improvement in precision in identifying known ADE, and a more than twofold signal enhancement when applied to the ADE rhabdomyolysis. The simplicity of the method assists in highlighting the etiology of the ADE by identifying structurally similar drugs. A set of drugs with strong evidence from both AERS and molecular fingerprint-based modeling is constructed for further analysis. Conclusion The results demonstrate that the proposed methodology could be used as a pharmacovigilance decision support tool to facilitate ADE detection. PMID:21946238

  14. Dependent Prior: An Application in Spinal Anaesthesia Drug Therapy on SBP in Cesarean patients.

    Directory of Open Access Journals (Sweden)

    Atanu Bhattacharjee

    2013-12-01

    Full Text Available Cesarean section is widely used operation procedure in the world. The regional anesthesia is preferred than general anesthesia. The risk of fetus is higher in general than in regional anesthesia. The drug treatment effect on regional anesthesia plays an important role to control the systolic blood pressure (SBP during the surgery. The goal of this work is to know the effective drug to control the SBP among cesarean anesthetic patients. The dependent prior with Bayesian approach is applied in the binary response data set. The secondary data in anesthesia has been applied to compare the two drug treatments, viz. (1 Phenylephrine and (2 Ephedrine, in cesarean patients with spinal anesthesia. In both drug groups the mean of SBP has been found controlled over the duration of the surgery. No rapid changes of SBP level among the patients are observed. At the end of study it is found that the means of SBP cesarean anesthetic patients are found higher in Phenylephrine group. The Bayesian dependent prior is found to offer effective tool for drug treatment effect comparison. The drug treatment effect Ephedrine is found to be more effective to control the SBP over the duration of surgery than Phenylephrine.

  15. Application of X-ray microanalysis to the study of drug uptake in cell culture

    International Nuclear Information System (INIS)

    Reasor, M.J.; Lee, P.; Kirk, R.G.

    1990-01-01

    X-ray microanalysis has been used previously to study the accumulation of iodine in alveolar macrophages of rats treated with the iodinated drug, amiodarone. Due to metabolism of the drug in vivo, primarily to desethylamiodarone, it was not possible to identify the source of the iodine signal. In the present study we have utilized primary cell cultures of alveolar macrophages to study the intracellular accumulation of each of these drug species in vitro. Neither drug is metabolized by these cells in culture, permitting characterization of the accumulation of each independent of the other. Cells were incubated with equimolar concentrations of either amiodarone or desethylamiodarone for 42 hr, and X-ray microanalysis of freeze-dried cryosections of cells was used to quantify accumulation by monitoring the iodine signal associated with each drug. For both drug exposures, the highest iodine content was present in amorphous bodies and dense granules, consistent with the pattern following in vivo exposure. Higher levels of desethylamiodarone, compared to amiodarone, were measured in all compartments of the cells. The results of the in vitro investigation further demonstrate the utility of X-ray microanalysis in the study of the cellular response to amiodarone and desethylamiodarone

  16. Europium-doped amorphous calcium phosphate porous nanospheres: preparation and application as luminescent drug carriers

    Directory of Open Access Journals (Sweden)

    Zhang Kui-Hua

    2011-01-01

    Full Text Available Abstract Calcium phosphate is the most important inorganic constituent of biological tissues, and synthetic calcium phosphate has been widely used as biomaterials. In this study, a facile method has been developed for the fabrication of amorphous calcium phosphate (ACP/polylactide-block-monomethoxy(polyethyleneglycol hybrid nanoparticles and ACP porous nanospheres. Europium-doping is performed to enable photoluminescence (PL function of ACP porous nanospheres. A high specific surface area of the europium-doped ACP (Eu3+:ACP porous nanospheres is achieved (126.7 m2/g. PL properties of Eu3+:ACP porous nanospheres are investigated, and the most intense peak at 612 nm is observed at 5 mol% Eu3+ doping. In vitro cytotoxicity experiments indicate that the as-prepared Eu3+:ACP porous nanospheres are biocompatible. In vitro drug release experiments indicate that the ibuprofen-loaded Eu3+:ACP porous nanospheres show a slow and sustained drug release in simulated body fluid. We have found that the cumulative amount of released drug has a linear relationship with the natural logarithm of release time (ln(t. The Eu3+:ACP porous nanospheres are bioactive, and can transform to hydroxyapatite during drug release. The PL properties of drug-loaded nanocarriers before and after drug release are also investigated.

  17. Assistance algorithm of nursing for amiodarone intravenous infusion

    Directory of Open Access Journals (Sweden)

    Francimar Tinoco de Oliveira

    2014-12-01

    Full Text Available This study aimed at identifying scientific publication on phlebitis caused by amiodarone and proposes a nursing care algorithm for interventions in intravenous amiodarone administration grounded in the Infusion Nursing Society and the Center for Disease Control and Prevention. It is a descriptive study mediated by integrative review in MedLine, LILACS, IBECS, BDENF, Cochrane Library and Scielo bases, published from 2006 to 2013. The sample consisted of nine articles. The evidence pointed the incidence of phlebitis due to the infusion of amiodarone and the need to control this event. The algorithm proposed shows the materials to be used and the procedure of drug administration in order to minimize injury. Besides subsidizing the development of future studies, this algorithm also promotes the incorporation of the best recommendation for the interventionist clinical practice.

  18. REVIEW ARTICLE – Intravenous paracetamol in pediatrics: A global perspective

    Directory of Open Access Journals (Sweden)

    Muzammil Irshad, MBBS

    2012-12-01

    Full Text Available Intravenous (IV Paracetamol is an excellent post operative analgesic and antipyretic in children. Efficacy and tolerability of IV Propacetamol have been established in pediatric practice. It is believed that paracetamol works by inhibiting cyclooxygenase-2 (COX-2 enzymes. Studies bring to light that therapeutic doses of IV acetaminophen are effective and tolerable in children with least chances of hepatotoxicity. However, overdose toxicity has been reported in children and drug induced hypotension in febrile critically ill patients. Therapeutic doses according to body weight of neonates and children can be administered in hospital settings. Special education of health care staff regarding precise dose and solution is necessary to assess the role of IV paracetamol preparation in pediatric practice.

  19. Effects of Intrarenal and Intravenous Infusion of the Phosphodiesterase 3 Inhibitor Milrinone on Renin Secretion

    Science.gov (United States)

    Kumagai, Kazuhiro; Reid, Ian A.

    1994-01-01

    We have reported that administration of the phosphodiesterase III inhibitor milrinone increases renin secretion in conscious rabbits. The aim of the present study was to determine if the increase in renin secretion results from a direct renal action of milrinone, or from an indirect extrarenal effect of the drug. This was accomplished by comparing the effects of intrarenal and intravenous infusion of graded doses of milrinone on plasma renin activity in unilaterally nephrectomized conscious rabbits. Milrinone was infused into the renal artery in doses of 0.01, 0.1 and 1.0 micro-g/kg/min, and intravenously in the same rabbits in doses of 0.01, 0.1, 1.0 and 10 micro-g/kg/min. Each dose was infused for 15 min. No intrarenal dose of milrinone altered plasma renin activity or arterial pressure, although at the highest dose, there was a small increase in heart rate. Intravenous infusion of milrinone at 1.0 micro-g/kg/min increased plasma renin activity to 176 +/- 55% of the control value (P less than 0.05). Heart rate increased but arterial pressure did not change. Intravenous infusion of milrinone at 1O micro-g/kg/min increased plasma renin activity to 386 +/- 193% of control in association with a decrease in arterial pressure and an increase in heart rate. These results confirm that milrinone increases renin secretion, and indicate that the stimulation is due to an extrarenal effect of the drug.

  20. Association Between Using Smartphone Dating Applications and Alcohol and Recreational Drug Use in Conjunction With Sexual Activities in College Students.

    Science.gov (United States)

    Choi, Edmond P H; Wong, Janet Y H; Lo, Herman H M; Wong, Wendy; Chio, Jasmine H M; Fong, Daniel Y T

    2017-03-21

    The association between using smartphone dating applications (apps) and substance use in conjunction with sexual activities was only examined in homosexual men. This association was poorly understood in heterosexual samples. To explore the association between using dating apps and alcohol, and use of recreational drug in conjunction with sexual activities in college students. 666 students from four universities in Hong Kong were recruited in this cross-sectional study in the year 2015. Outcome measures included the use of dating apps, sexual history, and drug and alcohol use. Multivariable logistic regressions were employed. The use of dating apps for more than 1 year was found to be associated with recreational drug use in conjunction with sexual activities (adjusted odds ratio: 7.23). Other risk factors of recreational drug use in conjunction with sexual activities included being bisexual/homosexual male, a smoker, and having one's first sexual intercourse at the age of less than 16 years. The use of dating apps was not a risk factor for alcohol consumption in conjunction with sexual activities. Risk factors for alcohol consumption in conjunction with sexual activities included being older, having monthly income more than HKD5,000, and a smoker. Furthermore, risk factors for alcohol consumption in conjunction with the last sexual activity included currently being in a dating relationship, a smoker, and having sex with a casual partner. Using dating apps is an emerging risk factor of drug misuse. Interventions for practising safe sex and preventing drug use should be targeted at dating app users.