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Sample records for matrix type transdermal

  1. Preparation and characterization of metoprolol tartrate containing matrix type transdermal drug delivery system.

    Science.gov (United States)

    Malipeddi, Venkata Ramana; Awasthi, Rajendra; Ghisleni, Daniela Dal Molim; de Souza Braga, Marina; Kikuchi, Irene Satiko; de Jesus Andreoli Pinto, Terezinha; Dua, Kamal

    2017-02-01

    The present study aimed to develop matrix-type transdermal drug delivery system (TDDS) of metoprolol tartrate using polyvinyl pyrrolidone (PVP) and polyvinyl alcohol (PVA). The transdermal films were evaluated for physical parameters, Fourier transform infrared spectroscopy analysis (FTIR), differential scanning calorimetry (DSC), in vitro drug release, in vitro skin permeability, skin irritation test and stability studies. The films were found to be tough, non-sticky, easily moldable and possess good tensile strength. As the concentration of PVA was increased, the tensile strength of the films was also increased. Results of FTIR spectroscopy and DSC revealed the absence of any drug-polymer interactions. In vitro release of metoprolol followed zero-order kinetics and the mechanism of release was found to be diffusion rate controlled. In vitro release studies of metoprolol using Keshary-Chein (vertical diffusion cell) indicated 65.5 % drug was released in 24 h. In vitro skin permeation of metoprolol transdermal films showed 58.13 % of the drug was released after 24 h. In vitro skin permeation of metoprolol followed zero-order kinetics in selected formulations. The mechanism of release was found to be diffusion rate controlled. In a 22-day skin irritation test, tested formulation of transdermal films did not exhibit any allergic reactions, inflammation, or contact dermatitis. The transdermal films showed good stability in the 180-day stability study. It can be concluded that the TDDS of MPT can help in bypassing the first-pass effect and will provide patient improved compliance, without sacrificing the therapeutic advantages of the drugs.

  2. Development of domperidone bilayered matrix type transdermal patches: physicochemical, in vitro and ex vivo characterization

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    S.K Madishetti

    2010-09-01

    Full Text Available "nBackground and the purpose of the study: Domperidone (DOM is a dopamine- receptor (D2 antagonist, which is widely used in the treatment of motion-sickness. The pharmacokinetic parameters make DOM a suitable candidate for transdermal delivery. The purpose of the present investigation was to develop transdermal delivery systems for DOM and to evaluate their physicochemical characteristics, in vitro release an ex vivo permeation through rat abdominal skin and their mechanical properties. "nMethods: Bilayered matrix type transdermal drug delivery systems (TDDS of DOM were prepared by film casting technique using hydroxypropyl methyl cellulose as primary and Eudragit RL 100 as secondary layers. Brij-35 was incorporated as a solubilizer, d-limonene and propylene glycol were employed as permeation enhancer and plasticizer respectively. The prepared TDDS were extensively evaluated for in vitro release, moisture absorption, moisture content, water vapor transmission, ex vivo permeation through rat abdominal skin, mechanical properties and stability studies. The physicochemical interaction between DOM and polymers were investigated by Differential Scanning Calorimetry (DSC and Fourier Transform Infrared Spectroscopy (FTIR. "nResults: All the formulations exhibited satisfactory physicochemical and mechanical characteristics. The optimized formulation F6 showed maximum cumulative percentage of drug release (90.7%, permeation (6806.64 μg in 24 hrs, flux (86.02 μg /hr/cm2 and permeation coefficient of 0.86x10-2 cm/hr. Values of tensile strength (4.34 kg/mm2 and elastic modulus (5.89 kg/cm2 revealed that formulation F6 was strong but not brittle. DSC and FTIR studies showed no evidence of interaction between the drug and polymers. A shelf life of 2 years is predicted for the TDDS. Conclusions: Domperidone bilayered matrix type transdermal therapeutic systems could be prepared with the required flux and suitable mechanical properties.

  3. Evaluation of Mechanical Properties of Nonsteroidal Anti-Inflammatory Matrix Type Transdermal Therapeutic Systems

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    Antonoaea Paula

    2017-06-01

    Full Text Available Objective: Transdermal therapeutic systems (TTSs represent an intensely studied alternative to oral delivery of non-steroid anti-inflammatory drugs (NSAIDs in the treatment of rheumatic diseases due to its ability of avoiding the side effects of the oral route. This study aims to present the evaluation of the mechanical properties of three NSAIDs (meloxicam, tenoxicam and indomethacin individually included in four type of polymeric matrixes, as part of new formulations development process. Methods: 12 products in form of TTS matrixes were prepared by solvent casting evaporation technique, using hydroxypropyl methylcellulose (HPMC 15000, HPMC E5 and/or ethylcellulose as matrix-forming polymers. Each of the resulted products was evaluated by determining the water vapor absorption, desorption or transmission in controlled atmosphere humidity (evaluation of porosity; the elongation capacity, tensile strength and bioadhesiveness (evaluation of mechanical properties. Results: The analysis of three groups of the experimental data expressed as averages on each group was necessary, in order to identify the parameters which statistically are critically influenced by the ingredients associated in the TTSs matrix compositions. Analysis by normality tests, variance and correlation tests (Anova, Pearson enabled evaluation of the effect of NSAID type vs. the effect of polymer matrix type on the parameters of the NSAID TTS matrix. Conclusions: Meloxicam incorporated in the structure of HPMC 15000 polymeric matrix favors its viscoelastic structure. Ethylcellulose functions as plasticizer and supports the matrix bioadhesiveness. HPMC E5 does not meet the requirements for TTS preparation in the used experimental conditions.

  4. Development of matrix type transdermal patches of lercanidipine hydrochloride: physicochemical and in-vitro characterization

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    T Mamatha

    2010-03-01

    Full Text Available Background and the purpose of the study: Lercanidipine hydrochloride (LRDP is used in the treatment of hypertension because of its selectivity and specificity on the smooth vascular cells. The pharmacokinetic parameters make LRDP a suitable candidate for transdermal delivery. The purpose of the study was to select a suitable formulation for the development of transdermal drug-delivery system (TDDS of LRDP and to determine the effect of penetration enhancer, limonene on drug permeation. Methods: The matrix type TDDS of LRDP were prepared by solvent evaporation technique. Formulations A1, A2, A3, A4, A5 and A6 were composed of Eudragit RL100 (ERL and hydroxypropyl methyl cellulose (HPMC in 1.5:8.5, 3:7, 4:6, 6:4, 7:3 and 8.5:1.5 ratios respectively. All the six formulations carried 10 mg of LRDP/patch area, 8 % v/w of d-limonene as a penetration enhancer, 20 % v/w of propylene glycol as plasticizer in methanol and dichloromethane as solvent system. The prepared TDDS were evaluated for physicochemical characteristics, in-vitro release, ex-vivo permeation and skin irritation. The ex-vivo permeation studies were carried out across excised rat skin using Franz diffusion cell. Results: All the formulations exhibited satisfactory physicochemical characteristics. Cumulative percentage of the drug released in 24 hrs from the six formulations were 82.0 %, 74.9 %, 63.2 %, 63.5 %, 59.8 % and 53.5 % respectively. Corresponding values for the cumulative amounts of the drug permeated across the rat skin for the above matrix films were 2644.5, 2347.2, 2249.5, 1933.4, 2021.5 and 1663.4 µg/cm2 respectively. By fitting the data into zero order, first order and Higuchi model, it was concluded that drug release from matrix films followed Higuchi model and the mechanism of the drug release was diffusion mediated. The patches were seemingly free of potentially hazardous skin irritation.  Conclusions: The patches composed of ERL, HPMC (1.5:8.5 with 8 % v/w limonene as

  5. Population pharmacokinetic model of transdermal nicotine delivered from a matrix-type patch.

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    Linakis, Matthew W; Rower, Joseph E; Roberts, Jessica K; Miller, Eleanor I; Wilkins, Diana G; Sherwin, Catherine M T

    2017-12-01

    Nicotine addiction is an issue faced by millions of individuals worldwide. As a result, nicotine replacement therapies, such as transdermal nicotine patches, have become widely distributed and used. While the pharmacokinetics of transdermal nicotine have been extensively described using noncompartmental methods, there are few data available describing the between-subject variability in transdermal nicotine pharmacokinetics. The aim of this investigation was to use population pharmacokinetic techniques to describe this variability, particularly as it pertains to the absorption of nicotine from the transdermal patch. A population pharmacokinetic parent-metabolite model was developed using plasma concentrations from 25 participants treated with transdermal nicotine. Covariates tested in this model included: body weight, body mass index, body surface area (calculated using the Mosteller equation) and sex. Nicotine pharmacokinetics were best described with a one-compartment model with absorption based on a Weibull distribution and first-order elimination and a single compartment for the major metabolite, cotinine. Body weight was a significant covariate on apparent volume of distribution of nicotine (exponential scaling factor 1.42). After the inclusion of body weight in the model, no other covariates were significant. This is the first population pharmacokinetic model to describe the absorption and disposition of transdermal nicotine and its metabolism to cotinine and the pharmacokinetic variability between individuals who were administered the patch. © 2017 The British Pharmacological Society.

  6. Transdermal fentanyl matrix patches Matrifen and Durogesic DTrans are bioequivalent

    DEFF Research Database (Denmark)

    Kress, Hans G; Boss, Hildegard; Delvin, Thomas

    2010-01-01

    AIM: The pharmacokinetic profiles of the two commercially available transdermal fentanyl patches Matrifen (100 microg/h) and Durogesic DTrans (100 microg/h), used to manage severe chronic pain, were compared regarding their systemic exposure, rate of absorption, and safety. METHODS: Transdermal m...

  7. Numerical modelling of transdermal delivery from matrix systems: parametric study and experimental validation with silicone matrices.

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    Snorradóttir, Bergthóra S; Jónsdóttir, Fjóla; Sigurdsson, Sven Th; Másson, Már

    2014-08-01

    A model is presented for transdermal drug delivery from single-layered silicone matrix systems. The work is based on our previous results that, in particular, extend the well-known Higuchi model. Recently, we have introduced a numerical transient model describing matrix systems where the drug dissolution can be non-instantaneous. Furthermore, our model can describe complex interactions within a multi-layered matrix and the matrix to skin boundary. The power of the modelling approach presented here is further illustrated by allowing the possibility of a donor solution. The model is validated by a comparison with experimental data, as well as validating the parameter values against each other, using various configurations with donor solution, silicone matrix and skin. Our results show that the model is a good approximation to real multi-layered delivery systems. The model offers the ability of comparing drug release for ibuprofen and diclofenac, which cannot be analysed by the Higuchi model because the dissolution in the latter case turns out to be limited. The experiments and numerical model outlined in this study could also be adjusted to more general formulations, which enhances the utility of the numerical model as a design tool for the development of drug-loaded matrices for trans-membrane and transdermal delivery. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  8. Effect of Microneedle Type on Transdermal Permeation of Rizatriptan.

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    Uppuluri, Chandrateja; Shaik, Ashraf Sultana; Han, Tao; Nayak, Atul; Nair, Karthik J; Whiteside, Benjamin R; Nalluri, Buchi N; Das, Diganta B

    2017-07-01

    The present study was aimed to investigate the effect of salient microneedle (MN) geometry parameters like length, density, shape and type on transdermal permeation of rizatriptan (RIZ). Studies were carried out using two types of MN devices viz. AdminPatch® arrays (ADM) (0.6, 0.9, 1.2 and 1.5 mm lengths) and laboratory-fabricated polymeric MNs (PMs) of 0.6 mm length. In the case of the PMs, arrays were applied three times at different places within a 1.77-cm 2 skin area (PM-3) to maintain the MN density closer to 0.6 mm ADM. Histological studies revealed that PM, owing to their geometry/design, formed wider and deeper microconduits when compared to ADM of similar length. Approximately 4.9- and 4.2-fold increases in the RIZ steady-state flux values were observed with 1.5 mm ADM and PM-3 applications when compared to the passive studies. A good correlation between different dimensionless parameters like the amount of RIZ permeated (C t /C s ), thickness (h/L) and surface area (S a /L 2 ) of the skin was observed with scaling analyses. Numerical simulations provided further information regarding the distribution of RIZ in MN-treated skin after application of different MNs. Overall, the study suggests that MN application enhances the RIZ transdermal permeation and the geometrical parameters of MNs play an important role in the degree enhancement.

  9. [Matrix transdermal systems for caffeine delivery based on polymer and emulsion compounds].

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    Kuznetsova, E G; Kuryleva, O M; Salomatina, L A; Sevast'ianov, V I

    2008-01-01

    The goal of this work was to develop and test transdermal therapeutic systems for caffeine delivery. In vitro experiments showed that the rate of caffeine diffusion through untreated rabbit skin from a transdermal therapeutic systems based on polymer compound containing 50 mg medicine was 67.2 (9.1 microg/cm2h; for a system based on emulsion compound it was 173 (19 microg/cm2h. Methods for studying the caffeine release rate and quantitative measurement of caffeine content in the emulsion-based transdermal therapeutic system were developed. These methods are required to obtain data for standard drug documentation. The results of in vivo experiments in rabbits showed the absence of irritating effect of the emulsion-based transdermal therapeutic system. The obtained data on the specific efficiency of the transdermal therapeutic systems for caffeine delivery (50 mg) in healthy volunteers showed that this medicine could be used as a nonnarcotic psychoactivator for improving mental and physical activities and attention concentration.

  10. Analyzing polymeric matrix for fabrication of a biodegradable microneedle array to enhance transdermal delivery.

    Science.gov (United States)

    Hwa, Kuo-Yuan; Chang, Vincent H S; Cheng, Yao-Yi; Wang, Yue-Da; Jan, Pey-Shynan; Subramani, Boopathi; Wu, Min-Ju; Wang, Bo-Kai

    2017-09-19

    Traditional drug delivery systems, using invasive, transdermal, and oral routes, are limited by various factors, such as the digestive system environment, skin protection, and sensory nerve stimulation. To improve the drug delivery system, we fabricated a polysaccharide-based, dissolvable microneedle-based array, which combines the advantages of both invasive and transdermal delivery systems, and promises to be an innovative solution for minimally invasive drug delivery. In this study, we designed a reusable aluminum mold that greatly improved the efficiency and convenience of microneedle fabrication. Physical characterization of the polysaccharides, individual or mixed at different ratios, was performed to identify a suitable molecule to fabricate the dissolvable microneedle. We used a vacuum deposition-based micro-molding method at low temperature to fabricate the model. Using a series of checkpoints from material into product, a systematic feedback mechanism was built into the "all-in-one" fabrication step, which helped to improve production yields. The physical properties of the fabricated microneedle were assessed. The cytotoxicity analysis and animal testing of the microneedle demonstrated the safety and compatibility of the microneedle, and the successful penetration and effective release of a model protein.

  11. Alghedon Fentanyl Transdermal System.

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    Romualdi, Patrizia; Santi, Patrizia; Candeletti, Sanzio

    2017-04-01

    The efficacy of transdermal fentanyl for cancer pain and chronic non-cancer pain (chronic lower back pain, rheumatoid arthritis, osteoarthritis, neuropathic pain) is well established. Several formulations of fentanyl transdermal systems have been developed to improve the drug delivery and prevent misuse of the active principle. The addition of a rate controlling membrane to the matrix system represented an important advance. The design and functional features of Alghedon patch are compared with other approved generic fentanyl transdermal systems, emphasizing the distinctiveness of Alghedon patch. Alghedon patch has no liquid component in the finished product, therefore no leakage of active ingredient from the system can occur. A rate-controlling membrane provides controlled release of the active substance from the matrix reservoir, ensuring that fentanyl delivery and entry into the microcirculation is not solely controlled by the skin's permeability to this active substance. Alghedon patch contains part of the drug (approximately 15%) in the skin-contact adhesive: this innovative solution allows to overcome a typical drawback of transdermal patches, i.e. the long lag-time before the drug appears in plasma after the first administration, and provides rapid analgesia during the first hours of administration. Alghedon Fentanyl Transdermal System employs materials commonly used in other transdermal applications and having established safety profiles. For each strength level, the fentanyl content - and, thus, the resulting residual fentanyl remaining in the patch after use - is at the lowest end of the range used in commercially available fentanyl patches, minimizing the potential for abuse and misuse.

  12. Research of Ultrasound-Mediated Transdermal Drug Delivery System Using Cymbal-Type Piezoelectric Composite Transducer

    Science.gov (United States)

    Huan, Huiting; Gao, Chunming; Liu, Lixian; Sun, Qiming; Zhao, Binxing; Yan, Laijun

    2015-06-01

    Transdermal drug delivery (TDD) implemented by especially low-frequency ultrasound is generally known as sonophoresis or phonophoresis which has drawn considerable wide attention. However, TDD has not yet achieved its full potential as an alternative to conventional drug delivery methods due to its bulky instruments. In this paper, a cymbal-type piezoelectric composite transducer (CPCT) which has advantages over a traditional ultrasound generator in weight, flexibility, and power consumption, is used as a substitute ultrasonicator to realize TDD. First, theoretical research on a CPCT based on the finite element analysis was carried out according to which a series of applicable CPCTs with bandwidths of 20 kHz to 100 kHz were elaborated. Second, a TDD experimental setup was built with previously fabricated CPCTs aimed at the administration of glucose. Finally, the TDD performance of glucose molecule transport in porcine skin was measured in vitro by quantifying the concentration of glucose, and the time variation curves were subsequently obtained. During the experiment, the driving wave form, frequency, and power consumption of the transducers were selected as the main elements which determined the efficacy of glucose delivery. The results indicate that the effectiveness of the CPCT-based delivery is constrained more by the frequency and intensity of ultrasound rather than the driving waveform. The light-weight, flexibility, and low-power consumption of a CPCT can potentially achieve effective TDD.

  13. Multicenter clinical study for evaluation of efficacy and safety of transdermal fentanyl matrix patch in treatment of moderate to severe cancer pain in 474 chinese cancer patients.

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    Zhu, Yu-Lin; Song, Guo-Hong; Liu, Duan-Qi; Zhang, Xi; Liu, Kui-Feng; Zang, Ai-Hua; Cheng, Ying; Cao, Guo-Chun; Liang, Jun; Ma, Xue-Zhen; Ding, Xin; Wang, Bin; Li, Wei-Lian; Hu, Zuo-Wei; Feng, Gang; Huang, Jiang-Jin; Zheng, Xiao; Jiao, Shun-Chang; Wu, Rong; Ren, Jun

    2011-12-01

    Although a new matrix formulation fentanyl has been used throughout the world for cancer pain management, few data about its efficacy and clinical outcomes associated with its use in Chinese patients have been obtained. This study aimed to assess the efficacy and safety of the new system in Chinese patients with moderate to severe cancer pain. A total of 474 patients with moderate to severe cancer pain were enrolled in this study and were treated with the new transdermal fentanyl matrix patch (TDF) up to 2 weeks. All the patients were asked to record pain intensity, side effects, quality of life (QOL), adherence and global satisfaction. The initial dose of fentanyl was 25 μg/h titrated with opioid or according to National Comprehensive Cancer Network (NCCN) guidelines. Transdermal fentanyl was changed every three days. After 2 weeks. The mean pain intensity of the 459 evaluated patients decreased significantly from 5.63±1.26 to 2.03±1.46 (P<0.0001). The total remission rate was 91.29%, of which moderate remission rate 53.16%, obvious remission rate 25.49% and complete remission rate 12.64%. The rate of adverse events was 33.75%, 18.78% of which were moderate and 3.80% were severe. The most frequent adverse events were constipation and nausea. No fatal events were observed. The quality of life was remarkably improved after the treatment (P<0.0001). The new TDF is effective and safe in treating patients with moderate to severe cancer pain, and can significantly improve the quality of life.

  14. Transdermal granisetron.

    Science.gov (United States)

    Duggan, Sean T; Curran, Monique P

    2009-01-01

    Granisetron is a highly selective serotonin 5-HT(3) receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting. The transdermal granisetron system delivers continuous granisetron (3.1 mg/day) into the systemic circulation (via passive diffusion) for up to 7 days. In a large phase III trial in cancer patients receiving multi-day (3-5 days) moderately or highly emetogenic chemotherapy, transdermal granisetron applied 24-48 hours prior to chemotherapy and remaining in place for 7 days was noninferior to oral granisetron 2 mg once daily administered for 3-5 days 1 hour prior to chemotherapy. Efficacy was assessed according to the proportion of patients achieving complete response (no vomiting and/or retching, no more than mild nausea, no rescue medication) from the first day, until 24 hours after the start of the last day, of administration of the chemotherapy regimen. In a phase II trial in patients with cancer receiving single-day, moderately-emetogenic chemotherapy, transdermal granisetron applied at least 24 hours prior to chemotherapy and removed after 5 days was as effective as a single oral dose of granisetron 2 mg in achieving total control (no nausea, no vomiting/retching, no use of rescue medication and no study withdrawal) during the delayed (24-120 hours; primary endpoint) period after chemotherapy. Transdermal granisetron was generally well tolerated in clinical trials, with few adverse events being treatment related.

  15. Electron beam processed transdermal delivery system for administration of an anti-anginal agent

    Science.gov (United States)

    Kotiyan, P. N.; Vavia, P. R.; Bharadwaj, Y. K.; Sabarwal, S.; Majali, A. B.

    2002-12-01

    Electron beam irradiation was used to synthesize a matrix type transdermal system of isosorbide dinitrate, an effective anti-anginal agent. The drug was dissolved in two monomeric systems, 2-ethylhexyl acrylate (EHA) and 2-ethylhexyl acrylate : methyl methacrylate (9 : 1). The solutions were then directly irradiated on a backing membrane (Scotchpak ®1006) at different doses to get transdermal patches. The developed systems were evaluated for residual monomer content, equilibrium weight swelling ratio, weight uniformity, thickness uniformity, drug content, peel strength, in vitro release and skin permeation kinetics. They possessed excellent tack and adhesive properties. In the case of isosorbide dinitrate-EHA systems, an increase in the peel strength values with respect to the skin was observed with increasing radiation doses. The systems exhibited promising skin permeation kinetics favorable for transdermal drug delivery. The radiation stability of the drug in the pure solid state form was also assessed.

  16. Electron beam processed transdermal delivery system for administration of an anti-anginal agent

    Energy Technology Data Exchange (ETDEWEB)

    Kotiyan, P.N. E-mail: pramila-kotiyan@uiowa.edu; Vavia, P.R.; Bharadwaj, Y.K.; Sabarwal, S.; Majali, A.B

    2002-12-01

    Electron beam irradiation was used to synthesize a matrix type transdermal system of isosorbide dinitrate, an effective anti-anginal agent. The drug was dissolved in two monomeric systems, 2-ethylhexyl acrylate (EHA) and 2-ethylhexyl acrylate : methyl methacrylate (9 : 1). The solutions were then directly irradiated on a backing membrane (Scotchpak[reg]1006) at different doses to get transdermal patches. The developed systems were evaluated for residual monomer content, equilibrium weight swelling ratio, weight uniformity, thickness uniformity, drug content, peel strength, in vitro release and skin permeation kinetics. They possessed excellent tack and adhesive properties. In the case of isosorbide dinitrate-EHA systems, an increase in the peel strength values with respect to the skin was observed with increasing radiation doses. The systems exhibited promising skin permeation kinetics favorable for transdermal drug delivery. The radiation stability of the drug in the pure solid state form was also assessed.

  17. Optimization of Biopolymer Based Transdermal Films of Metoclopramide as an Alternative Delivery Approach

    Directory of Open Access Journals (Sweden)

    Betül Aktar

    2014-05-01

    Full Text Available The objectives of this study were to develop and to characterize sodium alginate based matrix-type transdermal films of metoclopramide hydrochloride (MTC in order to improve patient compliance to treatment. The suitability of sodium alginate was shown to be a natural film former in terms of the physicochemical, mechanical, and bioadhesive features of the MTC loaded transdermal films. Terpinolene provided the highest drug release among the different terpenes (nerolidol, eucalyptol, dl-limonene, or terpinolene assessed as enhancer. Attenuated Total Reflectance Infrared (ATR-FTIR spectroscopy analysis performed to evaluate the effect of the transdermal films on skin barrier confirmed enhancer induced lipid bilayer disruption in stratum corneum, indicating its permeation enhancement effect.

  18. Electron beam processed transdermal delivery system for administration of an anti-anginal agent

    International Nuclear Information System (INIS)

    Kotiyan, P.N.; Vavia, P.R.; Bharadwaj, Y.K.; Sabarwal, S.; Majali, A.B.

    2002-01-01

    Electron beam irradiation was used to synthesize a matrix type transdermal system of isosorbide dinitrate, an effective anti-anginal agent. The drug was dissolved in two monomeric systems, 2-ethylhexyl acrylate (EHA) and 2-ethylhexyl acrylate : methyl methacrylate (9 : 1). The solutions were then directly irradiated on a backing membrane (Scotchpak[reg]1006) at different doses to get transdermal patches. The developed systems were evaluated for residual monomer content, equilibrium weight swelling ratio, weight uniformity, thickness uniformity, drug content, peel strength, in vitro release and skin permeation kinetics. They possessed excellent tack and adhesive properties. In the case of isosorbide dinitrate-EHA systems, an increase in the peel strength values with respect to the skin was observed with increasing radiation doses. The systems exhibited promising skin permeation kinetics favorable for transdermal drug delivery. The radiation stability of the drug in the pure solid state form was also assessed

  19. Stereomicroscopic imaging technique for the quantification of cold flow in drug-in-adhesive type of transdermal drug delivery systems.

    Science.gov (United States)

    Krishnaiah, Yellela S R; Katragadda, Usha; Khan, Mansoor A

    2014-05-01

    Cold flow is a phenomenon occurring in drug-in-adhesive type of transdermal drug delivery systems (DIA-TDDS) because of the migration of DIA coat beyond the edge. Excessive cold flow can affect their therapeutic effectiveness, make removal of DIA-TDDS difficult from the pouch, and potentially decrease available dose if any drug remains adhered to pouch. There are no compendial or noncompendial methods available for quantification of this critical quality attribute. The objective was to develop a method for quantification of cold flow using stereomicroscopic imaging technique. Cold flow was induced by applying 1 kg force on punched-out samples of marketed estradiol DIA-TDDS (model product) stored at 25°C, 32°C, and 40°C/60% relative humidity (RH) for 1, 2, or 3 days. At the end of testing period, dimensional change in the area of DIA-TDDS samples was measured using image analysis software, and expressed as percent of cold flow. The percent of cold flow significantly decreased (p < 0.001) with increase in size of punched-out DIA-TDDS samples and increased (p < 0.001) with increase in cold flow induction temperature and time. This first ever report suggests that dimensional change in the area of punched-out samples stored at 32°C/60%RH for 2 days applied with 1 kg force could be used for quantification of cold flow in DIA-TDDS. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  20. Synthesis of conjugated chitosan and its effect on drug permeation from transdermal patches.

    Science.gov (United States)

    Satheeshababu, B K; Shivakumar, K L

    2013-03-01

    The aim of this study was to synthesis the conjugated chitosan by covalent attachment of thiol moieties to the cationic polymer, mediated by a carbodiimide to improve permeation properties of chitosan. Thioglycolic acid was covalently attached to chitosan by the formation of amide bonds between the primary amino groups of the polymer and the carboxylic acid groups of thioglycolic acid. Hence, these polymers are called as thiomers or thiolated polymers. Conjugation of chitosan was confirmed by Fourier transform-infrared and differential scanning calorimetric analysis. Matrix type transdermal patches of carvedilol were prepared using the different proportions of chitosan and chitosan-thioglycolic acid conjugates (2:0, 1.7:0.3, 1.4:0.6, 1:1, 0.6:1.4 and 0.3:1.7) by solvent casting technique. Prepared matrix type patches were evaluated for their physicochemical characterization followed by in vitro evaluation. Selected formulations were subjected for their ex vivo studies on Wistar albino rat skin and human cadaver skin using the modified Franz diffusion cell. As the proportion of conjugated chitosan increased, the transdermal patches showed increased drug permeation. The mechanism of drug release was found to be nonFickian profiles. The present study concludes that the transdermal patches of carvedilol using conjugated chitosan with different proportions of chitosan were successfully developed to provide improved drug permeation. The transdermal patches can be a good approach to improve drug bioavailability by bypassing the extensive hepatic first-pass metabolism of the drug.

  1. Natural oils as skin permeation enhancers for transdermal delivery of olanzapine: in vitro and in vivo evaluation.

    Science.gov (United States)

    Aggarwal, Geeta; Dhawan, Sanju; HariKumar, S L

    2012-03-01

    The feasibility of development of transdermal delivery system of olanzapine utilizing natural oils as permeation enhancers was investigated. Penetration enhancing potential of corn (maize) oil, groundnut oil and jojoba oil on in vitro permeation of olanzapine across rat skin was studied. The magnitude of flux enhancement factor with corn oil, groundnut oil and jojoba oil was 7.06, 5.31 and 1.9 respectively at 5mg/ml concentration in solvent system. On the basis of in vitro permeation studies, eudragit based matrix type transdermal patches of olanzapine were fabricated using optimized concentrations of natural oils as permeation enhancers. All transdermal patches were found to be uniform with respect to physical characteristics. The interaction studies carried out by comparing the results of ultraviolet, HPLC and FTIR analyses for the pure drug, polymers and mixture of drug and polymers indicated no chemical interaction between the drug and excipients. Corn oil containing unsaturated fatty acids was found to be promising natural permeation enhancer for transdermal delivery of olanzapine with greatest cumulative amount of drug permeated (1010.68 μg/cm²/h) up to 24 h and caused no skin irritation. The fabricated transdermal patches were found to be stable. The pharmacokinetic characteristics of the final optimized matrix patch (T2) were determined after transdermal application to rabbits. The calculated relative bioavailability of TDDS was 113.6 % as compared to oral administration of olanzapine. The therapeutic effectiveness of optimized transdermal system was confirmed by tranquillizing activity in rotarod and grip mice model.

  2. Gold nanorods in an oil-base formulation for transdermal treatment of type 1 diabetes in mice

    Science.gov (United States)

    Nose, Keisuke; Pissuwan, Dakrong; Goto, Masahiro; Katayama, Yoshiki; Niidome, Takuro

    2012-05-01

    Efficient transdermal insulin delivery to the systemic circulation would bring major benefit to diabetic patients. We investigated the possibility of using gold nanorods (GNRs) that formed a complex with an edible surfactant and insulin (INS) in an oil phase to form a solid-in-oil (SO) formulation (SO-INS-GNR) for transdermal treatment of diabetes. Diabetic mice comprised the model for our study. In vitro, there was high penetration of insulin through the stratum corneum (SC) and the dermis in mouse skin treated with an SO-INS-GNR complex plus near-infrared (NIR) light irradiation. Blood glucose levels in the diabetic mice were significantly decreased after treatment with SO-INS-GNR plus irradiation. To our knowledge, this is the first study to use gold nanorods for systemic insulin delivery through the skin. The use of an SO-INS-GNR complex combined with NIR irradiation may provide the possibility of transdermal insulin delivery to diabetic patients.Efficient transdermal insulin delivery to the systemic circulation would bring major benefit to diabetic patients. We investigated the possibility of using gold nanorods (GNRs) that formed a complex with an edible surfactant and insulin (INS) in an oil phase to form a solid-in-oil (SO) formulation (SO-INS-GNR) for transdermal treatment of diabetes. Diabetic mice comprised the model for our study. In vitro, there was high penetration of insulin through the stratum corneum (SC) and the dermis in mouse skin treated with an SO-INS-GNR complex plus near-infrared (NIR) light irradiation. Blood glucose levels in the diabetic mice were significantly decreased after treatment with SO-INS-GNR plus irradiation. To our knowledge, this is the first study to use gold nanorods for systemic insulin delivery through the skin. The use of an SO-INS-GNR complex combined with NIR irradiation may provide the possibility of transdermal insulin delivery to diabetic patients. Electronic supplementary information (ESI) available. See DOI: 10

  3. Design, development, physicochemical, and in vitro and in vivo evaluation of transdermal patches containing diclofenac diethylammonium salt.

    Science.gov (United States)

    Arora, Priyanka; Mukherjee, Biswajit

    2002-09-01

    In this study, matrix-type transdermal patches containing diclofenac diethylamine were prepared using different ratios of polyvinylpyrrolidone (PVP) and ethylcellulose (EC) by solvent evaporation technique. The drug matrix film of PVP and EC was casted on a polyvinylalcohol backing membrane. All the prepared formulations were subjected to physical studies (moisture content, moisture uptake, and flatness), in vitro release studies and in vitro skin permeation studies. In vitro permeation studies were performed across cadaver skin using a modified diffusion cell. Variations in drug release profiles among the formulations studied were observed. Based on a physicochemical and in vitro skin permeation study, formulation PA4 (PVP/EC, 1:2) and PA5 (PVP/EC, 1:5) were chosen for further in vivo experiments. The antiinflammatory effect and a sustaining action of diclofenac diethylamine from the two transdermal patches selected were studied by inducing paw edema in rats with 1% w/v carrageenan solution. When the patches were applied half an hour before the subplantar injection of carrageenan in the hind paw of male Wistar rats, it was observed that formulation PA4 produced 100% inhibition of paw edema in rats 12 h after carrageenan insult, whereas in the case of formulation PA5, 4% mean paw edema was obtained half an hour after the carrageenan injection and the value became 19.23% 12 h after the carrageenan insult. The efficacy of transdermal patches was also compared with the marketed Voveran gel and it was found that PA4 transdermal patches produced a better result as compared with the Voveran gel. Hence, it can be reasonably concluded that diclofenac diethylamine can be formulated into the transdermal matrix type patches to sustain its release characteristics and the polymeric composition (PVP/EC, 1:2) was found to be the best choice for manufacturing transdermal patches of diclofenac diethylamine among the formulations studied. Copyright 2002 Wiley-Liss, Inc.

  4. Investigations on the viscoelastic performance of pressure sensitive adhesives in drug-in-adhesive type transdermal films.

    Science.gov (United States)

    Wolff, Hans-Michael; Irsan; Dodou, Kalliopi

    2014-08-01

    We aimed to investigate the effect of solubility parameter and drug concentration on the rheological behaviour of drug-in-adhesive films intended for transdermal application. Films were prepared over a range of drug concentrations (5%, 10% and 20% w/w) using ibuprofen, benzoic acid, nicotinic acid and lidocaine as model drugs in acrylic (Duro-Tak 87-4287 and Duro-Tak 87900A) or silicone (Bio-PSA 7-4301 and Bio-PSA 7-4302) pressure sensitive adhesives (PSAs). Saturation status of films was determined using light microscopy. Viscoelastic parameters were measured in rheology tests at 32°C. Subsaturated films had lower viscoelastic moduli whereas saturated films had higher moduli than the placebo films and/or a concentration-dependent increase in their modulus. Saturation concentration of each drug in the films was reflected by decreasing/increasing viscoelastic patterns. The viscoelastic windows (VWs) of the adhesive and drug-in-adhesive films clearly depicted the effect of solubility parameter differences, molar concentration of drug in the adhesive film and differences in PSA chemistry. Drug solubility parameters and molar drug concentrations have an impact on rheological patterns and thus on the adhesive performance of tested pressure sensitive adhesives intended for use in transdermal drug delivery systems. Use of the Flory equation in its limiting form was appropriate to predict drug solubility in the tested formulations.

  5. Granisetron Transdermal Patch

    Science.gov (United States)

    Granisetron transdermal patches are used to prevent nausea and vomiting caused by chemotherapy. Granisetron is in a class of medications called 5HT3 ... Granisetron transdermal comes as a patch to apply to the skin. It is usually applied 24 to ...

  6. Estradiol Transdermal Patch

    Science.gov (United States)

    ... menopause (change of life; the end of monthly menstrual periods). Transdermal estradiol is also used to prevent ... patch. Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.

  7. Transdermal drug delivery

    OpenAIRE

    Prausnitz, Mark R.; Langer, Robert

    2008-01-01

    Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, non-cavitational ultrasound and iontophoresis have also resulted in clinical products; the ability ...

  8. TRANSDERMAL DRUG DELIVERY SYSTEM: REVIEW

    OpenAIRE

    Vishvakarama Prabhakar; Agarwal Shivendra; Sharma Ritika; Saurabh Sharma

    2012-01-01

    Various new technologies have been developed for the transdermal delivery of some important drugs. Today about 74% of drugs are taken orally and are found not to be as effective as desired. To improve such characters transdermal drug delivery system was emerged. Drug delivery through the skin to achieve a systemic effect of a drug is commonly known as transdermal drug delivery and differs from traditional topical drug delivery. Transdermal drug delivery systems (TDDS) are dosage forms involve...

  9. Transdermal drug delivery

    Science.gov (United States)

    Prausnitz, Mark R.; Langer, Robert

    2009-01-01

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

  10. Inert matrix fuel in dispersion type fuel elements

    Energy Technology Data Exchange (ETDEWEB)

    Savchenko, A.M. [A.A. Bochvar All-Russia Research Institute of Inorganic Materials (VNIINM) 123060, P.O. Box 369, Rogova Street, 5A, Moscow (Russian Federation)]. E-mail: sav@bochvar.ru; Vatulin, A.V. [A.A. Bochvar All-Russia Research Institute of Inorganic Materials (VNIINM) 123060, P.O. Box 369, Rogova Street, 5A, Moscow (Russian Federation); Morozov, A.V. [A.A. Bochvar All-Russia Research Institute of Inorganic Materials (VNIINM) 123060, P.O. Box 369, Rogova Street, 5A, Moscow (Russian Federation); Sirotin, V.L. [A.A. Bochvar All-Russia Research Institute of Inorganic Materials (VNIINM) 123060, P.O. Box 369, Rogova Street, 5A, Moscow (Russian Federation); Dobrikova, I.V. [A.A. Bochvar All-Russia Research Institute of Inorganic Materials (VNIINM) 123060, P.O. Box 369, Rogova Street, 5A, Moscow (Russian Federation); Kulakov, G.V. [A.A. Bochvar All-Russia Research Institute of Inorganic Materials (VNIINM) 123060, P.O. Box 369, Rogova Street, 5A, Moscow (Russian Federation); Ershov, S.A. [A.A. Bochvar All-Russia Research Institute of Inorganic Materials (VNIINM) 123060, P.O. Box 369, Rogova Street, 5A, Moscow (Russian Federation); Kostomarov, V.P. [A.A. Bochvar All-Russia Research Institute of Inorganic Materials (VNIINM) 123060, P.O. Box 369, Rogova Street, 5A, Moscow (Russian Federation); Stelyuk, Y.I. [A.A. Bochvar All-Russia Research Institute of Inorganic Materials (VNIINM) 123060, P.O. Box 369, Rogova Street, 5A, Moscow (Russian Federation)

    2006-06-30

    The advantages of using inert matrix fuel (IMF) as a dispersion fuel in an aluminium alloy matrix are considered, in particular, low temperatures in the fuel centre, achievable high burn-ups, serviceability in transients and an environmentally friendly process of fuel rod fabrication. Two main versions of IMF are under development at A.A. Bochvar Institute, i.e. heterogeneous or isolated distribution of plutonium. The out-of-pile results on IMF loaded with uranium dioxide as plutonium simulator are presented. Fuel elements with uranium dioxide composition fabricated at A.A. Bochvar Institute are currently under MIR tests (RIAR, Dimitrovgrad). The fuel elements reached a burn-up of 88 MW d kg{sup -1} (equivalent to the burn up of the standard uranium dioxide pelletized fuel) without loss of leak-tightness of the cladding. The feasibility of fabricating IMF of these particular types with plutonium dioxide is considered with a view to in-pile irradiation.

  11. Inert matrix fuel in dispersion type fuel elements

    Science.gov (United States)

    Savchenko, A. M.; Vatulin, A. V.; Morozov, A. V.; Sirotin, V. L.; Dobrikova, I. V.; Kulakov, G. V.; Ershov, S. A.; Kostomarov, V. P.; Stelyuk, Y. I.

    2006-06-01

    The advantages of using inert matrix fuel (IMF) as a dispersion fuel in an aluminium alloy matrix are considered, in particular, low temperatures in the fuel centre, achievable high burn-ups, serviceability in transients and an environmentally friendly process of fuel rod fabrication. Two main versions of IMF are under development at A.A. Bochvar Institute, i.e. heterogeneous or isolated distribution of plutonium. The out-of-pile results on IMF loaded with uranium dioxide as plutonium simulator are presented. Fuel elements with uranium dioxide composition fabricated at A.A. Bochvar Institute are currently under MIR tests (RIAR, Dimitrovgrad). The fuel elements reached a burn-up of 88 MW d kg-1 (equivalent to the burn up of the standard uranium dioxide pelletized fuel) without loss of leak-tightness of the cladding. The feasibility of fabricating IMF of these particular types with plutonium dioxide is considered with a view to in-pile irradiation.

  12. Perspectives on Transdermal Electroporation

    Science.gov (United States)

    Ita, Kevin

    2016-01-01

    Transdermal drug delivery offers several advantages, including avoidance of erratic absorption, absence of gastric irritation, painlessness, noninvasiveness, as well as improvement in patient compliance. With this mode of drug administration, there is no pre-systemic metabolism and it is possible to increase drug bioavailability and half-life. However, only a few molecules can be delivered across the skin in therapeutic quantities. This is because of the hindrance provided by the stratum corneum. Several techniques have been developed and used over the last few decades for transdermal drug delivery enhancement. These include sonophoresis, iontophoresis, microneedles, and electroporation. Electroporation, which refers to the temporary perturbation of the skin following the application of high voltage electric pulses, has been used to increase transcutaneous flux values by several research groups. In this review, transdermal electroporation is discussed and the use of the technique for percutaneous transport of low and high molecular weight compounds described. This review also examines our current knowledge regarding the mechanisms of electroporation and safety concerns arising from the use of this transdermal drug delivery technique. Safety considerations are especially important because electroporation utilizes high voltage pulses which may have deleterious effects in some cases. PMID:26999191

  13. Recent trends in challenges and opportunities of Transdermal drug delivery system

    OpenAIRE

    P.M.Patil; P.D.Chaudhari; Jalpa K.Patel; K.A.Kedar; P.P.Katolkar

    2012-01-01

    Drug delivery system relates to the production of a drug, its delivery medium, and the way of administration. Drug delivery systems are even used for administering nitroglycerin. Transdermal drug delivery system is the system in which the delivery of the active ingredients of the drug occurs by the means of skin. Various types of transdermal patches are used. There are various methods to enhance the transdermal drug delivery system. But using microfabricated microneedles drugs are delivered v...

  14. A new once-a-day fentanyl citrate patch (Fentos Tape) could be a new treatment option in patients with end-of-dose failure using a 72-h transdermal fentanyl matrix patch.

    Science.gov (United States)

    Koike, Kazuhiko; Terui, Takeshi; Nagasako, Tomokazu; Horiuchi, Iori; Machino, Takayuki; Kusakabe, Toshiro; Hirayama, Yasuo; Mihara, Hiroyoshi; Yamakage, Michiaki; Kato, Junji; Nishisato, Takuji; Ishitani, Kunihiko

    2016-03-01

    The recommended dosing interval for transdermal fentanyl is every 72 h. However, some patients will have "end-of-dose failure," which may be seen as an increase of episodes of severe pain flares at the third day after application of the patch. A new once-a-day fentanyl patch was developed in Japan since 2010. This study aimed to assess the efficacy of the once-a-day fentanyl citrate patch for patients with cancer-related pain receiving the 72-h transdermal fentanyl not lasting 72 h. We performed a cross-sectional retrospective analysis of 445 inpatients with the 72-h transdermal fentanyl at Higashi Sapporo Hospital. We could switch to the once-a-day fentanyl citrate patch if patients reported inadequate pain relief beyond 48 h after application of the 72-h transdermal fentanyl. Patients recorded baseline scores for background pain intensity (PI) and the frequency of use of daily rescue medication for breakthrough cancer pain (BTcP). Of all patients, 10.1% showed the increase in PI of 30% or more baseline PI on the third day after application of the 72-h transdermal fentanyl. Of patients, 84.4% were converted from equivalent dose of the 72-h transdermal fentanyl to the once-a-day fentanyl citrate patch. On the third day after switching, 60.5% of patients showed a reduction of more than 30% from baseline PI. Switching to the once-a-day fentanyl citrate patch significantly reduced the mean frequency of daily rescue dose for BTcP. A once-a-day fentanyl citrate patch provided stable pain control. Its use may be considered as the dominant strategy for patients receiving a 72-h transdermal fentanyl not lasting 72 h.

  15. Modified Baptista type chaotic cryptosystem via matrix secret key

    International Nuclear Information System (INIS)

    Ariffin, M.R.K.; Noorani, M.S.M.

    2008-01-01

    In 1998, M.S. Baptista proposed a chaotic cryptosystem using the ergodicity property of the simple low-dimensional and chaotic logistic equation. Since then, many cryptosystems based on Baptista's work have been proposed. However, over the years research has shown that this cryptosystem is predictable and vulnerable to attacks and is widely discussed. Among the weaknesses are the non-uniform distribution of ciphertexts and succumbing to the one-time pad attack (a type of chosen plaintext attack). In this Letter, our objective is to modify the chaotic cryptographic scheme proposed previously. We use a matrix secret key such that the cryptosystem would no longer succumb to the one-time pad attack

  16. Encapsulated Curcumin for Transdermal Administration

    African Journals Online (AJOL)

    Purpose: To develop a proniosomal carrier system of curcumin for transdermal delivery. Methods: Proniosomes of curcumin were prepared by encapsulation of the drug in a mixture of Span 80, cholesterol and diethyl ether by ether injection method, and then investigated as a transdermal drug delivery system (TDDS).

  17. Transdermal hyoscine induced unilateral mydriasis.

    LENUS (Irish Health Repository)

    Hannon, Breffni

    2012-03-20

    The authors present a case of unilateral mydriasis in a teenager prescribed transdermal hyoscine hydrobromide (scopolamine) for chemotherapy induced nausea and vomiting. The authors discuss the ocular side-effects associated with this particular drug and delivery system and the potential use of transdermal hyoscine as an antiemetic agent in this group.

  18. Elastic vesicles for transdermal drug delivery of hydrophilic drugs: a comparison of important physicochemical characteristics of different vesicle types.

    Science.gov (United States)

    Ntimenou, Vassiliki; Fahr, Alfred; Antimisiaris, Sophia G

    2012-08-01

    The aim of this study is to evaluate the influence of different lipid vesicular systems on the skin permeation ability of hydrophilic molecules, and understand if and which vesicle physicochemical properties may be used as predictive tools. Calcein and carboxyfluorescein were used as hydrophilic drug models. All vesicles (conventional liposomes [CLs], transfersomes [TRs] and invasomes [INVs]), were characterized for particle size distribution, zeta-potential, vesicular shape and morphology, encapsulation efficiency, integrity, colloidal stability, elasticity and finally in vitro human skin permeation. Dynamic light scattering (DLS) and cryo-transmission electron microscopy (cryo-TEM) defined that almost all vesicles had spherical structure, low polydispersity (PI Elasticity values (measured by extrusion through membranes) were in the order INVs > TRs > CLs. Three vesicle types were selected (having different elasticity) and in vitro skin permeation experiments demonstrated that calcein permeation was minimal from an aqueous solution, slightly enhanced from CLs, and enhanced by 1.8 and 7.2 times from TRs and INVs, respectively. Permeation and elasticity values were correlated by rank order but not linearly, indicating that elasticity can be used as a crude predictive tool for enhancement of skin transport. Drug encapsulation efficiency was not found to be an important factor in the current study.

  19. 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

  20. 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.

  1. Angiogenic Type I Collagen Extracellular Matrix Integrated with Recombinant Bacteriophages Displaying Vascular Endothelial Growth Factors.

    Science.gov (United States)

    Yoon, Junghyo; Korkmaz Zirpel, Nuriye; Park, Hyun-Ji; Han, Sewoon; Hwang, Kyung Hoon; Shin, Jisoo; Cho, Seung-Woo; Nam, Chang-Hoon; Chung, Seok

    2016-01-21

    Here, a growth-factor-integrated natural extracellular matrix of type I collagen is presented that induces angiogenesis. The developed matrix adapts type I collagen nanofibers integrated with synthetic colloidal particles of recombinant bacteriophages that display vascular endothelial growth factor (VEGF). The integration is achieved during or after gelation of the type I collagen and the matrix enables spatial delivery of VEGF into a desired region. Endothelial cells that contact the VEGF are found to invade into the matrix to form tube-like structures both in vitro and in vivo, proving the angiogenic potential of the matrix. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. A Golub-Kahan-type reduction method for matrix pairs

    NARCIS (Netherlands)

    Hochstenbach, M.E.; Reichel, L.; Yu, X.

    2015-01-01

    We describe a novel method for reducing a pair of large matrices {A;B} to a pair of small matrices {H;K}. The method is an extension of Golub-Kahan bidiagonalization to matrix pairs, and simplifies to the latter method when B is the identity matrix. Applications to Tikhonov regularization of large

  3. A Golub-Kahan-type reduction method for matrix pairs

    NARCIS (Netherlands)

    Hochstenbach, M.E.; Reichel, L.; Yu, X.

    2015-01-01

    We describe a novel method for reducing a pair of large matrices {A,B} to a pair of small matrices {H,K}. The method is an extension of Golub–Kahan bidiagonalization to matrix pairs, and simplifies to the latter method when B is the identity matrix. Applications to Tikhonov regularization of large

  4. Transdermal Delivery of Drugs with Microneedles—Potential and Challenges

    Directory of Open Access Journals (Sweden)

    Kevin Ita

    2015-06-01

    Full Text Available Transdermal drug delivery offers a number of advantages including improved patient compliance, sustained release, avoidance of gastric irritation, as well as elimination of pre-systemic first-pass effect. However, only few medications can be delivered through the transdermal route in therapeutic amounts. Microneedles can be used to enhance transdermal drug delivery. In this review, different types of microneedles are described and their methods of fabrication highlighted. Microneedles can be fabricated in different forms: hollow, solid, and dissolving. There are also hydrogel-forming microneedles. A special attention is paid to hydrogel-forming microneedles. These are innovative microneedles which do not contain drugs but imbibe interstitial fluid to form continuous conduits between dermal microcirculation and an attached patch-type reservoir. Several microneedles approved by regulatory authorities for clinical use are also examined. The last part of this review discusses concerns and challenges regarding microneedle use.

  5. Development of edge effects around experimental ecosystem hotspots is affected by edge density and matrix type

    Science.gov (United States)

    Ecological edge effects are sensitive to landscape context. In particular, edge effects can be altered by matrix type and by the presence of other nearby edges. We experimentally altered patch configurations in an African savanna to determine how edge density and matrix type influence edge effect de...

  6. Metal matrix composites. Part 1. Types, properties, applications

    International Nuclear Information System (INIS)

    Edil da Costa, C.; Velasco Lopez, F.; Torralba Castello, M.

    2000-01-01

    An overview on the state of the art of metal matrix composites used in the automotive and aerospace industries is made. These materials usually are based on light alloys (Al, Ti and Mg) and reinforced with fibres or particles. In this review, it is presented a general scope on the different MMCs families, about their properties and their main applications. (Author) 61 refs

  7. Role of pressure-sensitive adhesives in transdermal drug delivery systems.

    Science.gov (United States)

    Lobo, Shabbir; Sachdeva, Sameer; Goswami, Tarun

    2016-01-01

    Transdermal drug delivery systems (TDDS) are employed for the delivery of drugs across skin into the systemic circulation. Pressure-sensitive adhesive (PSA) is one of the most critical components used in a TDDS. The primary function of PSA is to help in adhesion of patch to skin, but more importantly it acts as a matrix for the drug and other excipients. Hence, apart from adhesion of the patch, PSA also affects other critical quality attributes of the TDDS such as drug delivery, flux through skin and physical and chemical stability of the finished product. This review article provides a summary of the adhesives used in various types of TDDS. In particular, this review will cover the design types of TDDS, categories of PSAs and their evaluation and regulatory aspects.

  8. Transdermal and Topical Drug Administration in the Treatment of Pain

    Directory of Open Access Journals (Sweden)

    Wojciech Leppert

    2018-03-01

    Full Text Available The comprehensive treatment of pain is multidimodal, with pharmacotherapy playing a key role. An effective therapy for pain depends on the intensity and type of pain, the patients’ age, comorbidities, and appropriate choice of analgesic, its dose and route of administration. This review is aimed at presenting current knowledge on analgesics administered by transdermal and topical routes for physicians, nurses, pharmacists, and other health care professionals dealing with patients suffering from pain. Analgesics administered transdermally or topically act through different mechanisms. Opioids administered transdermally are absorbed into vessels located in subcutaneous tissue and, subsequently, are conveyed in the blood to opioid receptors localized in the central and peripheral nervous system. Non–steroidal anti–inflammatory drugs (NSAIDs applied topically render analgesia mainly through a high concentration in the structures of the joint and a provision of local anti–inflammatory effects. Topically administered drugs such as lidocaine and capsaicin in patches, capsaicin in cream, EMLA cream, and creams containing antidepressants (i.e., doxepin, amitriptyline act mainly locally in tissues through receptors and/or ion channels. Transdermal and topical routes offer some advantages over systemic analgesic administration. Analgesics administered topically have a much better profile for adverse effects as they relieve local pain with minimal systemic effects. The transdermal route apart from the above-mentioned advantages and provision of long period of analgesia may be more convenient, especially for patients who are unable to take drugs orally. Topically and transdermally administered opioids are characterised by a lower risk of addiction compared to oral and parenteral routes.

  9. On the S-matrix of type-0 string theory

    International Nuclear Information System (INIS)

    DeWolfe, Oliver; Roiban, Radu; Spradlin, Marcus; Volovich, Anastasia; Walcher, Johannes

    2003-01-01

    The recent discovery of non-perturbatively stable two-dimensional string back-grounds and their dual matrix models allows the study of complete scattering matrices in string theory. In this note we adapt work of Moore, Plesser, and Ramgoolam on the bosonic string to compute the exact S-matrices of 0A and 0B string theory in two dimensions. Unitarity of the 0B theory requires the inclusion of massless soliton sectors carrying RR scalar charge as asymptotic states. We propose a regularization of IR divergences and find transition probabilities that distinguish the otherwise energetically degenerate soliton sectors. Unstable D-branes can decay into distinct soliton sectors. (author)

  10. Type II pp-wave matrix models from point-like gravitons

    International Nuclear Information System (INIS)

    Lozano, Yolanda; RodrIguez-Gomez, Diego

    2006-01-01

    The BMN Matrix model can be regarded as a theory of coincident M-theory gravitons, which expand by Myers dielectric effect into the 2-sphere and 5-sphere giant graviton vacua of the theory. In this note we show that, in the same fashion, Matrix String theory in Type IIA pp-wave backgrounds arises from the action for coincident Type IIA gravitons. In Type IIB, we show that the action for coincident gravitons in the maximally supersymmetric pp-wave background gives rise to a Matrix model which supports fuzzy 3-sphere giant graviton vacua with the right behavior in the classical limit. We discuss the relation between our Matrix model and the Tiny Graviton Matrix theory

  11. Downregulation of membrane type-matrix metalloproteinases in the inflamed or injured central nervous system

    DEFF Research Database (Denmark)

    Toft-Hansen, Henrik; Babcock, Alicia A; Millward, Jason M

    2007-01-01

    BACKGROUND: Matrix metalloproteinases (MMPs) are thought to mediate cellular infiltration in central nervous system (CNS) inflammation by cleaving extracellular matrix proteins associated with the blood-brain barrier. The family of MMPs includes 23 proteinases, including six membrane type-MMPs (M...

  12. Transdermal hormone therapy in postmenopausal women: A review of metabolic effects and drug delivery technologies

    Directory of Open Access Journals (Sweden)

    Nathan W Kopper

    2008-10-01

    Full Text Available Nathan W Kopper, Jennifer Gudeman, Daniel J ThompsonKV Pharmaceutical, St. Louis, MO, USAAbstract: Vasomotor symptoms (VMS associated with menopause can cause significant discomfort and decrease the quality of life for women in the peri-menopausal and post-menopausal stages of life. Hormone therapy (HT is the mainstay of treatment for menopausal symptoms and is currently the only therapy proven effective for VMS. Numerous HT options are available to treat VMS, including estrogen-only and estrogen-progestogen combination products to meet the needs of both hysterectomized and nonhysterectomized women. In addition to selecting an appropriate estrogen or estrogen-progestogen combination, consideration should be given to the route of administration to best suit the needs of the patient. Delivery systems for hormone therapy include oral tablets, transdermal patches, transdermal topical (nonpatch products, and intravaginal preparations. Oral is currently the most commonly utilized route of administration in the United States. However, evidence suggests that oral delivery may lead to some undesirable physiologic effects caused by significant gut and hepatic metabolism. Transdermal drug delivery may mitigate some of these effects by avoiding gut and hepatic first-pass metabolism. Advantages of transdermal delivery include the ability to administer unmetabolized estradiol directly to the blood stream, administration of lower doses compared to oral products, and minimal stimulation of hepatic protein production. Several estradiol transdermal delivery technologies are available, including various types of patches, topical gels, and a transdermal spray.Keywords: estradiol, hormone therapy, menopause, transdermal drug delivery, vasomotor symptoms

  13. Distribution of the Determinant of the Sample Correlation Matrix: Monte Carlo Type One Error Rates.

    Science.gov (United States)

    Reddon, John R.; And Others

    1985-01-01

    Computer sampling from a multivariate normal spherical population was used to evaluate the type one error rates for a test of sphericity based on the distribution of the determinant of the sample correlation matrix. (Author/LMO)

  14. Extracellular matrix of smooth muscle cells: interaction of collagen type V with heparan sulfate proteoglycan

    International Nuclear Information System (INIS)

    Gay, S.; Hoeoek, M.; Gay, R.E.; Magargal, W.W.; Reynertson, R.H.

    1986-01-01

    Alteration in the extracellular matrix produced by smooth muscle cells may play a role in the development of atherosclerotic lesions. Consequently the authors have initiated studies on the structural organization of the extracellular matrix produced by cultured smooth muscle cells. Immunohisotological examination of this matrix using well-characterized mono- and polyclonal antibodies showed a partial codistribution of heparan sulfate (HS) proteoglycans with a number of different matrix components including collagen types I, III, IV, V and VI, laminin and fibronectin. Subsequent binding studies between isolated matrix proteins and HS showed that the polysaccharide interacts strongly with type V collagen and to a lesser extent with fibronectin as well as collagen types III and VI. The interaction between type V and HS was readily inhibited by heparin and highly sulfated HS but not be dermatan sulfate, chondroitin sulfate or HS with a low sulfate content. Furthermore, [ 35 S]-HS proteoglycans isolated from cultured smooth muscle cells could be adsorbed on a column of sepharose conjugated with native type V collagen and eluted in a salt gradient. Hence, the interaction between type V and HS may play a major part in stabilizing the extracellular matrix of the vessel wall

  15. Synthesis and characterization of modified starch/polybutadiene as novel transdermal drug delivery system.

    Science.gov (United States)

    Saboktakin, Mohammad Reza; Akhyari, Shahab; Nasirov, Fizuli A

    2014-08-01

    Transdermal drug delivery systems are topically administered medicaments in the form of patches that deliver drugs for systemic effects at a predetermined and controlled rate. It works very simply in which drug is applied inside the patch and it is worn on skin for long period of time. Polymer matrix, drug, permeation enhancers are the main components of transdermal drug delivery systems. The objective of the present study was to develop the modified starch and 1,4-cis polybutadiene nanoparticles as novel polymer matrix system. We have been studied the properties of a novel transdermal drug delivery system with clonidine as drug model. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Transdermal Spray in Hormone Delivery

    African Journals Online (AJOL)

    market for the delivery system and ongoing development of transdermal sprays for hormone ... (DOAJ), African Journal Online, Bioline International, Open-J-Gate and Pharmacy Abstracts ... patches and gels have been very popular owing ... This product was developed for ... In a safety announcement, the US Food and.

  17. On the Road to Development of an in Vitro Permeation Test (IVPT) Model to Compare Heat Effects on Transdermal Delivery Systems: Exploratory Studies with Nicotine and Fentanyl.

    Science.gov (United States)

    Shin, Soo Hyeon; Ghosh, Priyanka; Newman, Bryan; Hammell, Dana C; Raney, Sam G; Hassan, Hazem E; Stinchcomb, Audra L

    2017-09-01

    At elevated temperatures, the rate of drug release and skin permeation from transdermal delivery systems (TDS) may be higher than at a normal skin temperature. The aim of this study was to compare the effect of heat on the transdermal delivery of two model drugs, nicotine and fentanyl, from matrix-type TDSs with different formulations, using in vitro permeation tests (IVPT). IVPT experiments using pig skin were performed on two nicotine and three fentanyl TDSs. Both continuous and transient heat exposures were investigated by applying heat either for the maximum recommended TDS wear duration or for short duration. Continuous heat exposure for the two nicotine TDSs resulted in different effects, showing a prolonged heat effect for one product but not the other. The J max enhancement ratio due to the continuous heat effect was comparable between the two nicotine TDS, but significantly different (p drug from the skin depot after TDS removal differently for two drugs, with fentanyl exhibiting a longer heat effect. This exploratory work suggests that an IVPT study may be able to discriminate differences in transdermal drug delivery when different TDS are exposed to elevated temperatures. However, the clinical significance of IVPT heat effects studies should be further explored by conducting in vivo clinical studies with similar study designs.

  18. Enhanced Transdermal Permeability via Constructing the Porous Structure of Poloxamer-Based Hydrogel

    Directory of Open Access Journals (Sweden)

    Wen-Yi Wang

    2016-11-01

    Full Text Available A major concern for transdermal drug delivery systems is the low bioavailability of targeted drugs primarily caused by the skin’s barrier function. The resistance to the carrier matrix for the diffusion and transport of drugs, however, is routinely ignored. This study reports a promising and attractive approach to reducing the resistance to drug transport in the carrier matrix, to enhance drug permeability and bioavailability via enhanced concentration-gradient of the driving force for transdermal purposes. This approach simply optimizes and reconstructs the porous channel structure of the carrier matrix, namely, poloxamer 407 (P407-based hydrogel matrix blended with carboxymethyl cellulose sodium (CMCs. Addition of CMCs was found to distinctly improve the porous structure of the P407 matrix. The pore size approximated to normal distribution as CMCs were added and the fraction of pore number was increased by over tenfold. Transdermal studies showed that P407/CMCs saw a significant increase in drug permeability across the skin. This suggests that P407/CMC with improved porous structure exhibits a feasible and promising way for the development of transdermal therapy with high permeability and bioavailability, thereby avoiding or reducing use of any chemical enhancers.

  19. Formulation, in vitro and in vivo evaluation of transdermal patches containing risperidone.

    Science.gov (United States)

    Aggarwal, Geeta; Dhawan, Sanju; Hari Kumar, S L

    2013-01-01

    The efficacy of oral risperidone treatment in prevention of schizophrenia is well known. However, oral side effects and patient compliance is always a problem for schizophrenics. In this study, risperidone was formulated into matrix transdermal patches to overcome these problems. The formulation factors for such patches, including eudragit RL 100 and eudragit RS 100 as matrix forming polymers, olive oil, groundnut oil and jojoba oil in different concentrations as enhancers and amount of drug loaded were investigated. The transdermal patches containing risperidone were prepared by solvent casting method and characterized for physicochemical and in vitro permeation studies through excised rat skin. Among the tested preparations, formulations with 20% risperidone, 3:2 ERL 100 and ERS 100 as polymers, mixture of olive oil and jojoba oil as enhancer, exhibited greatest cumulative amount of drug permeated (1.87 ± 0.09 mg/cm(2)) in 72 h, so batch ROJ was concluded as optimized formulation and assessed for pharmacokinetic, pharmacodynamic and skin irritation potential. The pharmacokinetic characteristics of the optimized risperidone patch were determined using rabbits, while orally administered risperidone in solution was used for comparison. The calculated relative bioavailability of risperidone transdermal patch was 115.20% with prolonged release of drug. Neuroleptic efficacy of transdermal formulation was assessed by rota-rod and grip test in comparison with control and marketed oral formulations with no skin irritation. This suggests the transdermal application of risperidone holds promise for improved bioavailability and better management of schizophrenia in long-term basis.

  20. The extracellular matrix of Gadus morhua muscle contains types III, V, VI and IV collagens in addition to type I

    DEFF Research Database (Denmark)

    Brüggemann, Dagmar Adeline; Lawson, M.A.

    2005-01-01

    Confocal microscopy and immuno‐histochemistry were used to examine collagens in the extracellular matrix of cod Gadus morhua swimming muscle. In addition to the well known presence of type I fibrous collagen, types III and VI were also found in the myocommata and the endomysium. The beaded collagen......, type VI, was found in the endomysium and the network forming collagen, type IV, was found in the basement membrane. This is the first report of type V collagen in cod muscle and of types II, IV and VI in the muscle of a teleost....

  1. Genetic Variation in the Matrix Metalloproteinase Genes and Diabetic Nephropathy in Type 1 Diabetes

    OpenAIRE

    Kure, Masahiko; Pezzolesi, Marcus G.; Poznik, G. David; Katavetin, Pisut; Skupien, Jan; Dunn, Jonathon S.; Mychaleckyj, Josyf C.; Warram, James H.; Krolewski, Andrzej S.

    2011-01-01

    Genetic data support the notion that polymorphisms in members of the matrix metalloproteinase (MMP) family of genes play an important role in extracellular matrix remodeling and contribute to the pathogenesis of vascular disease. To identify novel genetic markers for diabetic nephropathy (DN), we examined the relationship between MMP gene polymorphisms and DN in the Genetics of Kidneys in Diabetes (GoKinD) population. Genotypic data from the Genetic Association Information Network (GAIN) type...

  2. Application of run length matrix to magnetic resonance imaging diagnosis of alzheimer-type dementia

    International Nuclear Information System (INIS)

    Kaeriyama, Tomoharu; Kodama, Naoki; Shimada, Tetsuo; Fukumoto, Ichiro

    2002-01-01

    To examine the possibility of diagnosing Alzheimer-type dementia, we studied this condition using the run length matrix, on head MR images of 29 Alzheimer-type dementia patients (8 men, 21 women, 78.7±6.7 years) and healthy elderly controls (10 men, 19 women, 72.3±8.7 years). The results showed that differences in GLN (gray level nonuniformity) and RLN (run length nonuniformity) were statistically significant. Furthermore, discriminant analysis based on GLN and RLN showed a rate of sensitivity of 69.0%, specificity 86.2%, and correct classification 77.6%. Although this rate of correct classification is inferior to the planimetric and volumetric methods, run length matrix is only one method of texture analysis. The results of this study indicate the possibility of MR imaging-based diagnosis of Alzheimer-type dementia with texture analysis including a run length matrix. (author)

  3. Effect of the type of radiation on the degradation behavior of polymer matrix composites

    International Nuclear Information System (INIS)

    Egusa, Shigenori

    1992-01-01

    Four kinds of polymer matrix composites (filler: E-glass or carbon fiber cloth; matrix; epoxy or polyimide resin) were irradiated with neutrons and 60 Co γ-rays at room temperature or at 5 K. Three-point bend tests were then carried out at 77 K. Comparison of the neutron and γ-ray irradiation effects shows that the radiation sensitivity of the glass/epoxy and glass/polyimide composites is 1.8-2.6 times higher to neutrons than to γ-rays, indicating a higher sensitivity of the epoxy and polyimide matrix resins to recoil protons than to γ-rays. Absorbed dose calculations, on the other hand, show that the spatial distribution of the microscopic energy deposition in polymer matrix composites is inhomogeneous for neutrons, although almost homogeneous for γ-rays. In addition, the neutron irradiation of boron-containing E-glass fiber composites produces additional radiation damage due to a 10 B(n,α) 7 Li reaction in the glass fibers, thus significantly enhancing a decrease in the composite strength. These facts indicate that as far as polymer matrix composites are concerned, the irradiation effects of neutrons will be rather difficult to simulate with different types of radiation such as protons and carbon ions from an ion accelerator. Thus, it may be prudent that such simulation irradiation be carried out mainly for pure resins to be used as matrix in polymer matrix composites. (author)

  4. Chondrogenic properties of collagen type XI, a component of cartilage extracellular matrix.

    Science.gov (United States)

    Li, Ang; Wei, Yiyong; Hung, Clark; Vunjak-Novakovic, Gordana

    2018-08-01

    Cartilage extracellular matrix (ECM) has been used for promoting tissue engineering. However, the exact effects of ECM on chondrogenesis and the acting mechanisms are not well understood. In this study, we investigated the chondrogenic effects of cartilage ECM on human mesenchymal stem cells (MSCs) and identified the contributing molecular components. To this end, a preparation of articular cartilage ECM was supplemented to pellets of chondrogenically differentiating MSCs, pellets of human chondrocytes, and bovine articular cartilage explants to evaluate the effects on cell proliferation and the production of cartilaginous matrix. Selective enzymatic digestion and screening of ECM components were conducted to identify matrix molecules with chondrogenic properties. Cartilage ECM promoted MSC proliferation, production of cartilaginous matrix, and maturity of chondrogenic differentiation, and inhibited the hypertrophic differentiation of MSC-derived chondrocytes. Selective digestion of ECM components revealed a contributory role of collagens in promoting chondrogenesis. The screening of various collagen subtypes revealed strong chondrogenic effect of collagen type XI. Finally, collagen XI was found to promote production and inhibit degradation of cartilage matrix in human articular chondrocyte pellets and bovine articular cartilage explants. Our results indicate that cartilage ECM promotes chondrogenesis and inhibits hypertrophic differentiation in MSCs. Collagen type XI is the ECM component that has the strongest effects on enhancing the production and inhibiting the degradation of cartilage matrix. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Chemical Penetration Enhancers for Transdermal Drug Delivery ...

    African Journals Online (AJOL)

    for transdermal administration. The permeation of drug through skin can be enhanced by both chemical penetration enhancement and physical methods. In this review, we have discussed the chemical penetration enhancement technology for transdermal drug delivery as well as the probable mechanisms of action.

  6. Chosen interval methods for solving linear interval systems with special type of matrix

    Science.gov (United States)

    Szyszka, Barbara

    2013-10-01

    The paper is devoted to chosen direct interval methods for solving linear interval systems with special type of matrix. This kind of matrix: band matrix with a parameter, from finite difference problem is obtained. Such linear systems occur while solving one dimensional wave equation (Partial Differential Equations of hyperbolic type) by using the central difference interval method of the second order. Interval methods are constructed so as the errors of method are enclosed in obtained results, therefore presented linear interval systems contain elements that determining the errors of difference method. The chosen direct algorithms have been applied for solving linear systems because they have no errors of method. All calculations were performed in floating-point interval arithmetic.

  7. The interaction between bitumen matrix and chemical components of radioactive wastes of WWER type

    International Nuclear Information System (INIS)

    Selucky, P.; Sazavsky, P.; Peka, V.; Krupka, M.

    2000-01-01

    The interaction between bitumen matrix and chemical components of WWER type radioactive wastes was studied. So called ''cold'' model bitumen products were prepared and compared with real products using macroDTA method. On the basis of obtained curves, the evaluation of bitumen product fire risks was performed with the aim to minimize risks of bituminization process. (authors)

  8. A Control Method of Current Type Matrix Converter for Plasma Control Coil Power Supply

    International Nuclear Information System (INIS)

    Shimada, K.; Matsukawa, M.; Kurihara, K.; Jun-ichi Itoh

    2006-01-01

    In exploration to a tokamak fusion reactor, the control of plasma instabilities of high β plasma such as neoclassical tearing mode (NTM), resistive wall mode (RWM) etc., is the key issue for steady-state sustainment. One of the proposed methods to avoid suppressing RWM is that AC current having a phase to work for reduction the RWM growth is generated in a coil (sector coil) equipped spirally on the plasma vacuum vessel. To stabilize RWM, precise and fast real-time feedback control of magnetic field with proper amplitude and frequency is necessary. This implies that an appropriate power supply dedicated for such an application is expected to be developed. A matrix converter as one of power supply candidates for this purpose could provide a solution The matrix converter, categorized in an AC/AC direct converter composed of nine bi-directional current switches, has a great feature that a large energy storage element is unnecessary in comparison with a standard existing AC/AC indirect converter, which is composed of an AC/DC converter and a DC/AC inverter. It is also advantageous in cost and size of its applications. Fortunately, a voltage type matrix converter has come to be available at the market recently, while a current type matrix converter, which is advantageous for fast control of the large-inductance coil current, has been unavailable. On the background above mentioned, we proposed a new current type matrix converter and its control method applicable to a power supply with fast response for suppressing plasma instabilities. Since this converter is required with high accuracy control, the gate control method is adopted to three-phase switching method using middle phase to reduce voltage and current waveforms distortion. The control system is composed of VME-bus board with DSP (Digital Signal Processor) and FPGA (Field Programmable Gate Array) for high speed calculation and control. This paper describes the control method of a current type matrix converter

  9. Asymptotic Bethe ansatz S-matrix and Landau-Lifshitz-type effective 2d actions

    International Nuclear Information System (INIS)

    Roiban, R; Tirziu, A; Tseytlin, A A

    2006-01-01

    Motivated by the desire to relate Bethe ansatz equations for anomalous dimensions found on the gauge-theory side of the AdS/CFT correspondence to superstring theory on AdS 5 x S 5 we explore a connection between the asymptotic S-matrix that enters the Bethe ansatz and an effective two-dimensional quantum field theory. The latter generalizes the standard 'non-relativistic' Landau-Lifshitz (LL) model describing low-energy modes of ferromagnetic Heisenberg spin chain and should be related to a limit of superstring effective action. We find the exact form of the quartic interaction terms in the generalized LL-type action whose quantum S-matrix matches the low-energy limit of the asymptotic S-matrix of the spin chain of Beisert, Dippel and Staudacher (BDS). This generalizes to all orders in the 't Hooft coupling λ an earlier computation of Klose and Zarembo of the S-matrix of the standard LL model. We also consider a generalization to the case when the spin-chain S-matrix contains an extra 'string' phase and determine the exact form of the LL 4-vertex corresponding to the low-energy limit of the ansatz of Arutyunov, Frolov and Staudacher (AFS). We explain the relation between the resulting 'non-relativistic' non-local action and the second-derivative string sigma model. We comment on modifications introduced by strong-coupling corrections to the AFS phase. We mostly discuss the SU(2) sector but also present generalizations to the SL(2) and SU(1|1) sectors, confirming universality of the dressing phase contribution by matching the low-energy limit of the AFS-type spin-chain S-matrix with tree-level string-theory S-matrix

  10. Evaluation of mesotherapy as a transdermal drug delivery tool.

    Science.gov (United States)

    Kim, S; Kye, J; Lee, M; Park, B

    2016-05-01

    There has been no research about the exact mechanism of transdermal drug delivery during mesotherapy. We aimed to evaluate whether the commercial mesogun can be an appropriate technique for a transdermal drug delivery. We injected blue ink into the polyurethane foam or pig skin with three types of mesotherapy using a commercial mesogun, or local made intradermal injector, or a manual injection of syringe. To assess the internal pressure of the cylinder and drug delivery time, we designed the evaluation setup using a needle tip pressure transducer. All types of injectors induced adequate penetration of blue ink into the polyurethane foam without backflow. In the pig skin, blue ink leaked out rapidly with the backward movement of the needle in the commercial mesogun in contrast to the local made injector or the manual injection of syringe. When the time for backward movement of the syringe approaches 1000 ms, the cylinder pressure of the syringe is saturated at around 25 mmHg which can be translated into the dermal pressure of the pig skin. There should be sufficient time between the insertion and withdrawal of the needle of injector for the adequate transdermal drug delivery and it must be considered for mesotherapy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Evaluation of matrix type mucoadhesive tablets containing indomethacin for buccal application.

    Science.gov (United States)

    Ikeuchi-Takahashi, Yuri; Sasatsu, Masanaho; Onishi, Hiraku

    2013-09-10

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are administered for pain relief from oral mucositis. However, the systemic administration of NSAIDs is limited due to systemic side effects. To avoid these side effects and treat local lesions effectively, a matrix type mucoadhesive tablet was developed. A mixture of hard fat, ethylcellulose (EC) and polyethylene glycol (PEG) was used as a matrix base, and indomethacin (IMC) was used as the principal agent. In tablets consisting of hard fat, EC and IMC, the drug release was sustained. In tablets consisting of hard fat, EC, considerable amounts of PEG and IMC, the drug release was relatively increased and IMC existed as the molecular phase or in an amorphous state. The in vitro adhesive force of the tablets consisting of hard fat, EC, considerable amounts of PEG and IMC was significantly increased as compared with the tablets consisting of hard fat and IMC. A significantly high tissue concentration and significantly low plasma concentration were observed after buccal administration of this matrix type mucoadhesive tablet as compared with that after oral administration of IMC. Thus, the matrix type mucoadhesive tablet has good potential as a preparation for the treatment of pain due to oral aphtha. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Matrix and reservoir-type multipurpose vaginal rings for controlled release of dapivirine and levonorgestrel.

    Science.gov (United States)

    Boyd, Peter; Fetherston, Susan M; McCoy, Clare F; Major, Ian; Murphy, Diarmaid J; Kumar, Sandeep; Holt, Jonathon; Brimer, Andrew; Blanda, Wendy; Devlin, Brid; Malcolm, R Karl

    2016-09-10

    A matrix-type silicone elastomer vaginal ring providing 28-day continuous release of dapivirine (DPV) - a lead candidate human immunodeficiency virus type 1 (HIV-1) microbicide compound - has recently demonstrated moderate levels of protection in two Phase III clinical studies. Here, next-generation matrix and reservoir-type silicone elastomer vaginal rings are reported for the first time offering simultaneous and continuous in vitro release of DPV and the contraceptive progestin levonorgestrel (LNG) over a period of between 60 and 180days. For matrix-type vaginal rings comprising initial drug loadings of 100, 150 or 200mg DPV and 0, 16 or 32mg LNG, Day 1 daily DPV release values were between 4132 and 6113μg while Day 60 values ranged from 284 to 454μg. Daily LNG release ranged from 129 to 684μg on Day 1 and 2-91μg on Day 60. Core-type rings comprising one or two drug-loaded cores provided extended duration of in vitro release out to 180days, and maintained daily drug release rates within much narrower windows (either 75-131μg/day or 37-66μg/day for DPV, and either 96-150μg/day or 37-57μg/day for LNG, depending on core ring configuration and ignoring initial lag release effect for LNG) compared with matrix-type rings. The data support the continued development of these devices as multi-purpose prevention technologies (MPTs) for HIV prevention and long-acting contraception. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. The influence of matrix composition and reinforcement type on the properties of polysialate composites

    Science.gov (United States)

    Hammell, James A.

    There is a critical need for the development of materials for eliminating fire as a cause of death in aircraft accidents. Currently available composites that use organic matrices not only deteriorate at temperatures above 300°C but also emit toxic fumes. The results presented in this dissertation focus on the development of an inorganic matrix that does not burn or emit toxic fumes. The matrix, known as polysialate, can withstand temperatures in excess of 1000°C. The matrix behaves like a ceramic, but does not need high curing temperatures, so it can be processed like many common organic matrices. The major parameters evaluated in this dissertation are: (i) Influence of reinforcement type, (ii) Matrix formulation for both wet-dry durability and high temperature resistance, (iii) Influence of processing variables such as moisture reduction and storage, (iv) Tensile strain capacity of modified matrices and matrices reinforced with ceramic microfibers and discrete carbon fibers, and (v) analytical modeling of mechanical properties. For the reinforcement type; carbon, glass, and stainless steel wire fabrics were investigated. Carbon fabrics with 1, 3, 12, and 50k tows were used. A matrix chemical formulation that can withstand wetting and drying was developed. This formulation was tested at high temperatures to ascertain its stability above 400°C. On the topic of processing, shelf life of prepregged fabric layers and efficient moisture removal methods were studied. An analytical model based on layered reinforcement was developed for analyzing flexural specimens. It is shown that the new inorganic matrix can withstand wetting and drying, and also high temperature. The layered reinforcement concept provides accurate prediction of strength and stiffness for composites reinforced with 1k and 3k tows. The prepregged fabric layers can be stored for 14 days at -15°C without losing strength.

  14. Deformed type 0A matrix model and super-Liouville theory for fermionic black holes

    International Nuclear Information System (INIS)

    Ahn, Changrim; Kim, Chanju; Park, Jaemo; Suyama, Takao; Yamamoto, Masayoshi

    2006-01-01

    We consider a c-circumflex = 1 model in the fermionic black hole background. For this purpose we consider a model which contains both the N 1 and the N = 2 super-Liouville interactions. We propose that this model is dual to a recently proposed type 0A matrix quantum mechanics model with vortex deformations. We support our conjecture by showing that non-perturbative corrections to the free energy computed by both the matrix model and the super-Liouville theories agree exactly by treating the N = 2 interaction as a small perturbation. We also show that a two-point function on sphere calculated from the deformed type 0A matrix model is consistent with that of the N = 2 super-Liouville theory when the N = 1 interaction becomes small. This duality between the matrix model and super-Liouville theories leads to a conjecture for arbitrary n-point correlation functions of the N = 1 super-Liouville theory on the sphere

  15. Microneedle-based drug delivery systems for transdermal route.

    Science.gov (United States)

    Pierre, Maria Bernadete Riemma; Rossetti, Fabia Cristina

    2014-03-01

    Transdermal delivery offers an attractive, noninvasive administration route but it is limited by the skin's barrier to penetration. Minimally invasive techniques, such as the use of microneedles (MNs), bypass the stratum corneum (SC) barrier to permit the drug's direct access to the viable epidermis. These novel micro devices have been developed to puncture the skin for the transdermal delivery of hydrophilic drugs and macromolecules, including peptides, DNA and other molecules, that would otherwise have difficulty passing the outermost layer of the skin, the SC. Using the tools of the microelectronics industry, MNs have been fabricated with a range of sizes, shapes and materials. MNs have been shown to be robust enough to penetrate the skin and dramatically increase the skin permeability of several drugs. Moreover, MNs have reduced needle insertion pain and tissue trauma and provided controlled delivery across the skin. This review focuses on the current state of the art in the transdermal delivery of drugs using various types of MNs and developments in the field of microscale devices, as well as examples of their uses and clinical safety.

  16. Two types of mineral-related matrix vesicles in the bone mineralization of zebrafish

    International Nuclear Information System (INIS)

    Yang, L; Zhang, Y; Cui, F Z

    2007-01-01

    Two types of mineral-related matrix vesicle, multivesicular body (MVB) and monovesicle, were detected in the skeletal bone of zebrafish. Transmission electron microscopy and energy dispersive spectroscopy (EDS) analyses of the vesicular inclusions reveal that both types of vesicles contain calcium and phosphorus, suggesting that these vesicles may be involved in mineral ion delivery for the bone mineralization of zebrafish. However, their size and substructure are quite different. Monovesicles, whose diameter ranges from 100 nm to 550 nm, are similar to the previously reported normal matrix vesicles, while MVBs have a larger size of 700-1000 nm in nominal diameter and possess a substructure that is composed of smaller vesicles with their average size around 100 nm. The presence of mineral-related MVBs, which is first identified in zebrafish bone, indicates that the mineralization-associated transportation process of mineral ions is more complicated than is ordinarily imagined

  17. Transdermal optogenetic peripheral nerve stimulation

    Science.gov (United States)

    Maimon, Benjamin E.; Zorzos, Anthony N.; Bendell, Rhys; Harding, Alexander; Fahmi, Mina; Srinivasan, Shriya; Calvaresi, Peter; Herr, Hugh M.

    2017-06-01

    Objective: A fundamental limitation in both the scientific utility and clinical translation of peripheral nerve optogenetic technologies is the optical inaccessibility of the target nerve due to the significant scattering and absorption of light in biological tissues. To date, illuminating deep nerve targets has required implantable optical sources, including fiber-optic and LED-based systems, both of which have significant drawbacks. Approach: Here we report an alternative approach involving transdermal illumination. Utilizing an intramuscular injection of ultra-high concentration AAV6-hSyn-ChR2-EYFP in rats. Main results: We demonstrate transdermal stimulation of motor nerves at 4.4 mm and 1.9 mm depth with an incident laser power of 160 mW and 10 mW, respectively. Furthermore, we employ this technique to accurately control ankle position by modulating laser power or position on the skin surface. Significance: These results have the potential to enable future scientific optogenetic studies of pathologies implicated in the peripheral nervous system for awake, freely-moving animals, as well as a basis for future clinical studies.

  18. A Transdermal Measurement Platform Based on Microfluidics

    Directory of Open Access Journals (Sweden)

    Wen-Ying Huang

    2017-01-01

    Full Text Available The Franz diffusion cell is one of the most widely used devices to evaluate transdermal drug delivery. However, this static and nonflowing system has some limitations, such as a relatively large solution volume and skin area and the development of gas bubbles during sampling. To overcome these disadvantages, this study provides a proof of concept for miniaturizing models of transdermal delivery by using a microfluidic chip combined with a diffusion cell. The proposed diffusion microchip system requires only 80 μL of sample solution and provides flow circulation. Two model compounds, Coomassie Brilliant Blue G-250 and potassium ferricyanide, were successfully tested for transdermal delivery experiments. The diffusion rate is high for a high sample concentration or a large membrane pore size. The developed diffusion microchip system, which is feasible, can be applied for transdermal measurement in the future.

  19. MUSIC-type imaging of a thin penetrable inclusion from its multi-static response matrix

    International Nuclear Information System (INIS)

    Park, Won-Kwang; Lesselier, Dominique

    2009-01-01

    The imaging of a thin inclusion, with dielectric and/or magnetic contrasts with respect to the embedding homogeneous medium, is investigated. A MUSIC-type algorithm operating at a single time-harmonic frequency is developed in order to map the inclusion (that is, to retrieve its supporting curve) from scattered field data collected within the multi-static response matrix. Numerical experiments carried out for several types of inclusions (dielectric and/or magnetic ones, straight or curved ones), mostly single inclusions and also two of them close by as a straightforward extension, illustrate the pros and cons of the proposed imaging method

  20. MUSIC-type imaging of a thin penetrable inclusion from its multi-static response matrix

    Science.gov (United States)

    Park, Won-Kwang; Lesselier, Dominique

    2009-07-01

    The imaging of a thin inclusion, with dielectric and/or magnetic contrasts with respect to the embedding homogeneous medium, is investigated. A MUSIC-type algorithm operating at a single time-harmonic frequency is developed in order to map the inclusion (that is, to retrieve its supporting curve) from scattered field data collected within the multi-static response matrix. Numerical experiments carried out for several types of inclusions (dielectric and/or magnetic ones, straight or curved ones), mostly single inclusions and also two of them close by as a straightforward extension, illustrate the pros and cons of the proposed imaging method.

  1. Transport efficiency in transdermal drug delivery: What is the role of fluid microstructure?

    Science.gov (United States)

    Liuzzi, Roberta; Carciati, Antonio; Guido, Stefano; Caserta, Sergio

    2016-03-01

    Interaction of microstructured fluids with skin is ubiquitous in everyday life, from the use of cosmetics, lotions, and drugs, to personal care with detergents or soaps. The formulation of microstructured fluids is crucial for the control of the transdermal transport. In biomedical applications transdermal delivery is an efficient approach, alternative to traditional routes like oral and parenteral administration, for local release of drugs. Poor skin permeability, mainly due to its outer layer, which acts as the first barrier against the entry of external compounds, greatly limits the applicability of transdermal delivery. In this review, we focus on recent studies on the improvement of skin transport efficiency by using microemulsions (ME). Quantitative techniques, which are able to investigate both skin morphology and penetration processes, are also reviewed. ME are increasingly used as transdermal systems due to their low preparation cost, stability and high bioavailability. ME may act as penetration enhancers for many active principles, but ME microstructure should be chosen appropriately considering several factors such as ratio and type of ingredients and physic-chemical properties of the active components. ME microstructure is strongly affected by the flow conditions applied during processing, or during spreading and rubbing onto skin. Although the role played by ME microstructure has been generally recognized, the skin transport mechanisms associated with different ME microstructures are still to be elucidated and further investigations are required to fully exploit the potential of ME in transdermal delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Spray-on transdermal drug delivery systems.

    Science.gov (United States)

    Ibrahim, Sarah A

    2015-02-01

    Transdermal drug delivery possesses superior advantages over other routes of administration, particularly minimizing first-pass metabolism. Transdermal drug delivery is challenged by the barrier nature of skin. Numerous technologies have been developed to overcome the relatively low skin permeability, including spray-on transdermal systems. A transdermal spray-on system (TSS) usually consists of a solution containing the drug, a volatile solvent and in many cases a chemical penetration enhancer. TSS promotes drug delivery via the complex interplay between solvent evaporation and drug-solvent drag into skin. The volatile solvent carries the drug into the upper layers of the stratum corneum, and as the volatile solvent evaporates, an increase in the thermodynamic activity of the drug occurs resulting in an increased drug loading in skin. TSS is easily applied, delivering flexible drug dosage and associated with lower incidence of skin irritation. TSS provides a fast-drying product where the volatile solvent enables uniform drug distribution with minimal vehicle deposition on skin. TSS ensures precise dose administration that is aesthetically appealing and eliminates concerns of residual drug associated with transdermal patches. Furthermore, it provides a better alternative to traditional transdermal products due to ease of product development and manufacturing.

  3. Transdermal patches: history, development and pharmacology

    Science.gov (United States)

    Pastore, Michael N; Kalia, Yogeshvar N; Horstmann, Michael; Roberts, Michael S

    2015-01-01

    Transdermal patches are now widely used as cosmetic, topical and transdermal delivery systems. These patches represent a key outcome from the growth in skin science, technology and expertise developed through trial and error, clinical observation and evidence-based studies that date back to the first existing human records. This review begins with the earliest topical therapies and traces topical delivery to the present-day transdermal patches, describing along the way the initial trials, devices and drug delivery systems that underpin current transdermal patches and their actives. This is followed by consideration of the evolution in the various patch designs and their limitations as well as requirements for actives to be used for transdermal delivery. The properties of and issues associated with the use of currently marketed products, such as variability, safety and regulatory aspects, are then described. The review concludes by examining future prospects for transdermal patches and drug delivery systems, such as the combination of active delivery systems with patches, minimally invasive microneedle patches and cutaneous solutions, including metered-dose systems. PMID:25560046

  4. Membrane-type matrix metalloproteases as diverse effectors of cancer progression.

    Science.gov (United States)

    Turunen, S Pauliina; Tatti-Bugaeva, Olga; Lehti, Kaisa

    2017-11-01

    Membrane-type matrix metalloproteases (MT-MMP) are pivotal regulators of cell invasion, growth and survival. Tethered to the cell membranes by a transmembrane domain or GPI-anchor, the six MT-MMPs can exert these functions via cell surface-associated extracellular matrix degradation or proteolytic protein processing, including shedding or release of signaling receptors, adhesion molecules, growth factors and other pericellular proteins. By interactions with signaling scaffold or cytoskeleton, the C-terminal cytoplasmic tail of the transmembrane MT-MMPs further extends their functionality to signaling or structural relay. MT-MMPs are differentially expressed in cancer. The most extensively studied MMP14/MT1-MMP is induced in various cancers along malignant transformation via pathways activated by mutations in tumor suppressors or proto-oncogenes and changes in tumor microenvironment including cellular heterogeneity, extracellular matrix composition, tissue oxygenation, and inflammation. Classically such induction involves transcriptional programs related to epithelial-to-mesenchymal transition. Besides inhibition by endogenous tissue inhibitors, MT-MMP activities are spatially and timely regulated at multiple levels by microtubular vesicular trafficking, dimerization/oligomerization, other interactions and localization in the actin-based invadosomes, in both tumor and the stroma. The functions of MT-MMPs are multifaceted within reciprocal cellular responses in the evolving tumor microenvironment, which poses the importance of these proteases beyond the central function as matrix scissors, and necessitates us to rethink MT-MMPs as dynamic signaling proteases of cancer. This article is part of a Special Issue entitled: Matrix Metalloproteinases edited by Rafael Fridman. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Propolis Modifies Collagen Types I and III Accumulation in the Matrix of Burnt Tissue

    Directory of Open Access Journals (Sweden)

    Pawel Olczyk

    2013-01-01

    Full Text Available Wound healing represents an interactive process which requires highly organized activity of various cells, synthesizing cytokines, growth factors, and collagen. Collagen types I and III, serving as structural and regulatory molecules, play pivotal roles during wound healing. The aim of this study was to compare the propolis and silver sulfadiazine therapeutic efficacy throughout the quantitative and qualitative assessment of collagen types I and III accumulation in the matrix of burnt tissues. Burn wounds were inflicted on pigs, chosen for the evaluation of wound repair because of many similarities between pig and human skin. Isolated collagen types I and III were estimated by the surface plasmon resonance method with a subsequent collagenous quantification using electrophoretic and densitometric analyses. Propolis burn treatment led to enhanced collagens and its components expression, especially during the initial stage of the study. Less expressed changes were observed after silver sulfadiazine (AgSD application. AgSD and, with a smaller intensity, propolis stimulated accumulation of collagenous degradation products. The assessed propolis therapeutic efficacy, throughout quantitatively and qualitatively analyses of collagen types I and III expression and degradation in wounds matrix, may indicate that apitherapeutic agent can generate favorable biochemical environment supporting reepithelization.

  6. Transdermic absorption of Melagenina II

    International Nuclear Information System (INIS)

    Hernandez Gonzalez, I.; Martinez Lopez, B.; Ruiz Pena, M.; Caso Pena, R.

    1997-01-01

    The transdermic absorption of Melagenina II (MII) was evaluated. MII was a labelled with 125I by the yodogen method and purified by column chromatography with Sephadex LH-20 in ethanol: water (7:3). In vitro absorption of ( 125I ) - MII thought human skin was carried out in Keshary-Chien modified diffusion cells. Tape stripping method was applied after 24 hours to evaluate the accumulated activity in dermis and epidermis. In vivo assays were performed in Sprague Dawley rats to analyze absorption of MII until 24 hours after a single application and for five days a low penetrability of the drug while in vivo there were not found blood levels significantly greater than zero , nevertheless and important amount of radioactivity was found in feces and urine. The activity was concentrated mainly in the application site in both models

  7. Challenges and opportunities in dermal/transdermal delivery

    OpenAIRE

    Paudel, Kalpana S; Milewski, Mikolaj; Swadley, Courtney L; Brogden, Nicole K; Ghosh, Priyanka; Stinchcomb, Audra L

    2010-01-01

    Transdermal drug delivery is an exciting and challenging area. There are numerous transdermal delivery systems currently available on the market. However, the transdermal market still remains limited to a narrow range of drugs. Further advances in transdermal delivery depend on the ability to overcome the challenges faced regarding the permeation and skin irritation of the drug molecules. Emergence of novel techniques for skin permeation enhancement and development of methods to lessen skin i...

  8. Matrix metalloproteinase-9-mediated type III collagen degradation as a novel serological biochemical marker for liver fibrogenesis

    DEFF Research Database (Denmark)

    Veidal, Sanne S; Vassiliadis, Efstathios; Barascuk, Natasha

    2010-01-01

    During fibrogenesis in the liver, in which excessive remodelling of the extracellular matrix (ECM) occurs, both the quantity of type III collagen (CO3) and levels of matrix metalloproteinases (MMPs), including MMP-9, increase significantly. MMPs play major roles in ECM remodelling, via...

  9. Research on Matrix-type Packet Loss Compensation Scheme for Wireless Video Transmission on Subway

    Directory of Open Access Journals (Sweden)

    Fan Qing-Wu

    2017-01-01

    Full Text Available As the mainstream wireless LAN technology, Wi-Fi can achieve fast data transfer. With the subway moving in a high speed, video data transmission between the metro and the ground is achieved through Wi-Fi technology. This paper aims at solving the Caton problem caused by switching packet loss in the process of playing real-time video on the train terminal, and proposes matrix-type packet loss compensation scheme. Finally, the feasibility of the scheme is verified by experiments.

  10. Some Recent Advances in Transdermal Drug Delivery Systems ...

    African Journals Online (AJOL)

    Some Recent Advances in Transdermal Drug Delivery Systems. ... Advances in Transdermal Drug Delivery Systems. EC Ibezim, B Kabele-Toge, CO Anie, C Njoku. Abstract. Transdermal delivery systems are forms of drug delivery involving the dermis, as distinct from topical, oral or other forms of parenteral dosage forms.

  11. Matrix metalloproteinase 2 and membrane type 1 matrix metalloproteinase co-regulate axonal outgrowth of mouse retinal ganglion cells

    DEFF Research Database (Denmark)

    Gaublomme, Djoere; Buyens, Tom; De Groef, Lies

    2014-01-01

    regenerative therapies, an improved understanding of axonal outgrowth and the various molecules influencing it, is highly needed. Matrix metalloproteinases (MMPs) constitute a family of zinc-dependent proteases that were sporadically reported to influence axon outgrowth. Using an ex vivo retinal explant model......, but not MMP-9, are involved in this process. Furthermore, administration of a novel antibody to MT1-MMP that selectively blocks pro-MMP-2 activation revealed a functional co-involvement of these proteinases in determining RGC axon outgrowth. Subsequent immunostainings showed expression of both MMP-2 and MT1...... nervous system is lacking in adult mammals, thereby impeding recovery from injury to the nervous system. Matrix metalloproteinases (MMPs) constitute a family of zinc-dependent proteases that were sporadically reported to influence axon outgrowth. Inhibition of specific MMPs reduced neurite outgrowth from...

  12. Exploration of ethyl anthranilate-loaded monolithic matrix-type prophylactic polymeric patch

    Directory of Open Access Journals (Sweden)

    Johirul Islam

    2017-10-01

    Full Text Available Compromised stability of pharmaceutical formulations loaded with volatiles is a serious problem associated with devices designed to deliver volatile compounds. The present study has been focused to evaluate the stability potential of matrix-type polymeric patches composed of volatile ethyl anthranilate for prophylaxis against vector-borne diseases. Ethyl anthranilate-loaded matrix-type polymeric patches were fabricated by solvent evaporation method on an impermeable backing membrane and attached to temporary release liners. Stability testing of the polymeric patches was performed as per the International Conference on Harmonization (ICH guidelines for 6 months under accelerated conditions. In addition, the quantification of residual solvents was also performed as per the ICH guidelines. After conducting the stability studies for 6 months, the optimized patches showed the best possible results with respect to uniformity of drug content, physical appearance, and other analytical parameters. Furthermore, the amount of residual solvent was found well below the accepted limit. Thus, the present report outlined the analytical parameters to be evaluated to ensure the stability of a certain devices consisting of volatile compounds.

  13. Design of distributed PID-type dynamic matrix controller for fractional-order systems

    Science.gov (United States)

    Wang, Dawei; Zhang, Ridong

    2018-01-01

    With the continuous requirements for product quality and safety operation in industrial production, it is difficult to describe the complex large-scale processes with integer-order differential equations. However, the fractional differential equations may precisely represent the intrinsic characteristics of such systems. In this paper, a distributed PID-type dynamic matrix control method based on fractional-order systems is proposed. First, the high-order approximate model of integer order is obtained by utilising the Oustaloup method. Then, the step response model vectors of the plant is obtained on the basis of the high-order model, and the online optimisation for multivariable processes is transformed into the optimisation of each small-scale subsystem that is regarded as a sub-plant controlled in the distributed framework. Furthermore, the PID operator is introduced into the performance index of each subsystem and the fractional-order PID-type dynamic matrix controller is designed based on Nash optimisation strategy. The information exchange among the subsystems is realised through the distributed control structure so as to complete the optimisation task of the whole large-scale system. Finally, the control performance of the designed controller in this paper is verified by an example.

  14. Transdermal rivastigmine: management of cutaneous adverse events and review of the literature.

    Science.gov (United States)

    Greenspoon, Jill; Herrmann, Nathan; Adam, David N

    2011-07-01

    Alzheimer's disease is a chronic neurodegenerative disorder resulting in part from the degeneration of cholinergic neurons in the brain. Rivastigmine, a cholinesterase inhibitor, is commonly used as a treatment for dementia due to its ability to moderate cholinergic neurotransmission; however, treatment with oral rivastigmine can lead to gastrointestinal adverse effects such as nausea and vomiting. Transdermal administration of rivastigmine can minimize these adverse effects by providing continuous delivery of the medication, while maintaining the effectiveness of the oral treatment. While the transdermal form of rivastigmine has been found to have fewer systemic adverse effects compared with the oral form, cutaneous reactions, such as contact dermatitis, can lead to discontinuation of the drug in its transdermal form. Lack of patient compliance with regard to applying the patch to the designated site, applying the patch for the correct length of time or rotating patch application sites increases the risk of cutaneous adverse reactions. This article outlines the diagnosis and management of irritant contact dermatitis and allergic contact dermatitis secondary to transdermal rivastigmine. The large majority of reactions to transdermal patches are of an irritant type, which can be diagnosed clinically by the presence of a pruritic, erythematous, eczematous plaque strictly confined to the borders of the patch. In contrast, an allergic reaction can be differentiated by the presence of vesicles and/or oedema, erythema beyond the boundaries of the transdermal patch and lack of improvement of the lesion 48 hours after removal of the offending treatment. By encouraging the patient to follow a regular rotation schedule for the patch, and using lipid-based emollients for irritant dermatitis and pre- and post-treatment topical corticosteroids for allergic dermatitis, cutaneous reactions can often be alleviated and patients can continue with their medication regimen. Other

  15. Permeation enhancer strategies in transdermal drug delivery.

    Science.gov (United States)

    Marwah, Harneet; Garg, Tarun; Goyal, Amit K; Rath, Goutam

    2016-01-01

    Today, ∼74% of drugs are taken orally and are not found to be as effective as desired. To improve such characteristics, transdermal drug delivery was brought to existence. This delivery system is capable of transporting the drug or macromolecules painlessly through skin into the blood circulation at fixed rate. Topical administration of therapeutic agents offers many advantages over conventional oral and invasive techniques of drug delivery. Several important advantages of transdermal drug delivery are prevention from hepatic first pass metabolism, enhancement of therapeutic efficiency and maintenance of steady plasma level of the drug. Human skin surface, as a site of drug application for both local and systemic effects, is the most eligible candidate available. New controlled transdermal drug delivery systems (TDDS) technologies (electrically-based, structure-based and velocity-based) have been developed and commercialized for the transdermal delivery of troublesome drugs. This review article covers most of the new active transport technologies involved in enhancing the transdermal permeation via effective drug delivery system.

  16. Myth or Reality-Transdermal Magnesium?

    Science.gov (United States)

    Gröber, Uwe; Werner, Tanja; Vormann, Jürgen; Kisters, Klaus

    2017-07-28

    In the following review, we evaluated the current literature and evidence-based data on transdermal magnesium application and show that the propagation of transdermal magnesium is scientifically unsupported. The importance of magnesium and the positive effects of magnesium supplementation are extensively documented in magnesium deficiency, e.g., cardiovascular disease and diabetes mellitus. The effectiveness of oral magnesium supplementation for the treatment of magnesium deficiency has been studied in detail. However, the proven and well-documented oral magnesium supplementation has become questioned in the recent years through intensive marketing for its transdermal application (e.g., magnesium-containing sprays, magnesium flakes, and magnesium salt baths). In both, specialist and lay press as well as on the internet, there are increasing numbers of articles claiming the effectiveness and superiority of transdermal magnesium over an oral application. It is claimed that the transdermal absorption of magnesium in comparison to oral application is more effective due to better absorption and fewer side effects as it bypasses the gastrointestinal tract.

  17. Monocyte matrix metalloproteinase production in Type 2 diabetes and controls – a cross sectional study

    Directory of Open Access Journals (Sweden)

    Davies Isabel R

    2003-03-01

    Full Text Available Abstract Background Coronary plaque rupture may result from localised over expression of matrix metalloproteinases (MMPs within the plaque by infiltrating monocyte – macrophages. As MMP expression can be promoted by the modified lipoproteins, oxidative stress and hyperglycaemia that characterises Type 2 diabetes, we hypothesised that peripheral monocytes in these patients, exposed to these factors in vivo, would demonstrate increased MMP production compared to controls. Methods We examined peripheral venous monocyte expression of MMP and tissue inhibitor of metalloproteinase-1 (TIMP-1 in 18 controls and 22 subjects with Type 2 diabetes and no previous cardiovascular complications. Results No significant difference in MMP-1, 3 or 9 or TIMP-1 production was observed between control and diabetes groups. Conclusions Monocyte MMP-1, 3, and 9, and TIMP-1, production are not abnormal in Type 2 diabetes. This data cannot be extrapolated to monocyte – macrophage behaviour in the vessel wall, but it does suggest MMP and TIMP-1 expression prior to monocyte infiltration and transformation are not abnormal in Type 2 diabetes.

  18. Realizing three generations of the Standard Model fermions in the type IIB matrix model

    International Nuclear Information System (INIS)

    Aoki, Hajime; Nishimura, Jun; Tsuchiya, Asato

    2014-01-01

    We discuss how the Standard Model particles appear from the type IIB matrix model, which is considered to be a nonperturbative formulation of superstring theory. In particular, we are concerned with a constructive definition of the theory, in which we start with finite-N matrices and take the large-N limit afterwards. In that case, it was pointed out recently that realizing chiral fermions in the model is more difficult than it had been thought from formal arguments at N=∞ and that introduction of a matrix version of the warp factor is necessary. Based on this new insight, we show that two generations of the Standard Model fermions can be realized by considering a rather generic configuration of fuzzy S"2 and fuzzy S"2×S"2 in the extra dimensions. We also show that three generations can be obtained by squashing one of the S"2’s that appear in the configuration. Chiral fermions appear at the intersections of the fuzzy manifolds with nontrivial Yukawa couplings to the Higgs field, which can be calculated from the overlap of their wave functions.

  19. Universality and the dynamical space-time dimensionality in the Lorentzian type IIB matrix model

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Yuta [KEK Theory Center, High Energy Accelerator Research Organization,1-1 Oho, Tsukuba, Ibaraki 305-0801 (Japan); Nishimura, Jun [KEK Theory Center, High Energy Accelerator Research Organization,1-1 Oho, Tsukuba, Ibaraki 305-0801 (Japan); Graduate University for Advanced Studies (SOKENDAI),1-1 Oho, Tsukuba, Ibaraki 305-0801 (Japan); Tsuchiya, Asato [Department of Physics, Shizuoka University,836 Ohya, Suruga-ku, Shizuoka 422-8529 (Japan)

    2017-03-27

    The type IIB matrix model is one of the most promising candidates for a nonperturbative formulation of superstring theory. In particular, its Lorentzian version was shown to exhibit an interesting real-time dynamics such as the spontaneous breaking of the 9-dimensional rotational symmetry to the 3-dimensional one. This result, however, was obtained after regularizing the original matrix integration by introducing “infrared” cutoffs on the quadratic moments of the Hermitian matrices. In this paper, we generalize the form of the cutoffs in such a way that it involves an arbitrary power (2p) of the matrices. By performing Monte Carlo simulation of a simplified model, we find that the results become independent of p and hence universal for p≳1.3. For p as large as 2.0, however, we find that large-N scaling behaviors do not show up, and we cannot take a sensible large-N limit. Thus we find that there is a certain range of p in which a universal large-N limit can be taken. Within this range of p, the dynamical space-time dimensionality turns out to be (3+1), while for p=2.0, where we cannot take a sensible large-N limit, we observe a (5+1)d structure.

  20. Attenuation of endocrine-exocrine pancreatic communication in type 2 diabetes: pancreatic extracellular matrix ultrastructural abnormalities.

    Science.gov (United States)

    Hayden, Melvin R; Patel, Kamlesh; Habibi, Javad; Gupta, Deepa; Tekwani, Seema S; Whaley-Connell, Adam; Sowers, James R

    2008-01-01

    Ultrastructural observations reveal a continuous interstitial matrix connection between the endocrine and exocrine pancreas, which is lost due to fibrosis in rodent models and humans with type 2 diabetes mellitus (T2DM). Widening of the islet-exocrine interface appears to result in loss of desmosomes and adherens junctions between islet and acinar cells and is associated with hypercellularity consisting of pericytes and inflammatory cells in T2DM pancreatic tissue. Organized fibrillar collagen was closely associated with pericytes, which are known to differentiate into myofibroblasts-pancreatic stellate cells. Of importance, some pericyte cellular processes traverse both the connecting islet-exocrine interface and the endoacinar interstitium of the exocrine pancreas. Loss of cellular paracrine communication and extracellular matrix remodeling fibrosis in young animal models and humans may result in a dysfunctional insulino-acinar-ductal-incretin gut hormone axis, resulting in pancreatic insufficiency and glucagon-like peptide deficiency, which are known to exist in prediabetes and overt T2DM in humans.

  1. Human Kunitz-type protease inhibitor engineered for enhanced matrix retention extends longevity of fibrin biomaterials.

    Science.gov (United States)

    Briquez, Priscilla S; Lorentz, Kristen M; Larsson, Hans M; Frey, Peter; Hubbell, Jeffrey A

    2017-08-01

    Aprotinin is a broad-spectrum serine protease inhibitor used in the clinic as an anti-fibrinolytic agent in fibrin-based tissue sealants. However, upon re-exposure, some patients suffer from hypersensitivity immune reactions likely related to the bovine origin of aprotinin. Here, we aimed to develop a human-derived substitute to aprotinin. Based on sequence homology analyses, we identified the Kunitz-type protease inhibitor (KPI) domain of human amyloid-β A4 precursor protein as being a potential candidate. While KPI has a lower intrinsic anti-fibrinolytic activity than aprotinin, we reasoned that its efficacy is additionally limited by its fast release from fibrin material, just as aprotinin's is. Thus, we engineered KPI variants for controlled retention in fibrin biomaterials, using either covalent binding through incorporation of a substrate for the coagulation transglutaminase Factor XIIIa or through engineering of extracellular matrix protein super-affinity domains for sequestration into fibrin. We showed that both engineered KPI variants significantly slowed plasmin-mediated fibrinolysis in vitro, outperforming aprotinin. In vivo, our best engineered KPI variant (incorporating the transglutaminase substrate) extended fibrin matrix longevity by 50%, at a dose at which aprotinin did not show efficacy, thus qualifying it as a competitive substitute of aprotinin in fibrin sealants. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  2. Activity and expression of urokinase-type plasminogen activator and matrix metalloproteinases in human colorectal cancer

    International Nuclear Information System (INIS)

    Kim, Tae-Dong; Song, Kyoung-Sub; Li, Ge; Choi, Hoon; Park, Hae-Duck; Lim, Kyu; Hwang, Byung-Doo; Yoon, Wan-Hee

    2006-01-01

    Matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and urokinase-type plasminogen activator (uPA) are involved in colorectal cancer invasion and metastasis. There is still debate whether the activity of MMP-2 and MMP-9 differs between tumors located in the colon and rectum. We designed this study to determine any differences in the expression of MMP-2, MMP-9 and uPA system between colon and rectal cancer tissues. Cancer tissue samples were obtained from colon carcinoma (n = 12) and rectal carcinomas (n = 10). MMP-2 and MMP-9 levels were examined using gelatin zymography and Western blotting; their endogenous inhibitors, tissue inhibitor of metalloproteinase-2 (TIMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1), were assessed by Western blotting. uPA, uPAR and PAI-1 were examined using enzyme-linked immunosorbent assay (ELISA). The activity of uPA was assessed by casein-plasminogen zymography. In both colon and rectal tumors, MMP-2, MMP-9 and TIMP-1 protein levels were higher than in corresponding paired normal mucosa, while TIMP-2 level in tumors was significantly lower than in normal mucosa. The enzyme activities or protein levels of MMP-2, MMP-9 and their endogenous inhibitors did not reach a statistically significant difference between colon and rectal cancer compared with their normal mucosa. In rectal tumors, there was an increased activity of uPA compared with the activity in colon tumors (P = 0.0266), however urokinase-type plasminogen activator receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1) showed no significant difference between colon and rectal cancer tissues. These findings suggest that uPA may be expressed differentially in colon and rectal cancers, however, the activities or protein levels of MMP-2, MMP-9, TIMP-1, TIMP-2, PAI-1 and uPAR are not affected by tumor location in the colon or the rectum

  3. Identification of membrane-type 1 matrix metalloproteinase tyrosine phosphorylation in association with neuroblastoma progression

    International Nuclear Information System (INIS)

    Nyalendo, Carine; Sartelet, Hervé; Barrette, Stéphane; Ohta, Shigeru; Gingras, Denis; Béliveau, Richard

    2009-01-01

    Neuroblastoma is a pediatric tumor of neural crest cells that is clinically characterized by its variable evolution, from spontaneous regression to malignancy. Despite many advances in neuroblastoma research, 60% of neuroblastoma, which are essentially metastatic cases, are associated with poor clinical outcome due to the lack of effectiveness of current therapeutic strategies. Membrane-type 1 matrix metalloproteinase (MT1-MMP, MMP-14), an enzyme involved in several steps in tumor progression, has previously been shown to be associated with poor clinical outcome for neuroblastoma. Based on our recent demonstration that MT1-MMP phosphorylation is involved in the growth of fibrosarcoma tumors, we examined the potential role of phosphorylated MT1-MMP in neuroblastoma progression. Tyrosine phosphorylated MT1-MMP was immunostained on tissue microarray samples from 55 patients with neuroblastoma detected by mass screening (known to be predominantly associated with favourable outcome), and from 234 patients with standard diagnosed neuroblastoma. In addition, the effects of a non phosphorylable version of MT1-MMP on neuroblastoma cell migration and proliferation were investigated within three-dimensional collagen matrices. Although there is no correlation between the extent of tyrosine phosphorylation of MT1-MMP (pMT1-MMP) and MYCN amplification or clinical stage, we observed greater phosphorylation of pMT1-MMP in standard neuroblastoma, while it is less evident in neuroblastoma from mass screening samples (P = 0.0006) or in neuroblastoma samples from patients younger than one year (P = 0.0002). In vitro experiments showed that overexpression of a non-phosphorylable version of MT1-MMP reduced MT1-MMP-mediated neuroblastoma cell migration and proliferation within a three-dimensional type I collagen matrix, suggesting a role for the phosphorylated enzyme in the invasive properties of neuroblastoma cells. Overall, these results suggest that tyrosine phosphorylated MT1-MMP

  4. Dissolving Microneedle Arrays for Transdermal Delivery of Amphiphilic Vaccines.

    Science.gov (United States)

    An, Myunggi; Liu, Haipeng

    2017-07-01

    Amphiphilic vaccine based on lipid-polymer conjugates is a new type of vaccine capable of self-delivering to the immune system. When injected subcutaneously, amphiphilic vaccines efficiently target antigen presenting cells in the lymph nodes (LNs) via a unique albumin-mediated transport and uptake mechanism and induce potent humoral and cellular immune responses. However, whether this new type of vaccine can be administrated via a safe, convenient microneedle-based transdermal approach remains unstudied. For such skin barrier-disruption systems, a simple application of microneedle arrays (MNs) is desired to disrupt the stratum corneum, and for rapid and pain-free self-administration of vaccines into the skin, the anatomic place permeates with an intricate mesh of lymphatic vessels draining to LNs. Here the microneedle transdermal approach is combined with amphiphilic vaccines to create a simple delivery approach which efficiently traffic molecular vaccines into lymphatics and draining LNs. The rapid release of amphiphilic vaccines into epidermis upon application of dissolving MNs to the skin of mice generates potent cellular and humoral responses, comparable or superior to those elicited by traditional needle-based immunizations. The results suggest that the amphiphilic vaccines delivered by dissolving MNs can provide a simple and safer vaccination method with enhanced vaccine efficacy. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. The effect of carrier type on bone regeneration of demineralized bone matrix in vivo.

    Science.gov (United States)

    Tavakol, Shima; Khoshzaban, Ahad; Azami, Mahmoud; Kashani, Iraj Ragerdi; Tavakol, Hani; Yazdanifar, Mahbube; Sorkhabadi, Seyed Mahdi Rezayat

    2013-11-01

    Demineralized bone matrix (DBM) is a bone substitute biomaterial used as an excellent grafting material. Some factors such as carrier type might affect the healing potential of this material. The background data discuss the present status of the field: Albumin as a main protein in blood and carboxymethyl cellulose (CMC) were applied frequently in the DBM gels. We investigated the bone-repairing properties of 2 DBMs with different carriers. Bone regeneration in 3 groups of rat calvaria treated with DBM from the Iranian Tissue Bank Research and Preparation Center, DBM from Hans Biomed Corporation, and an empty cavity was studied. Albumin and CMC as carriers were used. The results of bone regeneration in the samples after 1, 4, and 8 weeks of implantation were compared. The block of the histologic samples was stained with hematoxylin and eosin, and the percentage area of bone formation was calculated using the histomorphometry method. The results of in vivo tests showed a significantly stronger new regenerated bone occupation in the DBM with albumin carrier compared with the one with CMC 8 weeks after the implantation. The 2 types of DBM had a significant difference in bone regeneration. This difference is attributed to the type of carriers. Albumin could improve mineralization and bioactivity compared with CMC.

  6. Hydroxychloroquine induces inhibition of collagen type II and oligomeric matrix protein COMP expression in chondrocytes

    Directory of Open Access Journals (Sweden)

    Tao Li

    2016-06-01

    Full Text Available The aim of this study was to investigate the effect of hydroxychloroquine on the level of collagen type II and oligomeric matrix protein COMP expression in chondrocytes of knee osteoarthritis. The rate of growth in cartilage cells was analyzed using MTT assay whereas the Col-2 and COMP expression levels were detected by RT-PCR and Western blotting analyses. For the determination of MMP-13 expression, ELISA test was used. The results revealed no significant change in the rate of cartilage cell proliferation in hydroxychloroquine-treated compared to untreated cells. Hydroxychloro-quine treatment exhibited concentration- and time-dependent effect on the inhibition of collagen type II and COMP expression in chondrocytes. However, its treatment caused a significant enhancement in the expression levels of MMP-13 compared to the untreated cells. Therefore, hydroxychloro-quine promotes expression of MMP-13 and reduces collagen type II and COMP expression levels in chondrocytes without any significant change in the growth of cells.

  7. Matrix-type multiple reciprocity boundary element method for solving three-dimensional two-group neutron diffusion equations

    International Nuclear Information System (INIS)

    Itagaki, Masafumi; Sahashi, Naoki.

    1997-01-01

    The multiple reciprocity boundary element method has been applied to three-dimensional two-group neutron diffusion problems. A matrix-type boundary integral equation has been derived to solve the first and the second group neutron diffusion equations simultaneously. The matrix-type fundamental solutions used here satisfy the equation which has a point source term and is adjoint to the neutron diffusion equations. A multiple reciprocity method has been employed to transform the matrix-type domain integral related to the fission source into an equivalent boundary one. The higher order fundamental solutions required for this formulation are composed of a series of two types of analytic functions. The eigenvalue itself is also calculated using only boundary integrals. Three-dimensional test calculations indicate that the present method provides stable and accurate solutions for criticality problems. (author)

  8. The central role of vascular extracellular matrix and basement membrane remodeling in metabolic syndrome and type 2 diabetes: the matrix preloaded

    Directory of Open Access Journals (Sweden)

    Tyagi Suresh C

    2005-06-01

    Full Text Available Abstract The vascular endothelial basement membrane and extra cellular matrix is a compilation of different macromolecules organized by physical entanglements, opposing ionic charges, chemical covalent bonding, and cross-linking into a biomechanically active polymer. These matrices provide a gel-like form and scaffolding structure with regional tensile strength provided by collagens, elasticity by elastins, adhesiveness by structural glycoproteins, compressibility by proteoglycans – hyaluronans, and communicability by a family of integrins, which exchanges information between cells and between cells and the extracellular matrix of vascular tissues. Each component of the extracellular matrix and specifically the capillary basement membrane possesses unique structural properties and interactions with one another, which determine the separate and combined roles in the multiple diabetic complications or diabetic opathies. Metabolic syndrome, prediabetes, type 2 diabetes mellitus, and their parallel companion (atheroscleropathy are associated with multiple metabolic toxicities and chronic injurious stimuli. The adaptable quality of a matrix or form genetically preloaded with the necessary information to communicate and respond to an ever-changing environment, which supports the interstitium, capillary and arterial vessel wall is individually examined.

  9. Matrix metalloproteinase-9-mediated type III collagen degradation as a novel serological biochemical marker for liver fibrogenesis

    DEFF Research Database (Denmark)

    Veidal, Sanne S; Vassiliadis, Efstathios; Barascuk, Natasha

    2010-01-01

    During fibrogenesis in the liver, in which excessive remodelling of the extracellular matrix (ECM) occurs, both the quantity of type III collagen (CO3) and levels of matrix metalloproteinases (MMPs), including MMP-9, increase significantly. MMPs play major roles in ECM remodelling, via...... their activity in the proteolytic degradation of extracellular macromolecules such as collagens, resulting in the generation of specific cleavage fragments. These neo-epitopes may be used as markers of fibrosis....

  10. Improvement in transdermal drug delivery performance by graphite oxide/temperature-responsive hydrogel composites with micro heater

    International Nuclear Information System (INIS)

    Yun, Jumi; Lee, Dae Hoon; Im, Ji Sun; Kim, Hyung-Il

    2012-01-01

    Transdermal drug delivery system (TDDS) was prepared with temperature-responsive hydrogel. The graphite was oxidized and incorporated into hydrogel matrix to improve the thermal response of hydrogel. The micro heater was fabricated to control the temperature precisely by adopting a joule heating method. The drug in hydrogel was delivered through a hairless mouse skin by controlling temperature. The efficiency of drug delivery was improved obviously by incorporation of graphite oxide due to the excellent thermal conductivity and the increased interfacial affinity between graphite oxide and hydrogel matrix. The fabricated micro heater was effective in controlling the temperature over lower critical solution temperature of hydrogel precisely with a small voltage less than 1 V. The cell viability test on graphite oxide composite hydrogel showed enough safety for using as a transdermal drug delivery patch. The performance of TDDS could be improved noticeably based on temperature-responsive hydrogel, thermally conductive graphite oxide, and efficient micro heater. - Graphical abstract: The high-performance transdermal drug delivery system could be prepared by combining temperature-responsive hydrogel, thermally conductive graphite oxide with improved interfacial affinity, and efficient micro heater fabricated by a joule heating method. Highlights: ► High performance of transdermal drug delivery system with an easy control of voltage. ► Improved thermal response of hydrogel by graphite oxide incorporation. ► Efficient micro heater fabricated by a joule heating method.

  11. Improvement in transdermal drug delivery performance by graphite oxide/temperature-responsive hydrogel composites with micro heater

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Jumi [Department of Fine Chemical Engineering and Applied Chemistry, BK21-E2M, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Lee, Dae Hoon [Environment Research Division, Korea Institute of Machinery and Materials, 171 Jang-dong, Yusong-gu, Daejeon 305-343 (Korea, Republic of); Im, Ji Sun [Department of Fine Chemical Engineering and Applied Chemistry, BK21-E2M, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Kim, Hyung-Il, E-mail: hikim@cnu.ac.kr [Department of Fine Chemical Engineering and Applied Chemistry, BK21-E2M, Chungnam National University, Daejeon 305-764 (Korea, Republic of)

    2012-08-01

    Transdermal drug delivery system (TDDS) was prepared with temperature-responsive hydrogel. The graphite was oxidized and incorporated into hydrogel matrix to improve the thermal response of hydrogel. The micro heater was fabricated to control the temperature precisely by adopting a joule heating method. The drug in hydrogel was delivered through a hairless mouse skin by controlling temperature. The efficiency of drug delivery was improved obviously by incorporation of graphite oxide due to the excellent thermal conductivity and the increased interfacial affinity between graphite oxide and hydrogel matrix. The fabricated micro heater was effective in controlling the temperature over lower critical solution temperature of hydrogel precisely with a small voltage less than 1 V. The cell viability test on graphite oxide composite hydrogel showed enough safety for using as a transdermal drug delivery patch. The performance of TDDS could be improved noticeably based on temperature-responsive hydrogel, thermally conductive graphite oxide, and efficient micro heater. - Graphical abstract: The high-performance transdermal drug delivery system could be prepared by combining temperature-responsive hydrogel, thermally conductive graphite oxide with improved interfacial affinity, and efficient micro heater fabricated by a joule heating method. Highlights: Black-Right-Pointing-Pointer High performance of transdermal drug delivery system with an easy control of voltage. Black-Right-Pointing-Pointer Improved thermal response of hydrogel by graphite oxide incorporation. Black-Right-Pointing-Pointer Efficient micro heater fabricated by a joule heating method.

  12. On the role of type IX collagen in the extracellular matrix of cartilage: type IX collagen is localized to intersections of collagen fibrils

    OpenAIRE

    1986-01-01

    The tissue distribution of type II and type IX collagen in 17-d-old chicken embryo was studied by immunofluorescence using polyclonal antibodies against type II collagen and a peptic fragment of type IX collagen (HMW), respectively. Both proteins were found only in cartilage where they were co-distributed. They occurred uniformly throughout the extracellular matrix, i.e., without distinction between pericellular, territorial, and interterritorial matrices. Tissues that undergo endochondral bo...

  13. Matrix Metalloproteinase Activity in Infections by an Encephalitic Virus, Mouse Adenovirus Type 1

    Science.gov (United States)

    Ashley, Shanna L.; Pretto, Carla D.; Stier, Matthew T.; Kadiyala, Padma; Castro-Jorge, Luiza; Hsu, Tien-Huei; Doherty, Robert; Carnahan, Kelly E.; Castro, Maria G.; Lowenstein, Pedro R.

    2017-01-01

    ABSTRACT Mouse adenovirus type 1 (MAV-1) infection causes encephalitis in susceptible strains of mice and alters the permeability of infected brains to small molecules, which indicates disruption of the blood-brain barrier (BBB). Under pathological conditions, matrix metalloproteinases (MMPs) can disrupt the BBB through their proteolytic activity on basement membrane and tight junction proteins. We examined whether MAV-1 infection alters MMP activity in vivo and in vitro. Infected MAV-1-susceptible SJL mice had higher MMP2 and MMP9 activity in brains, measured by gelatin zymography, than mock-infected mice. Infected MAV-1-resistant BALB/c mice had MMP activity levels equivalent to those in mock infection. Primary SJL mouse brain endothelial cells (a target of MAV-1 in vivo) infected ex vivo with MAV-1 had no difference in activities of secreted MMP2 and MMP9 from mock cells. We show for the first time that astrocytes and microglia are also infected in vivo by MAV-1. Infected mixed primary cultures of astrocytes and microglia had higher levels of MMP2 and MMP9 activity than mock-infected cells. These results indicate that increased MMP activity in the brains of MAV-1-infected susceptible mice may be due to MMP activity produced by endothelial cells, astrocytes, and microglia, which in turn may contribute to BBB disruption and encephalitis in susceptible mice. IMPORTANCE RNA and DNA viruses can cause encephalitis; in some cases, this is accompanied by MMP-mediated disruption of the BBB. Activated MMPs degrade extracellular matrix and cleave tight-junction proteins and cytokines, modulating their functions. MAV-1 infection of susceptible mice is a tractable small-animal model for encephalitis, and the virus causes disruption of the BBB. We showed that MAV-1 infection increases enzymatic activity of two key MMPs known to be secreted and activated in neuroinflammation, MMP2 and MMP9, in brains of susceptible mice. MAV-1 infects endothelial cells, astrocytes, and

  14. The spatial-temporal characteristics of type I collagen-based extracellular matrix.

    Science.gov (United States)

    Jones, Christopher Allen Rucksack; Liang, Long; Lin, Daniel; Jiao, Yang; Sun, Bo

    2014-11-28

    Type I collagen abounds in mammalian extracellular matrix (ECM) and is crucial to many biophysical processes. While previous studies have mostly focused on bulk averaged properties, here we provide a comprehensive and quantitative spatial-temporal characterization of the microstructure of type I collagen-based ECM as the gelation temperature varies. The structural characteristics including the density and nematic correlation functions are obtained by analyzing confocal images of collagen gels prepared at a wide range of gelation temperatures (from 16 °C to 36 °C). As temperature increases, the gel microstructure varies from a "bundled" network with strong orientational correlation between the fibers to an isotropic homogeneous network with no significant orientational correlation, as manifested by the decaying of length scales in the correlation functions. We develop a kinetic Monte-Carlo collagen growth model to better understand how ECM microstructure depends on various environmental or kinetic factors. We show that the nucleation rate, growth rate, and an effective hydrodynamic alignment of collagen fibers fully determines the spatiotemporal fluctuations of the density and orientational order of collagen gel microstructure. Also the temperature dependence of the growth rate and nucleation rate follow the prediction of classical nucleation theory.

  15. Film forming systems for topical and transdermal drug delivery

    Directory of Open Access Journals (Sweden)

    Kashmira Kathe

    2017-11-01

    Full Text Available Skin is considered as an important route of administration of drugs for both local and systemic effects. The effectiveness of topical therapy depends on the physicochemical properties of the drug and adherence of the patient to the treatment regimen as well as the system's ability to adhere to skin during the therapy so as to promote drug penetration through the skin barrier. Conventional formulations for topical and dermatological administration of drugs have certain limitations like poor adherence to skin, poor permeability and compromised patient compliance. For the treatment of diseases of body tissues and wounds, the drug has to be maintained at the site of treatment for an effective period of time. Topical film forming systems are such developing drug delivery systems meant for topical application to the skin, which adhere to the body, forming a thin transparent film and provide delivery of the active ingredients to the body tissue. These are intended for skin application as emollient or protective and for local action or transdermal penetration of medicament for systemic action. The transparency is an appreciable feature of this polymeric system which greatly influences the patient acceptance. In the current discussion, the film forming systems are described as a promising choice for topical and transdermal drug delivery. Further the various types of film forming systems (sprays/solutions, gels and emulsions along with their evaluation parameters have also been reviewed.

  16. Nanostructured lipid carriers for transdermal delivery of acid labile lansoprazole.

    Science.gov (United States)

    Lin, Wen Jen; Duh, Yi Shein

    2016-11-01

    The aim of this study was to develop nanostructured lipid carriers (NLCs) for transdermal delivery of acid-labile lansoprazole (LPZ). The drug loading, particle size, zeta potential, thermal behavior and stability of NLCs were evaluated. The particle size of NLCs was in the range of 90-210nm and the zeta potential was -61.9 to +3.2mV dependent of the compositions. Stearylamine (SA) prevented lansoprazole degradation and maintained drug stable in NLCs. The anionic sodium dodecyl sulfate (SDS) adsorbed on the lipid surface and formed complex with cationic SA to prevent NLCs aggregation. The effects of type (e.g., isopropyl myristate (IPM), menthol) and concentration (e.g., 1.25, 2.50, 3.75%w/w) of enhancers on penetration of lansoprazole NLC hydrogels were investigated in vitro using Wistar rat skin. The steady-state flux of lansoprazole NLC hydrogel containing 3.75% IPM was the highest which was enhanced by 2.7 folds as compared to enhancer-free NLC hydrogel. In vivo pharmacokinetics of lansoprazole following transdermal delivery of NLC hydrogel showed that the elimination of drug was significantly reduced and the mean residence time of drug was prominently prolonged as compared to intravenous drug solution (p<0.005). The accumulation of drug in the skin and continuous penetration of drug through the skin accounted for the maintenance of drug concentration for at least 24h. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. One-point functions of non-SUSY operators at arbitrary genus in a matrix model for type IIA superstrings

    International Nuclear Information System (INIS)

    Kuroki, Tsunehide; Sugino, Fumihiko

    2017-01-01

    In the previous paper, the authors pointed out correspondence between a supersymmetric double-well matrix model and two-dimensional type IIA superstring theory on a Ramond–Ramond background from the viewpoint of symmetry and spectrum. This was confirmed by agreement between planar correlation functions in the matrix model and tree-level amplitudes in the superstring theory. In order to investigate the correspondence further, in this paper we compute correlation functions to all order of genus expansion in the double scaling limit of the matrix model. One-point functions of operators protected by supersymmetry terminate at some finite order, whereas those of unprotected operators yield non-Borel summable series. The behavior of the latter is characteristic in string perturbation series, providing further evidence that the matrix model describes a string theory. Moreover, instanton corrections to the planar one-point functions are also computed, and universal logarithmic scaling behavior is found for non-supersymmetric operators.

  18. One-point functions of non-SUSY operators at arbitrary genus in a matrix model for type IIA superstrings

    Energy Technology Data Exchange (ETDEWEB)

    Kuroki, Tsunehide, E-mail: kuroki@dg.kagawa-nct.ac.jp [General Eduction, National Institute of Technology, Kagawa College, 551 Kohda, Takuma-cho, Mitoyo, Kagawa 769-1192 (Japan); Sugino, Fumihiko, E-mail: fusugino@gmail.com [Okayama Institute for Quantum Physics, Furugyocho 1-7-36, Naka-ku, Okayama 703-8278 (Japan)

    2017-06-15

    In the previous paper, the authors pointed out correspondence between a supersymmetric double-well matrix model and two-dimensional type IIA superstring theory on a Ramond–Ramond background from the viewpoint of symmetry and spectrum. This was confirmed by agreement between planar correlation functions in the matrix model and tree-level amplitudes in the superstring theory. In order to investigate the correspondence further, in this paper we compute correlation functions to all order of genus expansion in the double scaling limit of the matrix model. One-point functions of operators protected by supersymmetry terminate at some finite order, whereas those of unprotected operators yield non-Borel summable series. The behavior of the latter is characteristic in string perturbation series, providing further evidence that the matrix model describes a string theory. Moreover, instanton corrections to the planar one-point functions are also computed, and universal logarithmic scaling behavior is found for non-supersymmetric operators.

  19. Challenges and opportunities in dermal/transdermal delivery

    Science.gov (United States)

    Paudel, Kalpana S; Milewski, Mikolaj; Swadley, Courtney L; Brogden, Nicole K; Ghosh, Priyanka; Stinchcomb, Audra L

    2010-01-01

    Transdermal drug delivery is an exciting and challenging area. There are numerous transdermal delivery systems currently available on the market. However, the transdermal market still remains limited to a narrow range of drugs. Further advances in transdermal delivery depend on the ability to overcome the challenges faced regarding the permeation and skin irritation of the drug molecules. Emergence of novel techniques for skin permeation enhancement and development of methods to lessen skin irritation would widen the transdermal market for hydrophilic compounds, macromolecules and conventional drugs for new therapeutic indications. As evident from the ongoing clinical trials of a wide variety of drugs for various clinical conditions, there is a great future for transdermal delivery of drugs. PMID:21132122

  20. A commentary on transdermal drug delivery systems in clinical trials.

    Science.gov (United States)

    Watkinson, Adam C

    2013-09-01

    The number of drugs available as marketed transdermal products is limited to those that exhibit the correct physicochemical and pharmacokinetic properties that enable their effective delivery across the skin. In this respect, there are less than 20 drugs that are currently marketed in the US and EU as products that deliver systemic levels of their active ingredients. An analysis of clinical trials conducted in the transdermal sector shows a similar picture with only nine drugs accounting for approximately 80% of all transdermal clinical trials listed on ClinicalTrials.gov. Those drugs for which there are very few transdermal trials listed consist mostly of molecules that are inherently unsuitable for transdermal delivery and serve as a clear warning to drug developers that the science that governs transdermal drug delivery is well reflected by the successes and failures of drugs in development as well as those that make it to the market. Copyright © 2013 Wiley Periodicals, Inc.

  1. Combined role of type IX collagen and cartilage oligomeric matrix protein in cartilage matrix assembly: Cartilage oligomeric matrix protein counteracts type IX collagen-induced limitation of cartilage collagen fibril growth in mouse chondrocyte cultures

    NARCIS (Netherlands)

    Blumbach, K.; Bastiaansen-Jenniskens, Y.M.; Groot, J. de; Paulsson, M.; Osch, G.J.V.M. van; Zaucke, F.

    2009-01-01

    Objective. Defects in the assembly and composition of cartilage extracellular matrix are likely to result in impaired matrix integrity and increased susceptibility to cartilage degeneration. The aim of this study was to determine the functional interaction of the collagen fibril-associated proteins

  2. A Comprehensive Review on: Transdermal drug delivery systems.

    OpenAIRE

    Kharat, Rekha; Bathe, Ritesh Suresh

    2016-01-01

    Transdermal drug delivery system was introduced to overcome the difficulties of drug delivery through oral route. Despite their relatively higher costs, transdermal delivery systems have proved advantageous for delivery of selected drugs, such as estrogens, testosterone, clonidine and nitro-glycerine. Transdermal delivery provides a leading edge over injectable and oral routes by increasing patient compliance and avoiding first pass metabolism respectively. Topical  administration  of  therap...

  3. Membrane-type-3 matrix metalloproteinase (MT3-MMP functions as a matrix composition-dependent effector of melanoma cell invasion.

    Directory of Open Access Journals (Sweden)

    Olga Tatti

    Full Text Available In primary human melanoma, the membrane-type matrix metalloproteinase, MT3-MMP, is overexpressed in the most aggressive nodular-type tumors. Unlike MT1-MMP and MT2-MMP, which promote cell invasion through basement membranes and collagen type I-rich tissues, the function of MT3-MMP in tumor progression remains unclear. Here, we demonstrate that MT3-MMP inhibits MT1-MMP-driven melanoma cell invasion in three-dimensional collagen, while yielding an altered, yet MT1-MMP-dependent, form of expansive growth behavior that phenocopies the formation of nodular cell colonies. In melanoma cell lines originating from advanced primary or metastatic lesions, endogenous MT3-MMP expression was associated with limited collagen-invasive potential. In the cell lines with highest MT3-MMP expression relative to MT1-MMP, collagen-invasive activity was increased following stable MT3-MMP gene silencing. Consistently, MT3-MMP overexpression in cells derived from less advanced superficially spreading melanoma lesions, or in the MT3-MMP knockdown cells, reduced MT1-MMP-dependent collagen invasion. Rather than altering MT1-MMP transcription, MT3-MMP interacted with MT1-MMP in membrane complexes and reduced its cell surface expression. By contrast, as a potent fibrinolytic enzyme, MT3-MMP induced efficient invasion of the cells in fibrin, a provisional matrix component frequently found at tumor-host tissue interfaces and perivascular spaces of melanoma. Since MT3-MMP was significantly upregulated in biopsies of human melanoma metastases, these results identify MT3-MMP as a matrix-dependent modifier of the invasive tumor cell functions during melanoma progression.

  4. Casein gene expression in mouse mammary epithelial cell lines: Dependence upon extracellular matrix and cell type

    International Nuclear Information System (INIS)

    Medina, D.; Oborn, C.J.; Li, M.L.; Bissell, M.J.

    1987-01-01

    The COMMA-D mammary cell line exhibits mammary-specific functional differentiation under appropriate conditions in cell culture. The cytologically heterogeneous COMMA-D parental line and the clonal lines DB-1, TA-5, and FA-1 derived from the COMMA-D parent were examined for similar properties of functional differentiation. In monolayer cell culture, the cell lines DB-1, TA-5, FA-1, and MA-4 were examined for expression of mammary-specific and epithelial-specific proteins by an indirect immunofluorescence assay. The clonal cell lines were relatively homogeneous in their respective staining properties and seemed to represent three subpopulations found in the heterogeneous parental COMMA-D lines. None of the four clonal lines appeared to represent myoepithelial cells. The cell lines were examined for expression of β-casein mRNA in the presence or absence of prolactin. The inducibility of β-casein in the COMMA-D cell line was further enhanced by a reconstituted basement membrane preparation enriched in laminin, collagen IV, and proteoglycans. These results support the hypothesis that the functional response of inducible mammary cell populations is a result of interaction among hormones, multiple extracellular matrix components, and specific cell types

  5. Interaction of glutaric aciduria type 1-related glutaryl-CoA dehydrogenase with mitochondrial matrix proteins.

    Directory of Open Access Journals (Sweden)

    Jessica Schmiesing

    Full Text Available Glutaric aciduria type 1 (GA1 is an inherited neurometabolic disorder caused by mutations in the GCDH gene encoding glutaryl-CoA dehydrogenase (GCDH, which forms homo- and heteromeric complexes in the mitochondrial matrix. GA1 patients are prone to the development of encephalopathic crises which lead to an irreversible disabling dystonic movement disorder. The clinical and biochemical manifestations of GA1 vary considerably and lack correlations to the genotype. Using an affinity chromatography approach we report here for the first time on the identification of mitochondrial proteins interacting directly with GCDH. Among others, dihydrolipoamide S-succinyltransferase (DLST involved in the formation of glutaryl-CoA, and the β-subunit of the electron transfer flavoprotein (ETFB serving as electron acceptor, were identified as GCDH binding partners. We have adapted the yellow fluorescent protein-based fragment complementation assay and visualized the oligomerization of GCDH as well as its direct interaction with DLST and ETFB in mitochondria of living cells. These data suggest that GCDH is a constituent of multimeric mitochondrial dehydrogenase complexes, and the characterization of their interrelated functions may provide new insights into the regulation of lysine oxidation and the pathophysiology of GA1.

  6. Influence of matrix type on tree community assemblages along tropical dry forest edges.

    Science.gov (United States)

    Benítez-Malvido, Julieta; Gallardo-Vásquez, Julio César; Alvarez-Añorve, Mariana Y; Avila-Cabadilla, Luis Daniel

    2014-05-01

    • Anthropogenic habitat edges have strong negative consequences for the functioning of tropical ecosystems. However, edge effects on tropical dry forest tree communities have been barely documented.• In Chamela, Mexico, we investigated the phylogenetic composition and structure of tree assemblages (≥5 cm dbh) along edges abutting different matrices: (1) disturbed vegetation with cattle, (2) pastures with cattle and, (3) pastures without cattle. Additionally, we sampled preserved forest interiors.• All edge types exhibited similar tree density, basal area and diversity to interior forests, but differed in species composition. A nonmetric multidimensional scaling ordination showed that the presence of cattle influenced species composition more strongly than the vegetation structure of the matrix; tree assemblages abutting matrices with cattle had lower scores in the ordination. The phylogenetic composition of tree assemblages followed the same pattern. The principal plant families and genera were associated according to disturbance regimes as follows: pastures and disturbed vegetation (1) with cattle and (2) without cattle, and (3) pastures without cattle and interior forests. All habitats showed random phylogenetic structures, suggesting that tree communities are assembled mainly by stochastic processes. Long-lived species persisting after edge creation could have important implications in the phylogenetic structure of tree assemblages.• Edge creation exerts a stronger influence on TDF vegetation pathways than previously documented, leading to new ecological communities. Phylogenetic analysis may, however, be needed to detect such changes. © 2014 Botanical Society of America, Inc.

  7. Cardiac Fibroblast-Dependent Extracellular Matrix Accumulation Is Associated with Diastolic Stiffness in Type 2 Diabetes

    Science.gov (United States)

    Hutchinson, Kirk R.; Lord, C. Kevin; West, T. Aaron; Stewart, James A.

    2013-01-01

    Cardiovascular complications are a leading cause of death in patients with type 2 diabetes mellitus (T2DM). Diastolic dysfunction is one of the earliest manifestations of diabetes-induced changes in left ventricular (LV) function, and results from a reduced rate of relaxation and increased stiffness. The mechanisms responsible for increased stiffness are not completely understood. Chronic hyperglycemia, advanced glycation endproducts (AGEs), and increased levels of proinflammatory and profibrotic cytokines are molecular pathways known to be involved in regulating extracellular matrix (ECM) synthesis and accumulation resulting in increased LV diastolic stiffness. Experiments were conducted using a genetically-induced mouse model of T2DM generated by a point mutation in the leptin receptor resulting in nonfunctional leptin receptors (db/db murine model). This study correlated changes in LV ECM and stiffness with alterations in basal activation of signaling cascades and expression of profibrotic markers within primary cultures of cardiac fibroblasts from diabetic (db/db) mice with nondiabetic (db/wt) littermates as controls. Primary cultures of cardiac fibrobroblasts were maintained in 25 mM glucose (hyperglycemic-HG; diabetic db/db) media or 5 mM glucose (normoglycemic-NG, nondiabetic db/wt) media. The cells then underwent a 24-hour exposure to their opposite (NG; diabetic db/db) media or 5 mM glucose (HG, nondiabetic db/wt) media. Protein analysis demonstrated significantly increased expression of type I collagen, TIMP-2, TGF-β, PAI-1 and RAGE in diabetic db/db cells as compared to nondiabetic db/wt, independent of glucose media concentration. This pattern of protein expression was associated with increased LV collagen accumulation, myocardial stiffness and LV diastolic dysfunction. Isolated diabetic db/db fibroblasts were phenotypically distinct from nondiabetic db/wt fibroblasts and exhibited a profibrotic phenotype in normoglycemic conditions. PMID:23991045

  8. Multiscale modeling of transdermal drug delivery

    Science.gov (United States)

    Rim, Jee Eun

    2006-04-01

    This study addresses the modeling of transdermal diffusion of drugs, to better understand the permeation of molecules through the skin, and especially the stratum corneum, which forms the main permeation barrier of the skin. In transdermal delivery of systemic drugs, the drugs diffuse from a patch placed on the skin through the epidermis to the underlying blood vessels. The epidermis is the outermost layer of the skin and can be further divided into the stratum corneum (SC) and the viable epidermis layers. The SC consists of keratinous cells (corneocytes) embedded in the lipid multi-bilayers of the intercellular space. It is widely accepted that the barrier properties of the skin mostly arises from the ordered structure of the lipid bilayers. The diffusion path, at least for lipophilic molecules, seems to be mainly through the lipid bilayers. Despite the advantages of transdermal drug delivery compared to other drug delivery routes such as oral dosing and injections, the low percutaneous permeability of most compounds is a major difficulty in the wide application of transdermal drug delivery. In fact, many transdermal drug formulations include one or more permeation enhancers that increase the permeation of the drug significantly. During the last two decades, many researchers have studied percutaneous absorption of drugs both experimentally and theoretically. However, many are based on pharmacokinetic compartmental models, in which steady or pseudo-steady state conditions are assumed, with constant diffusivity and partitioning for single component systems. This study presents a framework for studying the multi-component diffusion of drugs coupled with enhancers through the skin by considering the microstructure of the stratum corneum (SC). A multiscale framework of modeling the transdermal diffusion of molecules is presented, by first calculating the microscopic diffusion coefficient in the lipid bilayers of the SC using molecular dynamics (MD). Then a

  9. Downregulation of membrane type-matrix metalloproteinases in the inflamed or injured central nervous system

    Directory of Open Access Journals (Sweden)

    Millward Jason M

    2007-09-01

    Full Text Available Abstract Background Matrix metalloproteinases (MMPs are thought to mediate cellular infiltration in central nervous system (CNS inflammation by cleaving extracellular matrix proteins associated with the blood-brain barrier. The family of MMPs includes 23 proteinases, including six membrane type-MMPs (MT-MMPs. Leukocyte infiltration is an integral part of the pathogenesis of autoimmune inflammation in the CNS, as occurs in multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE, as well as in the response to brain trauma and injury. We have previously shown that gene expression of the majority of MMPs was upregulated in the spinal cord of SJL mice with severe EAE induced by adoptive transfer of myelin basic protein-reactive T cells, whereas four of the six MT-MMPs (MMP-15, 16, 17 and 24 were downregulated. The two remaining MT-MMPs (MMP-14 and 25 were upregulated in whole tissue. Methods We used in vivo models of CNS inflammation and injury to study expression of MT-MMP and cytokine mRNA by real-time RT-PCR. Expression was also assessed in microglia sorted from CNS by flow cytometry, and in primary microglia cultures following treatment with IFNγ. Results We now confirm the expression pattern of MT-MMPs in the B6 mouse, independent of effects of adjuvant. We further show expression of all the MT-MMPs, except MMP-24, in microglia. Microglia isolated from mice with severe EAE showed statistically significant downregulation of MMP-15, 17 and 25 and lack of increase in levels of other MT-MMPs. Downregulation of MT-MMPs was also apparent following CNS injury. The pattern of regulation of MT-MMPs in neuroinflammation showed no association with expression of the proinflammatory cytokines TNFα, IL-1β, or IFNγ. Conclusion CNS inflammation and injury leads to downregulation in expression of the majority of MT-MMPs. Microglia in EAE showed a general downregulation of MT-MMPs, and our findings suggest that MT-MMP levels may

  10. Formulation, characterization and clinical evaluation of propranolol hydrochloride gel for transdermal treatment of superficial infantile hemangioma.

    Science.gov (United States)

    Zhou, Wenhu; He, Shiying; Yang, Yijun; Jian, Dan; Chen, Xiang; Ding, Jinsong

    2015-01-01

    The objective of the present study is to formulate and characterize propranolol hydrochloride (PPL · HCl) gel, and to evaluate the efficacy of this formulation in transdermal treatment for superficial infantile hemangioma (IH). The transdermal PPL · HCl gel was prepared by a direct swelling method, which chose hydroxypropyl methylcellulose (HPMC) as the matrix and used terpenes plus alcohols as permeation enhancer. Permeation studies of PPL · HCl were carried out with modified Franz diffusion cells through piglet skin. Our results pointed to that among all studied permeation enhancers, farnesol plus isopropanol was the most effective combination (Q24, 6027.4 ± 563.1 μg/cm(2), ER, 6.8), which was significantly higher than that of control gel (p homemade PPL · HCl oral solution as a control. Clinical studies also confirmed the excellent therapeutic response and few side effects of the PPL · HCl gel. These results suggest that transdermal application of the PPL · HCl gel is an effective and safe formulation in treating superficial IH.

  11. Carbon nanotubes buckypapers for potential transdermal drug delivery

    International Nuclear Information System (INIS)

    Schwengber, Alex; Prado, Héctor J.; Zilli, Darío A.; Bonelli, Pablo R.

    2015-01-01

    Drug loaded buckypapers based on different types of carbon nanotubes (CNTs) were prepared and characterized in order to evaluate their potentialities for the design of novel transdermal drug delivery systems. Lab-synthesized CNTs as well as commercial samples were employed. Clonidine hydrochloride was used as model drug, and the influence of composition of the drug loaded buckypapers and processing variables on in vitro release profiles was investigated. To examine the influence of the drug nature the evaluation was further extended to buckypapers prepared with flurbiprofen and one type of CNTs, their selection being based on the results obtained with the former drug. Scanning electronic microscopy images indicated that the model drugs were finely dispersed on the CNTs. Differential scanning calorimetry, and X-ray diffraction pointed to an amorphous state of both drugs in the buckypapers. A higher degree of CNT–drug superficial interactions resulted in a slower release of the drug. These interactions were in turn affected by the type of CNTs employed (single wall or multiwall CNTs), their functionalization with hydroxyl or carboxyl groups, the chemical structure of the drug, and the CNT:drug mass ratio. Furthermore, the application of a second layer of drug free CNTs on the loaded buckypaper, led to decelerate the drug release and to reduce the burst effect. - Highlights: • Drug loaded buckypapers from carbon nanotubes were prepared and characterized. • Their potentialities for transdermal drug delivery applications were evaluated. • Characteristics of carbon nanotubes and the structure of the drug affected release • A higher carbon nanotube:drug mass ratio decelerated release • Up to one week controlled release profiles were obtained for the drug flurbiprofen

  12. Carbon nanotubes buckypapers for potential transdermal drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Schwengber, Alex [PINMATE-Departamento de Industrias, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, C1428EGA Buenos Aires (Argentina); Prado, Héctor J. [PINMATE-Departamento de Industrias, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, C1428EGA Buenos Aires (Argentina); Cátedra de Tecnología Farmacéutica II, Departamento de Tecnología Farmacéutica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, C1113AAD Buenos Aires (Argentina); Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Av. Rivadavia 1917, C1033AAJ Buenos Aires (Argentina); Zilli, Darío A. [PINMATE-Departamento de Industrias, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, C1428EGA Buenos Aires (Argentina); Bonelli, Pablo R. [PINMATE-Departamento de Industrias, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, C1428EGA Buenos Aires (Argentina); Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Av. Rivadavia 1917, C1033AAJ Buenos Aires (Argentina); and others

    2015-12-01

    Drug loaded buckypapers based on different types of carbon nanotubes (CNTs) were prepared and characterized in order to evaluate their potentialities for the design of novel transdermal drug delivery systems. Lab-synthesized CNTs as well as commercial samples were employed. Clonidine hydrochloride was used as model drug, and the influence of composition of the drug loaded buckypapers and processing variables on in vitro release profiles was investigated. To examine the influence of the drug nature the evaluation was further extended to buckypapers prepared with flurbiprofen and one type of CNTs, their selection being based on the results obtained with the former drug. Scanning electronic microscopy images indicated that the model drugs were finely dispersed on the CNTs. Differential scanning calorimetry, and X-ray diffraction pointed to an amorphous state of both drugs in the buckypapers. A higher degree of CNT–drug superficial interactions resulted in a slower release of the drug. These interactions were in turn affected by the type of CNTs employed (single wall or multiwall CNTs), their functionalization with hydroxyl or carboxyl groups, the chemical structure of the drug, and the CNT:drug mass ratio. Furthermore, the application of a second layer of drug free CNTs on the loaded buckypaper, led to decelerate the drug release and to reduce the burst effect. - Highlights: • Drug loaded buckypapers from carbon nanotubes were prepared and characterized. • Their potentialities for transdermal drug delivery applications were evaluated. • Characteristics of carbon nanotubes and the structure of the drug affected release • A higher carbon nanotube:drug mass ratio decelerated release • Up to one week controlled release profiles were obtained for the drug flurbiprofen.

  13. Transdermal drug delivery: approaches and significance

    OpenAIRE

    Murthy, SATHYANARAYANA

    2012-01-01

    S Narasimha MurthyDepartment of Pharmaceutics, The University of Mississippi, USATransdermal drug delivery systems deliver drugs through the skin as an alternative to oral, intravascular, subcutaneous, and transmucosal routes. Potential advantages of transdermal delivery include, but are not limited to, elimination of first-pass metabolism, steady delivery/blood levels, better patient compliance, reduced systemic drug interactions, possible dose intervention, avoidance of medically assisted d...

  14. Regulation of Membrane-Type 4 Matrix Metalloproteinase by SLUG Contributes to Hypoxia-Mediated Metastasis

    Directory of Open Access Journals (Sweden)

    Chi-Hung Huang

    2009-12-01

    Full Text Available The hypoxic tumor environment has been shown to be critical to cancer metastasis through the promotion of angiogenesis, induction of epithelial-mesenchymal transition (EMT, and acquisition of invasive potential. However, the impact of hypoxia on the expression profile of the proteolytic enzymes involved in invasiveness is relatively unknown. Membrane-type 4 matrix metalloproteinase (MT4-MMP is a glycosyl-phosphatidyl inositol-anchored protease that has been shown to be overexpressed in human cancers. However, detailed mechanisms regarding the regulation and function of MT4-MMP expression in tumor cells remain unknown. Here, we demonstrate that hypoxia or overexpression of hypoxia-inducible factor-1α (HIF-1α induced MT4-MMP expression in human cancer cells. Activation of SLUG, a transcriptional factor regulating the EMT process of human cancers, by HIF-1α was critical for the induction of MT4-MMP under hypoxia. SLUG regulated the transcription of MT4-MMP through direct binding to the E-box located in its proximal promoter. Short-interference RNA-mediated knockdown of MT4-MMP attenuated in vitro invasiveness and in vivo pulmonary colonization of tumor cells without affecting cell migratory ability. MT4-MMP promoted invasiveness and pulmonary colonization through modulation of the expression profile of MMPs and angiogenic factors. Finally, coexpression of HIF-1α and MT4-MMP in human head and neck cancer was predictive of a worse clinical outcome. These findings establish a novel signaling pathway for hypoxia-mediated metastasis and elucidate the underlying regulatory mechanism and functional significance of MT4-MMP in cancer metastasis.

  15. Formulation and evaluation of a novel matrix-type orally disintegrating Ibuprofen tablet.

    Science.gov (United States)

    Tayebi, Hoda; Mortazavi, Seyed Alireza

    2011-01-01

    Orally disintegrating tablets (ODTs) are capable of turning quickly into a liquid dosage form in contact with the saliva, thus possessing the advantages of both the solid dosage forms particularly stability and liquid dosage forms specially ease of swallowing and pre-gastric absorption of drug. The aim of this study was to prepare a novel matrix-type buccal fast disintegrating ibuprofen tablet formulation using special polymers, water soluble excipients, super-disintegrants and quickly soluble granules. For this purpose different tablet formulations of ibuprofen were prepared. The amount of ibuprofen in each formulation was 100 mg. Eight groups of formulation were prepared (A-H series), accounting for a total number of 45 formulations. Formulations prepared were examined in terms of different physicochemical tests including powder/granule flowability, appearance, thickness, uniformity of weight, hardness, friability and disintegration time. Results of formulation F22a (in series F), was found to be acceptable, making it the chosen formulation for further studies. Then, by adding various flavorants and sweeteners to this formulation, complementary series of formulations, named G and H, were prepared. Following the comparison of their taste with each other through asking 10 volunteers, the most suitable formulation regarding the taste, being formulation F22s, was chosen as the ultimate formulation. This formulation had PVP, ibuprofen and croscarmellose as the intra-granular components and xylitol and saccharin as the extra-granular ingredients. Formulation F22s was found to be acceptable in terms of physicochemical tests conducted, showing quick disintegration within the buccal cavity, appropriate hardness and rather low friability. Hence formulation F22s was selected as the final formulation.

  16. Development and evaluation of accelerated drug release testing methods for a matrix-type intravaginal ring.

    Science.gov (United States)

    Externbrink, Anna; Eggenreich, Karin; Eder, Simone; Mohr, Stefan; Nickisch, Klaus; Klein, Sandra

    2017-01-01

    Accelerated drug release testing is a valuable quality control tool for long-acting non-oral extended release formulations. Currently, several intravaginal ring candidates designed for the long-term delivery of steroids or anti-infective drugs are being in the developing pipeline. The present article addresses the demand for accelerated drug release methods for these formulations. We describe the development and evaluation of accelerated release methods for a steroid releasing matrix-type intravaginal ring. The drug release properties of the formulation were evaluated under real-time and accelerated test conditions. Under real-time test conditions drug release from the intravaginal ring was strongly affected by the steroid solubility in the release medium. Under sufficient sink conditions that were provided in release media containing surfactants drug release was Fickian diffusion driven. Both temperature and hydro-organic dissolution media were successfully employed to accelerate drug release from the formulation. Drug release could be further increased by combining the temperature effect with the application of a hydro-organic release medium. The formulation continued to exhibit a diffusion controlled release kinetic under the investigated accelerated conditions. Moreover, the accelerated methods were able to differentiate between different prototypes of the intravaginal ring that exhibited different release profiles under real-time test conditions. Overall, the results of the present study indicate that both temperature and hydro-organic release media are valid parameters for accelerating drug release from the intravaginal ring. Variation of either a single or both parameters yielded release profiles that correlated well with real-time release. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Fibulin-1 is a marker for arterial extracellular matrix alterations in type 2 diabetes

    DEFF Research Database (Denmark)

    Cangemi, Claudia; Skov, Vibe; Poulsen, Michael Kjaer

    2011-01-01

    Extracellular matrix alterations are important elements in the arterial changes seen in diabetes, being associated with increased vascular stiffness and the development of cardiovascular diseases. However, no biomarkers for diabetes-related arterial changes have been defined.......Extracellular matrix alterations are important elements in the arterial changes seen in diabetes, being associated with increased vascular stiffness and the development of cardiovascular diseases. However, no biomarkers for diabetes-related arterial changes have been defined....

  18. Effects of vehicles and enhancers on transdermal delivery of clebopride.

    Science.gov (United States)

    Rhee, Yun-Seok; Huh, Jai-Yong; Park, Chun-Woong; Nam, Tae-Young; Yoon, Koog-Ryul; Chi, Sang-Cheol; Park, Eun-Seok

    2007-09-01

    The effects of vehicles and penetration enhancers on the skin permeation of clebopride were evaluated using Franz type diffusion cells fitted with excised rat dorsal skins. The binary vehicle system, diethylene glycol monoethyl ether/isopropyl myristate (40/60, w/w), significantly enhanced the skin permeation rate of clebopride. The skin permeation enhancers, oleic acid and ethanol when used in the binary vehicle system, resulted in relatively high clebopride skin permeation rates. A gel formulation consisting of 1.5% (w/w) clebopride, 5% (w/w) oleic acid, and 7% (w/w) gelling agent with the binary vehicle system resulted in a permeation rate of 28.90 microg/cm2/h. Overall, these results highlight the potential of clebopride formulation for the transdermal route.

  19. Associations between advanced glycation endproducts and matrix metalloproteinases and its inhibitor in individuals with type 1 diabetes

    DEFF Research Database (Denmark)

    Peeters, S A; Engelen, L; Buijs, J

    2018-01-01

    the production of MMPs and/or TIMP-1. Therefore, we investigated associations between specific AGEs and MMP-1, -2, -3, -9, and -10, and TIMP-1 in individuals with type 1 diabetes. METHODS: In 670 type 1 diabetic individuals we determined serum levels of protein-bound AGEs Nε-(carboxymethyl)lysine (CML), Nε-(carboxyethyl)lysine......AIMS: Advanced glycation endproducts (AGEs) and altered extracellular matrix remodeling by matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP) are associated with vascular complications in type 1 diabetes. Experimental studies have shown that AGEs regulate...... (CEL), 5-hydro-5-methylimidazolone (MG-H1) and pentosidine, and MMP-1, -2, -3, -9, and -10, and TIMP-1. We performed linear regression analyses to investigate associations between AGEs and markers of the MMP-TIMP system. Analyses were adjusted for age, sex, HbA1c and duration of diabetes...

  20. THE EFFECT OF TYPE ZEOLITE ON THE GAS TRANSPORT PROPERTIES OF POLYIMIDE-BASED MIXED MATRIX MEMBRANES

    Directory of Open Access Journals (Sweden)

    Tutuk Djoko Kusworo

    2012-01-01

    Full Text Available The permeation rates of O2, N2, CO2 and CH4 has been studied for polyimide-polyethersulfone (PI/PES blends-zeolite mixed matrix membranes synthesized in our laboratory. The study investigated the effect of zeolite loading and different zeolite type on the gas separation performance of these mixed matrix membranes. Frequency shifts and absorption intensity changes in the FTIR spectra of the PI/PES blends as compared with those of the pure polymers indicate that there is a mixing of polymer blends at the molecular level. Differential scanning calorimetry measurements of pure and PI/PES blends membranes have showed one unique glass transition temperature that supports the miscible character of the PI/PES mixture. The PI/PES-zeolite 4A mixed matrix membrane with 25 wt % zeolite loading produced the highest O2/N2 and CO2/CH4 selectivity of around 7.45 and 46.05, respectively.

  1. A Three-Phase Dual-Input Matrix Converter for Grid Integration of Two AC Type Energy Resources

    DEFF Research Database (Denmark)

    Liu, Xiong; Wang, Peng; Chiang Loh, Poh

    2013-01-01

    This paper proposes a novel dual-input matrix converter (DIMC) to integrate two three-phase ac type energy resources to a power grid. The proposed matrix converter is developed based on the traditional indirect matrix converter under reverse power flow operation mode, but with its six......-to-output voltage boost capability since power flows from the converter’s voltage source side to its current source side. Commanded currents can be extracted from the two input sources to the grid. The proposed control and modulation schemes guarantee sinusoidal input and output waveforms as well as unity input......-switch voltage source converter replaced by a nine-switch configuration. With the additional three switches, the proposed DIMC can provide six in put terminals, which make it possible to integrate two independent ac sources into a single grid-tied power electronics interface. The proposed converter has input...

  2. Matrix Degradation in Human Immunodeficiency Virus Type 1-Associated Tuberculosis and Tuberculosis Immune Reconstitution Inflammatory Syndrome: A Prospective Observational Study.

    Science.gov (United States)

    Walker, Naomi F; Wilkinson, Katalin A; Meintjes, Graeme; Tezera, Liku B; Goliath, Rene; Peyper, Janique M; Tadokera, Rebecca; Opondo, Charles; Coussens, Anna K; Wilkinson, Robert J; Friedland, Jon S; Elkington, Paul T

    2017-07-01

    Extensive immunopathology occurs in human immunodeficiency virus (HIV)/tuberculosis (TB) coinfection, but the underlying molecular mechanisms are not well-defined. Excessive matrix metalloproteinase (MMP) activity is emerging as a key process but has not been systematically studied in HIV-associated TB. We performed a cross-sectional study of matrix turnover in HIV type 1 (HIV-1)-infected and -uninfected TB patients and controls, and a prospective cohort study of HIV-1-infected TB patients at risk of TB immune reconstitution inflammatory syndrome (TB-IRIS), in Cape Town, South Africa. Sputum and plasma MMP concentrations were quantified by Luminex, plasma procollagen III N-terminal propeptide (PIIINP) by enzyme-linked immunosorbent assay, and urinary lipoarabinomannan (LAM) by Alere Determine TB LAM assay. Peripheral blood mononuclear cells from healthy donors were cultured with Mycobacterium tuberculosis and extracellular matrix in a 3D model of TB granuloma formation. MMP activity differed between HIV-1-infected and -uninfected TB patients and corresponded with specific TB clinical phenotypes. HIV-1-infected TB patients had reduced pulmonary MMP concentrations, associated with reduced cavitation, but increased plasma PIIINP, compared to HIV-1-uninfected TB patients. Elevated extrapulmonary extracellular matrix turnover was associated with TB-IRIS, both before and during TB-IRIS onset. The predominant collagenase was MMP-8, which was likely neutrophil derived and M. tuberculosis-antigen driven. Mycobacterium tuberculosis-induced matrix degradation was suppressed by the MMP inhibitor doxycycline in vitro. MMP activity in TB differs by HIV-1 status and compartment, and releases matrix degradation products. Matrix turnover in HIV-1-infected patients is increased before and during TB-IRIS, informing novel diagnostic strategies. MMP inhibition is a potential host-directed therapy strategy for prevention and treatment of TB-IRIS. © The Author 2017. Published by Oxford

  3. Current advances in the fabrication of microneedles for transdermal delivery

    NARCIS (Netherlands)

    Indermun, S.; Luttge, R.; Choonara, Y.E.; Kumar, Pradeep; Toit, Du L.C.; Modi, G.; Pillay, V.

    2014-01-01

    The transdermal route is an excellent site for drug delivery due to the avoidance of gastric degradation and hepatic metabolism, in addition to easy accessibility. Although offering numerous attractive advantages, many available transdermal systems are not able to deliver drugs and other compounds

  4. TRANSDERMAL DRUG DELIVERY AND METHODS TO ENHANCE IT

    Directory of Open Access Journals (Sweden)

    E. G. Kuznetsova

    2016-01-01

    Full Text Available The paper presents the common methods employed in recent years for enhancing transdermal delivery of drug substances when applying transdermal therapeutic delivery systems. The chemical, physical and mechanical methods to enhance the transport of macromolecular compounds through the skin are considered in details. 

  5. Nanoethosomes for transdermal delivery of tropisetron HCl: multi-factorial predictive modeling, characterization, and ex vivo skin permeation.

    Science.gov (United States)

    Abdel Messih, Hanaa A; Ishak, Rania A H; Geneidi, Ahmed S; Mansour, Samar

    2017-06-01

    The aim of the present work is to exclusively optimize and model the effect of phospholipid type either egg phosphatidylcholine (EPC) or soybean phosphatidylcholine (SPC), together with other formulation variables, on the development of nano-ethosomal systems for transdermal delivery of a water-soluble antiemetic drug. Tropisetron HCl (TRO) is available as hard gelatin capsules and IV injections. The transdermal delivery of TRO is considered as a novel alternative route supposing to improve BAV as well as patient convenience. TRO-loaded ethanolic vesicular systems were prepared by hot technique. The effect of formulation variables were optimized through a response surface methodology using 3 × 2 2 -level full factorial design. The concentrations of both PC (A) and ethanol (B) and PC type (C) were the factors, while entrapment efficiency (Y 1 ), vesicle size (Y 2 ), polydispersity index (Y 3 ), and zeta potential (Y 4 ) were the responses. The drug permeation across rat skin from selected formulae was studied. Particle morphology, drug-excipient interactions, and vesicle stability were also investigated. The results proved the critical role of all formulation variables on ethosomal characteristics. The suggested models for all responses showed good predictability. Only the concentration of phospholipid, irrespective to PC type, had a significant effect on the transdermal flux (p transdermal TRO delivery.

  6. Disruption of fibronectin matrix affects type IV collagen, fibrillin and laminin deposition into extracellular matrix of human trabecular meshwork (HTM) cells.

    Science.gov (United States)

    Filla, Mark S; Dimeo, Kaylee D; Tong, Tiegang; Peters, Donna M

    2017-12-01

    Fibronectin fibrils are a major component of the extracellular matrix (ECM) of the trabecular meshwork (TM). They are a key mediator of the formation of the ECM which controls aqueous humor outflow and contributes to the pathogenesis of glaucoma. The purpose of this work was to determine if a fibronectin-binding peptide called FUD, derived from the Streptococcus pyogenes Functional Upstream Domain of the F1 adhesin protein, could be used to control fibronectin fibrillogenesis and hence ECM formation under conditions where its expression was induced by treatment with the glucocorticoid dexamethasone. FUD was very effective at preventing fibronectin fibrillogenesis in the presence or absence of steroid treatment as well as the removal of existing fibronectin fibrils. Disruption of fibronectin fibrillogenesis by FUD also disrupted the incorporation of type IV collagen, laminin and fibrillin into the ECM. The effect of FUD on these other protein matrices, however, was found to be dependent upon the maturity of the ECM when FUD was added. FUD effectively disrupted the incorporation of these other proteins into matrices when added to newly confluent cells that were forming a nascent ECM. In contrast, FUD had no effect on these other protein matrices if the cell cultures already possessed a pre-formed, mature ECM. Our studies indicate that FUD can be used to control fibronectin fibrillogenesis and that these fibrils play a role in regulating the assembly of other ECM protein into matrices involving type IV collagen, laminin, and fibrillin within the TM. This suggests that under in vivo conditions, FUD would selectively disrupt fibronectin fibrils and de novo assembly of other proteins into the ECM. Finally, our studies suggest that targeting fibronectin fibril assembly may be a viable treatment for POAG as well as other glaucomas involving excessive or abnormal matrix deposition of the ECM. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Effect of landscape matrix type on nesting ecology of the Northern Cardinal

    Science.gov (United States)

    R.A. Sargent; J.C. Kilgo; B.R. Chapman; K.V. Miller

    2015-01-01

    Spatial distribution of forests relative to other habitats in a landscape may influence nest success of songbirds. For example, nest predation in mature forests increases as the percentage of clear-cut land in the surrounding matrix increases (Yahner and Scott 1988). Blake and Karr (1987) noted that birds breeding in forest fragments may incorporate adjacent habitats,...

  8. One-point functions of non-SUSY operators at arbitrary genus in a matrix model for type IIA superstrings

    Directory of Open Access Journals (Sweden)

    Tsunehide Kuroki

    2017-06-01

    Full Text Available In the previous paper, the authors pointed out correspondence between a supersymmetric double-well matrix model and two-dimensional type IIA superstring theory on a Ramond–Ramond background from the viewpoint of symmetry and spectrum. This was confirmed by agreement between planar correlation functions in the matrix model and tree-level amplitudes in the superstring theory. In order to investigate the correspondence further, in this paper we compute correlation functions to all order of genus expansion in the double scaling limit of the matrix model. One-point functions of operators protected by supersymmetry terminate at some finite order, whereas those of unprotected operators yield non-Borel summable series. The behavior of the latter is characteristic in string perturbation series, providing further evidence that the matrix model describes a string theory. Moreover, instanton corrections to the planar one-point functions are also computed, and universal logarithmic scaling behavior is found for non-supersymmetric operators.

  9. A Human Nuclear Shuttling Protein That Interacts with Human Immunodeficiency Virus Type 1 Matrix Is Packaged into Virions

    Science.gov (United States)

    Gupta, Kalpana; Ott, David; Hope, Thomas J.; Siliciano, Robert F.; Boeke, Jef D.

    2000-01-01

    Active nuclear import of the human immunodeficiency virus type 1 (HIV-1) preintegration complex (PIC) is essential for the productive infection of nondividing cells. Nuclear import of the PIC is mediated by the HIV-1 matrix protein, which also plays several critical roles during viral entry and possibly during virion production facilitating the export of Pr55Gag and genomic RNA. Using a yeast two-hybrid screen, we identified a novel human virion-associated matrix-interacting protein (VAN) that is highly conserved in vertebrates and expressed in most human tissues. Its expression is upregulated upon activation of CD4+ T cells. VAN is efficiently incorporated into HIV-1 virions and, like matrix, shuttles between the nucleus and cytoplasm. Furthermore, overexpression of VAN significantly inhibits HIV-1 replication in tissue culture. We propose that VAN regulates matrix nuclear localization and, by extension, both nuclear import of the PIC and export of Pr55Gag and viral genomic RNA during virion production. Our data suggest that this regulatory mechanism reflects a more global process for regulation of nucleocytoplasmic transport. PMID:11090181

  10. A Fast Newton-Shamanskii Iteration for a Matrix Equation Arising from M/G/1-Type Markov Chains

    Directory of Open Access Journals (Sweden)

    Pei-Chang Guo

    2017-01-01

    Full Text Available For the nonlinear matrix equations arising in the analysis of M/G/1-type and GI/M/1-type Markov chains, the minimal nonnegative solution G or R can be found by Newton-like methods. We prove monotone convergence results for the Newton-Shamanskii iteration for this class of equations. Starting with zero initial guess or some other suitable initial guess, the Newton-Shamanskii iteration provides a monotonically increasing sequence of nonnegative matrices converging to the minimal nonnegative solution. A Schur decomposition method is used to accelerate the Newton-Shamanskii iteration. Numerical examples illustrate the effectiveness of the Newton-Shamanskii iteration.

  11. 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.

  12. Generalized canonical formalism and the S-matrix of theories with constraints of the general type

    International Nuclear Information System (INIS)

    Fradkina, T.Ye.

    1987-01-01

    A canonical quantization method is given for systems with first and second class constraints of arbitrary rank. The effectiveness of the method is demonstrated using sample Yang-Mills and gravitational fields. A correct expression is derived for the S-matrix of theories that are momentum-quadratic within the scope of canonical gauges, including ghost fields. Generalized quantization is performed and the S-matrix is derived in configurational space for theories of relativistic membranes representing a generalization of theories of strings to the case of an extended spatial implementation. It is demonstrated that the theory of membranes in n+l-dimensional space is a system with rank-n constraints

  13. Transdermal delivery of paeonol using cubic gel and microemulsion gel

    Science.gov (United States)

    Luo, Maofu; Shen, Qi; Chen, Jinjin

    2011-01-01

    Background The aim of this study was to develop new systems for transdermal delivery of paeonol, in particular microemulsion gel and cubic gel formulations. Methods Various microemulsion vehicles were prepared using isopropyl myristate as an oil phase, polyoxyethylated castor oil (Cremophor® EL) as a surfactant, and polyethylene glycol 400 as a cosurfactant. In the optimum microemulsion gel formulation, carbomer 940 was selected as the gel matrix, and consisted of 1% paeonol, 4% isopropyl myristate, 28% Cremophor EL/polyethylene glycol 400 (1:1), and 67% water. The cubic gel was prepared containing 3% paeonol, 30% water, and 67% glyceryl monooleate. Results A skin permeability test using excised rat skins indicated that both the cubic gel and microemulsion gel formulations had higher permeability than did the paeonol solution. An in vivo pharmacokinetic study done in rats showed that the relative bioavailability of the cubic gel and microemulsion gel was enhanced by about 1.51-fold and 1.28-fold, respectively, compared with orally administered paeonol suspension. Conclusion Both the cubic gel and microemulsion gel formulations are promising delivery systems to enhance the skin permeability of paeonol, in particular the cubic gel. PMID:21904450

  14. Three-dimensional structure of the human immunodeficiency virus type 1 matrix protein.

    Science.gov (United States)

    Massiah, M A; Starich, M R; Paschall, C; Summers, M F; Christensen, A M; Sundquist, W I

    1994-11-25

    The HIV-1 matrix protein forms an icosahedral shell associated with the inner membrane of the mature virus. Genetic analyses have indicated that the protein performs important functions throughout the viral life-cycle, including anchoring the transmembrane envelope protein on the surface of the virus, assisting in viral penetration, transporting the proviral integration complex across the nuclear envelope, and localizing the assembling virion to the cell membrane. We now report the three-dimensional structure of recombinant HIV-1 matrix protein, determined at high resolution by nuclear magnetic resonance (NMR) methods. The HIV-1 matrix protein is the first retroviral matrix protein to be characterized structurally and only the fourth HIV-1 protein of known structure. NMR signal assignments required recently developed triple-resonance (1H, 13C, 15N) NMR methodologies because signals for 91% of 132 assigned H alpha protons and 74% of the 129 assignable backbone amide protons resonate within chemical shift ranges of 0.8 p.p.m. and 1 p.p.m., respectively. A total of 636 nuclear Overhauser effect-derived distance restraints were employed for distance geometry-based structure calculations, affording an average of 13.0 NMR-derived distance restraints per residue for the experimentally constrained amino acids. An ensemble of 25 refined distance geometry structures with penalties (sum of the squares of the distance violations) of 0.32 A2 or less and individual distance violations under 0.06 A was generated; best-fit superposition of ordered backbone heavy atoms relative to mean atom positions afforded root-mean-square deviations of 0.50 (+/- 0.08) A. The folded HIV-1 matrix protein structure is composed of five alpha-helices, a short 3(10) helical stretch, and a three-strand mixed beta-sheet. Helices I to III and the 3(10) helix pack about a central helix (IV) to form a compact globular domain that is capped by the beta-sheet. The C-terminal helix (helix V) projects away

  15. Pre design processing of waste of ex-resin without materials matrix from nuclear power plant type PWR 1000 MW

    International Nuclear Information System (INIS)

    Cerdas Tarigan

    2010-01-01

    Have been done pre design processing of waste ex-resin without capacities matrix materials from nuclear power plant type PWR 1000 MW During the time radioactive waste of ex-resin processed to use process of immobilization use matrix materials like mixture cement and epoxy resin and then conditioning. This process is not effective and efficient because end result volume of end product bigger than volume early operation system and maintenance of its installation more difficult. To overcome this created a design of technology processing of waste of ex- resin without matrix materials through process of strainer, drying and conditioning represent technological innovation newly processing of radioactive waste of ex-resin. Besides this process more effective and efficient, volume of end product waste much more small from volume early and operation system and maintenance of its easier installation. Pre design is expected to be used as a basis to make conceptual of pre design installation of strainer, drying and conditioning for the processing of waste of ex-resin from nuclear power plant type PWR 1000 MW. (author)

  16. System of matrix metalloproteinases and cytokine secretion in type 2 diabetes mellitus and impaired carbohydrate tolerance associated with arterial hypertension.

    Science.gov (United States)

    Kologrivova, I V; Suslova, T E; Koshel'skaya, O A; Vinnitskaya, I V; Trubacheva, O A

    2014-03-01

    The study included patients with type 2 diabetes mellitus and impaired carbohydrate tolerance associated with arterial hypertension, patients with arterial hypertension, and healthy volunteers. We evaluated the levels of matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), tissue inhibitor of metalloproteinase type 1 (TIMP-1), glucose, insulin, C-peptide, glycated hemoglobin, and spontaneous and mitogen-activated cytokine secretion (IL-2, IL4, IL-6, IL-10, IL-17, TNF-α, and IFN-γ). Patients with type 2 diabetes mellitus in combination with arterial hypertension exhibited maximum TIMP-1 levels and TIMP-1/MMP-2, TIMP-1/ MMP-9 ratios as well as enhanced secretion of TNF-α, IL-6, IL-17 and reduced secretion of IL-10 in comparison with healthy individuals. The observed shifts are probably determined the development of systemic hyperinsulinemia in patients suffering from type 2 diabetes mellitus coupled with arterial hypertension.

  17. Low‑dose halofuginone inhibits the synthesis of type I collagen without influencing type II collagen in the extracellular matrix of chondrocytes.

    Science.gov (United States)

    Li, Zeng; Fei, Hao; Wang, Zhen; Zhu, Tianyi

    2017-09-01

    Full‑thickness and large area defects of articular cartilage are unable to completely repair themselves and require surgical intervention, including microfracture, autologous or allogeneic osteochondral grafts, and autologous chondrocyte implantation. A large proportion of regenerative cartilage exists as fibrocartilage, which is unable to withstand impacts in the same way as native hyaline cartilage, owing to excess synthesis of type I collagen in the matrix. The present study demonstrated that low‑dose halofuginone (HF), a plant alkaloid isolated from Dichroa febrifuga, may inhibit the synthesis of type I collagen without influencing type II collagen in the extracellular matrix of chondrocytes. In addition, HF was revealed to inhibit the phosphorylation of mothers against decapentaplegic homolog (Smad)2/3 and promoted Smad7 expression, as well as decrease the synthesis of type I collagen synthesis. Results from the present study indicated that HF treatment suppressed the synthesis of type I collagen by inhibiting the transforming growth factor‑β signaling pathway in chondrocytes. These results may provide an alternative solution to the problems associated with fibrocartilage, and convert fibrocartilage into hyaline cartilage at the mid‑early stages of cartilage regeneration. HF may additionally be used to improve monolayer expansion or 3D cultures of seed cells for the tissue engineering of cartilage.

  18. Extracellular matrix of cultured glial cells: Selective expression of chondroitin 4-sulfate by type-2 astrocytes and their progenitors

    International Nuclear Information System (INIS)

    Gallo, V.; Bertolotto, A.

    1990-01-01

    We have studied the extracellular matrix composition of cultured glial cells by immunocytochemistry with different monoclonal and polyclonal antibodies. Double immunofluorescence experiments and metabolic labeling with [3H]glucosamine performed in different types of cerebellar and cortical cultures showed that bipotential progenitors for type-2 astrocytes and for oligodendrocytes synthesize chondroitin sulfate (CS) and deposit this proteoglycan in their extracellular matrix. The distribution of the various [3H]glucosamine-labeled glycosaminoglycans between the intracellular and the extracellular space was different. CS was present both within the cells and in the culture medium, although in different amounts. Bi-potential progenitors became also O4-positive during their development in vitro. At the stage of O4-positivity they were still stained with antibodies against CS. However, when the progenitor cells were maintained in serum-free medium and differentiated into Gal-C-positive oligodendrocytes, they became CS-negative. In the presence of fetal calf serum in the culture medium, the bipotential progenitors differentiated into GFAP-positive type-2 astrocytes. These cells still expressed CS: their Golgi area and their surface were stained with anti-CS antibodies. Staining with monoclonal antibodies specific for different types of CS (4-sulfate, 6-sulfate, and unsulfated) revealed that both bipotential progenitors and type-2 astrocytes synthesized only chondroitin 4-sulfate. Type-1 astrocytes were negative for both the polyclonal and the monoclonal anti-CS antibodies. Finally, type-2 astrocytes and their progenitors were weakly stained with anti-laminin antibodies and unstained with anti-fibronectin. Type-1 astrocytes were positive for both anti-laminin and anti-fibronectin antibodies and appeared to secrete fibronectin in the extracellular space

  19. In vitro transdermal delivery of caffeine, theobromine, theophylline and catechin from extract of Guarana, Paullinia Cupana.

    Science.gov (United States)

    Heard, Charles M; Johnson, Sarah; Moss, Gary; Thomas, Chris P

    2006-07-06

    Extracts of guarana (Paullinia cupana) feature as putatively stimulating ingredients in a number of foods, drinks and dietary/herbal supplements. The objective of this work was to investigate in vitro the transdermal delivery of the major pharmacologically active compounds contained in guarana extract. Saturated solutions of guarana were prepared in polyethylene glycol 400 (PEG400), propylene glycol (PG) and H(2)O at 32 degrees C. Guarana extract was also formulated in Duro-tak 2287 transdermal adhesive in a range of concentrations and the diffusional release was determined in addition to adhesive properties. Transdermal delivery across full thickness pig ear skin was investigated in vitro using Franz-type diffusion cells, with reverse-phase HPLC being used for the quantification of the permeation of theobromine (TB), theophylline (TP), (+)-catechin (C) and caffeine (CF). Based upon a combination of release and adhesive property data a patch containing 5.55 mg guarana extract cm(-2) was deemed optimal. The general trend for the delivery of the 4 analytes was: water >5.55 mg cm(-2) patch approximately PG>PEG400. For CF the greatest steady state flux was obtained from the water vehicle: 19 microg cm(-2)h(-1), with approximately 420 microg cm(-2) permeating after 24h. This was some 6x times more than from the drug-in-adhesive patch and 10x greater than PG, a well-known penetration enhancer, and 50x that of the 'regular' excipient PEG400. A water vehicle also provided the greatest delivery of TB (0.45 microg cm(-2) h(-1)), TP (0.022 microg cm(-2) h(-1)), and C (0.10 microg cm(-2) h(-1)). An inverse relationship was noted between lipophilicity and k(p) in each vehicle. The simultaneous transdermal delivery of the major actives of guarana was established, with permeation rates being highly concentration and vehicle dependent.

  20. Matrix-type effect on the magnetotransport properties of Ni–AlO and Ni–NbO composite systems

    Energy Technology Data Exchange (ETDEWEB)

    Stognei, O. V., E-mail: sto@sci.vrn.ru; Maliki, A. J.; Grebennikov, A. A.; Semenenko, K. I.; Bulovatskaya, E. O.; Sitnikov, A. V. [Voronezh State Technical University (Russian Federation)

    2016-06-15

    The effect of the insulating-matrix material on the electronic and magnetic properties of nanocomposites is investigated in the Ni{sub x}(Al{sub 2}O{sub 3}){sub 100–x} metal–insulator system and the Ni{sub x}(Nb{sub 2}O{sub 5}){sub 100–x} metal–semiconductor system. It is established that the characteristics of composites determined by electron transport through the matrix (the electrical resistivity, the position of the electrical percolation threshold, the magnetoresistance effect) depend on the material type. Replacement of the matrix from Al{sub 2}O{sub 3} to Nb{sub 2}O{sub 5} results in a decrease in the electrical resistivity by two–three orders of magnitude, a decrease in the magnetic resistivity by more than an order of magnitude, and in displacement of the percolation threshold from 40 to 30 at % of Ni. In this case, the magnetic properties of the composites are independent of the type of matrix: the concentration of the magnetic percolation threshold is identical in the two systems (~45 at % of Ni), and the coercive force of the samples occurring beyond the percolation threshold is close in magnitude (5–8 and 12–18 Oe) in the Ni{sub x}(Nb{sub 2}O{sub 5}){sub 100–x} and Ni{sub x}(Al{sub 2}O{sub 3}){sub 100–x} composites, respectively.

  1. Influence of hyperbaric oxygen on biomechanics and structural bone matrix in type 1 diabetes mellitus rats.

    Directory of Open Access Journals (Sweden)

    Pedro Henrique Justino Oliveira Limirio

    Full Text Available The aim of this study was to evaluate the biomechanics and structural bone matrix in diabetic rats subjected to hyperbaric oxygen therapy (HBO.Twenty-four male rats were divided into the following groups: Control; Control + HBO; Diabetic, and Diabetic + HBO. Diabetes was induced with streptozotocin (STZ in the diabetic Groups. After 30 days, HBO was performed every 48h in HBO groups and all animals were euthanized 60 days after diabetic induction. The femur was submitted to a biomechanical (maximum strength, energy-to-failure and stiffness and Attenuated Total Reflectance Fourier transform infrared (ATR-FTIR analyses (crosslink ratio, crystallinity index, matrix-to-mineral ratio: Amide I + II/Hydroxyapatite (M:MI and Amide III + Collagen/HA (M:MIII.In biomechanical analysis, diabetic animals showed lower values of maximum strength, energy and stiffness than non-diabetic animals. However, structural strength and stiffness were increased in groups with HBO compared with non-HBO. ATR-FTIR analysis showed decreased collagen maturity in the ratio of crosslink peaks in diabetic compared with the other groups. The bone from the diabetic groups showed decreased crystallinity compared with non-diabetic groups. M:MI showed no statistical difference between groups. However, M:MIII showed an increased matrix mineral ratio in diabetic+HBO and control+HBO compared with control and diabetic groups. Correlations between mechanical and ATR-FTIR analyses showed significant positive correlation between collagen maturity and stiffness.Diabetes decreased collagen maturation and the mineral deposition process, thus reducing biomechanical properties. Moreover, the study showed that HBO improved crosslink maturation and increased maximum strength and stiffness in the femur of T1DM animals.

  2. Influence of hyperbaric oxygen on biomechanics and structural bone matrix in type 1 diabetes mellitus rats.

    Science.gov (United States)

    Limirio, Pedro Henrique Justino Oliveira; da Rocha Junior, Huberth Alexandre; Morais, Richarlisson Borges de; Hiraki, Karen Renata Nakamura; Balbi, Ana Paula Coelho; Soares, Priscilla Barbosa Ferreira; Dechichi, Paula

    2018-01-01

    The aim of this study was to evaluate the biomechanics and structural bone matrix in diabetic rats subjected to hyperbaric oxygen therapy (HBO). Twenty-four male rats were divided into the following groups: Control; Control + HBO; Diabetic, and Diabetic + HBO. Diabetes was induced with streptozotocin (STZ) in the diabetic Groups. After 30 days, HBO was performed every 48h in HBO groups and all animals were euthanized 60 days after diabetic induction. The femur was submitted to a biomechanical (maximum strength, energy-to-failure and stiffness) and Attenuated Total Reflectance Fourier transform infrared (ATR-FTIR) analyses (crosslink ratio, crystallinity index, matrix-to-mineral ratio: Amide I + II/Hydroxyapatite (M:MI) and Amide III + Collagen/HA (M:MIII)). In biomechanical analysis, diabetic animals showed lower values of maximum strength, energy and stiffness than non-diabetic animals. However, structural strength and stiffness were increased in groups with HBO compared with non-HBO. ATR-FTIR analysis showed decreased collagen maturity in the ratio of crosslink peaks in diabetic compared with the other groups. The bone from the diabetic groups showed decreased crystallinity compared with non-diabetic groups. M:MI showed no statistical difference between groups. However, M:MIII showed an increased matrix mineral ratio in diabetic+HBO and control+HBO compared with control and diabetic groups. Correlations between mechanical and ATR-FTIR analyses showed significant positive correlation between collagen maturity and stiffness. Diabetes decreased collagen maturation and the mineral deposition process, thus reducing biomechanical properties. Moreover, the study showed that HBO improved crosslink maturation and increased maximum strength and stiffness in the femur of T1DM animals.

  3. Enhancement of the bioavailability of an antihypertensive drug by transdermal protransfersomal system: formulation and in vivo study.

    Science.gov (United States)

    Morsi, Nadia M; Aboelwafa, Ahmed A; Dawoud, Marwa H S

    2018-06-01

    Timolol Maleate (TiM), a nonselective β-adrenergic blocker, is a potent highly effective agent for management of hypertension. The drug suffers from poor oral bioavailability (50%) due to its first pass effect and a short elimination half-life of 4 h; resulting in its frequent administration. Transdermal formulation may circumvent these problems in the form of protransfersomes. The aim of this study is to develop and optimize transdermal protransfersomal system of Timolol Maleate by film deposition on carrier method where protransfersomes were converted to transfersomes upon skin hydration following transdermal application under occlusive conditions. Two 2 3 full factorial designs were employed to investigate the influence of three formulation variables which were; phosphatidyl choline: surfactant molar ratio, carrier: mixture and the type of SAA each on particle size, drug entrapment efficiency and release rate. The optimized formulation was evaluated regarding permeation through hairless rat skin and compared with oral administration of aqueous solution on male Wistar rats. Optimized protransfersomal system had excellent permeation rate through shaved rat skin (780.69 μg/cm 2 /h) and showed six times increase in relative bioavailability with prolonged plasma profile up to 72 h. A potential protransfresomal transdermal system was successfully developed and factorial design was found to be a smart tool in its optimization.

  4. Transdermal testosterone replacement therapy in men

    Directory of Open Access Journals (Sweden)

    Ullah MI

    2014-01-01

    Full Text Available M Iftekhar Ullah,1 Daniel M Riche,1,2 Christian A Koch1,31Department of Medicine, University of Mississippi Medical Center, 2Department of Pharmacy Practice, The University of Mississippi, 3GV (Sonny Montgomery VA Medical Center, Jackson, MS, USAAbstract: Androgen deficiency syndrome in men is a frequently diagnosed condition associated with clinical symptoms including fatigue, decreased libido, erectile dysfunction, and metabolic syndrome. Serum testosterone concentrations decline steadily with age. The prevalence of androgen deficiency syndrome in men varies depending on the age group, known and unknown comorbidities, and the respective study group. Reported prevalence rates may be underestimated, as not every man with symptoms of androgen deficiency seeks treatment. Additionally, men reporting symptoms of androgen deficiency may not be correctly diagnosed due to the vagueness of the symptom quality. The treatment of androgen deficiency syndrome or male hypogonadism may sometimes be difficult due to various reasons. There is no consensus as to when to start treating a respective man or with regards to the best treatment option for an individual patient. There is also lack of familiarity with treatment options among general practitioners. The formulations currently available on the market are generally expensive and dose adjustment protocols for each differ. All these factors add to the complexity of testosterone replacement therapy. In this article we will discuss the general indications of transdermal testosterone replacement therapy, available formulations, dosage, application sites, and recommended titration schedule.Keywords: hypogonadism, transdermal, testosterone, sexual function, testosterone replacement therapy, estradiol

  5. Capsule Typing of Haemophilus influenzae by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry.

    Science.gov (United States)

    Månsson, Viktor; Gilsdorf, Janet R; Kahlmeter, Gunnar; Kilian, Mogens; Kroll, J Simon; Riesbeck, Kristian; Resman, Fredrik

    2018-03-01

    Encapsulated Haemophilus influenzae strains belong to type-specific genetic lineages. Reliable capsule typing requires PCR, but a more efficient method would be useful. We evaluated capsule typing by using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Isolates of all capsule types (a-f and nontypeable; n = 258) and isogenic capsule transformants (types a-d) were investigated. Principal component and biomarker analyses of mass spectra showed clustering, and mass peaks correlated with capsule type-specific genetic lineages. We used 31 selected isolates to construct a capsule typing database. Validation with the remaining isolates (n = 227) showed 100% sensitivity and 92.2% specificity for encapsulated strains (a-f; n = 61). Blinded validation of a supplemented database (n = 50) using clinical isolates (n = 126) showed 100% sensitivity and 100% specificity for encapsulated strains (b, e, and f; n = 28). MALDI-TOF mass spectrometry is an accurate method for capsule typing of H. influenzae.

  6. Circulating matrix metalloproteinases are associated with arterial stiffness in patients with type 1 diabetes

    DEFF Research Database (Denmark)

    Peeters, Stijn A.; Engelen, Lian; Buijs, Jacqueline

    2017-01-01

    BACKGROUND: Altered regulation of extracellular matrix (ECM) composition by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) may contribute to arterial stiffening. We investigated associations between circulating MMP-1, -2, -3, -9, -10 and TIMP-1, and carotid......). Linear regression analyses were used to investigate cross-sectional associations between circulating levels of MMP-1, -2, -3, -9, -10, and TIMP-1 and cfPWV (n = 614) as well as office PP (n = 1517). Data on 24-h brachial and 24-h central PP were available in 638 individuals from PROFIL. Analyses were...... was associated with cfPWV [β per 1 SD higher lnMMP3 0.29 m/s (0.02; 0.55)]. In addition, brachial and central 24-h PP measurements in PROFIL were significantly associated with MMP-2 [(1.40 (0.47:2.33) and 1.43 (0.63:2.23)]. Pooled data analysis showed significant associations of circulating levels of MMP-1...

  7. Transdermal thiol-acrylate polyethylene glycol hydrogel synthesis using near infrared light

    Science.gov (United States)

    Chung, Solchan; Lee, Hwangjae; Kim, Hyung-Seok; Kim, Min-Gon; Lee, Luke P.; Lee, Jae Young

    2016-07-01

    Light-induced polymerization has been widely applied for hydrogel synthesis, which conventionally involves the use of ultraviolet or visible light to activate a photoinitiator for polymerization. However, with these light sources, transdermal gelation is not efficient and feasible due to their substantial interactions with biological systems, and thus a high power is required. In this study, we used biocompatible and tissue-penetrating near infrared (NIR) light to remotely trigger a thiol-acrylate reaction for efficient in vivo gelation with good controllability. Our gelation system includes gold nanorods as a photothermal agent, a thermal initiator, diacrylate polyethylene glycol (PEG), and thiolated PEG. Irradiation with a low-power NIR laser (0.3 W cm-2) could induce gelation via a mixed-mode reaction with a small increase in temperature (~5 °C) under the optimized conditions. We also achieved successful transdermal gelation via the NIR-assisted photothermal thiol-acryl reactions. This new type of NIR-assisted thiol-acrylate polymerization provides new opportunities for in situ hydrogel formation for injectable hydrogels and delivery of drugs/cells for various biomedical applications.Light-induced polymerization has been widely applied for hydrogel synthesis, which conventionally involves the use of ultraviolet or visible light to activate a photoinitiator for polymerization. However, with these light sources, transdermal gelation is not efficient and feasible due to their substantial interactions with biological systems, and thus a high power is required. In this study, we used biocompatible and tissue-penetrating near infrared (NIR) light to remotely trigger a thiol-acrylate reaction for efficient in vivo gelation with good controllability. Our gelation system includes gold nanorods as a photothermal agent, a thermal initiator, diacrylate polyethylene glycol (PEG), and thiolated PEG. Irradiation with a low-power NIR laser (0.3 W cm-2) could induce gelation

  8. Delayed-type hypersensitivity lesions in the central nervous system are prevented by inhibitors of matrix metalloproteinases.

    Science.gov (United States)

    Matyszak, M K; Perry, V H

    1996-09-01

    We have studied the effect of an inhibitor of matrix metalloproleinases, BB-1101, on a delayed-type hypersensitivity (DTH) response in the CNS. We used a recently described model in which heat-killed bacillus Calmette-Guérin (BCG) sequestered behind the blood-brain barrier (BBB) is targeted by a T-cell mediated response after subcutaneous injection of BCG (Matyszak and Perry, 1995). The DTH lesions are characterised by breakdown of the BBB, macrophage and lymphocyte infiltration and tissue damage including myelin loss. Treatment with BB-1101, which is not only a potent inhibitor of matrix metalloproteinases but also strongly inhibits TNF-alpha release, dramatically attenuated the CNS lesions. Breakdown of the BBB and the recruitment of T-cells into the site of the lesion were significantly reduced. There were many fewer inflammatory macrophages in DTH lesions than in comparable lesions from untreated animals. There was also significantly less myelin damage (assessed by staining with anti-MBP antibody). The DTH response in animals treated with dexamethasone was also reduced, but to a lesser degree. No significant effect was seen after administration of pentoxifylline, a phosphodiesterase inhibitor with effects including the inhibition of TNF-alpha production. Our results suggest that inhibitors of matrix metalloproteinases may be of considerable therapeutic benefit in neuroinflammatory diseases.

  9. Messenger RNA for membrane-type 2 matrix metalloproteinase, MT2-MMP, is expressed in human placenta of first trimester.

    Science.gov (United States)

    Bjørn, S F; Hastrup, N; Larsen, J F; Lund, L R; Pyke, C

    2000-01-01

    An intimately regulated cell surface activation of matrix metalloproteinases (MMPs) is believed to be of critical importance for the control of trophoblast invasion. A histological investigation of the expression and localization of three different MMPs, the membrane-type matrix metalloproteinases 1 and 2 (MT1-MMP, MT2-MMP) and matrix metalloproteinase 2 (MMP-2/gelatinase A) was performed by in situ hybridization on consecutive sections from human placentae of first trimester pregnancies. Cytokeratin immunostaining identified trophoblast cells. Both normal and tubal implantation sites were studied. We observed a high degree of coexpression of MT2-MMP, MT1-MMP and MMP-2 mRNAs in single extravillous cytotrophoblasts that had invaded the endometrium and tubal wall. Furthermore, mRNAs for all three genes were also seen in cytotrophoblasts of cell islands. In contrast to this coexpression pattern, MT2-MMP expression was absent from cell columns and decidual cells, in which signals for MT1-MMP and MMP-2 mRNAs were seen. The present data on the cellular expression of MT2-MMP mRNA in placenta extend our knowledge of the proteolytic events that take place during early pregnancy. The data suggest that MT2-MMP, capable of activating MMP-2 in vitro, is involved in the invasion of extravillous cytotrophoblast, possibly related to the physiological activation of MMP-2. Copyright 2000 Harcourt Publishers Ltd.

  10. Topical and transdermal drug delivery: principles and practice

    National Research Council Canada - National Science Library

    Benson, Heather A. E; Watkinson, Adam C

    2012-01-01

    .... Providing an overview of the current science in drug and cosmetic application to and through the skin, Topical and Transdermal Drug Delivery includes treatment of skin conditions, skin permeation...

  11. 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.

  12. Modified Transdermal Technologies: Breaking the Barriers of Drug ...

    African Journals Online (AJOL)

    In-depth analysis, formulation approaches, applications, advantages and disadvantages of these newer technologies are discussed. Keywords: Transdermal drug delivery, microneedles, macroflux, iontophoresis, ultrasound, powderject, skin abrasion. > Tropical Journal of Pharmaceutical Research Vol. 6 (1) 2007: pp. 633- ...

  13. Penetration Enhancement Effect of Turpentine Oil on Transdermal ...

    African Journals Online (AJOL)

    inflammation drastically affect the quality of life after SCI. ... inhibitors may reduce spinal cord ischemic injury. [11]. Various .... Healthy male Wistar rats (200-250 g) were used ..... Guy RH. Transdermal science and technology an update.

  14. Exact Wigner surmise type evaluation of the spacing distribution in the bulk of the scaled random matrix ensembles

    International Nuclear Information System (INIS)

    Forrester, P.J.; Witte, N.S.

    2000-01-01

    Random matrix ensembles with orthogonal and unitary symmetry correspond to the cases of real symmetric and Hermitian random matrices respectively. We show that the probability density function for the corresponding spacings between consecutive eigenvalues can be written exactly in the Wigner surmise type form a(s) e-b(s) for a simply related to a Painleve transcendent and b its anti-derivative. A formula consisting of the sum of two such terms is given for the symplectic case (Hermitian matrices with real quaternion elements)

  15. Semiclassics for matrix Hamiltonians: The Gutzwiller trace formula with applications to graphene-type systems

    Science.gov (United States)

    Vogl, M.; Pankratov, O.; Shallcross, S.

    2017-07-01

    We present a tractable and physically transparent semiclassical theory of matrix-valued Hamiltonians, i.e., those that describe quantum systems with internal degrees of freedoms, based on a generalization of the Gutzwiller trace formula for a n ×n dimensional Hamiltonian H (p ̂,q ̂) . The classical dynamics is governed by n Hamilton-Jacobi (HJ) equations that act in a phase space endowed with a classical Berry curvature encoding anholonomy in the parallel transport of the eigenvectors of H (p ,q ) ; these vectors describe the internal structure of the semiclassical particles. At the O (ℏ1) level and for nondegenerate HJ systems, this curvature results in an additional semiclassical phase composed of (i) a Berry phase and (ii) a dynamical phase resulting from the classical particles "moving through the Berry curvature". We show that the dynamical part of this semiclassical phase will, generally, be zero only for the case in which the Berry phase is topological (i.e., depends only on the winding number). We illustrate the method by calculating the Landau spectrum for monolayer graphene, the four-band model of AB bilayer graphene, and for a more complicated matrix Hamiltonian describing the silicene band structure. Finally, we apply our method to an inhomogeneous system consisting of a strain engineered one-dimensional moiré in bilayer graphene, finding localized states near the Dirac point that arise from electron trapping in a semiclassical moiré potential. The semiclassical density of states of these localized states we show to be in perfect agreement with an exact quantum mechanical calculation of the density of states.

  16. Efficient Transdermal Delivery of Benfotiamine in an Animal Model

    OpenAIRE

    Varadi, Gyula; Zhu, Zhen; G. Carter, Stephen

    2015-01-01

    We designed a transdermal system to serve as a delivery platform for benfotiamine utilizing the attributes of passive penetration enhancing molecules to penetrate through the outer layers of skin combined with the advance of incorporating various peripherally-acting vasodilators to enhance drug uptake.  Benfotiamine, incorporated into this transdermal formulation, was applied to skin in an animal model in order to determine the ability to deliver this thiamine pro-drug effectively to the sub-...

  17. Rotigotine transdermal patch for the treatment of Parkinson's Disease.

    Science.gov (United States)

    Perez-Lloret, Santiago; Rey, María Verónica; Ratti, Pietro Lucca; Rascol, Olivier

    2013-02-01

    Rotigotine, a non-ergot dopamine agonist, has been developed as a novel transdermal formulation. The rotigotine transdermal patch has received EMEA marketing authorization for the treatment of adult patients with early or advanced Parkinson's disease (PD) or with moderate to severe restless legs syndrome (RLS). FDA originally granted a marketing authorization for early PD, which was later suspended, and is now studying the authorization for RLS. The aim of this review is to review the pharmacokinetics, pharmacodynamics as well as the clinical efficacy and tolerability of the rotigotine transdermal patch in PD. Source material was identified using a PubMed search for the term 'rotigotine' and PD. Articles published up to January 2011 or abstract submitted to most relevant international neurology congresses were reviewed. The rotigotine transdermal patch is efficacious for the treatment of PD. Tolerability profile appears to be well within the range of that observed with other non-ergot dopamine agonists in PD. Application-site reactions were the most frequent adverse event, and they were considered mild to moderate in the majority of cases. The rotigotine transdermal patch offers a safe and efficacious alternative for the treatment of PD. Further studies should focus on the possibility that continuous dopamine stimulation by means of the transdermal patch has any influence on levodopa-related motor complications. © 2012 The Authors Fundamental and Clinical Pharmacology © 2012 Société Française de Pharmacologie et de Thérapeutique.

  18. Statistically optimized fast dissolving microneedle transdermal patch of meloxicam: A patient friendly approach to manage arthritis.

    Science.gov (United States)

    Amodwala, Sejal; Kumar, Praveen; Thakkar, Hetal P

    2017-06-15

    The long term administration of Meloxicam for the management of arthritis, a chronic disorder, results in gastrointestinal disturbances leading to poor patient compliance. Considering the favorable molecular weight, therapeutic dose, biological half-life and log P value of meloxicam for transdermal delivery, its fast dissolving microneedle patch, with an ability to breach the stratum corneum and efficiently deliver the cargo to deeper skin layers, were developed. Microneedle patch of low molecular weight polyvinyl alcohol and polyvinylpyrrolidone was prepared using Polydimethylsiloxane micromolds. The ratio of polyvinyl alcohol to polyvinyl pyrrolidone and solid content of matrix solution was optimized to achieve maximum needle strength. The optimized batch was extensively evaluated for in vitro dissolution, drug release, stability, ex vivo skin permeation/deposition, histopathology and in vivo pharmacodynamic study. The patch containing 9:1 polyvinyl alcohol to polyvinylpyrrolidone ratio with 50% solid content had shown maximum axial needle fracture force (0.9N) suitable for penetrating the skin. The optimized batch was found to be fast dissolving and released almost 100% drug in 60min following dissolution controlled kinetics. The formulation showed a significant drug deposition within skin (63.37%) and an improved transdermal flux (1.60μg/cm 2 /h) with a 2.58 fold enhancement in permeation as compared to plain drug solution. The formulation showed a comparable anti-inflammatory activity in rats when compared to its existing approved marketed oral tablet. Histopathology and stability evaluations demonstrated acceptable safety and shelf-life of the developed formulation. The successful verification of safety, efficacy and stability of microneedle patch advocated the suitability of the formulation for transdermal use. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. In Vitro Expression of the Extracellular Matrix Components Aggrecan, Collagen Types I and II by Articular Cartilage-Derived Chondrocytes.

    Science.gov (United States)

    Schneevoigt, J; Fabian, C; Leovsky, C; Seeger, J; Bahramsoltani, M

    2017-02-01

    The extracellular matrix (ECM) of hyaline cartilage is perfectly suited to transmit articular pressure load to the subchondral bone. Pressure is transferred by a high amount of aggrecan-based proteoglycans and collagen type II fibres in particular. After any injury, the hyaline cartilage is replaced by fibrocartilage, which is low in proteoglycans and contains collagen type I predominantly. Until now, long-term results of therapeutic procedures including cell-based therapies like autologous chondrocyte transplantation (ACT) lead to a replacement tissue meeting the composition of fibrocartilage. Therefore, it is of particular interest to discover how and to what extent isolation and in vitro cultivation of chondrocytes affect the cells and their expression of ECM components. Hyaline cartilage-derived chondrocytes were cultivated in vitro and observed microscopically over a time period of 35 days. The expression of collagen type I, collagen type II and aggrecan was analysed using RT-qPCR and Western blot at several days of cultivation. Chondrocytes presented a longitudinal shape for the entire cultivation period. While expression of collagen type I prevailed within the first days, only prolonged cultivation led to an increase in collagen type II and aggrecan expression. The results indicate that chondrocyte isolation and in vitro cultivation lead to a dedifferentiation at least to the stage of chondroprogenitor cells. © 2016 Blackwell Verlag GmbH.

  20. Influence of ceramic particulate type on microstructure and tensile strength of aluminum matrix composites produced using friction stir processing

    Directory of Open Access Journals (Sweden)

    I. Dinaharan

    2016-06-01

    Full Text Available Friction stir processing (FSP was applied to produce aluminum matrix composites (AMCs. Aluminum alloy AA6082 was used as the matrix material. Various ceramic particles, such as SiC, Al2O3, TiC, B4C and WC, were used as reinforcement particle. AA6082 AMCs were produced using a set of optimized process parameters. The microstructure was studied using optical microscopy, filed emission scanning electron microscopy and electron back scattered diagram. The results indicated that the type of ceramic particle did not considerably vary the microstructure and ultimate tensile strength (UTS. Each type of ceramic particle provided a homogeneous dispersion in the stir zone irrespective of the location and good interfacial bonding. Nevertheless, AA6082/TiC AMC exhibited superior hardness and wear resistance compared to other AMCs produced in this work under the same set of experimental conditions. The strengthening mechanisms and the variation in the properties are correlated to the observed microstructure. The details of fracture mode are further presented.

  1. Unlocking Solar for Low- and Moderate-Income Residents: A Matrix of Financing Options by Resident, Provider, and Housing Type

    Energy Technology Data Exchange (ETDEWEB)

    Cook, Jeffrey J. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Bird, Lori A. [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2018-01-02

    Historically the low and moderate income (LMI) market has been underserved by solar photovoltaics (PV), in part due to the unique barriers LMI residents face to participation in the PV market. The intent of this report is to identify the most promising strategies state policymakers might consider to finance PV for LMI customers across three housing types: single family, multi-family, and manufactured housing. The result is a financing matrix that documents the first and second tier financing options states may consider for each housing type. The first tier options were selected based upon their potential impact on LMI PV deployment. Second tier financing approaches could also be used to achieve state policy goals, but may not have as much effect on the relevant LMI market segment. Nevertheless, each financing option comes with tradeoffs that state policymakers may wish to consider when they make decisions about which financing approaches are best suited to achieve their LMI PV deployment goals.

  2. Computational Characterization of Type I collagen-based Extra-cellular Matrix

    Science.gov (United States)

    Liang, Long; Jones, Christopher Allen Rucksack; Lin, Daniel; Jiao, Yang; Sun, Bo

    2015-03-01

    A model of extracellular matrix (ECM) of collagen fibers has been built, in which cells could communicate with distant partners via fiber-mediated long-range-transmitted stress states. The ECM is modeled as a spring-like fiber network derived from skeletonized confocal microscopy data. Different local and global perturbations have been performed on the network, each followed by an optimized global Monte-Carlo (MC) energy minimization leading to the deformed network in response to the perturbations. In the optimization, a highly efficient local energy update procedure is employed and force-directed MC moves are used, which results in a convergence to the energy minimum state 20 times faster than the commonly used random displacement trial moves in MC. Further analysis and visualization of the distribution and correlation of the resulting force network reveal that local perturbations can give rise to global impacts: the force chains formed with a linear extent much further than the characteristic length scale associated with the perturbation sites and average fiber length. This behavior provides a strong evidence for our hypothesis of fiber-mediated long-range force transmission in ECM networks and the resulting long-range cell-cell mechanical signaling. ASU Seed Grant.

  3. Electrospun polymeric nanofibers for transdermal drug delivery

    Directory of Open Access Journals (Sweden)

    Mahya Rahmani

    2017-04-01

    Full Text Available Conventional transdermal drug delivery systems (TDDS have been designed for drug delivery through the skin. These systems use the permeability property of stratum corneum, the outermost surface layer of the skin. Applying polymeric micro and nanofibers in drug delivery has recently attracted great attention and the electrospinning technique is the preferred method for polymeric micro-nanofibers fabrication with a great potential for drug delivery. More studies in the field of nanofibers containing drug are divided two categories: first, preparation and characterization of nanofibers containing drug and second, investigation of their therapeutic applications. Drugs used in electrospun nanofibers can be categorized into three main groups, including antibiotics and antimicrobial agents, anti-inflammatory agents and vitamins with therapeutic applications. In this paper, we review the application of electrospun polymeric scaffolds in TDDS and also introduce several pharmaceutical and therapeutic agents which have been used in polymer nanofibrous patches.

  4. Microneedle Coating Techniques for Transdermal Drug Delivery

    Directory of Open Access Journals (Sweden)

    Rita Haj-Ahmad

    2015-11-01

    Full Text Available Drug administration via the transdermal route is an evolving field that provides an alternative to oral and parenteral routes of therapy. Several microneedle (MN based approaches have been developed. Among these, coated MNs (typically where drug is deposited on MN tips are a minimally invasive method to deliver drugs and vaccines through the skin. In this review, we describe several processes to coat MNs. These include dip coating, gas jet drying, spray coating, electrohydrodynamic atomisation (EHDA based processes and piezoelectric inkjet printing. Examples of process mechanisms, conditions and tested formulations are provided. As these processes are independent techniques, modifications to facilitate MN coatings are elucidated. In summary, the outcomes and potential value for each technique provides opportunities to overcome formulation or dosage form limitations. While there are significant developments in solid degradable MNs, coated MNs (through the various techniques described have potential to be utilized in personalized drug delivery via controlled deposition onto MN templates.

  5. Effect of Human Serum and 2 Different Types of Platelet Concentrates on Human Meniscus Cell Migration, Proliferation, and Matrix Formation.

    Science.gov (United States)

    Freymann, Undine; Metzlaff, Sebastian; Krüger, Jan-Philipp; Hirsh, Glen; Endres, Michaela; Petersen, Wolf; Kaps, Christian

    2016-06-01

    To evaluate the effect of 10% human serum (HS), 5% platelet-rich plasma (PRP), and 5% autologous conditioned plasma (ACP) on migration, proliferation, and extracellular matrix (ECM) synthesis of human meniscus cells. Cell migration and proliferation on stimulation with HS, PRP, and ACP were assessed by chemotaxis assays and measurement of genomic DNA content. Meniscus cells were cultivated in pellets stimulated with 10% HS, 5% PRP, or 5% ACP. Meniscal ECM formation was evaluated by histochemical staining of collagen type I, type II, and proteoglycans and by analysis of fibrochondrocyte marker gene expression. Human meniscus cells were significantly attracted by all 3 blood-derived products (10% HS and 5% ACP: P = .0001, 5% PRP: P = .0002). Cell proliferation at day 9 was significantly increased on stimulation with 10% HS (P = .0001) and 5% PRP (P = .0002) compared with 5% ACP and controls. Meniscus cell pellet cultures showed the formation of a well-structured meniscal ECM with deposition of collagen type I, type II, and proteoglycans on stimulation with 10% HS, whereas 5% PRP or 5% ACP resulted in the formation of an inhomogeneous and more fibrous ECM. Stimulation with 10% HS and 5% ACP showed a significant induction of fibrochondrocyte marker genes such as aggrecan (HS: P = .0002, ACP: P = .0147), cartilage oligomeric matrix protein (HS: P = .0002, ACP: P = .0005), and biglycan (HS: P = .0002, ACP: P = .0003), whereas PRP showed no inducing effect. Among all tested blood-derived products, only stimulation with HS showed the formation of a meniscal ECM as well as positive cell proliferating and migrating effects in vitro. Regarding a potential biological repair of nonvascular meniscus lesions, our results may point toward the use of HS as a beneficial augment in regenerative meniscus repair approaches. Our findings may suggest that HS might be a beneficial augment for meniscus repair. Copyright © 2016 Arthroscopy Association of North America. Published

  6. [Comparative study on transdermal osmosis in vitro of Aconitum brachypodium liniment, gel and patcher].

    Science.gov (United States)

    Lin, Ya-ping; Zhao, Ying; Zhang, Yong-ping; Liang, Guang-yi

    2007-02-01

    To study the transdermal osmosis process of Aconitum brachypodum's liniment, gel and patcher to provide basis for selecting dosage form and controlling the quality. Taking the cumulate rate of transdermal as index, a imitated Fick's diffusion device was used for the investigating the transdermal osmosis course of the three preparations. The best transdermal mathematics models are obtained and the relations between the transdermal course and the release course are analysed. The three preparations have different characteristics of transdermal osmosis course. The liniment meets dynamics 0 order process, the gel and the patcher meet dynamic 0 order process of non-corroded drug system. And the relation is good cubic equation between their transdermal course and release course. The transdermal osmosis experiment in vitro for three preparations can provide basis for selecting dosage form and the quality control in future studies.

  7. Analysis of nifedipine content in transdermal drug delivery system using non-destructive visible spectrophotometry technique

    International Nuclear Information System (INIS)

    Normaizira Hamidi; Normaizira Hamidi; Normaizira Hamidi; Mohd Nasir Taib; Mohd Nasir Taib; Wui, Wong Tin; Wui, Wong Tin

    2008-01-01

    The applicability of visible spectrophotometry technique as a tool to determine the drug content of polymeric film for use as a transdermal drug delivery system was investigated. Hydroxypropylmethycellulose (HPMC) was selected as the matrix polymer and nifedipine as the model drug. Blank and nifedipine-loaded HPMC films were prepared using the solvent evaporation method. The absorbance spectra of these films under the visible wavelengths between 400 and 800 nm were assessed and compared against the drug content values obtained by means of the conventional destructive UV- spectrophotometry technique. The latter required the use of a solvent system which contained methanol, a harmful organic component in pharmaceutical applications. The results indicated that the absorbance values, attributed to nifedipine, at the wavelengths of 545, 585, 638 and 755nm were significantly correlated to the drug content values obtained using the chemical assay method (Pearson correlation value: r = 0.990 and p < 0.01). The visible spectrophotometry technique is potentially suitable for use to determine the nifedipine content of films owing to its nature of characterization of transdermal drug delivery system which does not require sample destruction during the process of measurement. The samples are recoverable from test and analysis of the entire batch of samples is possible without the need of solvents and chemical reagents. (author)

  8. Plasma matrix metalloproteinases are associated with incident cardiovascular disease and all-cause mortality in patients with type 1 diabetes

    DEFF Research Database (Denmark)

    Peeters, S A; Engelen, L; Buijs, J

    2017-01-01

    BACKGROUND: Altered regulation of extracellular matrix remodeling by matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP) may contribute to vascular complications in type 1 diabetes. We investigated associations between plasma MMP-1, -2, -3, -9, -10 and TIMP-1...... differences in plasma MMP-1, -2, -3, -9, -10, and TIMP-1-levels in patients with and without a cardiovascular event and in those who died vs survivors. All analyses were adjusted for age, sex, duration of diabetes, HbA1c, nephropathy and for other conventional cardiovascular risk factors. RESULTS: After...... adjustment for potential confounders, higher MMP-2 plasma levels were significantly associated with higher incidence of cardiovascular events [HR 1.49 (95% CI 1.11; 1.99)], and higher plasma levels of MMP-1 [1.38 (1.07; 1.78)], MMP-2 [1.60 (1.19; 2.15)] and MMP-3 [1.39 (1.05; 1.85)] were associated with all...

  9. Stability Analysis of a Matrix Converter Drive: Effects of Input Filter Type and the Voltage Fed to the Modulation Algorithm

    Directory of Open Access Journals (Sweden)

    M. Hosseini Abardeh

    2015-03-01

    Full Text Available The matrix converter instability can cause a substantial distortion in the input currents and voltages which leads to the malfunction of the converter. This paper deals with the effects of input filter type, grid inductance, voltage fed to the modulation algorithm and the synchronous rotating digital filter time constant on the stability and performance of the matrix converter. The studies are carried out using eigenvalues of the linearized system and simulations. Two most common schemes for the input filter (LC and RLC are analyzed. It is shown that by a proper choice of voltage input to the modulation algorithm, structure of the input filter and its parameters, the need for the digital filter for ensuring the stability can be resolved. Moreover, a detailed model of the system considering the switching effects is simulated and the results are used to validate the analytical outcomes. The agreement between simulation and analytical results implies that the system performance is not deteriorated by neglecting the nonlinear switching behavior of the converter. Hence, the eigenvalue analysis of the linearized system can be a proper indicator of the system stability.

  10. The dimer interface of the membrane type 1 matrix metalloproteinase hemopexin domain: crystal structure and biological functions.

    Science.gov (United States)

    Tochowicz, Anna; Goettig, Peter; Evans, Richard; Visse, Robert; Shitomi, Yasuyuki; Palmisano, Ralf; Ito, Noriko; Richter, Klaus; Maskos, Klaus; Franke, Daniel; Svergun, Dmitri; Nagase, Hideaki; Bode, Wolfram; Itoh, Yoshifumi

    2011-03-04

    Homodimerization is an essential step for membrane type 1 matrix metalloproteinase (MT1-MMP) to activate proMMP-2 and to degrade collagen on the cell surface. To uncover the molecular basis of the hemopexin (Hpx) domain-driven dimerization of MT1-MMP, a crystal structure of the Hpx domain was solved at 1.7 Å resolution. Two interactions were identified as potential biological dimer interfaces in the crystal structure, and mutagenesis studies revealed that the biological dimer possesses a symmetrical interaction where blades II and III of molecule A interact with blades III and II of molecule B. The mutations of amino acids involved in the interaction weakened the dimer interaction of Hpx domains in solution, and incorporation of these mutations into the full-length enzyme significantly inhibited dimer-dependent functions on the cell surface, including proMMP-2 activation, collagen degradation, and invasion into the three-dimensional collagen matrix, whereas dimer-independent functions, including gelatin film degradation and two-dimensional cell migration, were not affected. These results shed light on the structural basis of MT1-MMP dimerization that is crucial to promote cellular invasion.

  11. Opioids Switching with Transdermal Systems in Chronic Cancer Pain

    Directory of Open Access Journals (Sweden)

    Barbarisi M

    2009-05-01

    Full Text Available Abstract Background Due to tolerance development and adverse side effects, chronic pain patients frequently need to be switched to alternative opioid therapy Objective To assess the efficacy and tolerability of an alternative transdermally applied (TDS opioid in patients with chronic cancer pain receiving insufficient analgesia using their present treatment. Methods A total of 32 patients received alternative opioid therapy, 16 were switched from buprenorphine to fentanyl and 16 were switched from fentanyl to buprenorphine. The dosage used was 50% of that indicated in equipotency conversion tables. Pain relief was assessed at weekly intervals for the next 3 weeks Results Pain relief as assessed by VAS, PPI, and PRI significantly improved (p Conclusion Opioid switching at 50% of the calculated equianalgesic dose produced a significant reduction in pain levels and rescue medication. The incidence of side effects decreased and no new side effects were noted. Further studies are required to provide individualized treatment for patients according to their different types of cancer.

  12. Effects of Sizes and Conformations of Fish-Scale Collagen Peptides on Facial Skin Qualities and Transdermal Penetration Efficiency

    OpenAIRE

    Chai, Huey-Jine; Li, Jing-Hua; Huang, Han-Ning; Li, Tsung-Lin; Chan, Yi-Lin; Shiau, Chyuan-Yuan; Wu, Chang-Jer

    2010-01-01

    Fish-scale collagen peptides (FSCPs) were prepared using a given combination of proteases to hydrolyze tilapia (Oreochromis sp.) scales. FSCPs were determined to stimulate fibroblast cells proliferation and procollagen synthesis in a time- and dose-dependent manner. The transdermal penetration capabilities of the fractionationed FSCPs were evaluated using the Franz-type diffusion cell model. The heavier FSCPs, 3500 and 4500?Da, showed higher cumulative penetration capability as opposed to the...

  13. Exercise-induced regulation of matrix metalloproteinases in the skeletal muscle of subjects with type 2 diabetes

    DEFF Research Database (Denmark)

    Scheede-Bergdahl, Celena; Bergdahl, Andreas; Schjerling, Peter

    2014-01-01

    -training. At baseline, there were no effects of diabetes on MMP or TIMP mRNA or protein. mRNA and protein response to training was similar in both groups, except active MMP-2 protein was elevated post training in T2DM only. Our results indicate that exercise-induced stimulation of MMPs is preserved in skeletal muscle......Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMP) play a critical role during vascular remodelling, in both health and disease. Impaired MMP regulation is associated with many diabetes-related complications. This study examined whether exercise-induced regulation of MMPs...... is maintained in the skeletal muscle of patients with uncomplicated type 2 diabetes (T2DM). Subjects [12 T2DM, 9 healthy control subjects (CON)] underwent 8 weeks of physical training. Messenger RNA (mRNA) was measured at baseline, during and after 8 weeks of training. Protein was measured pre- and post...

  14. Myosin-1E interacts with FAK proline-rich region 1 to induce fibronectin-type matrix

    DEFF Research Database (Denmark)

    Heim, Joel B; Squirewell, Edwin J; Neu, Ancilla

    2017-01-01

    Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase involved in development and human disease, including cancer. It is currently thought that the four-point one, ezrin, radixin, moesin (FERM)-kinase domain linker, which contains autophosphorylation site tyrosine (Y) 397, is not required...... for in vivo FAK function until late midgestation. Here, we directly tested this hypothesis by generating mice with FAK Y397-to-phenylalanine (F) mutations in the germline. We found that Y397F embryos exhibited reduced mesodermal fibronectin (FN) and osteopontin expression and died during mesoderm development...... and other FN-type matrix in both mouse embryonic fibroblasts and human melanoma. Our data support a model in which FAK Y397 autophosphorylation is required for FAK function in vivo and is positively regulated by MYO1E....

  15. Contributions in the Preparation and Processing of Composite Material Type Silumin 3 - Reinforced Matrix with S235JR Steel Mesh

    Directory of Open Access Journals (Sweden)

    Remus Belu-Nica

    2015-07-01

    Full Text Available In the paper are presented concrete data on developing technological batches of metal composite material (MCM type Silumin 3-reinforced matrix with steel mesh S235JR, with the indicating of the parameter and of the distinct stages of work. The samples from prepared batches were cut along and across by water jet abrasive process and were subjected to a destructive testing program and microstructural examination, obtaining results in concordance with the desired quality. The abrasive material used for cut was GMA granite with the average mesh of 80, the particle size ranging between 150-300 µm, density 2300 kg/m3 and melting point 1240°C.

  16. Peptide-chaperone-directed transdermal protein delivery requires energy.

    Science.gov (United States)

    Ruan, Renquan; Jin, Peipei; Zhang, Li; Wang, Changli; Chen, Chuanjun; Ding, Weiping; Wen, Longping

    2014-11-03

    The biologically inspired transdermal enhanced peptide TD1 has been discovered to specifically facilitate transdermal delivery of biological macromolecules. However, the biological behavior of TD1 has not been fully defined. In this study, we find that energy is required for the TD1-mediated transdermal protein delivery through rat and human skins. Our results show that the permeation activity of TD1-hEGF, a fusion protein composed of human epidermal growth factor (hEGF) and the TD1 sequence connected with a glycine-serine linker (GGGGS), can be inhibited by the energy inhibitor, rotenone or oligomycin. In addition, adenosine triphosphate (ATP), the essential energetic molecule in organic systems, can effectively facilitate the TD1 directed permeation of the protein-based drug into the skin in a dose-dependent fashion. Our results here demonstrate a novel energy-dependent permeation process during the TD1-mediated transdermal protein delivery that could be valuable for the future development of promising new transdermal drugs.

  17. Salivary matrix metalloproteinase (MMP-8) levels and gelatinase (MMP-9) activities in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Collin, H L; Sorsa, T; Meurman, J H; Niskanen, L; Salo, T; Rönkä, H; Konttinen, Y T; Koivisto, A M; Uusitupa, M

    2000-10-01

    We studied the salivary levels and activities of the matrix metalloproteinases (MMP) -8 and -9 in 45 type 2 diabetic patients and 77 control subjects. The patients' mean glycosylated haemoglobin (HbA1c) was 8.7%, indicating an unsatisfactory metabolic control of the disease. The MMP levels were further related to the clinical and microbiological periodontal findings as well as to salivary flow rate and other factors. The salivary flow rate, albumin and amylase concentrations were similar in type 2 diabetic patients to those in the control group. The mean gingival and periodontal pocket indexes were higher in the diabetes group. The number of potential periodontopathogenic bacteria was lower, however, in the diabetic than in the control group. Zymography and immunoblotting revealed that the major MMPs in the type 2 diabetic patients' saliva were MMP-8 and MMP-9. Salivary MMP levels and activities in type 2 diabetic patients were in general similar to those in the control group. However, the correlation coefficients using multiple regression analysis revealed that gingival bleeding, pocket depths and HbA1c were associated with increased MMP-8 levels which, in turn, were negatively predicted by elevated plasma lipid peroxide levels in the diabetic group. Our data on salivary MMP-8 and -9 do not support the concept of generalized neutrophil dysfunction in unbalanced diabetes. Moreover, plasma lipid peroxidation levels reflecting the increased oxidative burden, which is generated mainly by triggered neutrophils, do not indicate neutrophil dysfunction due to diabetes, but may rather be related to the increased tissue damage in an uncontrolled disease. However. advanced periodontitis in type 2 diabetes seems to be related to elevated salivary MMP-8 levels which might be useful in monitoring periodontal disease in diabetes.

  18. Synergistic effect of iontophoresis and chemical enhancers on transdermal permeation of tolterodine tartrate for the treatment of overactive bladder

    Directory of Open Access Journals (Sweden)

    D. Prasanthi

    2013-01-01

    Full Text Available Purpose The objective of the study was to evaluate the synergistic transdermal permeation effect of chemical enhancers and iontophoresis technique on tolterodine tartrate (TT transdermal gel and to evaluate its pharmacokinetic properties. Materials and Methods Taguchi robust design was used for optimization of formulations. Skin permeation rates were evaluated using the Keshary-chein type diffusion cells in order to optimize the gel formulation. In-vivo studies of the optimized formulation were performed in a rabbit model and histopathology studies of optimized formulation were performed on rats. Results Transdermal gels were formulated successfully using Taguchi robust design method. The type of penetration enhancer, concentration of penetration enhancer, current density and pulse on/off ratio were chosen as independent variables. Type of penetration enhancer was found to be the significant factor for all the responses. Permeation parameters were evaluated when maximum cumulative amount permeated in 24 hours (Q24 was 145.71 ± 2.00µg/cm2 by CIT4 formulation over control (91.89 ± 2.30µg/cm2. Permeation was enhanced by 1.75 fold by CIT4 formulation. Formulation CIT4 containing nerolidol (5% and iontophoretic variables applied (0.5mA/cm2 and pulse on/off ratio 3:1 was optimized. In vivo studies with optimized formulation CIT4 showed increase in AUC and T1/2 when compared to oral suspension in rabbits. The histological studies showed changes in dermis indicating the effect of penetration enhancers and as iontophoresis was continued only for two cycles in periodic fashion so it did not cause any skin damage observed in the slides. Conclusion Results indicated that iontophoresis in combination with chemical enhancers is an effective method for transdermal administration of TT in the treatment of overactive bladder.

  19. Effect of components (polymer, plasticizer and solvent as a variable in fabrication of diclofenac transdermal patch

    Directory of Open Access Journals (Sweden)

    Chetna Modi

    2012-01-01

    Full Text Available Transdermal drug delivery influence consumer acceptance and marked increase in bioavailability of some drugs which undergoes hepatic first-pass metabolism. Fabrication of transdermal patch requires lots of attention regarding the amount of components used for it. Because of varied nature of polymer and plasticizer, transdermal patches have different properties and different drug release. This study is on the basis to evaluate the amount to be needed for fabrication of diclofenac transdermal patch. Study shows that Hydroxy Propyl Methyl Cellulose has great influence on transdermal patch, if it is used alone in combination with glycerin or PEG-4000 plasticizer.

  20. Effects of Sizes and Conformations of Fish-Scale Collagen Peptides on Facial Skin Qualities and Transdermal Penetration Efficiency

    Directory of Open Access Journals (Sweden)

    Huey-Jine Chai

    2010-01-01

    Full Text Available Fish-scale collagen peptides (FSCPs were prepared using a given combination of proteases to hydrolyze tilapia (Oreochromis sp. scales. FSCPs were determined to stimulate fibroblast cells proliferation and procollagen synthesis in a time- and dose-dependent manner. The transdermal penetration capabilities of the fractionationed FSCPs were evaluated using the Franz-type diffusion cell model. The heavier FSCPs, 3500 and 4500 Da, showed higher cumulative penetration capability as opposed to the lighter FSCPs, 2000 and 1300 Da. In addition, the heavier seemed to preserve favorable coiled structures comparing to the lighter that presents mainly as linear under confocal scanning laser microscopy. FSCPs, particularly the heavier, were concluded to efficiently penetrate stratum corneum to epidermis and dermis, activate fibroblasts, and accelerate collagen synthesis. The heavier outweighs the lighter in transdermal penetration likely as a result of preserving the given desired structure feature.

  1. Status of surfactants as penetration enhancers in transdermal drug delivery

    Directory of Open Access Journals (Sweden)

    Iti Som

    2012-01-01

    Full Text Available Surfactants are found in many existing therapeutic, cosmetic, and agro-chemical preparations. In recent years, surfactants have been employed to enhance the permeation rates of several drugs via transdermal route. The application of transdermal route to a wider range of drugs is limited due to significant barrier to penetration across the skin which is associated with the outermost stratum corneum layer. Surfactants have effects on the permeability characteristics of several biological membranes including skin. They have the potential to solubilize lipids within the stratum corneum. The penetration of the surfactant molecule into the lipid lamellae of the stratum corneum is strongly dependent on the partitioning behavior and solubility of surfactant. Surfactants ranging from hydrophobic agents such as oleic acid to hydrophilic sodium lauryl sulfate have been tested as permeation enhancer to improve drug delivery. This article reviews the status of surfactants as permeation enhancer in transdermal drug delivery of various drugs.

  2. Effect of Electron-Beam Irradiation on Bacterial Cellulose Membranes Used as Transdermal Drug Delivery Systems

    International Nuclear Information System (INIS)

    Stoica-Guzun, A.

    2006-01-01

    Multiple methods are used to modify material surfaces. Radiation is an effective tool for polymer surfaces modification in order to obtain transdermal systems with different controlled release properties. Bacterial cellulose is a promising biomaterial synthesized by Acetobacter xylinum. It has a distinctive ultrafine reticulated structure that may become a perfect matrix as an optimal wound healing environment. In this work, high energy irradiation (γ rays from 137 C s) was applied to modify bacterial cellulose membranes. The effect of varying irradiation doses on membranes permeability was studied. Tetracycline was involved in the study of diffusivity as model drug. Release and permeation of drug from irradiated and non-irradiated membranes were done using a diffusion cell. The membrane permeability was determined using a psudo-steady state analysis based on Fick's law

  3. LIM kinase1 modulates function of membrane type matrix metalloproteinase 1: implication in invasion of prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Chakrabarti Ratna

    2011-01-01

    Full Text Available Abstract Background LIM kinase 1 (LIMK1 is an actin and microtubule cytoskeleton modulatory protein that is overexpressed in a number of cancerous tissues and cells and also promotes invasion and metastasis of prostate and breast cancer cells. Membrane type matrix metalloproteinase 1 (MT1-MMP is a critical modulator of extracellular matrix (ECM turnover through pericellular proteolysis and thus plays crucial roles in neoplastic cell invasion and metastasis. MT1-MMP and its substrates pro-MMP-2 and pro-MMP-9 are often overexpressed in a variety of cancers including prostate cancer and the expression levels correlate with the grade of malignancy in prostate cancer cells. The purpose of this study is to determine any functional relation between LIMK1 and MT1-MMP and its implication in cell invasion. Results Our results showed that treatment with the hydroxamate inhibitor of MT1-MMP, MMP-2 and MMP-9 ilomastat inhibited LIMK1-induced invasion of benign prostate epithelial cells. Over expression of LIMK1 resulted in increased collagenolytic activity of MMP-2, and secretion of pro-MMP2 and pro-MMP-9. Cells over expressing LIMK1 also exhibited increased expression of MT1-MMP, transcriptional activation and its localization to the plasma membrane. LIMK1 physically associates with MT1-MMP and is colocalized with it to the Golgi vesicles. We also noted increased expression of both MT1-MMP and LIMK1 in prostate tumor tissues. Conclusion Our results provide new information on regulation of MT1-MMP function by LIMK1 and showed for the first time, involvement of MMPs in LIMK1 induced cell invasion.

  4. Microemulsions based transdermal drug delivery systems.

    Science.gov (United States)

    Vadlamudi, Harini C; Narendran, Hyndavi; Nagaswaram, Tejeswari; Yaga, Gowri; Thanniru, Jyotsna; Yalavarthi, Prasanna R

    2014-01-01

    Since the discovery of microemulsions by Jack H Schulman, there has been huge progress made in applying microemulsion systems in plethora of research and industrial process. Microemulsions are optically isotropic systems consisting of water, oil and amphiphile. These systems are beneficial due to their thermodynamic stability, optical clarity, ease of preparation, higher diffusion and absorption rates. Moreover, it has been reported that the ingredients of microemulsion can effectively overcome the diffusion barrier and penetrate through the stratum corneum of the skin. Hence it becomes promising for both transdermal and dermal drug delivery. However, low viscosity of microemulsion restrains its applicability in pharmaceutical industry. To overcome the above drawback, the low viscous microemulsions were added to viscous gel bases to potentiate its applications as topical drug delivery systems so that various drug related toxic effects and erratic drug absorption can be avoided. The present review deals with the microemulsions, various techniques involved in the development of organic nanoparticles. The review emphasized on microemulsion based systems such as hydrogels and organogels. The physicochemical characteristics, mechanical properties, rheological and stability principles involved in microemulsion based viscous gels were also explored.

  5. Transdermal delivery of diclofenac using microemulsions.

    Science.gov (United States)

    Kweon, Jang-Hoon; Chi, Sang-Cheol; Park, Eun-Seok

    2004-03-01

    A transdermal preparation containing diclofenac diethylammonium (DDA) was developed using an O/W microemulsion system. Of the oils tested, lauryl alcohol was chosen as the oil phase of the microemulsion, as it showed a good solubilizing capacity and excellent skin permeation rate of the drug. Pseudoternary phase diagrams were constructed to obtain the concentration range of oil, surfactant and cosurfactant for microemulsion formation, and the effect of these additives on skin permeation of DDA was evaluated with excised rat skins. The optimum formulation of the microemulsion consisted of 1.16% of DDA, 5% of lauryl alcohol, 60% of water in combination with the 34.54% of Labrasol (surfactant)/ethanol (cosurfactant) (1:2). The efficiency of formulation in the percutaneous absorption of DDA was dependent upon the contents of water and lauryl alcohol as well as Labrasol:ethanol mixing ratio. It was concluded that the percutaneous absorption of DDA from microemulsions was enhanced with increasing the lauryl alcohol and water contents, and with decreasing the Labrasol:ethanol mixing ratio in the formulation.

  6. Transdermal testosterone replacement therapy in men

    Science.gov (United States)

    Ullah, M Iftekhar; Riche, Daniel M; Koch, Christian A

    2014-01-01

    Androgen deficiency syndrome in men is a frequently diagnosed condition associated with clinical symptoms including fatigue, decreased libido, erectile dysfunction, and metabolic syndrome. Serum testosterone concentrations decline steadily with age. The prevalence of androgen deficiency syndrome in men varies depending on the age group, known and unknown comorbidities, and the respective study group. Reported prevalence rates may be underestimated, as not every man with symptoms of androgen deficiency seeks treatment. Additionally, men reporting symptoms of androgen deficiency may not be correctly diagnosed due to the vagueness of the symptom quality. The treatment of androgen deficiency syndrome or male hypogonadism may sometimes be difficult due to various reasons. There is no consensus as to when to start treating a respective man or with regards to the best treatment option for an individual patient. There is also lack of familiarity with treatment options among general practitioners. The formulations currently available on the market are generally expensive and dose adjustment protocols for each differ. All these factors add to the complexity of testosterone replacement therapy. In this article we will discuss the general indications of transdermal testosterone replacement therapy, available formulations, dosage, application sites, and recommended titration schedule. PMID:24470750

  7. Pharmacokinetics of the transdermal delivery of benfotiamine.

    Science.gov (United States)

    Zhu, Zhen; Varadi, Gyula; Carter, Stephen G

    2016-04-01

    Accumulation of advanced glycation endpoints is a trigger to the development of diabetic peripheral neuropathy, which is a common complication of diabetes. Oral administration of benfotiamine (BFT) has shown some preclinical and clinical promise as a treatment for diabetic peripheral neuropathy. The purpose of this study was to evaluate the method of transdermal delivery of BFT as a possible, viable route of administration for the treatment of diabetic peripheral neuropathy. A single application of 10 mg of BFT was given to guinea pigs topically. The levels of thiamine (T), thiamine monophosphate, thiamine diphosphate, S-benzoylthiamine and BFT were measured in the blood, skin and muscle at different time points within 24 h. At the 24-h time point, following the single BFT dose, the T level was increased 10× in the blood, more than 7× in the skin and almost 4× in the muscle compared to the untreated animals. The total T content (total) was increased 7× in the blood, 17× in the skin and 3× in the muscle compared to the untreated animals. This strong increase in the tissue levels of T and the associated metabolic derivatives levels found in the blood and local tissues following a single dose indicate that topically applied BFT may be a viable and advantageous delivery method for the treatment of diabetic peripheral neuropathy.

  8. Heat: A Highly Efficient Skin Enhancer for Transdermal Drug Delivery

    Directory of Open Access Journals (Sweden)

    Sabine Szunerits

    2018-02-01

    Full Text Available Advances in materials science and bionanotechnology have allowed the refinements of current drug delivery systems, expected to facilitate the development of personalized medicine. While dermatological topical pharmaceutical formulations such as foams, creams, lotions, gels, etc., have been proposed for decades, these systems target mainly skin-based diseases. To treat systemic medical conditions as well as localized problems such as joint or muscle concerns, transdermal delivery systems (TDDSs, which use the skin as the main route of drug delivery, are very appealing. Over the years, these systems have shown to offer important advantages over oral as well as intravenous drug delivery routes. Besides being non-invasive and painless, TDDSs are able to deliver drugs with a short-half-life time more easily and are well adapted to eliminate frequent administrations to maintain constant drug delivery. The possibility of self-administration of a predetermined drug dose at defined time intervals makes it also the most convenient personalized point-of-care approach. The transdermal market still remains limited to a narrow range of drugs. While small and lipophilic drugs have been successfully delivered using TDDSs, this approach fails to deliver therapeutic macromolecules due to size-limited transport across the stratum corneum, the outermost layer of the epidermis. The low permeability of the stratum corneum to water-soluble drugs as well as macromolecules poses important challenges to transdermal administration. To widen the scope of drugs for transdermal delivery, new procedures to enhance skin permeation to hydrophilic drugs and macromolecules are under development. Next to iontophoresis and microneedle-based concepts, thermal-based approaches have shown great promise to enhance transdermal drug delivery of different therapeutics. In this inaugural article for the section “Frontiers in Bioengineering and Biotechnology,” the advances in this field

  9. Heat: A Highly Efficient Skin Enhancer for Transdermal Drug Delivery.

    Science.gov (United States)

    Szunerits, Sabine; Boukherroub, Rabah

    2018-01-01

    Advances in materials science and bionanotechnology have allowed the refinements of current drug delivery systems, expected to facilitate the development of personalized medicine. While dermatological topical pharmaceutical formulations such as foams, creams, lotions, gels, etc., have been proposed for decades, these systems target mainly skin-based diseases. To treat systemic medical conditions as well as localized problems such as joint or muscle concerns, transdermal delivery systems (TDDSs), which use the skin as the main route of drug delivery, are very appealing. Over the years, these systems have shown to offer important advantages over oral as well as intravenous drug delivery routes. Besides being non-invasive and painless, TDDSs are able to deliver drugs with a short-half-life time more easily and are well adapted to eliminate frequent administrations to maintain constant drug delivery. The possibility of self-administration of a predetermined drug dose at defined time intervals makes it also the most convenient personalized point-of-care approach. The transdermal market still remains limited to a narrow range of drugs. While small and lipophilic drugs have been successfully delivered using TDDSs, this approach fails to deliver therapeutic macromolecules due to size-limited transport across the stratum corneum , the outermost layer of the epidermis. The low permeability of the stratum corneum to water-soluble drugs as well as macromolecules poses important challenges to transdermal administration. To widen the scope of drugs for transdermal delivery, new procedures to enhance skin permeation to hydrophilic drugs and macromolecules are under development. Next to iontophoresis and microneedle-based concepts, thermal-based approaches have shown great promise to enhance transdermal drug delivery of different therapeutics. In this inaugural article for the section "Frontiers in Bioengineering and Biotechnology," the advances in this field and the handful of

  10. Heat: A Highly Efficient Skin Enhancer for Transdermal Drug Delivery

    Science.gov (United States)

    Szunerits, Sabine; Boukherroub, Rabah

    2018-01-01

    Advances in materials science and bionanotechnology have allowed the refinements of current drug delivery systems, expected to facilitate the development of personalized medicine. While dermatological topical pharmaceutical formulations such as foams, creams, lotions, gels, etc., have been proposed for decades, these systems target mainly skin-based diseases. To treat systemic medical conditions as well as localized problems such as joint or muscle concerns, transdermal delivery systems (TDDSs), which use the skin as the main route of drug delivery, are very appealing. Over the years, these systems have shown to offer important advantages over oral as well as intravenous drug delivery routes. Besides being non-invasive and painless, TDDSs are able to deliver drugs with a short-half-life time more easily and are well adapted to eliminate frequent administrations to maintain constant drug delivery. The possibility of self-administration of a predetermined drug dose at defined time intervals makes it also the most convenient personalized point-of-care approach. The transdermal market still remains limited to a narrow range of drugs. While small and lipophilic drugs have been successfully delivered using TDDSs, this approach fails to deliver therapeutic macromolecules due to size-limited transport across the stratum corneum, the outermost layer of the epidermis. The low permeability of the stratum corneum to water-soluble drugs as well as macromolecules poses important challenges to transdermal administration. To widen the scope of drugs for transdermal delivery, new procedures to enhance skin permeation to hydrophilic drugs and macromolecules are under development. Next to iontophoresis and microneedle-based concepts, thermal-based approaches have shown great promise to enhance transdermal drug delivery of different therapeutics. In this inaugural article for the section “Frontiers in Bioengineering and Biotechnology,” the advances in this field and the handful of

  11. New screening methodology for selection of polymeric materials for transdermal drug delivery devices

    Science.gov (United States)

    Falcone, Roberto P.

    As medical advances extend the human lifespan, the level of chronic illnesses will increase and thus straining the needs of the health care system that, as a result, governments will need to balance expenses without upsetting national budgets. Therefore, the selection of a precise and affordable drug delivery technology is seen as the most practical solution for governments, health care professionals, and consumers. Transdermal drug delivery patches (TDDP) are one of the best economical technologies that are favored by pharmaceutical companies and physicians alike because it offers fewer complications when compared to other delivery technologies. TDDP provides increased efficiency, safety and convenience for the patient. The TDDP segment within the US and Global drug delivery markets were valued at 5.6 and 12.7 billion respectively in 2009. TDDP is forecasted to reach $31.5 billion in 2015. The present TDDP technology involves the fabrication of a patch that consists of a drug embedded in a polymeric matrix. The diffusion coefficient is determined from the slope of the cumulative drug release versus time. It is a trial and error method that is time and labor consuming. With all the advantages that TDDPs can offer, the methodology used to achieve the so-called optimum design has resulted in several incidents where the safety and design have been put to question in recent times (e.g. Fentanyl). A more logical screening methodology is needed. This work shows the use of a modified Duda Zielinsky equation (DZE). Experimental release curves from commercial are evaluated. The experimental and theoretical Diffusion Coefficient values are found to be within the limits specified in the patent literature. One interesting finding is that the accuracy of the DZE is closer to experimental values when the type of Molecular Shape and Radius are used. This work shows that the modified DZE could be used as an excellent screening tool to determine the optimal polymeric matrices that

  12. Comparative Evaluation of Three-Phase Isolated Matrix-Type PFC Rectifier Concepts for High Efficiency 380VDC Supplies of Future Telco and Data Centers

    DEFF Research Database (Denmark)

    Cortes, Patricio; Bortis, Dominik; Pittini, Riccardo

    2014-01-01

    rectifier and in many cases a mains transformer is used to provide galvanic isolation. In order to achieve a high efficiency in the DC voltage generation and to implement the required isolation, a single-stage concept, such as a matrix-type rectifier that enables PFC functionality and galvanic isolation...... in a single conversion, can be beneficial. In addition, due to the fact that with the matrix-type rectifier the galvanic isolation is performed with a high-frequency transformer, this results in a more compact rectifier system compared to conventional systems where the mains-frequency isolation transformer...... is located at the input of the PFC rectifier. In this paper, an overview of isolated matrix-type PFC rectifier topologies is given and a new converter circuit is proposed, analyzed and comparatively evaluated against another promising PFC rectifier concept, the phase-modular IMY-rectifier....

  13. Type VII collagen is enriched in the enamel organic matrix associated with the dentin-enamel junction of mature human teeth.

    Science.gov (United States)

    McGuire, Jacob D; Walker, Mary P; Mousa, Ahmad; Wang, Yong; Gorski, Jeff P

    2014-06-01

    The inner enamel region of erupted teeth is known to exhibit higher fracture toughness and crack growth resistance than bulk phase enamel. However, an explanation for this behavior has been hampered by the lack of compositional information for the residual enamel organic matrix. Since enamel-forming ameloblasts are known to express type VII collagen and type VII collagen null mice display abnormal amelogenesis, the aim of this study was to determine whether type VII collagen is a component of the enamel organic matrix at the dentin-enamel junction (DEJ) of mature human teeth. Immunofluorescent confocal microscopy of demineralized tooth sections localized type VII collagen to the organic matrix surrounding individual enamel rods near the DEJ. Morphologically, immunoreactive type VII collagen helical-bundles resembled the gnarled-pattern of enamel rods detected by Coomassie Blue staining. Western blotting of whole crown or enamel matrix extracts also identified characteristic Mr=280 and 230 kDa type VII dimeric forms, which resolved into 75 and 25 kDa bands upon reduction. As expected, the collagenous domain of type VII collagen was resistant to pepsin digestion, but was susceptible to purified bacterial collagenase. These results demonstrate the inner enamel organic matrix in mature teeth contains macromolecular type VII collagen. Based on its physical association with the DEJ and its well-appreciated capacity to complex with other collagens, we hypothesize that enamel embedded type VII collagen fibrils may contribute not only to the structural resilience of enamel, but may also play a role in bonding enamel to dentin. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Transdermal carbamate poisoning – a case of misuse

    Directory of Open Access Journals (Sweden)

    Lalit Kumar Rajbanshi

    2017-01-01

    Full Text Available Acute pesticide poisoning is a common mode of intentional self harm. Oral ingestion is the usual mode of poisoning. However, inhalation, accidental or occupational transdermal exposure leading to acute or chronic poisoning can be the other route of poisoning. It has been seen that the purpose of poising is suicidal intensity in most of the cases. We report an unusual case where the victim had acute pesticide poisoning through transdermal route that was intended for non suicidal purpose. The patient was managed successfully with immediate decontamination and adequate antidote.

  15. Type VII Collagen is Enriched in the Enamel Organic Matrix Associated with the Dentin-Enamel Junction of Mature Human Teeth

    OpenAIRE

    McGuire, Jacob D.; Walker, Mary P.; Mousa, Ahmad; Wang, Yong; Gorski, Jeff P.

    2014-01-01

    The inner enamel region of erupted teeth is known to exhibit higher fracture toughness and crack growth resistance than bulk phase enamel. However, an explanation for this behavior has been hampered by the lack of compositional information for the residual enamel organic matrix. Since enamel-forming ameloblasts are known to express type VII collagen and type VII collagen null mice display abnormal amelogenesis, the aim of this study was to determine whether type VII collagen is a component of...

  16. Efficacy of biorhythmic transdermal combined hormone treatment in relieving climacteric symptoms: a pilot study

    Directory of Open Access Journals (Sweden)

    B Formby

    2011-02-01

    Full Text Available B Formby, F SchmidtThe Rasmus Institute for Medical Research, Program in Reproductive Endocrinology, Santa Barbara, CA, USAObjective: To evaluate the efficacy of a combination of bioidentical combined 17β-estradiol and progesterone transdermal delivery system (lipophilic emulsion-type base to relieve climacteric symptoms. The hormonal replacement was given during a period of 6 months at four different cyclic doses to mimic the normal ovary secretory pattern.Design: An open, randomized, comparative, between-patient trial conducted over 6 months in 29 menopausal women with climacteric symptoms assessed with the Kupperman index at baseline and during treatments. Saliva and serum values of 17β-estradiol and progesterone were quantitated before treatment and after 3 and 6 months. Pharmacokinetic data following transdermal administration of 17β-estradiol (0.3 mg, daily and progesterone (100 mg, daily were calculated from saliva levels using high-performance liquid chromatography analysis.Results: Improvement in climacteric symptoms was reported in 93% of women evaluated before and after 3 and 6 months of treatment. Values of saliva 17β-estradiol increased after 6 months from 0.6 ± 0.3 pg/mL to 14.1 ± 3.3 pg/mL, and the values of serum 17β-estradiol increased from 3.3 ± 2.8 pg/mL to 80.6 ± 21.9 pg/mL. Of responders, 88% characterized symptom relief as complete. No adverse health-related events were attributed to the bioidentical hormone therapy. Time to maximum saliva concentrations (Tmax, in all experimental cases, was observed after 6 hours. Baseline values were reached within 24 hours, indicating a diurnal rhythm of 17β-estradiol seen in normally cyclic women over the 24-hour period, ie, its daily biological rhythm.Conclusion: Percutaneous absorption of 17β-estradiol, as well as the absorption of progesterone, was associated with relief of climacteric symptoms. The cyclical transdermal delivery of combined bioidentical hormones may be

  17. Membrane Type-1 Matrix Metalloproteinase Expression in Acute Myeloid Leukemia and Its Upregulation by Tumor Necrosis Factor-α

    Directory of Open Access Journals (Sweden)

    Anna Janowska-Wieczorek

    2012-07-01

    Full Text Available Membrane type-1 matrix metalloproteinase (MT1-MMP has been implicated in tumor invasion, as well as trafficking of normal hematopoietic cells, and acts as a physiologic activator of proMMP-2. In this study we examined MT1-MMP expression in primary acute myeloid leukemia (AML cells. Because tumor necrosis factor (TNF-α is known to be elevated in AML, we also investigated the effect of TNF-α on MT1-MMP expression. We found (i MT1-MMP mRNA expression in 41 out of 43 primary AML samples tested; (ii activation of proMMP-2 in co-cultures of AML cells with normal bone marrow stromal cells; and (iii inhibition of proMMP-2 activation and trans-Matrigel migration of AML cells by gene silencing using MT1-MMP siRNA. Moreover, recombinant human TNF-α upregulated MT1-MMP expression in AML cells resulting in enhanced proMMP-2 activation and trans-Matrigel migration. Thus, AML cells express MT1-MMP and TNF-α enhances it leading to increased MMP-2 activation and most likely contributing to the invasive phenotype. We suggest that MT1-MMP, together with TNF-α, should be investigated as potential therapeutic targets in AML.

  18. Membrane Type-1 Matrix Metalloproteinase Expression in Acute Myeloid Leukemia and Its Upregulation by Tumor Necrosis Factor-α

    International Nuclear Information System (INIS)

    Marquez-Curtis, Leah A.; Shirvaikar, Neeta; Turner, A. Robert; Mirza, Imran; Surmawala, Amir; Larratt, Loree M.; Janowska-Wieczorek, Anna

    2012-01-01

    Membrane type-1 matrix metalloproteinase (MT1-MMP) has been implicated in tumor invasion, as well as trafficking of normal hematopoietic cells, and acts as a physiologic activator of proMMP-2. In this study we examined MT1-MMP expression in primary acute myeloid leukemia (AML) cells. Because tumor necrosis factor (TNF)-α is known to be elevated in AML, we also investigated the effect of TNF-α on MT1-MMP expression. We found (i) MT1-MMP mRNA expression in 41 out of 43 primary AML samples tested; (ii) activation of proMMP-2 in co-cultures of AML cells with normal bone marrow stromal cells; and (iii) inhibition of proMMP-2 activation and trans-Matrigel migration of AML cells by gene silencing using MT1-MMP siRNA. Moreover, recombinant human TNF-α upregulated MT1-MMP expression in AML cells resulting in enhanced proMMP-2 activation and trans-Matrigel migration. Thus, AML cells express MT1-MMP and TNF-α enhances it leading to increased MMP-2 activation and most likely contributing to the invasive phenotype. We suggest that MT1-MMP, together with TNF-α, should be investigated as potential therapeutic targets in AML

  19. Prion Fragment Peptides Are Digested with Membrane Type Matrix Metalloproteinases and Acquire Enzyme Resistance through Cu2+-Binding

    Directory of Open Access Journals (Sweden)

    Aya Kojima

    2014-05-01

    Full Text Available Prions are the cause of neurodegenerative disease in humans and other mammals. The structural conversion of the prion protein (PrP from a normal cellular protein (PrPC to a protease-resistant isoform (PrPSc is thought to relate to Cu2+ binding to histidine residues. In this study, we focused on the membrane-type matrix metalloproteinases (MT-MMPs such as MT1-MMP and MT3-MMP, which are expressed in the brain as PrPC-degrading proteases. We synthesized 21 prion fragment peptides. Each purified peptide was individually incubated with recombinant MT1-MMP or MT3-MMP in the presence or absence of Cu2+ and the cleavage sites determined by LC-ESI-MS analysis. Recombinant MMP-7 and human serum (HS were also tested as control. hPrP61-90, from the octapeptide-repeat region, was cleaved by HS but not by the MMPs tested here. On the other hand, hPrP92-168 from the central region was cleaved by MT1-MMP and MT3-MMP at various sites. These cleavages were inhibited by treatment with Cu2+. The C-terminal peptides had higher resistance than the central region. The data obtained from this study suggest that MT-MMPs expressed in the brain might possess PrPC-degrading activity.

  20. Proof of Concept: Matrix metalloproteinase inhibitor decreases inflammation and improves muscle insulin sensitivity in people with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Frankwich Karen

    2012-10-01

    Full Text Available Abstract Background Obesity is a state of subclinical inflammation resulting in loss of function of insulin receptors and decreased insulin sensitivity. Inhibition of the inflammatory enzymes, matrix metalloproteinases (MMPs, for 6 months in rodent models restores insulin receptor function and insulin sensitivity. Methods This 12-week double-blind, randomized, placebo (PL-controlled proof-of-concept study was performed to determine if the MMP inhibitor (MMPI, doxycycline, decreased global markers of inflammation and enhanced muscle insulin sensitivity in obese people with type 2 diabetes (DM2. The study included non-DM2 controls (n = 15, and DM2 subjects randomized to PL (n = 13 or doxycycline 100 mg twice daily (MMPI; n = 11. All participants were evaluated on Day 1; MMPI and PL groups were also evaluated after 84 days of treatment. Results There was a significant decrease in inflammatory markers C-reactive protein (P  Conclusions This study demonstrated short term treatment of people with diabetes with an MMPI resulted in decreased inflammation and improved insulin sensitivity. Larger, longer studies are warranted to determine if doxycycline can improve glucose control in people with diabetes. Trial Registration Clinicaltrials.gov NCT01375491

  1. Förster-type energy transfer as a probe for changes in local fluctuations of the protein matrix.

    Science.gov (United States)

    Somogyi, B; Matkó, J; Papp, S; Hevessy, J; Welch, G R; Damjanovich, S

    1984-07-17

    Much evidence, on both theoretical and experimental sides, indicates the importance of local fluctuations (in energy levels, conformational substates, etc.) of the macromolecular matrix in the biological activity of proteins. We describe here a novel application of the Förster-type energy-transfer process capable of monitoring changes both in local fluctuations and in conformational states of macromolecules. A new energy-transfer parameter, f, is defined as an average transfer efficiency, [E], normalized by the actual average quantum efficiency of the donor fluorescence, [phi D]. A simple oscillator model (for a one donor-one acceptor system) is presented to show the sensitivity of this parameter to changes in amplitudes of local fluctuations. The different modes of averaging (static, dynamic, and intermediate cases) occurring for a given value of the average transfer rate, [kt], and the experimental requirements as well as limitations of the method are also discussed. The experimental tests were performed on the ribonuclease T1-pyridoxamine 5'-phosphate conjugate (a one donor-one acceptor system) by studying the change of the f parameter with temperature, an environmental parameter expectedly perturbing local fluctuations of proteins. The parameter f increased with increasing temperature as expected on the basis of the oscillator model, suggesting that it really reflects changes of fluctuation amplitudes (significant changes in the orientation factor, k2, as well as in the spectral properties of the fluorophores can be excluded by anisotropy measurements and spectral investigations). Possibilities of the general applicability of the method are also discussed.

  2. Membrane Type-1 Matrix Metalloproteinase Expression in Acute Myeloid Leukemia and Its Upregulation by Tumor Necrosis Factor-α

    Energy Technology Data Exchange (ETDEWEB)

    Marquez-Curtis, Leah A.; Shirvaikar, Neeta [Canadian Blood Services R& D, Edmonton, Alberta T6G 2R8 (Canada); Turner, A. Robert [Departments of Medicine and Oncology, University of Alberta, Edmonton, Alberta T6G 2G3 (Canada); Mirza, Imran [Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta T6G 2B7 (Canada); Surmawala, Amir; Larratt, Loree M. [Departments of Medicine and Oncology, University of Alberta, Edmonton, Alberta T6G 2G3 (Canada); Janowska-Wieczorek, Anna, E-mail: anna.janowska@blood.ca [Canadian Blood Services R& D, Edmonton, Alberta T6G 2R8 (Canada); Departments of Medicine and Oncology, University of Alberta, Edmonton, Alberta T6G 2G3 (Canada)

    2012-07-25

    Membrane type-1 matrix metalloproteinase (MT1-MMP) has been implicated in tumor invasion, as well as trafficking of normal hematopoietic cells, and acts as a physiologic activator of proMMP-2. In this study we examined MT1-MMP expression in primary acute myeloid leukemia (AML) cells. Because tumor necrosis factor (TNF)-α is known to be elevated in AML, we also investigated the effect of TNF-α on MT1-MMP expression. We found (i) MT1-MMP mRNA expression in 41 out of 43 primary AML samples tested; (ii) activation of proMMP-2 in co-cultures of AML cells with normal bone marrow stromal cells; and (iii) inhibition of proMMP-2 activation and trans-Matrigel migration of AML cells by gene silencing using MT1-MMP siRNA. Moreover, recombinant human TNF-α upregulated MT1-MMP expression in AML cells resulting in enhanced proMMP-2 activation and trans-Matrigel migration. Thus, AML cells express MT1-MMP and TNF-α enhances it leading to increased MMP-2 activation and most likely contributing to the invasive phenotype. We suggest that MT1-MMP, together with TNF-α, should be investigated as potential therapeutic targets in AML.

  3. Studies on transdermal delivery enhancement of zidovudine.

    Science.gov (United States)

    Takmaz, Evrim Atilay; Inal, Ozge; Baykara, Tamer

    2009-01-01

    The purpose of this study was to investigate physicochemical characteristics and in vitro release of zidovudine from monolithic film of Eudragit RL 100 and ethyl cellulose. Films included 2.5% or 5% (w/w) zidovudine of the dry polymer weight were prepared in various ratios of polymers by solvent evaporation method from methanol/acetone solvent mixture. The release studies were carried out by vertical Franz cells (2.2 cm(2) area, 20 ml receptor fluid). Ex vivo studies were done on Wistar rat skin within the films F6 (Eudragit RL100) and F7 (Eudragit RL100/Ethylcellulose, 1:1) consisting 5% (w/w) zidovudine in comparison with the same amount of free drug. Either iontophoresis (0.1 and 0.5 mA/cm(2) direct currents, Ag/AgCl electrodes) or dimethyl sulfoxide (pretreatment of 1% and 5%, w/w, solutions) were used as enhancers. Films consisting of ethyl cellulose under the ratio of 50% (w/w) gave similar release profiles, and the highest in vitro cumulative released amount was achieved with F6 film which gave the closest results with the free drug. This result could be due to the high swelling capacity and re-crystallization inhibition effect of RL 100 polymer which also influenced the film homogenization. All the films were fitted to Higuchi release kinetics. It was also observed that both 0.5-mA/cm(2) current and 5% (w/w) dimethyl sulfoxide applications significantly increased the cumulative permeated amount of zidovudine after 8 h; however, the flux enhancement ratio was higher for 0.5-mA/cm(2) current application, especially within F6 film. Thus, it was concluded that Eudragit RL100 film (F6) could be further evaluated for the transdermal application of zidovudine.

  4. Mathematical model of water transport in Bacon and alkaline matrix-type hydrogen-oxygen fuel cells

    Science.gov (United States)

    Prokopius, P. R.; Easter, R. W.

    1972-01-01

    Based on general mass continuity and diffusive transport equations, a mathematical model was developed that simulates the transport of water in Bacon and alkaline-matrix fuel cells. The derived model was validated by using it to analytically reproduce various Bacon and matrix-cell experimental water transport transients.

  5. In vivo imaging of membrane type-1 matrix metalloproteinase with a novel activatable near-infrared fluorescence probe.

    Science.gov (United States)

    Shimizu, Yoichi; Temma, Takashi; Hara, Isao; Makino, Akira; Kondo, Naoya; Ozeki, Ei-Ichi; Ono, Masahiro; Saji, Hideo

    2014-08-01

    Membrane type-1 matrix metalloproteinase (MT1-MMP) is a protease activating MMP-2 that mediates cleavage of extracellular matrix components and plays pivotal roles in tumor migration, invasion and metastasis. Because in vivo noninvasive imaging of MT1-MMP would be useful for tumor diagnosis, we developed a novel near-infrared (NIR) fluorescence probe that can be activated following interaction with MT1-MMP in vivo. MT1-hIC7L is an activatable fluorescence probe comprised of anti-MT1-MMP monoclonal antibodies conjugated to self-assembling polymer micelles that encapsulate NIR dyes (IC7-1, λem : 858 nm) at concentrations sufficient to cause fluorescence self-quenching. In aqueous buffer, MT1-hIC7L fluorescence was suppressed to background levels and increased approximately 35.5-fold in the presence of detergent. Cellular uptake experiments revealed that in MT1-MMP positive C6 glioma cells, MT1-hIC7L showed significantly higher fluorescence that increased with time as compared to hIC7L, a negative control probe lacking the anti-MT1-MMP monoclonal antibody. In MT1-MMP negative MCF-7 breast adenocarcinoma cells, both MT1-hIC7L and hIC7L showed no obvious fluorescence. In addition, the fluorescence intensity of C6 cells treated with MT1-hIC7L was suppressed by pre-treatment with an MT1-MMP endocytosis inhibitor (P imaging using probes intravenously administered to tumor-bearing mice showed that MT1-hIC7L specifically visualized C6 tumors (tumor-to-background ratios: 3.8 ± 0.3 [MT1-hIC7L] vs 3.1 ± 0.2 [hIC7L] 48 h after administration, P fluorescence in MCF-7 tumors. Together, these results show that MT1-hIC7L would be a potential activatable NIR probe for specifically detecting MT1-MMP-expressing tumors. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  6. Galactosyl Pentadecene Reversibly Enhances Transdermal and Topical Drug Delivery

    Czech Academy of Sciences Publication Activity Database

    Kopečná, M.; Macháček, M.; Prchalová, Eva; Štěpánek, P.; Drašar, P.; Kotora, Martin; Vávrová, K.

    2017-01-01

    Roč. 34, č. 10 (2017), s. 2097-2108 ISSN 0724-8741 Institutional support: RVO:61388963 Keywords : galactoside * penetration enhancers * sugar * topical drug delivery * transdermal drug delivery Subject RIV: FR - Pharmacology ; Medidal Chemistry OBOR OECD: Pharmacology and pharmacy Impact factor: 3.002, year: 2016

  7. MICRONEEDLES AS A WAY TO INCREASE THE TRANSDERMAL INSULIN DELIVERY

    Directory of Open Access Journals (Sweden)

    E. G. Kuznetsova

    2016-01-01

    Full Text Available Aim: to prove the possibility of increasing the diffusion of insulin through the skin in vitro with pre-applying microneedles.Materials and methods. Microemulsion for transdermal therapeutic system of insulin has been used in vitro studies. Genetically engineered human insulin has been used in this research. Applicators with silicon microneedles (40 and 150 microns long have been used to enhance the diffusion fl ux of drug substance. The dynamics of insulin release from the transdermal therapeutic systems through the rabbit skin has been studied in glass Franz diffusion cells in analyzer diffusion of drugs HDT 1000 (Copley Scientifi c Ltd., UK. Insulin has been labeled with fl uorescein isothiocyanate to separate the insulin absorption spectrum from the spectra of native skin proteins at spectrophotometer measurements.Results. The amounts of insulin delivered through the skin in vitro after previous application of microneedles of 40 and 150 microns are 282.5 ± 61.1 and 372.3 ± 7.0 microgram, respectively. This is 1.4 and 1.9 times more than in the transdermal system without microneedles.Conclusion. The conditions for increasing the diffusion of insulin through the skin in a model transdermal therapeutic system with microneedles (length – 150 microns, duration of pre-application – 1 hour have been found.

  8. Assessment of simvastatin niosomes for pediatric transdermal drug delivery.

    Science.gov (United States)

    Zidan, Ahmed S; Hosny, Khaled M; Ahmed, Osama A A; Fahmy, Usama A

    2016-06-01

    The prevalence of childhood dyslipidemia increases and is considered as an important risk factor for the incidence of cardiovascular disease in the adulthood. To improve dosing accuracy and facilitate the determination of dosing regimens in function of the body weight, the proposed study aims at preparing transdermal niosomal gels of simvastatin as possible transdermal drug delivery system for pediatric applications. Twelve formulations were prepared to screen the influence of formulation and processing variables on critical niosomal characteristics. Nano-sized niosomes with 0.31 μm number-weighted size displayed highest simvastatin release rate with 8.5% entrapment capacity. The niosomal surface coverage by negative charges was calculated according to Langmuir isotherm with n = 0.42 to suggest that the surface association was site-independent, probably producing surface rearrangements. Hypolipidemic activities after transdermal administration of niosomal gels to rats showed significant reduction in cholesterol and triglyceride levels while increasing plasma high-density lipoproteins concentration. Bioavailability estimation in rats revealed an augmentation in simvastatin bioavailability by 3.35 and 2.9 folds from formulation F3 and F10, respectively, compared with oral drug suspension. Hence, this transdermal simvastatin niosomes not only exhibited remarkable potential to enhance its bioavailability and hypolipidemic activity but also considered a promising pediatric antihyperlipidemic formulation.

  9. Plasma Concentrations of Fentanyl Achieved With Transdermal Application in Chickens

    NARCIS (Netherlands)

    Delaski, Kristina M; Gehring, Ronette; Heffron, Brendan T; Negrusz, Adam; Gamble, Kathryn C

    2017-01-01

    Providing appropriate analgesia is an important concern in any species. Fentanyl, a μ-receptor specific opioid, use is common in mammalian species but has been incompletely evaluated for this purpose in avian species. Transdermal fentanyl patches were applied to domestic chickens (n = 10) of varying

  10. Transdermal Physostigmine—Absence of Effect on Topographic Brain Mapping

    Directory of Open Access Journals (Sweden)

    M. Y. Neufeld

    1993-01-01

    Full Text Available Nine patients with primary degenerative dementia (PDD participated in an open trial of transdermal physostigmine (TPh. In order to evaluate the neurophysiologic effects of TPh, EEG data were recorded and compared at baseline and following 2 months of continuous treatment. There was no significant effect of TPh on EEG spectra in patients with PDD.

  11. How can lipid nanocarriers improve transdermal delivery of olanzapine?

    Science.gov (United States)

    Iqbal, Nimra; Vitorino, Carla; Taylor, Kevin M G

    2017-06-01

    The development of a transdermal nanocarrier drug delivery system with potential for the treatment of psychiatric disorders, such as schizophrenia and bipolar disorder, is described. Lipid nanocarriers (LN), encompassing various solid:liquid lipid compositions were formulated and assessed as potential nanosystems for transdermal delivery of olanzapine. A previously optimized method of hot high pressure homogenization (HPH) was adopted for the production of the LN, which comprised solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and nanoemulsions (NE). Precirol  ® was selected as the solid lipid for progression of studies. SLN exhibited the best performance for transdermal delivery of olanzapine, based on in vitro release and permeation studies, coupled with results from physicochemical characterization of several solid:liquid lipid formulations. Stability tests, performed to give an indication of long-term storage behavior of the formulations, were in good agreement with previous studies for the best choice of solid:liquid lipid ratio. Overall, these findings highlight the SLN-based formulation as promising for the further inclusion in and production of transdermal patches, representing an innovative therapeutic approach.

  12. Efficacy and transdermal absorption of permethrin in scabies patients

    NARCIS (Netherlands)

    van der Rhee, H.J.; Farquhar, J A; Vermeulen, N P

    1989-01-01

    The clinical efficacy and transdermal absorption of permethrin, a new synthetic insecticide was investigated in ten scabies patients. All patients were successfully treated with one application of a cream, containing 5% permethrin. Apart from mild postscabies dermatitis no side-effects were

  13. Transferosomes - A vesicular transdermal delivery system for enhanced drug permeation

    Directory of Open Access Journals (Sweden)

    Reshmy Rajan

    2011-01-01

    Full Text Available Transdermal administration of drugs is generally limited by the barrier function of the skin. Vesicular systems are one of the most controversial methods for transdermal delivery of active substances. The interest in designing transdermal delivery systems was relaunched after the discovery of elastic vesicles like transferosomes, ethosomes, cubosomes, phytosomes, etc. This paper presents the composition, mechanisms of penetration, manufacturing and characterization methods of transferosomes as transdermal delivery systems of active substances. For a drug to be absorbed and distributed into organs and tissues and eliminated from the body, it must pass through one or more biological membranes/barriers at various locations. Such a movement of drug across the membrane is called as drug transport. For the drugs to be delivered to the body, they should cross the membranous barrier. The concept of these delivery systems was designed in an attempt to concentrate the drug in the tissues of interest, while reducing the amount of drug in the remaining tissues. Hence, surrounding tissues are not affected by the drug. In addition, loss of drug does not happen due to localization of drug, leading to get maximum efficacy of the medication. Therefore, the phospholipid based carrier systems are of considerable interest in this era.

  14. Transdermal deferoxamine prevents pressure-induced diabetic ulcers.

    Science.gov (United States)

    Duscher, Dominik; Neofytou, Evgenios; Wong, Victor W; Maan, Zeshaan N; Rennert, Robert C; Inayathullah, Mohammed; Januszyk, Michael; Rodrigues, Melanie; Malkovskiy, Andrey V; Whitmore, Arnetha J; Walmsley, Graham G; Galvez, Michael G; Whittam, Alexander J; Brownlee, Michael; Rajadas, Jayakumar; Gurtner, Geoffrey C

    2015-01-06

    There is a high mortality in patients with diabetes and severe pressure ulcers. For example, chronic pressure sores of the heels often lead to limb loss in diabetic patients. A major factor underlying this is reduced neovascularization caused by impaired activity of the transcription factor hypoxia inducible factor-1 alpha (HIF-1α). In diabetes, HIF-1α function is compromised by a high glucose-induced and reactive oxygen species-mediated modification of its coactivator p300, leading to impaired HIF-1α transactivation. We examined whether local enhancement of HIF-1α activity would improve diabetic wound healing and minimize the severity of diabetic ulcers. To improve HIF-1α activity we designed a transdermal drug delivery system (TDDS) containing the FDA-approved small molecule deferoxamine (DFO), an iron chelator that increases HIF-1α transactivation in diabetes by preventing iron-catalyzed reactive oxygen stress. Applying this TDDS to a pressure-induced ulcer model in diabetic mice, we found that transdermal delivery of DFO significantly improved wound healing. Unexpectedly, prophylactic application of this transdermal delivery system also prevented diabetic ulcer formation. DFO-treated wounds demonstrated increased collagen density, improved neovascularization, and reduction of free radical formation, leading to decreased cell death. These findings suggest that transdermal delivery of DFO provides a targeted means to both prevent ulcer formation and accelerate diabetic wound healing with the potential for rapid clinical translation.

  15. NMR characterisation and transdermal drug delivery potential of microemulsion systems

    DEFF Research Database (Denmark)

    Kreilgaard, Mads; Pedersen, E J; Jaroszewski, J W

    2000-01-01

    The purpose of this study was to investigate the influence of structure and composition of microemulsions (Labrasol/Plurol Isostearique/isostearylic isostearate/water) on their transdermal delivery potential of a lipophilic (lidocaine) and a hydrophilic model drug (prilocaine hydrochloride), and ...

  16. Design and Development of a Proniosomal Transdermal Drug ...

    African Journals Online (AJOL)

    Purpose: The aim of the study was to develop a proniosomal carrier system for captopril for the treatment of hypertension that is capable of efficiently delivering entrapped drug over an extended period of time. Method: The potential of proniosomes as a transdermal drug delivery system for captopril was investigated by ...

  17. Transdermal deferoxamine prevents pressure-induced diabetic ulcers

    Science.gov (United States)

    Duscher, Dominik; Neofytou, Evgenios; Wong, Victor W.; Maan, Zeshaan N.; Rennert, Robert C.; Januszyk, Michael; Rodrigues, Melanie; Malkovskiy, Andrey V.; Whitmore, Arnetha J.; Galvez, Michael G.; Whittam, Alexander J.; Brownlee, Michael; Rajadas, Jayakumar; Gurtner, Geoffrey C.

    2015-01-01

    There is a high mortality in patients with diabetes and severe pressure ulcers. For example, chronic pressure sores of the heels often lead to limb loss in diabetic patients. A major factor underlying this is reduced neovascularization caused by impaired activity of the transcription factor hypoxia inducible factor-1 alpha (HIF-1α). In diabetes, HIF-1α function is compromised by a high glucose-induced and reactive oxygen species-mediated modification of its coactivator p300, leading to impaired HIF-1α transactivation. We examined whether local enhancement of HIF-1α activity would improve diabetic wound healing and minimize the severity of diabetic ulcers. To improve HIF-1α activity we designed a transdermal drug delivery system (TDDS) containing the FDA-approved small molecule deferoxamine (DFO), an iron chelator that increases HIF-1α transactivation in diabetes by preventing iron-catalyzed reactive oxygen stress. Applying this TDDS to a pressure-induced ulcer model in diabetic mice, we found that transdermal delivery of DFO significantly improved wound healing. Unexpectedly, prophylactic application of this transdermal delivery system also prevented diabetic ulcer formation. DFO-treated wounds demonstrated increased collagen density, improved neovascularization, and reduction of free radical formation, leading to decreased cell death. These findings suggest that transdermal delivery of DFO provides a targeted means to both prevent ulcer formation and accelerate diabetic wound healing with the potential for rapid clinical translation. PMID:25535360

  18. Avanafil Liposomes as Transdermal Drug Delivery for Erectile ...

    African Journals Online (AJOL)

    Avanafil is slightly soluble in ethanol, practically insoluble in water ... transdermal permeability and bioavailability for the treatment of .... Table 1 shows that the EE had higher values for the MLVs .... reason is the lower solubility of avanafil at pH.

  19. Design and Development of Repaglinide Microemulsion Gel for Transdermal Delivery.

    Science.gov (United States)

    Shinde, Ujwala A; Modani, Sheela H; Singh, Kavita H

    2018-01-01

    Microemulsion formulation of repaglinide, a BCS class II hypoglycemic agent with limited oral bioavailability, was developed considering its solubility in various oils, surfactants, and cosurfactants. The pseudo-ternary phase diagrams for microemulsion regions were constructed by water titration method at K m 1:1 and characterized for optical birefringence, percentage transmittance, pH, refractive index, globule size, zeta potential, viscosity, drug content, and thermodynamic stability. To enhance the drug permeation and residence time, the optimized microemulsions having mean globule size of 36.15 ± 9.89 nm was gelled with xanthan gum. The developed microemulsion-based gel was characterized for globule size, zeta potential, pH, and drug content. All evaluation parameters upon gelling were found to be satisfactory. Ex vivo permeability study across rat skin demonstrated higher steady-state flux (P microemulsion of repaglinide in comparison to the repaglinide microemulsion gel. At the end of 24 h, the cumulative drug permeation from microemulsion and microemulsion gel was found to be 229.19 ± 24.34 and 180.84 ± 17.40 μg/cm 2 , respectively. The microemulsion formulation showed 12.30-fold increase in flux as compared to drug suspension with highest enhancement ratio (E r ) of 12.36. Whereas microemulsion gel exhibited 10.97-fold increase in flux (with highest E r , 11.78) as compared to repaglinide (RPG) suspension. In vivo efficacy study was performed in normal Sprague-Dawley rats by using oral glucose tolerance test. Results of RPG transdermal microemulsion gel demonstrated remarkable advantage over orally administered RPG by reducing the glucose level in controlled manner. Hence, it could be a new, alternative dosage form for effective therapy of type 2 diabetes mellitus.

  20. Characterisation and quantification of liposome-type nanoparticles in a beverage matrix using hydrodynamic chromatography and MALDI–TOF mass spectrometry

    NARCIS (Netherlands)

    Helsper, J.P.F.G.; Peters, R.J.B.; Brouwer, L.; Weigel, S.

    2013-01-01

    This paper describes the characterisation of liposome-type nanoparticles (NPs) dispersed in a beverage matrix. Characterisation is based on a two-step procedure: first, liposomes are separated on the basis of size in the nanometre range by use of hydrodynamic chromatography (HDC); second, chemical

  1. Regulation of Membrane-Type 4 Matrix Metalloproteinase by SLUG Contributes to Hypoxia-Mediated Metastasis12

    Science.gov (United States)

    Huang, Chi-Hung; Yang, Wen-Hao; Chang, Shyue-Yih; Tai, Shyh-Kuan; Tzeng, Cheng-Hwei; Kao, Jung-Yie; Wu, Kou-Juey; Yang, Muh-Hwa

    2009-01-01

    The hypoxic tumor environment has been shown to be critical to cancer metastasis through the promotion of angiogenesis, induction of epithelial-mesenchymal transition (EMT), and acquisition of invasive potential. However, the impact of hypoxia on the expression profile of the proteolytic enzymes involved in invasiveness is relatively unknown. Membrane-type 4 matrix metalloproteinase (MT4-MMP) is a glycosyl-phosphatidyl inositol-anchored protease that has been shown to be overexpressed in human cancers. However, detailed mechanisms regarding the regulation and function of MT4-MMP expression in tumor cells remain unknown. Here, we demonstrate that hypoxia or overexpression of hypoxia-inducible factor-1α (HIF-1α) induced MT4-MMP expression in human cancer cells. Activation of SLUG, a transcriptional factor regulating the EMT process of human cancers, by HIF-1α was critical for the induction of MT4-MMP under hypoxia. SLUG regulated the transcription of MT4-MMP through direct binding to the E-box located in its proximal promoter. Short-interference RNA-mediated knockdown of MT4-MMP attenuated in vitro invasiveness and in vivo pulmonary colonization of tumor cells without affecting cell migratory ability. MT4-MMP promoted invasiveness and pulmonary colonization through modulation of the expression profile of MMPs and angiogenic factors. Finally, coexpression of HIF-1α and MT4-MMP in human head and neck cancer was predictive of a worse clinical outcome. These findings establish a novel signaling pathway for hypoxia-mediated metastasis and elucidate the underlying regulatory mechanism and functional significance of MT4-MMP in cancer metastasis. PMID:20019845

  2. Non-enzymatic glycosylation of a type I collagen matrix: effects on osteoblastic development and oxidative stress

    Directory of Open Access Journals (Sweden)

    Barrio Daniel A

    2001-08-01

    Full Text Available Abstract Background The tissue accumulation of protein-bound advanced glycation endproducts (AGE may be involved in the etiology of diabetic chronic complications, including osteopenia. The aim of this study was to investigate the effect of an AGE-modified type I collagen substratum on the adhesion, spreading, proliferation and differentiation of rat osteosarcoma UMR106 and mouse non-transformed MC3T3E1 osteoblastic cells. We also studied the role of reactive oxygen species (ROS and nitric oxide synthase (NOS expression on these AGE-collagen mediated effects. Results AGE-collagen decreased the adhesion of UMR106 cells, but had no effect on the attachment of MC3T3E1 cells. In the UMR106 cell line, AGE-collagen also inhibited cellular proliferation, spreading and alkaline phosphatase (ALP activity. In preosteoblastic MC3T3E1 cells (24-hour culture, proliferation and spreading were significantly increased by AGE-collagen. After one week of culture (differentiated MC3T3E1 osteoblasts AGE-collagen inhibited ALP activity, but had no effect on cell number. In mineralizing MC3T3E1 cells (3-week culture AGE-collagen induced a decrease in the number of surviving cells and of extracellular nodules of mineralization, without modifying their ALP activity. Intracellular ROS production, measured after a 48-hour culture, was decreased by AGE-collagen in MC3T3E1 cells, but was increased by AGE-collagen in UMR106 cells. After a 24-hour culture, AGE-collagen increased the expression of endothelial and inducible NOS, in both osteoblastic cell lines. Conclusions These results suggest that the accumulation of AGE on bone extracellular matrix could regulate the proliferation and differentiation of osteoblastic cells. These effects appear to depend on the stage of osteoblastic development, and possibly involve the modulation of NOS expression and intracellular ROS pathways.

  3. Matrix-Geometric Solution for Two Node Tandem Queueing Systems with Phase-Type Servers Subject to Blocking and Failures

    National Research Council Canada - National Science Library

    Guen, Levent; Makowski, Armand M

    1987-01-01

    .... The corresponding rate matrix is given explicitly in terms of the modA parameters and the resulting closed-form expression provides the basis for an efficient calculation of the invariant probability vector...

  4. Transdermal delivery of curcumin via microemulsion.

    Science.gov (United States)

    Sintov, Amnon C

    2015-03-15

    The objective of this study was to evaluate the transdermal delivery potential of a new curcumin-containing microemulsion system. Three series of experiments were carried out to comprehend the system characteristics: (a) examining the influence of water content on curcumin permeation, (b) studying the effect of curcumin loading on its permeability, and (c) assessing the contribution of the vesicular nature of the microemulsion on permeability. The skin permeability of curcumin from microemulsions, which contained 5%, 10%, and 20% of water content (1% curcumin), was measured in vitro using excised rat skin. It has been shown that the permeability coefficient of CUR in a formulation containing 10% aqueous phase (ME-10) was twofold higher than the values obtained for formulations with 5% and 20% water (Papp=0.116 × 10(-3)± 0.052 × 10(-3)vs. 0.043 × 10(-3)± 0.022 × 10(-3) and 0.047 × 10(-3)± 0.025 × 10(-3)cm/h, respectively. A reasonable explanation for this phenomenon may be the reduction of both droplet size and droplets' concentration in the microemulsion as the aqueous phase decreased from 20% to 5%. It has also been shown that a linear correlation exists between the decrease in droplet size and the increase of curcumin loading in the microemulsion. In addition, it has been demonstrated that a micellar system, S/O-mix, and a plain solution of curcumin resulted in a significantly lower curcumin permeation relative to that presented by the microemulsion, Papp=0.018 × 10(-3)± 0.011 × 10(-3), 0.005 × 10(-3)± 0.002 × 10(-3), and 0.002 × 10(-3)± 0.000 × 10(-3)cm/h, respectively, vs. 0.110 × 10(-3)± 0.021 × 10(-3)cm/h for the microemulsion. The enhancement ratio (ER=Jss-ME/Jss-solution) of CUR permeated via 1% loaded microemulsion was 55. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Transdermal granisetron: a guide to its use in preventing nausea and vomiting induced by chemotherapy.

    Science.gov (United States)

    Keating, Gillian M; Duggan, Sean T; Curran, Monique P

    2012-09-01

    Transdermal granisetron (Sancuso®) is effective in the prevention of nausea and vomiting in patients with cancer who are receiving moderately or highly emetogenic chemotherapy for 3-5 days. Transdermal granisetron is noninferior to oral granisetron in this indication, and is generally well tolerated in this indication. Thus, transdermal granisetron provides a convenient option for the prevention of chemotherapy-induced nausea and vomiting, with the potential to improve patient compliance.

  6. Computational simulation of the microstructure of irradiation damaged regions for the plate type fuel of UO2 microspheres dispersed in stainless steel matrix

    International Nuclear Information System (INIS)

    Reis, S.C. dos; Lage, A.F.; Braga, D.; Ferraz, W.B.

    2006-01-01

    Plate type fuel elements have high efficiency of thermal transference what benefits the heat flux with high rates of power output. In reactor cores, fuel elements, in general, are subject to a high neutrons flux, high working temperatures, severe corrosion conditions, direct interference of fission products that result from nuclear reactions and radiation interaction-matter. For plate type fuels composed of ceramic particles dispersed in metallic matrix, one can observe the damage regions that arise due to the interaction fission products in the metallic matrix. Aiming at evaluating the extension of the damage regions in function of the particles and its diameters, in this paper, computational geometric simulations structure of plate type fuel cores, composed of UO 2 microspheres dispersed in stainless steel in several fractions of volume and diameters were carried out. The results of the simulations were exported to AutoCAD R where it was possible its visualization and analysis. (author)

  7. Minimization of CYP2D6 Polymorphic Differences and Improved Bioavailability via Transdermal Administration: Latrepirdine Example.

    Science.gov (United States)

    Chew, Marci L; Mordenti, Joyce; Yeoh, Thean; Ranade, Gautam; Qiu, Ruolun; Fang, Juanzhi; Liang, Yali; Corrigan, Brian

    2016-08-01

    Transdermal delivery has the potential to offer improved bioavailability by circumventing first-pass gut and hepatic metabolism. This study evaluated the pharmacokinetics of oral immediate release and transdermal latrepirdine in extensive and poor CYP2D6 metabolizers (EM/PM). Latrepirdine transdermal solution was prepared extemporaneously. The solution was applied with occlusive dressing to upper or middle back for 24 h. Each subject received a single dose of 8.14 mg oral, 5 mg transdermal, and 10 mg transdermal (EMs only) latrepirdine free base in a fixed sequence. Twelve EMs and 7 PMs (50-79 years) enrolled and completed the study. Latrepirdine was well tolerated following both routes of administration. Dose-normalized latrepirdine total exposures were approximately 11-fold and 1.5-fold higher in EMs and PMs, respectively following administration of transdermal relative to oral. Differences between EM and PM latrepirdine exposures were decreased, with PMs having 1.9- and 2.7-fold higher peak and total exposures, respectively, following transdermal administration compared to 11- and 20-fold higher exposures, respectively, following oral administration. Transdermal delivery can potentially mitigate the large intersubject differences observed with compounds metabolized primarily by CYP2D6. Transdermal delivery was readily accomplished in the clinic using an extemporaneously prepared solution [NCT00990613].

  8. Transdermal and intradermal delivery of therapeutic agents: application of physical technologies

    National Research Council Canada - National Science Library

    Banga, Ajay K

    2011-01-01

    .... Commercialization of transdermal drug delivery requires technology from many disciplines beyond pharmaceutical sciences, such as polymer chemistry, adhesion sciences, mass transport, web film coating...

  9. Baseline Design Compliance Matrix for the Type 4 In Situ Vapor Samplers and Supernate and Sludge and Soft Saltcake Grab Sampling

    International Nuclear Information System (INIS)

    BOGER, R.M.

    2000-01-01

    The DOE has identified a need to sample vapor space, exhaust ducts, supernate, sludge, and soft saltcake in waste tanks that store radioactive waste. This document provides the Design Compliance Matrix (DCM) for the Type 4 In-Situ Vapor Sampling (ISVS) system and the Grab Sampling System that are used for completing this type of sampling function. The DCM identifies the design requirements and the source of the requirements for the Type 4 ISVS system and the Grab Sampling system. The DCM is a single-source compilation design requirements for sampling and sampling support equipment and supports the configuration management of these systems

  10. Imaging with radiolabelled anti-membrane type 1 matrix metalloproteinase (MT1-MMP) antibody: potentials for characterizing atherosclerotic plaques

    Energy Technology Data Exchange (ETDEWEB)

    Kuge, Yuji [Kyoto University, Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto (Japan); Hokkaido University, Department of Tracer Kinetics and Bioanalysis, Graduate School of Medicine, Sapporo (Japan); Hokkaido University, Central Institute of Isotope Science, Sapporo (Japan); Takai, Nozomi; Ogawa, Yuki; Temma, Takashi; Nishigori, Kantaro; Ishino, Seigo; Kamihashi, Junko; Saji, Hideo [Kyoto University, Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto (Japan); Zhao, Yan [Hokkaido University, Department of Tracer Kinetics and Bioanalysis, Graduate School of Medicine, Sapporo (Japan); Kiyono, Yasushi [Kyoto University, Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto (Japan); University of Fukui, Biomedical Imaging Research Center, Fukui (Japan); Shiomi, Masashi [Kobe University Graduate School of Medicine, Institute for Experimental Animals, Kobe (Japan)

    2010-11-15

    Membrane type 1 matrix metalloproteinase (MT1-MMP) activates pro-MMP-2 and pro-MMP-13 to their active forms and plays important roles in the destabilization of atherosclerotic plaques. This study sought to determine the usefulness of {sup 99m}Tc-labelled monoclonal antibody (mAb), recognizing MT1-MMP, for imaging atherosclerosis in a rabbit model (WHHLMI rabbits). Anti-MT1-MMP monoclonal IgG{sub 3} and negative control IgG{sub 3} were radiolabelled with {sup 99m}Tc after derivatization with 6-hydrazinonicotinic acid (HYNIC) to yield {sup 99m}Tc-MT1-MMP mAb and {sup 99m}Tc-IgG{sub 3}, respectively. WHHLMI and control rabbits were injected with these radio-probes. The aorta was removed and radioactivity was measured at 24 h after the injection. Autoradiography and histological studies were performed. {sup 99m}Tc-MT1-MMP mAb accumulation in WHHLMI rabbit aortas was 5.4-fold higher than that of control rabbits. Regional {sup 99m}Tc-MT1-MMP mAb accumulation was positively correlated with MT1-MMP expression (r = 0.59, p < 0.0001), while {sup 99m}Tc-IgG{sub 3} accumulation was independent of MT1-MMP expression (r = 0.03, p = NS). The highest {sup 99m}Tc-MT1-MMP mAb accumulation was found in atheromatous lesions (4.8 {+-} 1.9, %ID x BW/mm{sup 2} x 10{sup 2}), followed in decreasing order by fibroatheromatous (1.8 {+-} 1.3), collagen-rich (1.6 {+-} 1.0) and neointimal lesions (1.5 {+-} 1.5). In contrast, {sup 99m}Tc-IgG{sub 3} accumulation was almost independent of the histological grade of lesions. Higher {sup 99m}Tc-MT1-MMP mAb accumulation in grade IV atheroma was shown in comparison with neointimal lesions or other more stable lesions. Nuclear imaging with {sup 99m}Tc-MT1-MMP mAb, in combination with CT and MRI, could provide new diagnostic imaging capabilities for detecting vulnerable plaques, although further investigations to improve target to blood ratios are strongly required. (orig.)

  11. Radioimmunodetection of membrane type-1 matrix metalloproteinase relevant to tumor malignancy with a pre-targeting method

    International Nuclear Information System (INIS)

    Sano, Kohei; Temma, Takashi; Kuge, Yuji; Kudo, Takashi; Kamihashi, Junko; Saji, Hideo; Zhao, Songji

    2010-01-01

    Since membrane type-1 matrix metalloproteinase (MT1-MMP) is exclusively expressed in tumors and is closely associated with metastasis and invasion, MT1-MMP is a potential target of radiotracers for the evaluation of tumor malignancy. In this study, we planned to visualize MT1-MMP in vivo by a two-step pre-targeting strategy using a streptavidin (SAv)-biotin system combined with anti-MT1-MMP monoclonal immunoglobulin (IgG) (anti-MT1-MMP monoclonal antibody (mAb)). Streptavidinylated anti-MT1-MMP mAb was synthesized by reacting biotinylated anti-MT1-MMP mAb with SAv. In the pre-targeting study, FM3A mouse breast carcinoma-implanted mice were injected with anti-MT1-MMP mAb-SAv, followed 72 h later with radioiodinated biotin, (3-[ 123/125 I]iodobenzoyl)norbiotinamide( 123/125 I-IBB). Biodistribution and imaging (single photon emission computed tomography (SPECT)/CT) data were collected at several time points in the 24 h period following introduction of the tracer. The comparison groups were injected with 125 I-IBB alone or with 125 I-IBB pre-targeted with negative control IgG-SAv. In the pre-targeting study for MT1-MMP, within 1 h of tracer injection, rapid tumor uptake and abrupt clearance from the blood of radioactivity (2.22, 0.87% injected dose/g at 1 h) were observed. The tumor to blood (T/B) radioactivity ratios were significantly higher than those from mice dosed with the pre-targeting negative control (p 125 I-IBB alone did not accumulate in tumors. SPECT/CT image analysis of FM3A bearing mice showed high-contrast tumor images after 3 h with minimal blood-pool activity. The present study that uses a pre-targeting method showed high T/B radioactivity ratios and clear tumor images of MT1-MMP. This imaging method may be useful for the clinical diagnosis of malignant tumors. (author)

  12. Imaging with radiolabelled anti-membrane type 1 matrix metalloproteinase (MT1-MMP) antibody: potentials for characterizing atherosclerotic plaques

    International Nuclear Information System (INIS)

    Kuge, Yuji; Takai, Nozomi; Ogawa, Yuki; Temma, Takashi; Nishigori, Kantaro; Ishino, Seigo; Kamihashi, Junko; Saji, Hideo; Zhao, Yan; Kiyono, Yasushi; Shiomi, Masashi

    2010-01-01

    Membrane type 1 matrix metalloproteinase (MT1-MMP) activates pro-MMP-2 and pro-MMP-13 to their active forms and plays important roles in the destabilization of atherosclerotic plaques. This study sought to determine the usefulness of 99m Tc-labelled monoclonal antibody (mAb), recognizing MT1-MMP, for imaging atherosclerosis in a rabbit model (WHHLMI rabbits). Anti-MT1-MMP monoclonal IgG 3 and negative control IgG 3 were radiolabelled with 99m Tc after derivatization with 6-hydrazinonicotinic acid (HYNIC) to yield 99m Tc-MT1-MMP mAb and 99m Tc-IgG 3 , respectively. WHHLMI and control rabbits were injected with these radio-probes. The aorta was removed and radioactivity was measured at 24 h after the injection. Autoradiography and histological studies were performed. 99m Tc-MT1-MMP mAb accumulation in WHHLMI rabbit aortas was 5.4-fold higher than that of control rabbits. Regional 99m Tc-MT1-MMP mAb accumulation was positively correlated with MT1-MMP expression (r = 0.59, p 99m Tc-IgG 3 accumulation was independent of MT1-MMP expression (r = 0.03, p = NS). The highest 99m Tc-MT1-MMP mAb accumulation was found in atheromatous lesions (4.8 ± 1.9, %ID x BW/mm 2 x 10 2 ), followed in decreasing order by fibroatheromatous (1.8 ± 1.3), collagen-rich (1.6 ± 1.0) and neointimal lesions (1.5 ± 1.5). In contrast, 99m Tc-IgG 3 accumulation was almost independent of the histological grade of lesions. Higher 99m Tc-MT1-MMP mAb accumulation in grade IV atheroma was shown in comparison with neointimal lesions or other more stable lesions. Nuclear imaging with 99m Tc-MT1-MMP mAb, in combination with CT and MRI, could provide new diagnostic imaging capabilities for detecting vulnerable plaques, although further investigations to improve target to blood ratios are strongly required. (orig.)

  13. Enhancement of transdermal delivery of ibuprofen using microemulsion vehicle.

    Science.gov (United States)

    Hu, Liandong; Hu, Qiaofeng; Yang, Jianxue

    2014-10-01

    The objective of this study was to find a stable microemulsion vehicle for transdermal delivery of ibuprofen to improve the skin permeability. Microemulsion was prepared using different sorts of oils, surfactants and co-surfactants. Pseudo-ternary phase diagrams were used to evaluate the microemulsion domain. The effects of oleic acid and surfactant mixture on skin permeation of ibuprofen were evaluated with excised skins. The optimum formulation F3 consisting of 6% oleic acid, 30% Cremophor RH40/Transcutol P (2:1, w/w) and 59% water phase, showed a high permeation rate of 42.98 µg/cm(2)/hr. The mean droplet size of microemulsion was about 43 nm and no skin irritation signs were observed on the skin of rabbits. These results indicated that this novel microemulsion is a useful formulation for the transdermal delivery of ibuprofen.

  14. Novel engineered systems for oral, mucosal and transdermal drug delivery.

    Science.gov (United States)

    Li, Hairui; Yu, Yuan; Faraji Dana, Sara; Li, Bo; Lee, Chi-Ying; Kang, Lifeng

    2013-08-01

    Technological advances in drug discovery have resulted in increasing number of molecules including proteins and peptides as drug candidates. However, how to deliver drugs with satisfactory therapeutic effect, minimal side effects and increased patient compliance is a question posted before researchers, especially for those drugs with poor solubility, large molecular weight or instability. Microfabrication technology, polymer science and bioconjugate chemistry combine to address these problems and generate a number of novel engineered drug delivery systems. Injection routes usually have poor patient compliance due to their invasive nature and potential safety concerns over needle reuse. The alternative non-invasive routes, such as oral, mucosal (pulmonary, nasal, ocular, buccal, rectal, vaginal), and transdermal drug delivery have thus attracted many attentions. Here, we review the applications of the novel engineered systems for oral, mucosal and transdermal drug delivery.

  15. Dissolving polymeric microneedle arrays for electrically assisted transdermal drug delivery.

    Science.gov (United States)

    Garland, Martin J; Caffarel-Salvador, Ester; Migalska, Katarzyna; Woolfson, A David; Donnelly, Ryan F

    2012-04-10

    It has recently been proposed that the combination of skin barrier impairment using microneedles (MNs) coupled with iontophoresis (ITP) may broaden the range of drugs suitable for transdermal delivery, as well as enabling the rate of delivery to be achieved with precise electronic control. However, no reports exist on the combination of ITP with in situ drug loaded polymeric MN delivery systems. Furthermore, although a number of studies have highlighted the importance of MN design for transdermal drug delivery enhancement, to date, there has been no systematic investigation of the influence of MN geometry on the performance of polymeric MN arrays which are designed to remain in contact with the skin during the period of drug delivery. As such, for the first time, this study reports on the effect of MN heigth and MN density upon the transdermal delivery of small hydrophilic compounds (theophylline, methylene blue, and fluorescein sodium) across neonatal porcine skin in vitro, with the optimised MN array design evaluated for its potential in the electrically faciliatated delivery of peptide (bovine insulin) and protein (fluorescein isothiocyanate-labelled bovine serum albumin (FTIC-BSA)) macromolecules. The results of the in vitro drug release investigations revealed that the extent of transdermal delivery was dependent upon the design of the MN array employed, whereby an increase in MN height and an increase in MN density led to an increase in the extent of transdermal drug delivery achieved 6h after MN application. Overall, the in vitro permeation studies revealed that the MN design containing 361 MNs/cm(2) of 600 μm height resulted in the greatest extent of transdermal drug delivery. As such, this design was evaluated for its potential in the MN mediated iontophoretic transdermal delivery. Whilst the combination of MN and ITP did not further enhance the extent of small molecular weight solute delivery, the extent of peptide/protein release was significantly

  16. Current advances in transdermal delivery of drugs for Alzheimer's disease

    Science.gov (United States)

    Nguyen, Thuy Trang; Giau, Vo Van; Vo, Tuong Kha

    2017-01-01

    Alzheimer's disease (AD) is a common, progressive, fatal neurodegenerative disorder, which will play an increasingly important role both socially and financially in the aging populations. Treatments for AD show modest improvements in cognition and global functioning among patients. Furthermore, the oral administration of treating AD has had some drawbacks that decrease the medication adherence and efficacy of the therapy. Transdermal drugs are proposed as an alternative remedy to overcome the disadvantages of current pharmaceutical dosage options for this chronic disorder. They could have different strengths, such as offering a stable diffusion of active substance, avoiding the first pass metabolism, and reducing system adverse reactions. This article reviews the technical principles, novel techniques of transdermal delivery drug, and prospects for future development for the management of cognitive and behavioral dysfunctions in AD patients. PMID:28706327

  17. Hybrid electrospun chitosan-phospholipids nanofibers for transdermal drug delivery

    DEFF Research Database (Denmark)

    Mendes, Ana Carina Loureiro; Gorzelanny, Christian; Halter, Natalia

    2016-01-01

    Chitosan (Ch) polysaccharide was mixed with phospholipids (P) to generate electrospun hybrid nanofibers intended to be used as platforms for transdermal drug delivery. Ch/P nanofibers exibithed average diameters ranging from 248 +/- 94 nm to 600 +/- 201 nm, depending on the amount of phospholipids...... used. Fourier Transformed Infra-Red (FTIR) spectroscopy and Dynamic Light Scattering (DLS) data suggested the occurrence of electrostatic interactions between amine groups of chitosan with the phospholipid counterparts. The nanofibers were shown to be stable for at least 7 days in Phosphate Buffer...... culture plate (control). The release of curcumin, diclofenac and vitamin B12, as model drugs, from Ch/P hybrid nanofibers was investigated, demonstrating their potential utilization as a transdermal drug delivery system....

  18. Inkjet printing of insulin microneedles for transdermal delivery.

    Science.gov (United States)

    Ross, Steven; Scoutaris, Nicolaos; Lamprou, Dimitrios; Mallinson, David; Douroumis, Dennis

    2015-08-01

    Inkjet printing technology was used to apply insulin polymeric layers on metal microneedles for transdermal delivery. A range of various polymers such as gelatin (GLN), polyvinyl caprolactame-polyvinyl acetate-polyethylene glycol (SOL), poly(2-ethyl-2-oxazoline) (POX) and trehalose (THL) were assessed for their capacity to form thin uniform and homogeneous layers that preserve insulin intact. Atomic force microscopy (AFM) showed homogeneous insulin-polymer layers without any phase separation while SOL demonstrated the best performance. Circular discroism (CD) analysis of rehydrated films showed that insulin's alpha helices and β-sheet were well preserved for THL and SOL. In contrast, GLN and POX insulin layers revealed small band shifts indicating possible conformational changes. Insulin release in Franz diffusion cells from MNs inserted into porcine skin showed rapid release rates for POX and GLN within the first 20 min. Inkjet printing was proved an effective approach for transdermal delivery of insulin in solid state.

  19. Current advances in transdermal delivery of drugs for Alzheimer's disease.

    Science.gov (United States)

    Nguyen, Thuy Trang; Giau, Vo Van; Vo, Tuong Kha

    2017-01-01

    Alzheimer's disease (AD) is a common, progressive, fatal neurodegenerative disorder, which will play an increasingly important role both socially and financially in the aging populations. Treatments for AD show modest improvements in cognition and global functioning among patients. Furthermore, the oral administration of treating AD has had some drawbacks that decrease the medication adherence and efficacy of the therapy. Transdermal drugs are proposed as an alternative remedy to overcome the disadvantages of current pharmaceutical dosage options for this chronic disorder. They could have different strengths, such as offering a stable diffusion of active substance, avoiding the first pass metabolism, and reducing system adverse reactions. This article reviews the technical principles, novel techniques of transdermal delivery drug, and prospects for future development for the management of cognitive and behavioral dysfunctions in AD patients.

  20. Evaluation of Diclofenac Prodrugs for Enhancing Transdermal Delivery

    OpenAIRE

    Lobo, Shabbir; Li, Henan; Farhan, Nashid; Yan, Guang

    2013-01-01

    The purpose of this study was to evaluate the approach of using diclofenac acid (DA) prodrugs for enhancing transdermal delivery. Methanol diclofenac ester (MD), ethylene glycol diclofenac ester (ED), glycerol diclofenac ester (GD), and 1,3-propylene glycol diclofenac ester (PD) were synthesized and evaluated for their physicochemical properties such as solubilities, octanol/water partition coefficients, stratum corneum/water partition coefficients, hydrolysis rates, and bioconversion rates. ...

  1. Current advances in transdermal delivery of drugs for alzheimer's disease

    OpenAIRE

    Thuy Trang Nguyen; Vo Van Giau; Tuong Kha Vo

    2017-01-01

    Alzheimer's disease (AD) is a common, progressive, fatal neurodegenerative disorder, which will play an increasingly important role both socially and financially in the aging populations. Treatments for AD show modest improvements in cognition and global functioning among patients. Furthermore, the oral administration of treating AD has had some drawbacks that decrease the medication adherence and efficacy of the therapy. Transdermal drugs are proposed as an alternative remedy to overcome the...

  2. Optimization of transdermal delivery using magainin pore-forming peptide

    OpenAIRE

    Kim, Yeu-Chun; Ludovice, Peter J.; Prausnitz, Mark R.

    2008-01-01

    The skin's outer layer of stratum corneum, which is a thin tissue containing multilamellar lipid bilayers, is the main barrier to drug delivery to the skin. To increase skin permeability, our previous work has shown large enhancement of transdermal permeation using a pore-forming peptide, magainin, which was formulated with N-lauroyl sarcosine (NLS) in 50% ethanol-in-PBS. Mechanistic analysis suggested that magainin and NLS can increase skin permeability by disrupting stratum corneum lipid st...

  3. Microneedles for Transdermal Biosensing: Current Picture and Future Direction.

    Science.gov (United States)

    Ventrelli, Letizia; Marsilio Strambini, Lucanos; Barillaro, Giuseppe

    2015-12-09

    A novel trend is rapidly emerging in the use of microneedles, which are a miniaturized replica of hypodermic needles with length-scales of hundreds of micrometers, aimed at the transdermal biosensing of analytes of clinical interest, e.g., glucose, biomarkers, and others. Transdermal biosensing via microneedles offers remarkable opportunities for moving biosensing technologies and biochips from research laboratories to real-field applications, and envisages easy-to-use point-of-care microdevices with pain-free, minimally invasive, and minimal-training features that are very attractive for both developed and emerging countries. In addition to this, microneedles for transdermal biosensing offer a unique possibility for the development of biochips provided with end-effectors for their interaction with the biological system under investigation. Direct and efficient collection of the biological sample to be analyzed will then become feasible in situ at the same length-scale of the other biochip components by minimally trained personnel and in a minimally invasive fashion. This would eliminate the need for blood extraction using hypodermic needles and reduce, in turn, related problems, such as patient infections, sample contaminations, analysis artifacts, etc. The aim here is to provide a thorough and critical analysis of state-of-the-art developments in this novel research trend, and to bridge the gap between microneedles and biosensors. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Development and evaluation of transdermal organogels containing nicorandil.

    Science.gov (United States)

    Madan, J R; Sagar, Banode; Chellappan, Dinesh K; Dua, Kamal

    2013-01-01

    The objective of the study was to formulate a transdermal product containing Nicorandil as a model drug, because it has been first drug of choice to treat angina and hypertension. A further objective was to reduce its side effects. The transdermal product was prepared using various synthetic and natural gelling agents such as Carbopol 934p, Carbopol 974p, HPMC K15M and HPMC K100M. Various penetration enhancers were incorporated to enhance the diffusion across the rat skin. A further objective was to formulate organogels and minimize the concentration of penetration enhancer to 50% of the concentration used in gels and yet to achieve the maximum drug release. The prepared formulations were evaluated for their physical appearance, viscosity, spreadability, drug content and freeze thaw cycle. Based on in vitro studies across rat skin and human cadaver skin it was concluded that Nicrorandil transdermal organogel formulation using HPMC K100M with 2% w/w Transcutol-P shows increase in cumulative diffusion of Nicorandil amongst all other formulations.

  5. Microneedles array with biodegradable tips for transdermal drug delivery

    Science.gov (United States)

    Iliescu, Ciprian; Chen, Bangtao; Wei, Jiashen; Tay, Francis E. H.

    2008-12-01

    The paper presented an enhancement solution for transdermal drug delivery using microneedles array with biodegradable tips. The microneedles array was fabricated by using deep reactive ion etching (DRIE) and the biodegradable tips were made to be porous by electrochemical etching process. The porous silicon microneedle tips can greatly enhance the transdermal drug delivery in a minimum invasion, painless, and convenient manner, at the same time; they are breakable and biodegradable. Basically, the main problem of the silicon microneedles consists of broken microneedles tips during the insertion. The solution proposed is to fabricate the microneedle tip from a biodegradable material - porous silicon. The silicon microneedles are fabricated using DRIE notching effect of reflected charges on mask. The process overcomes the difficulty in the undercut control of the tips during the classical isotropic silicon etching process. When the silicon tips were formed, the porous tips were then generated using a classical electrochemical anodization process in MeCN/HF/H2O solution. The paper presents the experimental results of in vitro release of calcein and BSA with animal skins using a microneedle array with biodegradable tips. Compared to the transdermal drug delivery without any enhancer, the microneedle array had presented significant enhancement of drug release.

  6. Future of the transdermal drug delivery market--have we barely touched the surface?

    Science.gov (United States)

    Watkinson, Adam C; Kearney, Mary-Carmel; Quinn, Helen L; Courtenay, Aaron J; Donnelly, Ryan F

    2016-01-01

    Transdermal drug delivery is the movement of drugs across the skin for absorption into the systemic circulation. Transfer of the drug can occur via passive or active means; passive transdermal products do not disrupt the stratum corneum to facilitate delivery whereas active technologies do. Due to the very specific physicochemical properties necessary for successful passive transdermal drug delivery, this sector of the pharmaceutical industry is relatively small. There are many well-documented benefits of this delivery route however, and as a result there is great interest in increasing the number of therapeutic substances that can be delivered transdermally. This review discusses the various transdermal products that are currently/have been marketed, and the paths that led to their success, or lack of. Both passive and active transdermal technologies are considered with the advantages and limitations of each highlighted. In addition to marketed products, technologies that are in the investigative stages by various pharmaceutical companies are reviewed. Passive transdermal drug delivery has made limited progress in recent years, however with the ongoing intense research into active technologies, there is great potential for growth within the transdermal delivery market. A number of active technologies have already been translated into marketed products, with other platforms including microneedles, rapidly progressing towards commercialisation.

  7. Efficacy of a single dose of a transdermal diclofenac patch as pre ...

    African Journals Online (AJOL)

    Background: We compared the analgesic efficacy of a transdermal diclofenac patch 100 mg (NuPatch® 100, Zydus Cadila, Ahmedabad, India) and intramuscular diclofenac sodium 75 mg (Voveran®, Novartis, India) for postoperative analgesia, and the associated side-effects of the transdermal diclofenac patch. Method: ...

  8. Transdermal administration of radiolabelled [14C]rotigotine by a patch formulation: A mass balance trial

    NARCIS (Netherlands)

    Cawello, W.; Wolff, H.M.; Meuling, W.J.A.; Horstmann, R.; Braun, M.

    2007-01-01

    Background and objective: The dopamine agonist rotigotine has been formulated in a silicone-based transdermal system for once-daily administration. The objective of the present study was to characterise the mass balance of rotigotine in humans after administration of a single transdermal patch

  9. Characterization of physicochemical properties of hydroxypropyl methylcellulose (HPMC) type 2208 and their influence on prolonged drug release from matrix tablets

    OpenAIRE

    Devjak Novak, Sabina; Šporar, Elena; Vrečer, Franc; Baumgartner, Saša

    2015-01-01

    The key physicochemical properties of functional excipients should be identified, and the influence of their variability on the properties of the final dosage form should be evaluated during the development phase. Excipients produced by different manufacturers and/or by differentb manufacturing processes should have comparable properties. Hydroxypropyl methylcellulose (HPMC) with a high molecular weight is a functional excipient often used in solid matrix systems with prolonged release of act...

  10. Type II collagen peptide is able to accelerate embryonic chondrocyte differentiation: an association with articular cartilage matrix resorption in osteoarthrosis

    Directory of Open Access Journals (Sweden)

    Elena Vasil'evna Chetina

    2010-01-01

    Conclusion. The effect of CP on gene expression and collagen decomposition activity depends on the morphotype of embryonic chondrocytes. Lack of effect of CP on collagen decomposition activity in both the embryonic hypertrophic chondrocytes and the cartilage explants from OA patients supports the hypothesis that the hypertrophic morphotype is a dominant morphotype of articular chondrocytes in OA. Moreover, collagen decomposition products can be involved in the resorption of matrix in OA and in the maintenance of chronic nature of the pathology.

  11. Accelerated stability testing of a transdermal patch composed of eserine and pralidoxime chloride for prophylaxis against (±-anatoxin A poisoning

    Directory of Open Access Journals (Sweden)

    Subham Banerjee

    2014-06-01

    Full Text Available The current study evaluated the stability potential of a transdermal patch composed of eserine and pralidoxime chloride for prophylaxis against (±-anatoxin A poisoning. The drug combinations were fabricated in an adhesive matrix system supported by a backing membrane and attached to a temporary release liner. Stability testing of the optimized formulation was established for 6 months under accelerated study conditions as per International Conference on Harmonisation guidelines. Results obtained after 6 months showed that the optimized patch formulation was stable with respect to drugs content, pH, diffusion, visual inspection, and other analytical parameters.

  12. beachmat: A Bioconductor C++ API for accessing high-throughput biological data from a variety of R matrix types.

    Directory of Open Access Journals (Sweden)

    Aaron T L Lun

    2018-05-01

    Full Text Available Biological experiments involving genomics or other high-throughput assays typically yield a data matrix that can be explored and analyzed using the R programming language with packages from the Bioconductor project. Improvements in the throughput of these assays have resulted in an explosion of data even from routine experiments, which poses a challenge to the existing computational infrastructure for statistical data analysis. For example, single-cell RNA sequencing (scRNA-seq experiments frequently generate large matrices containing expression values for each gene in each cell, requiring sparse or file-backed representations for memory-efficient manipulation in R. These alternative representations are not easily compatible with high-performance C++ code used for computationally intensive tasks in existing R/Bioconductor packages. Here, we describe a C++ interface named beachmat, which enables agnostic data access from various matrix representations. This allows package developers to write efficient C++ code that is interoperable with dense, sparse and file-backed matrices, amongst others. We evaluated the performance of beachmat for accessing data from each matrix representation using both simulated and real scRNA-seq data, and defined a clear memory/speed trade-off to motivate the choice of an appropriate representation. We also demonstrate how beachmat can be incorporated into the code of other packages to drive analyses of a very large scRNA-seq data set.

  13. beachmat: A Bioconductor C++ API for accessing high-throughput biological data from a variety of R matrix types.

    Science.gov (United States)

    Lun, Aaron T L; Pagès, Hervé; Smith, Mike L

    2018-05-01

    Biological experiments involving genomics or other high-throughput assays typically yield a data matrix that can be explored and analyzed using the R programming language with packages from the Bioconductor project. Improvements in the throughput of these assays have resulted in an explosion of data even from routine experiments, which poses a challenge to the existing computational infrastructure for statistical data analysis. For example, single-cell RNA sequencing (scRNA-seq) experiments frequently generate large matrices containing expression values for each gene in each cell, requiring sparse or file-backed representations for memory-efficient manipulation in R. These alternative representations are not easily compatible with high-performance C++ code used for computationally intensive tasks in existing R/Bioconductor packages. Here, we describe a C++ interface named beachmat, which enables agnostic data access from various matrix representations. This allows package developers to write efficient C++ code that is interoperable with dense, sparse and file-backed matrices, amongst others. We evaluated the performance of beachmat for accessing data from each matrix representation using both simulated and real scRNA-seq data, and defined a clear memory/speed trade-off to motivate the choice of an appropriate representation. We also demonstrate how beachmat can be incorporated into the code of other packages to drive analyses of a very large scRNA-seq data set.

  14. beachmat: A Bioconductor C++ API for accessing high-throughput biological data from a variety of R matrix types

    Science.gov (United States)

    Pagès, Hervé

    2018-01-01

    Biological experiments involving genomics or other high-throughput assays typically yield a data matrix that can be explored and analyzed using the R programming language with packages from the Bioconductor project. Improvements in the throughput of these assays have resulted in an explosion of data even from routine experiments, which poses a challenge to the existing computational infrastructure for statistical data analysis. For example, single-cell RNA sequencing (scRNA-seq) experiments frequently generate large matrices containing expression values for each gene in each cell, requiring sparse or file-backed representations for memory-efficient manipulation in R. These alternative representations are not easily compatible with high-performance C++ code used for computationally intensive tasks in existing R/Bioconductor packages. Here, we describe a C++ interface named beachmat, which enables agnostic data access from various matrix representations. This allows package developers to write efficient C++ code that is interoperable with dense, sparse and file-backed matrices, amongst others. We evaluated the performance of beachmat for accessing data from each matrix representation using both simulated and real scRNA-seq data, and defined a clear memory/speed trade-off to motivate the choice of an appropriate representation. We also demonstrate how beachmat can be incorporated into the code of other packages to drive analyses of a very large scRNA-seq data set. PMID:29723188

  15. Microneedle-assisted transdermal delivery of Zolmitriptan: effect of microneedle geometry, in vitro permeation experiments, scaling analyses and numerical simulations.

    Science.gov (United States)

    Uppuluri, Chandra Teja; Devineni, Jyothirmayee; Han, Tao; Nayak, Atul; Nair, Kartik J; Whiteside, Benjamin R; Das, Diganta B; Nalluri, Buchi N

    2017-08-01

    The present study was aimed to investigate the effect of salient microneedle (MN) geometry parameters like length, density, shape and type on transdermal permeation enhancement of Zolmitriptan (ZMT). Two types of MN devices viz. AdminPatch ® arrays (ADM) (0.6, 0.9, 1.2 and 1.5 mm lengths) and laboratory fabricated polymeric MNs (PM) of 0.6 mm length were employed. In the case of PMs, arrays were applied thrice at different places within a 1.77 cm 2 skin area (PM-3) to maintain the MN density closer to 0.6 mm ADM. Scaling analyses was done using dimensionless parameters like concentration of ZMT (C t /C s ), thickness (h/L) and surface area of the skin (Sa/L 2 ). Micro-injection molding technique was employed to fabricate PM. Histological studies revealed that the PM, owing to their geometry/design, formed wider and deeper microconduits when compared to ADM of similar length. Approximately 3.17- and 3.65-fold increase in ZMT flux values were observed with 1.5 mm ADM and PM-3 applications when compared to the passive studies. Good correlations were observed between different dimensionless parameters with scaling analyses. Numerical simulations, using MATLAB and COMSOL software, based on experimental data and histological images provided information regarding the ZMT skin distribution after MN application. Both from experimental studies and simulations, it was inferred that PM were more effective in enhancing the transdermal delivery of ZMT when compared to ADM. The study suggests that MN application enhances the ZMT transdermal permeation and the geometrical parameters of MNs play an important role in the degree of such enhancement.

  16. Proportion of collagen type II in the extracellular matrix promotes the differentiation of human adipose-derived mesenchymal stem cells into nucleus pulposus cells.

    Science.gov (United States)

    Tao, Yiqing; Zhou, Xiaopeng; Liu, Dongyu; Li, Hao; Liang, Chengzhen; Li, Fangcai; Chen, Qixin

    2016-01-01

    During degeneration process, the catabolism of collagen type II and anabolism of collagen type I in nucleus pulposus (NP) may influence the bioactivity of transplanted cells. Human adipose-derived mesenchymal stem cells (hADMSCs) were cultured as a micromass or in a series of gradual proportion hydrogels of a mix of collagen types I and II. Cell proliferation and cytotoxicity were detected using CCK-8 and LDH assays respectively. The expression of differentiation-related genes and proteins, including SOX9, aggrecan, collagen type I, and collagen type II, was examined using RT-qPCR and Western blotting. Novel phenotypic genes were also detected by RT-qPCR and western blotting. Alcian blue and dimethylmethylene blue assays were used to investigate sulfate proteoglycan expression, and PI3K/AKT, MAPK/ERK, and Smad signaling pathways were examined by Western blotting. The results showed collagen hydrogels have good biocompatibility, and cell proliferation increased after collagen type II treatment. Expressions of SOX9, aggrecan, and collagen type II were increased in a collagen type II dependent manner. Sulfate proteoglycan synthesis increased in proportion to collagen type II concentration. Only hADMSCs highly expressed NP cell marker KRT19 in collagen type II culture. Additionally, phosphorylated Smad3, which is associated with phosphorylated ERK, was increased after collagen type II-stimulation. The concentration and type of collagen affect hADMSC differentiation into NP cells. Collagen type II significantly ameliorates hADMSC differentiation into NP cells and promotes extracellular matrix synthesis. Therefore, anabolism of collagen type I and catabolism of type II may attenuate the differentiation and biosynthesis of transplanted stem cells. © 2016 International Union of Biochemistry and Molecular Biology.

  17. Effect of polymer type on characterization and filtration performances of multi-walled carbon nanotubes (MWCNT)-COOH-based polymeric mixed matrix membranes.

    Science.gov (United States)

    Sengur-Tasdemir, Reyhan; Mokkapati, Venkata R S S; Koseoglu-Imer, Derya Y; Koyuncu, Ismail

    2018-05-01

    Multi-walled carbon nanotubes (MWCNTs) can be used for the fabrication of mixed matrix polymeric membranes that can enhance filtration perfomances of the membranes by modifying membrane surface properties. In this study, detailed characterization and filtration performances of MWCNTs functionalized with COOH group, blended into polymeric flat-sheet membranes were investigated using different polymer types. Morphological characterization was carried out using atomic force microscopy, scanning electron microscopy and contact angle measurements. For filtration performance tests, protein, dextran, E. coli suspension, Xanthan Gum and real activated sludge solutions were used. Experimental data and analyses revealed that Polyethersulfone (PES) + MWCNT-COOH mixed matrix membranes have superior performance abilities compared to other tested membranes.

  18. A-centres build-up kinetics in the conductive matrix of pulled n-type silicon with calculation of their recharges at defect clusters

    International Nuclear Information System (INIS)

    Dolgolenko, A.P.; Fishchuk, I.I.

    1981-01-01

    Pulled n-Si samples with rho approximately 40 Ωcm are investigated after irradiation with different doses of fast-pile neutrons. It is known that the simple defects are created not only in the conductive matrix but also in the region of the space charge of defect clusters. Then the charge state, for example, of A-centres in the region of the space charge is defined by both, the temperature and the value of the electrostatical potential. If this circumstance is not taken into account the calculation of the conductive volume is not precise enough. In the present paper the temperature dependence of the volume fraction is calculated, in which the space charge of defect clusters occurs, taking into account the recharges of A-centres in the region of the space charge. Using the expression obtained the A-centres build-up kinetics in the conductive matrix of pulled n-type silicon is calculated. (author)

  19. The application of anethole, menthone, and eugenol in transdermal penetration of valsartan: Enhancement and mechanistic investigation.

    Science.gov (United States)

    Ahad, Abdul; Aqil, Mohd; Ali, Asgar

    2016-01-01

    The main barrier for transdermal delivery is the obstacle property of the stratum corneum. Many types of chemical penetration enhancers have been used to breach the skin barrier; among the penetration enhancers, terpenes are found as the most highly advanced, safe, and proven category. In the present investigation, the terpenes anethole, menthone, and eugenol were used to enhance the permeation of valsartan through rat skin in vitro and their enhancement mechanism was investigated. Skin permeation studies of valsartan across rat skin in the absence and the presence of terpenes at 1% w/v, 3% w/v, and 5% w/v in vehicle were carried out using the transdermal diffusion cell sampling system across rat skin and samples were withdrawn from the receptor compartment at 1, 2, 3, 4, 6, 8, 10, 12, and 24 h and analysed for drug content by the HPLC method. The mechanism of skin permeation enhancement of valsartan by terpenes treatment was evaluated by Fourier transform infrared spectroscopy (FTIR) analysis and differential scanning calorimetry (DSC). All the investigated terpenes provided a significant (p valsartan flux at a concentration of 1%, and less so at 3% and 5%. The effectiveness of terpenes at 1% concentration was in the following order: anethole > menthone > eugenol with 4.4-, 4.0-, and 3.0-fold enhancement ratio over control, respectively. DSC study showed that the treatment of stratum corneum with anethole shifted endotherm down to lower melting point while FTIR studies revealed that anethole produced maximum decrease in peak height and area than other two terpenes. The investigated terpenes can be successfully used as potential enhancers for the enhancement of skin permeation of lipophilic drug.

  20. Curcumin loaded chitin nanogels for skin cancer treatment via the transdermal route.

    Science.gov (United States)

    Mangalathillam, Sabitha; Rejinold, N Sanoj; Nair, Amrita; Lakshmanan, Vinoth-Kumar; Nair, Shantikumar V; Jayakumar, Rangasamy

    2012-01-07

    In this study, curcumin loaded chitin nanogels (CCNGs) were developed using biocompatible and biodegradable chitin with an anticancer curcumin drug. Chitin, as well as curcumin, is insoluble in water. However, the developed CCNGs form a very good and stable dispersion in water. The CCNGs were analyzed by DLS, SEM and FTIR and showed spherical particles in a size range of 70-80 nm. The CCNGs showed higher release at acidic pH compared to neutral pH. The cytotoxicity of the nanogels were analyzed on human dermal fibroblast cells (HDF) and A375 (human melanoma) cell lines and the results show that CCNGs have specific toxicity on melanoma in a concentration range of 0.1-1.0 mg mL(-1), but less toxicity towards HDF cells. The confocal analysis confirmed the uptake of CCNGs by A375. The apoptotic effect of CCNGs was analyzed by a flow-cytometric assay and the results indicate that CCNGs at the higher concentration of the cytotoxic range showed comparable apoptosis as the control curcumin, in which there was negligible apoptosis induced by the control chitin nanogels. The CCNGs showed a 4-fold increase in steady state transdermal flux of curcumin as compared to that of control curcumin solution. The histopathology studies of the porcine skin samples treated with the prepared materials showed loosening of the horny layer of the epidermis, facilitating penetration with no observed signs of inflammation. These results suggest that the formulated CCNGs offer specific advantage for the treatment of melanoma, the most common and serious type of skin cancer, by effective transdermal penetration.

  1. Characterization of physicochemical properties of hydroxypropyl methylcellulose (HPMC) type 2208 and their influence on prolonged drug release from matrix tablets.

    Science.gov (United States)

    Devjak Novak, S; Šporar, E; Baumgartner, S; Vrečer, F

    2012-07-01

    The key physicochemical properties of functional excipients should be identified, and the influence of their variability on the properties of the final dosage form should be evaluated during the development phase. Excipients produced by different manufacturers and/or by different manufacturing processes should have comparable properties. Hydroxypropyl methylcellulose (HPMC) with a high molecular weight is a functional excipient often used in solid matrix systems with prolonged release of active pharmaceutical ingredients (API). This study investigates whether HPMC manufactured by two manufacturers using different chemical procedures differs in particle-size distribution, particle shape, particle morphology, chemical composition, and dissolution of diclofenac sodium as a model drug. NIR spectroscopy was introduced and calibration models were developed to detect physical differences among HPMC batches from two different origins. The physical differences between HPMC samples were additionally confirmed with scanning electron microscopy (SEM), gas chromatography (GC) measurements, and dissolution testing of hydrophilic matrix tablets. Our results prove that, even if HPMC polymers manufactured from two different sources comply with the pharmacopeial specification, they significantly differ in physicochemical properties and thus influence the properties of the formulated dosage forms. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Prenatal cocaine increases striatal serotonin innervation without altering the patch/matrix organization of intrinsic cell types.

    Science.gov (United States)

    Snyder-Keller, A M; Keller, R W

    1993-08-20

    The effect of prenatal cocaine on the anatomical development of the striatum was examined. The distribution and density of dopaminergic innervation of the striatum of animals exposed to cocaine during the second and third week of gestation was not noticeably different from prenatally saline-injected or untreated controls at any age. The patch/matrix organization of the striatum also appeared unaltered: neurons exhibiting dense substance P staining were localized to patches that overlapped dopamine terminal patches early in development, and enkephalin- and calbindin-immunoreactive neurons were found segregated to the matrix. Histochemical staining for acetylcholinesterase and NADPH diaphorase also revealed no differences between prenatally cocaine-treated and control brains. Whereas prenatal cocaine treatment failed to modify the basic compartmental organization of the striatum, it did lead to a hyperinnervation of serotonin-immunoreactive fibers which developed slowly after birth. Thus prenatal exposure to cocaine is capable of altering the ingrowth of serotonergic projections to the striatum while producing no change in the organization of neurons intrinsic to the striatum.

  3. Evaluating adhesion reduction efficacy of type I/III collagen membrane and collagen-GAG resorbable matrix in primary flexor tendon repair in a chicken model.

    Science.gov (United States)

    Turner, John B; Corazzini, Rubina L; Butler, Timothy J; Garlick, David S; Rinker, Brian D

    2015-09-01

    Reduction of peritendinous adhesions after injury and repair has been the subject of extensive prior investigation. The application of a circumferential barrier at the repair site may limit the quantity of peritendinous adhesions while preserving the tendon's innate ability to heal. The authors compare the effectiveness of a type I/III collagen membrane and a collagen-glycosaminoglycan (GAG) resorbable matrix in reducing tendon adhesions in an experimental chicken model of a "zone II" tendon laceration and repair. In Leghorn chickens, flexor tendons were sharply divided using a scalpel and underwent repair in a standard fashion (54 total repairs). The sites were treated with a type I/III collagen membrane, collagen-GAG resorbable matrix, or saline in a randomized fashion. After 3 weeks, qualitative and semiquantitative histological analysis was performed to evaluate the "extent of peritendinous adhesions" and "nature of tendon healing." The data was evaluated with chi-square analysis and unpaired Student's t test. For both collagen materials, there was a statistically significant improvement in the degree of both extent of peritendinous adhesions and nature of tendon healing relative to the control group. There was no significant difference seen between the two materials. There was one tendon rupture observed in each treatment group. Surgical handling characteristics were subjectively favored for type I/III collagen membrane over the collagen-GAG resorbable matrix. The ideal method of reducing clinically significant tendon adhesions after injury remains elusive. Both materials in this study demonstrate promise in reducing tendon adhesions after flexor tendon repair without impeding tendon healing in this model.

  4. Optimization of Microemulsion Based Transdermal Gel of Triamcinolone.

    Science.gov (United States)

    Jagdale, Swati; Chaudhari, Bhagyashree

    2017-01-01

    Triamcinolone is a long acting corticosteroid used in the treatment of arthritis, eczema, psoriasis and similar conditions which cause inflammation. Triamcinolone has half-life of 88min. Prolonged oral use is associated with gastrointestinal adverse effects as peptic ulcer, abdominal distention and ulcerative esophagitis as described in various patents. Microemulgel offers advantage of better stability, better loading capacity and controlled release especially for drug with short half life. Objective of the present study was to optimize microemulgel based transdermal delivery of triamcinolone. Saturated solubility of triamcinolone in various oils, surfactants and co-surfactants is estimated. Pseudo-ternary phase diagrams were constructed to determine the region of transparent microemulsion. Microemulsion was evaluated for globule size (FE-SEM, zetasizer), % transmittance, pH, viscosity, conductivity etc. Design of experiment was used to optimize microemulsion based gel. Carbopol 971P and HPMC K100M were used as independent variables. Microemulsion based gel was evaluated for in-vitro as well as ex-vivo parameters. Microemulsion was formulated with oleic acid, lauroglycol FCC and propylene glycol. PDI 0.197 indicated microemulsion is mono-disperse. 32 factorial design gave batch F8 as optimized. Design expert suggested drug release; gel viscosity and bio-adhesive strength were three significant dependant factors affecting the transdermal delivery. F8 showed drug release 92.62.16±1.22% through egg membrane, 95.23±1.44% through goat skin after 8hr and Korsmeyer-Peppas release model was followed. It can be concluded that a stable, effective controlled release transdermal microemulgel was optimised for triamcinolone. This would be a promising tool to deliver triamcinolone with enhanced bioavailability and reduced dosing frequency. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Evaluation of paeonol-loaded transethosomes as transdermal delivery carriers.

    Science.gov (United States)

    Chen, Z X; Li, B; Liu, T; Wang, X; Zhu, Y; Wang, L; Wang, X H; Niu, X; Xiao, Y; Sun, Q

    2017-03-01

    Paeonol shows effective anti-allergic, anti-inflammatory and analgesic activities. However, because of its poor solubility in water and high volatility at room temperature, the application of this drug is restricted in the clinic. The objective of this research was to develop a biocompatible paeonol formulation with improved stability, skin delivery and pharmacokinetic efficiency. In this paper, paeonol-loaded vesicles were prepared using an ethanol injection method. Nano-vesicles were characterized for their physical properties and encapsulation efficiency (EE). Drug permeation behavior in vitro and deposition quantity in porcine ear skin were measured with a Valia-Chien (V-C) diffusion device. Additionally, a validated and sensitive high performance liquid chromatography (HPLC) method was developed to analyze paeonol concentrations in rat plasma after transdermal administration. The results showed that the particle-size order of the nano-vesicles was the following: transethosomes (122.5±7.5nm)transethosomes had a higher EE (85.5±5.2%), and they showed a spherical morphology with a smooth surface when viewed under a transmission electron microscope (TEM). In an in vitro permeation study, the paeonol transethosomes showed an enhanced transdermal flux of 95.7±8.8μg/cm 2 /h and a higher deposition quantity in porcine ear skin compared to the transfersomes. A one-compartment first-order absorption model could be used to describe the pharmacokinetics of paeonol in rats after transdermal administration. The AUC of the paeonol transethosomes was approximately 1.57- and 3.52-fold higher than those of the transfersomes and a saturated solution of paeonol in 35% ethanol, respectively. The results demonstrated that the paeonol transethosomes had a narrow size distribution, high encapsulation efficiency, and long residence in the plasma. This formulation remarkably enhanced the bioavailability of paeonol. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Developmental expression of membrane type 4-matrix metalloproteinase (Mt4-mmp/Mmp17) in the mouse embryo

    Science.gov (United States)

    Clemente, Cristina; Montalvo, María Gregoria; Seiki, Motoharu; Arroyo, Alicia G.

    2017-01-01

    Matrix metalloproteinases (MMPs) constitute a large group of endoproteases that play important functions during embryonic development, tumor metastasis and angiogenesis by degrading components of the extracellular matrix. Within this family, we focused our study on Mt4-mmp (also called Mmp17) that belongs to a distinct subset that is anchored to the cell surface via a glycosylphosphatidylinositol (GPI) moiety and with the catalytic site exposed to the extracellular space. Information about its function and substrates is very limited to date, and little has been reported on its role in the developing embryo. Here, we report a detailed expression analysis of Mt4-mmp during mouse embryonic development by using a LacZ reporter transgenic mouse line. We showed that Mt4-mmp is detected from early stages of development to postnatal stages following a dynamic and restricted pattern of expression. Mt4-mmp was first detected at E8.5 limited to the intersomitic vascularization, the endocardial endothelium and the dorsal aorta. Mt4-mmpLacZ/+ cells were also observed in the neural crest cells, somites, floor plate and notochord at early stages. From E10.5, expression localized in the limb buds and persists during limb development. A strong expression in the brain begins at E12.5 and continues to postnatal stages. Specifically, staining was observed in the olfactory bulb, cerebral cortex, hippocampus, striatum, septum, dorsal thalamus and the spinal cord. In addition, LacZ-positive cells were also detected during eye development, initially at the hyaloid artery and later on located in the lens and the neural retina. Mt4-mmp expression was confirmed by quantitative RT-PCR and western blot analysis in some embryonic tissues. Our data point to distinct functions for this metalloproteinase during embryonic development, particularly during brain formation, angiogenesis and limb development. PMID:28926609

  7. Large proteoglycan complexes and disturbed collagen architecture in the corneal extracellular matrix of mucopolysaccharidosis type VII (Sly syndrome).

    Science.gov (United States)

    Young, Robert D; Liskova, Petra; Pinali, Christian; Palka, Barbara P; Palos, Michalis; Jirsova, Katerina; Hrdlickova, Enkela; Tesarova, Marketa; Elleder, Milan; Zeman, Jiri; Meek, Keith M; Knupp, Carlo; Quantock, Andrew J

    2011-08-24

    Deficiencies in enzymes involved in proteoglycan (PG) turnover underlie a number of rare mucopolysaccharidoses (MPS), investigations of which can considerably aid understanding of the roles of PGs in corneal matrix biology. Here, the authors analyze novel pathologic changes in MPS VII (Sly syndrome) to determine the nature of PG-collagen associations in stromal ultrastructure. Transmission electron microscopy and electron tomography were used to investigate PG-collagen architectures and interactions in a cornea obtained at keratoplasty from a 22-year-old man with MPS VII, which was caused by a compound heterozygous mutation in the GUSB gene. Transmission electron microscopy showed atypical morphology of the epithelial basement membrane and Bowman's layer in MPS VII. Keratocytes were packed with cytoplasmic vacuoles containing abnormal glycosaminoglycan (GAG) material, and collagen fibrils were thinner than in normal cornea and varied considerably throughout anterior (14-32 nm), mid (13-42 nm), and posterior (17-39 nm) regions of the MPS VII stroma. PGs viewed in three dimensions were striking in appearance in that they were significantly larger than PGs in normal cornea and formed highly extended linkages with multiple collagen fibrils. Cellular changes in the MPS VII cornea resemble those in other MPS. However, the wide range of collagen fibril diameters throughout the stroma and the extensive matrix presence of supranormal-sized PG structures appear to be unique features of this disorder. The findings suggest that the accumulation of stromal chondroitin-, dermatan-, and heparan-sulfate glycosaminoglycans in the absence of β-glucuronidase-mediated degradation can modulate collagen fibrillogenesis.

  8. Iontophoretic transdermal drug delivery: a multi-layered approach.

    Science.gov (United States)

    Pontrelli, Giuseppe; Lauricella, Marco; Ferreira, José A; Pena, Gonçalo

    2017-12-11

    We present a multi-layer mathematical model to describe the transdermal drug release from an iontophoretic system. The Nernst-Planck equation describes the basic convection-diffusion process, with the electric potential obtained by solving the Laplace's equation. These equations are complemented with suitable interface and boundary conditions in a multi-domain. The stability of the mathematical problem is discussed in different scenarios and a finite-difference method is used to solve the coupled system. Numerical experiments are included to illustrate the drug dynamics under different conditions. © The authors 2016. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

  9. Chemistry, manufacturing and controls in passive transdermal drug delivery systems.

    Science.gov (United States)

    Goswami, Tarun; Audett, Jay

    2015-01-01

    Transdermal drug delivery systems (TDDS) are used for the delivery of the drugs through the skin into the systemic circulation by applying them to the intact skin. The development of TDDS is a complex and multidisciplinary affair which involves identification of suitable drug, excipients and various other components. There have been numerous problems reported with respect to TDDS quality and performance. These problems can be reduced by appropriately addressing chemistry, manufacturing and controls requirements, which would thereby result in development of robust TDDS product and processes. This article provides recommendations on the chemistry, manufacturing and controls focusing on the unique technical aspects of TDDS.

  10. Treatment of Severe Cancer Pain by Transdermal Fentanyl

    Directory of Open Access Journals (Sweden)

    Dženita Ljuca

    2010-05-01

    Full Text Available The goal of research was to determine the frequency, intensity, time of occurrence, duration and causes of breakthrough pain (BTP in patients whose carcinoma pain was treated by transdermal fentanyl. (TDF. A prospective study was conducted in a hospice for recumbent patients of the Centre for Palliative Care (hospice University Clinical Centre Tuzla from October 2009 to December 2010. 33 patients in terminal stage of carcinoma, who had been treated by transdermal fentanyl due to their excruciating pain (7-10 mark on numerica! scale with initial dosage of 25 μg as a strong opiate analgesic, were monitored within the time period of 10 days. In the statistics we used the even T - test, the Wilcox test and Mann -Whitney test. The difference was seen to be significant at p < 0,05. Treatment by transdermal fentanyl significantly reduces the intensity of strong carcinoma pain (p < 0.0001, with a frequent requirement for dose increase with bone metastasis. The intensity of BTP is higher compared to the pain experienced upon reception. The frequency and intensity of BTP are significantly reduced already in the second day of treatment by transdermal fentanyl (p = 0,0024. The BTP is most intense in patients with neck and head tumours (9,26 ± 0,66, and most frequent with abdomen and pelvic tumour. The biggest number of BTP (68.3 % occurs within first three days of treatment. BTP most frequently occurs in the evening or at night (between 18:00 and 06:00 h in 62,2 % of the cases, with the duration of usually less than 15 minutes (65,2% of the cases. In 61,6 % cases the occurrence of BTP is related to physical activities or psychosocial incidents, while the cause is undetermined in 38,4 % of examinees.BTP is most frequent within first three days of treatment by TDF. Using the optimal dosage a good control of carcinoma pain is enabled, regardless of the occurrence of bone metastasis, while it also helps reduce the frequency and intensity of BTP.

  11. Pharmacokinetic characteristics of formulated alendronate transdermal delivery systems in rats and humans.

    Science.gov (United States)

    Choi, Ahyoung; Gang, Hyesil; Whang, Jiae; Gwak, Hyesun

    2010-05-01

    The objective of this study was to examine the absorption of alendronate from formulated transdermal delivery systems in rats and humans. When alendronate was applied to rats by transdermal delivery systems (7.2 mg) and oral administration (30 mg/kg), a statistically significant difference was found in the amount remaining to be excreted at time t (Ae(t)) and the amount remaining to be excreted at time 0 (Ae(infinity)) (p transdermal delivery systems. There was a linear relationship (r(2) = 0.9854) between the drug loading dose and Ae(infinity). The Ae(infinity) values from the transdermal delivery system containing 6% caprylic acid (53.8 mg as alendronate) and an oral product (Fosamax), 70 mg as alendronate) in humans were 127.0 +/- 34.2 microg and 237.2 +/- 56.3 microg, respectively. The dose-adjusted relative Ae(infinity) ratio of the transdermal delivery system to oral product was calculated to be 69.7%. The long half-life of alendronate in the transdermal delivery system (50.6 +/- 6.4 h), compared to that of the oral product (3.5 +/- 1.1 h) could allow less-frequent dosing. In conclusion, this study showed that a transdermal delivery system containing 6% caprylic acid in PG could be a favorable alternative for alendronate administration.

  12. Numerical simulations of crystal growth in a transdermal drug delivery system

    Science.gov (United States)

    Zeng, Jianming; Jacob, Karl I.; Tikare, Veena

    2004-02-01

    Grain growth by precipitation and Ostwald ripening in an unstressed matrix of a dissolved crystallizable component was simulated using a kinetic Monte Carlo model. This model was used previously to study Ostwald ripening in the high crystallizable component regime and was shown to correctly simulate solution, diffusion and precipitation. In this study, the same model with modifications was applied to the low crystallizable regime of interest to the transdermal drug delivery system (TDS) community. We demonstrate the model's utility by simulating precipitation and grain growth during isothermal storage at different supersaturation conditions. The simulation results provide a first approximation for the crystallization occurring in TDS. It has been reported that for relatively higher temperature growth of drug crystals in TDS occurs only in the middle third of the polymer layer. The results from the simulations support these findings that crystal growth is limited to the middle third of the region, where the availability of crystallizable components is the highest, for cluster growth at relatively high temperature.

  13. Type XII and XIV collagens mediate interactions between banded collagen fibers in vitro and may modulate extracellular matrix deformability.

    Science.gov (United States)

    Nishiyama, T; McDonough, A M; Bruns, R R; Burgeson, R E

    1994-11-11

    Type XII and XIV collagens are very large molecules containing three extended globular domains derived from the amino terminus of each alpha chain and an interrupted triple helix. Both collagens are genetically and immunologically unique and have distinct distributions in many tissues. These collagens localize near the surface of banded collagen fibrils. The function of the molecules is unknown. We have prepared a mixture of native type XII and XIV collagens that is free of contaminating proteins by electrophoretic criteria. In addition, we have purified the collagenase-resistant globular domains of type XII or XIV collagens (XII-NC-3 or XIV-NC-3). In this study, we have investigated the effect of intact type XII and XIV and XII-NC-3 or XIV-NC-3 on the interactions between fibroblasts and type I collagen fibrils. We find that both type XII and XIV collagens promote collagen gel contraction mediated by fibroblasts, even in the absence of serum. The activity is present in the NC-3 domains. The effect is dose-dependent and is inhibited by denaturation. The effect of type XII NC-3 is inhibited by the addition of anti-XII antiserum. To elucidate the mechanism underlying this phenomenon, we examined the effect of XII-NC-3 or XIV-NC-3 on deformability of collagen gels by centrifugal force. XII-NC-3 or XIV-NC-3 markedly promotes gel compression after centrifugation. The effect is also inhibited by denaturation, and the activity of type XII-NC3 is inhibited by the addition of anti-XII antiserum. The results indicate that the effect of XII-NC-3 or XIV-NC-3 on collagen gel contraction by fibroblasts is not due to activation of cellular events but rather results from the increase in mobility of hydrated collagen fibrils within the gel. These studies suggest that collagen types XII and XIV may modulate the biomechanical properties of tissues.

  14. Treatment with subcutaneous and transdermal fentanyl: results from a population pharmacokinetic study in cancer patients.

    Science.gov (United States)

    Oosten, Astrid W; Abrantes, João A; Jönsson, Siv; de Bruijn, Peter; Kuip, Evelien J M; Falcão, Amílcar; van der Rijt, Carin C D; Mathijssen, Ron H J

    2016-04-01

    Transdermal fentanyl is effective for the treatment of moderate to severe cancer-related pain but is unsuitable for fast titration. In this setting, continuous subcutaneous fentanyl may be used. As data on the pharmacokinetics of continuous subcutaneous fentanyl are lacking, we studied the pharmacokinetics of subcutaneous and transdermal fentanyl. Furthermore, we evaluated rotations from the subcutaneous to the transdermal route. Fifty-two patients treated with subcutaneous and/or transdermal fentanyl for moderate to severe cancer-related pain participated. A population pharmacokinetic model was developed and evaluated using non-linear mixed-effects modelling. For rotations from subcutaneous to transdermal fentanyl, a 1:1 dose conversion ratio was used while the subcutaneous infusion was continued for 12 h (with a 50 % tapering after 6 h). A 6-h scheme with 50 % tapering after 3 h was simulated using the final model. A one-compartment model with first-order elimination and separate first-order absorption processes for each route adequately described the data. The estimated apparent clearance of fentanyl was 49.6 L/h; the absorption rate constant for subcutaneous and transdermal fentanyl was 0.0358 and 0.0135 h(-1), respectively. Moderate to large inter-individual and inter-occasion variability was found. Around rotation from subcutaneous to transdermal fentanyl, measured and simulated plasma fentanyl concentrations rose and increasing side effects were observed. We describe the pharmacokinetics of subcutaneous and transdermal fentanyl in one patient cohort and report several findings that are relevant for clinical practice. Further research is warranted to study the optimal scheme for rotations from the subcutaneous to the transdermal route.

  15. The Effect and Mechanism of Transdermal Penetration Enhancement of Fu's Cupping Therapy: New Physical Penetration Technology for Transdermal Administration with Traditional Chinese Medicine (TCM) Characteristics.

    Science.gov (United States)

    Xie, Wei-Jie; Zhang, Yong-Ping; Xu, Jian; Sun, Xiao-Bo; Yang, Fang-Fang

    2017-03-27

    In this paper, a new type of physical penetration technology for transdermal administration with traditional Chinese medicine (TCM) characteristics is presented. Fu's cupping therapy (FCT), was established and studied using in vitro and in vivo experiments and the penetration effect and mechanism of FCT physical penetration technology was preliminarily discussed. With 1-(4-chlorobenzoyl)-5-methoxy-2-methylindole-3-ylacetic acid (indomethacin, IM) as a model drug, the establishment of high, medium, and low references was completed for the chemical permeation system via in vitro transdermal tests. Furthermore, using chemical penetration enhancers (CPEs) and iontophoresis as references, the percutaneous penetration effect of FCT for IM patches was evaluated using seven species of in vitro diffusion kinetics models and in vitro drug distribution; the IM quantitative analysis method in vivo was established using ultra-performance liquid chromatography-tandem mass spectrometry technology (UPLC-MS/MS), and pharmacokinetic parameters: area under the zero and first moment curves from 0 to last time t (AUC 0-t , AUMC 0-t ), area under the zero and first moment curves from 0 to infinity (AUC 0-∞ , AUMC 0-∞ ), maximum plasma concentration (C max ) and mean residence time (MRT), were used as indicators to evaluate the percutaneous penetration effect of FCT in vivo. Additionally, we used the 3 K factorial design to study the joint synergistic penetration effect on FCT and chemical penetration enhancers. Through scanning electron microscopy (SEM) and transmission electron microscope (TEM) imaging, micro- and ultrastructural changes on the surface of the stratum corneum (SC) were observed to explore the FCT penetration mechanism. In vitro and in vivo skin permeation experiments revealed that both the total cumulative percutaneous amount and in vivo percutaneous absorption amount of IM using FCT were greater than the amount using CPEs and iontophoresis. Firstly, compared with

  16. Direct Application of Rep-PCR on Type I Sourdough Matrix to Monitor the Dominance and Persistence of a Lactobacillus plantarum Starter Throughout Back-Slopping.

    Science.gov (United States)

    Dolci, Paola; Cocolin, Luca

    2017-08-01

    This study describes the optimization and application of repetitive element-PCR (rep-PCR) technique directly on microbial DNA extracted from type I sourdoughs for fast monitoring of a Lb. plantarum starter strain (P1FMC) throughout daily back-slopping. The challenge was to follow and study the performance of a starter culture directly in sourdoughs without cultivation on selective media. The extraction of good quality microbial DNA suitable for amplification from a complex matrix such as dough was the first target. In addition, the objective to obtain a clear rep-PCR profile referable to a specific starter strain among a microbial community was pursued. Co-inoculum trials, in flour matrix, with Lb. plantarum P1FMC and L. lactis LC71 strains and, subsequently, type I sourdough back-slopping trials were performed. The rep-PCR amplification profiles obtained were clearly referable to that of Lb. plantarum P1FMC starter in both co-inoculum trials (also when it was present with one order of magnitude less with respect to L. lactis LC71) and back-slopping trials where it dominated the fermentation process with loads of 10 8 cfu g -1 and prevailed on the autochthonous microbiota. Thus, the approach proposed in this paper could be considered a methodological advancement, based on a culture-independent one-step rep-PCR, suitable for fast monitoring of starter performance. © 2017 Institute of Food Technologists®.

  17. Effect of type and percentage of reinforcement for optimization of the cutting force in turning of Aluminium matrix nanocomposites using response surface methodologies

    Energy Technology Data Exchange (ETDEWEB)

    Priyadarshi, Devinder [DAV Institute of Engineering and Technology, Jalandhar (India); Sharma, Rajesh Kumar [Institute of Technology, Hamirpur (India)

    2016-03-15

    Aluminium matrix composites (AMCs) now hold a significant share of raw materials in many applications. It is of prime importance to study the machinability of such composites so as to enhance their applicability. Sufficient work has been done for studying the machining of AMCs with particle reinforcements of micron range. This paper presents the study of AMCs with particle reinforcement of under micron range i.e. nanoparticles. This paper brings out the results of an experimental investigation of type and weight percent of nanoparticles on the tangential cutting force during turning operation. SiC, Gr and SiC-Gr (in equal proportions) were used with Al-6061 alloy as the matrix phase. The results indicate that composites with SiC require greater cutting force followed by hybrid and then Gr. Increase in the weight percent also significantly affected the magnitude of cutting force. RSM was used first to design and analyze the experiments and then to optimize the turning process and obtain optimal conditions of weight and type of reinforcements for turning operation.

  18. Absence of FKBP10 in recessive type XI osteogenesis imperfecta leads to diminished collagen cross-linking and reduced collagen deposition in extracellular matrix.

    Science.gov (United States)

    Barnes, Aileen M; Cabral, Wayne A; Weis, MaryAnn; Makareeva, Elena; Mertz, Edward L; Leikin, Sergey; Eyre, David; Trujillo, Carlos; Marini, Joan C

    2012-11-01

    Recessive osteogenesis imperfecta (OI) is caused by defects in genes whose products interact with type I collagen for modification and/or folding. We identified a Palestinian pedigree with moderate and lethal forms of recessive OI caused by mutations in FKBP10 or PPIB, which encode endoplasmic reticulum resident chaperone/isomerases FKBP65 and CyPB, respectively. In one pedigree branch, both parents carry a deletion in PPIB (c.563_566delACAG), causing lethal type IX OI in their two children. In another branch, a child with moderate type XI OI has a homozygous FKBP10 mutation (c.1271_1272delCCinsA). Proband FKBP10 transcripts are 4% of control and FKBP65 protein is absent from proband cells. Proband collagen electrophoresis reveals slight band broadening, compatible with ≈10% over-modification. Normal chain incorporation, helix folding, and collagen T(m) support a minimal general collagen chaperone role for FKBP65. However, there is a dramatic decrease in collagen deposited in culture despite normal collagen secretion. Mass spectrometry reveals absence of hydroxylation of the collagen telopeptide lysine involved in cross-linking, suggesting that FKBP65 is required for lysyl hydroxylase activity or access to type I collagen telopeptide lysines, perhaps through its function as a peptidylprolyl isomerase. Proband collagen to organics ratio in matrix is approximately 30% of normal in Raman spectra. Immunofluorescence shows sparse, disorganized collagen fibrils in proband matrix. Published 2012 Wiley Periodicals, Inc.*This article is a US Government work and, as such, is in the public domain of the United States of America.

  19. Development of antimigraine transdermal delivery systems of pizotifen malate.

    Science.gov (United States)

    Serna-Jiménez, C E; del Rio-Sancho, S; Calatayud-Pascual, M A; Balaguer-Fernández, C; Femenía-Font, A; López-Castellano, A; Merino, V

    2015-08-15

    The aim of this study was to develop and evaluate a transdermal delivery system of pizotifen malate. Pizotifen is frequently used in the preventive treatment of migraine, but is also indicated in eating disorders. In the course of the project, the effects of chemical enhancers such as ethanol, 1,8-cineole, limonene, azone and different fatty acids (decanoic, decenoic, dodecanoic, linoleic and oleic acids) were determined, first using a pizotifen solution. Steady state flux, diffusion and partition parameters were estimated by fitting the Scheuplein equation to the data obtained. Among the chemical enhancers studied, decenoic acid showed the highest enhancement activity, which seemed to be due to the length of its alkyl chain and unsaturation at the 9th carbon. The influence of iontophoresis and the involvement of electrotransport in said process was determined. The absorption profile obtained with iontophoresis was similar to that obtained with fatty acids and terpenes, though skin deposition of the drug was lower with the former. Transdermal delivery systems (TDS) of pizotifen were manufactured by including chemical enhancers, decenoic acid or oleic acid, and were subsequently characterized. When the results obtained with solutions were compared with those obtained with the TDS, a positive enhancement effect was observed with the latter with respect to the partitioning and diffusion of the drug across the skin. Our findings endorse the suitability of our TDS for delivering therapeutic amounts of pizotifen malate. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Hybrid electrospun chitosan-phospholipids nanofibers for transdermal drug delivery.

    Science.gov (United States)

    Mendes, Ana C; Gorzelanny, Christian; Halter, Natalia; Schneider, Stefan W; Chronakis, Ioannis S

    2016-08-20

    Chitosan (Ch) polysaccharide was mixed with phospholipids (P) to generate electrospun hybrid nanofibers intended to be used as platforms for transdermal drug delivery. Ch/P nanofibers exibithed average diameters ranging from 248±94nm to 600±201nm, depending on the amount of phospholipids used. Fourier Transformed Infra-Red (FTIR) spectroscopy and Dynamic Light Scattering (DLS) data suggested the occurrence of electrostatic interactions between amine groups of chitosan with the phospholipid counterparts. The nanofibers were shown to be stable for at least 7days in Phosphate Buffer Saline (PBS) solution. Cytotoxicity studies (WST-1 and LDH assays) demonstrated that the hybrid nanofibers have suitable biocompatibility. Fluorescence microscopy, also suggested that L929 cells seeded on top of the CH/P hybrid have similar metabolic activity comparatively to the cells seeded on tissue culture plate (control). The release of curcumin, diclofenac and vitamin B12, as model drugs, from Ch/P hybrid nanofibers was investigated, demonstrating their potential utilization as a transdermal drug delivery system. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Tolterodine Tartrate Proniosomal Gel Transdermal Delivery for Overactive Bladder

    Directory of Open Access Journals (Sweden)

    Rajan Rajabalaya

    2016-08-01

    Full Text Available The goal of this study was to formulate and evaluate side effects of transdermal delivery of proniosomal gel compared to oral tolterodine tartrate (TT for the treatment of overactive bladder (OAB. Proniosomal gels are surfactants, lipids and soy lecithin, prepared by coacervation phase separation. Formulations were analyzed for drug entrapment efficiency (EE, vesicle size, surface morphology, attenuated total reflectance Fourier transform infrared (ATR-FTIR spectroscopy, in vitro skin permeation, and in vivo effects. The EE was 44.87%–91.68% and vesicle size was 253–845 nm for Span formulations and morphology showed a loose structure. The stability and skin irritancy test were also carried out for the optimized formulations. Span formulations with cholesterol-containing formulation S1 and glyceryl distearate as well as lecithin containing S3 formulation showed higher cumulative percent of permeation such as 42% and 35%, respectively. In the in vivo salivary secretion model, S1 proniosomal gel had faster recovery, less cholinergic side effect on the salivary gland compared with that of oral TT. Histologically, bladder of rats treated with the proniosomal gel formulation S1 showed morphological improvements greater than those treated with S3. This study demonstrates the potential of proniosomal vesicles for transdermal delivery of TT to treat OAB.

  2. Evaluation of diclofenac prodrugs for enhancing transdermal delivery.

    Science.gov (United States)

    Lobo, Shabbir; Li, Henan; Farhan, Nashid; Yan, Guang

    2014-03-01

    Abstract Objective: The purpose of this study was to evaluate the approach of using diclofenac acid (DA) prodrugs for enhancing transdermal delivery. Methanol diclofenac ester (MD), ethylene glycol diclofenac ester (ED), glycerol diclofenac ester (GD) and 1,3-propylene glycol diclofenac ester (PD) were synthesized and evaluated for their physicochemical properties such as solubilities, octanol/water partition coefficients, stratum corneum/water partition coefficients, hydrolysis rates and bioconversion rates. In vitro fluxes across human epidermal membrane (HEM) in the Franz diffusion cell were determined on DA-, MD-, ED-, GD- and PD-saturated aqueous solutions. The formation of GD and ED led to the prodrugs with higher aqueous solubilities and lower partition coefficients than those of the parent drug. Prodrugs with improved aqueous solubility showed better fluxes across HEM in aqueous solution than that of the parent drug, with GD showing the highest aqueous solubility and also the highest flux. There is a linear relationship between the aqueous solubility and flux for DA, ED and PD, but GD and MD deviated from the linear line. Diclofenac prodrugs with improved hydrophilicity than the parent drug could be utilized for enhancing transdermal diclofenac delivery.

  3. Evaluation of Diclofenac Prodrugs for Enhancing Transdermal Delivery

    Science.gov (United States)

    Lobo, Shabbir; Li, Henan; Farhan, Nashid; Yan, Guang

    2016-01-01

    The purpose of this study was to evaluate the approach of using diclofenac acid (DA) prodrugs for enhancing transdermal delivery. Methanol diclofenac ester (MD), ethylene glycol diclofenac ester (ED), glycerol diclofenac ester (GD), and 1,3-propylene glycol diclofenac ester (PD) were synthesized and evaluated for their physicochemical properties such as solubilities, octanol/water partition coefficients, stratum corneum/water partition coefficients, hydrolysis rates, and bioconversion rates. In vitro fluxes across human epidermal membrane (HEM) in Franz diffusion cell were determined on DA, MD, ED, GD, and PD saturated aqueous solutions. The formation of GD and ED led to the prodrugs with higher aqueous solubilities and lower partition coefficients than those of the parent drug. Prodrugs with improved aqueous solubility showed better fluxes across HEM in aqueous solution than that of the parent drug, with GD showing the highest aqueous solubility and also the highest flux. There is a linear relationship between the aqueous solubility and flux for DA, ED and PD, but GD and MD deviated from the linear line. Overall, diclofenac prodrugs with improved hydrophilicity than the parent drug could be utilized for enhancing transdermal diclofenac delivery. PMID:24517636

  4. Recent developments in skin mimic systems to predict transdermal permeation.

    Science.gov (United States)

    Waters, Laura J

    2015-01-01

    In recent years there has been a drive to create experimental techniques that can facilitate the accurate and precise prediction of transdermal permeation without the use of in vivo studies. This review considers why permeation data is essential, provides a brief summary as to how skin acts as a natural barrier to permeation and discusses why in vivo studies are undesirable. This is followed by an in-depth discussion on the extensive range of alternative methods that have been developed in recent years. All of the major 'skin mimic systems' are considered including: in vitro models using synthetic membranes, mathematical models including quantitative structure-permeability relationships (QSPRs), human skin equivalents and chromatographic based methods. All of these model based systems are ideally trying to achieve the same end-point, namely a reliable in vitro-in vivo correlation, i.e. matching non-in vivo obtained data with that from human clinical trials. It is only by achieving this aim, that any new method of obtaining permeation data can be acknowledged as a potential replacement for animal studies, for the determination of transdermal permeation. In this review, the relevance and potential applicability of the various models systems will also be discussed.

  5. Efficient Transdermal Delivery of Benfotiamine in an Animal Model

    Directory of Open Access Journals (Sweden)

    Gyula Varadi

    2015-01-01

    Full Text Available We designed a transdermal system to serve as a delivery platform for benfotiamine utilizing the attributes of passive penetration enhancing molecules to penetrate through the outer layers of skin combined with the advance of incorporating various peripherally-acting vasodilators to enhance drug uptake.  Benfotiamine, incorporated into this transdermal formulation, was applied to skin in an animal model in order to determine the ability to deliver this thiamine pro-drug effectively to the sub-epithelial layers.  In this proof of concept study in guinea pigs, we found that a single topical application of either a solubilized form of benfotiamine (15 mg or a microcrystalline suspension form (25 mg resulted in considerable increases of the dephosphorylated benfotiamine (S-benzoylthiamine in the skin tissue as well as in significant increases in the thiamine and thiamine phosphate pools compared to control animals.  The presence of a ~8000x increase in thiamine and increases in its phosphorylated derivatives in the epidermis and dermis tissue of the test animals gives a strong indication that the topical treatment with benfotiamine works very well for the desired outcome of producing an intracellular increase of the activating cofactor pool for transketolase enzyme, which is implicated in the pathophysiology of diabetic neuropathy.

  6. Efficacy and safety of a transdermal contraceptive system.

    Science.gov (United States)

    Smallwood, G H; Meador, M L; Lenihan, J P; Shangold, G A; Fisher, A C; Creasy, G W

    2001-11-01

    To evaluate the efficacy, cycle control, compliance, and safety of a transdermal contraceptive system that delivers norelgestromin 150 microg and ethinyl estradiol 20 microg daily. In this open-label, 73-center study, 1672 healthy, ovulatory, sexually active women received ORTHO EVRA/EVRA for six (n = 1171) or 13 cycles (n = 501). The treatment regimen for each cycle was three consecutive 7-day patches (21 days) followed by 1 patch-free week. The overall and method-failure probabilities of pregnancy through 13 cycles were 0.7% and 0.4%, respectively. The incidence of breakthrough bleeding was low throughout the study. Perfect compliance (21 consecutive days of dosing, followed by a 7-day drug-free interval; no patch could be worn for more than 7 days) was achieved in 90% of subject cycles; only 1.9% of patches detached completely. Adverse events were typical of hormonal contraception, and most were mild-to-moderate in severity and not treatment limiting. The most common adverse events resulting in discontinuation were application site reactions (1.9%), nausea (1.8%), emotional lability (1.5%), headache (1.1%), and breast discomfort (1.0%). The transdermal contraceptive patch provides effective contraception and cycle control, and is well tolerated. The weekly change schedule for the contraceptive patch is associated with excellent compliance and wearability characteristics.

  7. The effect of transdermal nicotine patches on sleep and dreams.

    Science.gov (United States)

    Page, F; Coleman, G; Conduit, R

    2006-07-30

    This study was undertaken to determine the effect of 24-h transdermal nicotine patches on sleep and dream mentation in 15 smokers aged 20 to 33. Utilising a repeated measures design, it was found that more time awake and more ASDA micro-arousals occurred while wearing the nicotine patch compared to placebo. Also, the percentage of REM sleep decreased, but REM latency and the proportion of time spent in NREM sleep stages did not change significantly. Dream reports containing visual imagery, visual imagery ratings and the number of visualizable nouns were significantly greater from REM compared to Stage 2 awakenings, regardless of patch condition. However, a general interaction effect was observed. Stage 2 dream variables remained equivalent across nicotine and placebo conditions. Within REM sleep, more dream reports containing visual imagery occurred while wearing the nicotine patch, and these were rated as more vivid. The greater frequency of visual imagery reports and higher imagery ratings specifically from REM sleep suggests that previously reported dreaming side effects from 24-h nicotine patches may be specific to REM sleep. Combined with previous animal studies showing that transdermally delivered nicotine blocks PGO activity in REM sleep, the current results do no appear consistent with PGO-based hypotheses of dreaming, such as the Activation-Synthesis (AS) or Activation, Input and Modulation (AIM) models.

  8. Matrix metalloproteinase-2 and its correlation with basal membrane components laminin-5 and collagen type IV in paediatric burn patients measured with Surface Plasmon Resonance Imaging (SPRI) biosensors.

    Science.gov (United States)

    Weremijewicz, Artur; Matuszczak, Ewa; Sankiewicz, Anna; Tylicka, Marzena; Komarowska, Marta; Tokarzewicz, Anna; Debek, Wojciech; Gorodkiewicz, Ewa; Hermanowicz, Adam

    2018-01-30

    The purpose of this study was the determination of matrix metalloproteinase-2 and its correlation with basal membrane components laminin-5 and collagen type IV in the blood plasma of burn patients measured with Surface Plasmon Resonance Imaging (SPRI) biosensors. 31 children scalded by hot water who were managed at the Department of Paediatric Surgery between 2014-2015, after primarily presenting with burns in 4-20% TBSA were included into the study (age 9 months up to 14 years, mean age 2,5+1 years). There were 10 girls and 21 boys. Venous blood samples were drawn 2-6h, and 12-16h after the thermal injury, and on the subsequent days 3, 5 and 7. The matrix metalloproteinase-2, collagen type IV and laminin-5 concentrations were assessed using Surface Plasmon Resonance Imaging by the investigators blinded to the other data. The MMP-2, laminin-5 and collagen type IV concentrations in the blood plasma of patients with burns, were highest 12-16h after thermal injury, the difference was statistically significant. The MMP-2, laminin-5 and collagen type IV concentrations measured 3 days, 5 days and 7 days after the thermal injury, slowly decreased over time, and on the 7th day reached the normal range, when compared with the concentration measured in controls. Current work is the first follow-up study regarding MMP-2 in burns. MMP-2, laminin-5 and collagen type IV levels were elevated early after burn injury in the plasma of studied patients, and were highest 12-16h after the injury. MMP-2, laminin-5 and collagen type IV levels were not proportional to the severity of the burn. We believe in the possibility that the gradual decrease of MMP-2, collagen type IV and laminin-5 concentrations could be connected with the process of healing, but to prove it, more investigation is needed in this area. The SPR imaging biosensor is a good diagnostic tool for determination of MMP-2, laminin-5 and collagen type IV in blood plasma of patients with burns. Copyright © 2017 Elsevier Ltd

  9. On the possibility of reprocessing of fuel elements of dispersion type with copper matrix by pyrochemical methods

    International Nuclear Information System (INIS)

    Vasin, B.D.; Ivanov, V.A.; Shchetinskij, A.V.; Vavilov, S.K.; Savochkin, Yu.P.; Bychkov, A.V.; Kormilitsyn, M.V.

    2005-01-01

    A consideration is given to pyrochemical processes suitable for separation of uranium dioxide from structural materials when reprocessing cermet type fuel elements. The estimation of the possibility to apply liquid antimony and bismuth, potassium and copper chlorides melts is made. The specimens compacted of copper and uranium dioxide powders in a stainless steel can are used as simulators of fuel element sections. It is concluded that the dissolution of structural materials in molten salts at the stage of uranium dioxide concentration is the process of choice for reprocessing of dispersion type fuel elements [ru

  10. Non-unitarity of the leptonic mixing matrix in the TeV-scale type-I seesaw model

    International Nuclear Information System (INIS)

    Ohlsson, Tommy; Popa, Christoph; Zhang, He

    2010-01-01

    The non-unitarity effects in leptonic flavor mixing are regarded as one of the generic features of the type-I seesaw model. Therefore, we explore these effects in the TeV-scale type-I seesaw model, and show that there exist non-trivial correlations among the non-unitarity parameters, stemming from the typical flavor structure of the low-scale seesaw model. In general, it follows from analytical discussions and numerical results that all the six non-unitarity parameters are related to three model parameters, while the widely studied parameters η eτ and η μτ cannot be phenomenologically significant simultaneously.

  11. Matrix theory

    CERN Document Server

    Franklin, Joel N

    2003-01-01

    Mathematically rigorous introduction covers vector and matrix norms, the condition-number of a matrix, positive and irreducible matrices, much more. Only elementary algebra and calculus required. Includes problem-solving exercises. 1968 edition.

  12. Characterisation of botulinum toxins type A and B, by matrix-assisted laser desorption ionisation and electrospray mass spectrometry

    NARCIS (Netherlands)

    Baar, B.L.M. van; Hulst, A.G.; Jong, A.L. de; Wils, E.R.J.

    2002-01-01

    A method earlier developed for the mass spectrometric (MS) identification of tetanus toxin (TTx) was applied to botulinum toxins type A and B (BTxA and BTxB). Botulinum toxins are extremely neurotoxic bacterial toxins, likely to be used as biological warfare agent. Biologically active BTxA and BTxB

  13. Type VI collagen is associated with microfibrils and oxytalan fibers in the extracellular matrix of periodontium, mesenterium and periosteum

    NARCIS (Netherlands)

    Everts, V.; Niehof, A.; Jansen, D.; Beertsen, W.

    1998-01-01

    Type VI collagen was immunolocalized in several soft connective tissues at the light and electron microscopic level. Positive labeling was found in all tissues examined, periodontal ligament, gingiva, mesenterium and periosteum. The labeled structures could be divided into 2 categories: microfibrils

  14. Effect of matrix and particle type on rheological, textural and structural properties of broccoli pasta and noodles

    NARCIS (Netherlands)

    Silva, E.; Sagis, L.M.C.; Linden, van der E.; Scholten, E.

    2013-01-01

    Durum wheat semolina (DWS) pasta and sweet potato starch (SPS) noodles were incorporated with dif ferent volume fractions and types of broccoli powder (up to 20% v/v). The incorporation of high volume fractions of broccoli powder produced in-house in SPS noodles increases the modulus of the dough

  15. Hyaluronan-Based Nanohydrogels as Effective Carriers for Transdermal Delivery of Lipophilic Agents: Towards Transdermal Drug Administration in Neurological Disorders

    Directory of Open Access Journals (Sweden)

    Seong Uk Son

    2017-12-01

    Full Text Available We suggest a convenient nanoemulsion fabrication method to create hyaluronan (HA-based nanohydrogels for effective transdermal delivery. First, hyaluronan-conjugated dodecylamine (HA–Do HA-based polymers to load the lipophilic agents were synthesized with hyaluronan (HA and dodecylamine (Do by varying the substitution ratio of Do to HA. The synthetic yield of HA–Do was more than 80% (HA–Do (A: 82.7 ± 4.7%, HA–Do (B: 87.1 ± 3.9% and HA–Do (C: 81.4 ± 4.5%. Subsequently, nanohydrogels were fabricated using the nanoemulsion method. Indocyanine green (ICG simultaneously self-assembled with HA–Do, and the size depended on the substitution ratio of Do in HA–Do (nanohydrogel (A: 118.0 ± 2.2 nm, nanohydrogel (B: 121.9 ± 11.4 nm, and nanohydrogel (C: 142.2 ± 3.8 nm. The nanohydrogels were delivered into cells, and had excellent biocompatibility. Especially, nanohydrogel (A could deliver and permeate ICG into the deep skin layer, the dermis. This suggests that nanohydrogels can be potent transdermal delivery systems.

  16. Recent trends in the transdermal delivery of therapeutic agents used for the management of neurodegenerative diseases.

    Science.gov (United States)

    Ita, Kevin

    2017-06-01

    With the increasing proportion of the global geriatric population, it becomes obvious that neurodegenerative diseases will become more widespread. From an epidemiological standpoint, it is necessary to develop new therapeutic agents for the management of Alzheimer's disease, Parkinson's disease, multiple sclerosis and other neurodegenerative disorders. An important approach in this regard involves the use of the transdermal route. With transdermal drug delivery systems (TDDS), it is possible to modulate the pharmacokinetic profiles of these medications and improve patient compliance. Transdermal drug delivery has also been shown to be useful for drugs with short half-life and low or unpredictable bioavailability. In this review, several transdermal drug delivery enhancement technologies are being discussed in relation to the delivery of medications used for the management of neurodegenerative disorders.

  17. Conductive polymer nanotube patch for fast and controlled ex vivo transdermal drug delivery.

    Science.gov (United States)

    Nguyen, Thao M; Lee, Sebin; Lee, Sang Bok

    2014-10-01

    To uptake and release hydrophilic model drugs and insulin in a novel conductive polymer (CP) nanotube transdermal patch. The externally controlled transdermal delivery of model drugs and insulin were tested ex vivo and results were compared with CP films. The unique intrinsic properties of CPs provide electrostatic interaction between the model drugs and polymer backbone. When a pulsed potential was applied, the drug delivery release profile mimics that of injection delivery. With a constant potential applied, the release rate constants of the patch system were up to three-times faster than the control (0 V) and released approximately 80% more drug molecules over 24 h. The CP nanotube transdermal patch represents a new and promising drug method, specifically for hydrophilic molecules, which have been a large obstacle for conventional transdermal drug delivery systems.

  18. Turning theory into practice: the development of modern transdermal drug delivery systems and future trends.

    Science.gov (United States)

    Perumal, O; Murthy, S N; Kalia, Y N

    2013-01-01

    Despite its remarkable barrier function, the skin remains an attractive site for systemic drug delivery given its easy accessibility, large surface area and the possibility to bypass the gastrointestinal tract and the liver and so modify drug absorption kinetics. The pioneering work of Scheuplein, Higuchi and others in the 1960s helped to explain the processes involved in passive percutaneous absorption and led to the development of mathematical models to describe transdermal drug delivery. The intervening years have seen these theories turned to practice and a significant number of transdermal systems are now available including some that employ active drug delivery. This review briefly discusses the evolution of transdermal therapeutic systems over the years and the potential of newer transdermal technologies to deliver hydrophilic drugs and macromolecules through the skin. © 2013 S. Karger AG, Basel.

  19. Comparative enhancing effects of electret with chemical enhancers on transdermal delivery of meloxicam in vitro

    International Nuclear Information System (INIS)

    Cui, L L; Hou, X M; Li, G D; Jiang, J; Liang, Y Y; Xin, X

    2008-01-01

    Electret offers enhancing effect in transdermal drug delivery for altering of the arrangement of lipid molecules in the stratum corneum, forming many transient permeable apertures and enhancing the transdermal drug delivery. In this paper, meloxicam patch formulations were developed to make the comparative study of transdermal drug delivery between electret and chemical enhancers. Patches were made into control, electret, chemical enhancer and electret with chemical enhancer ones, according to the preparation procedure. The electret combined with chemical enhancer patch was designed to probe the incorporation between electret and chemical enhancer in transdermal drug delivery. The meloxicam release from the patch was found to increase in order of blank, chemical enhancer, electret and electret with chemical enhancer patch, in general.

  20. Transdermal and intradermal delivery of therapeutic agents: application of physical technologies

    National Research Council Canada - National Science Library

    Banga, Ajay K

    2011-01-01

    .... Advancements in science combined with the need for diverse drug delivery modalities have introduced a variety of transdermal and intradermal products for existing drugs at a fraction of the cost of new drug development...

  1. Dissolving and biodegradable microneedle technologies for transdermal sustained delivery of drug and vaccine

    Science.gov (United States)

    Hong, Xiaoyun; Wei, Liangming; Wu, Fei; Wu, Zaozhan; Chen, Lizhu; Liu, Zhenguo; Yuan, Weien

    2013-01-01

    Microneedles were first conceptualized for drug delivery many decades ago, overcoming the shortages and preserving the advantages of hypodermic needle and conventional transdermal drug-delivery systems to some extent. Dissolving and biodegradable microneedle technologies have been used for transdermal sustained deliveries of different drugs and vaccines. This review describes microneedle geometry and the representative dissolving and biodegradable microneedle delivery methods via the skin, followed by the fabricating methods. Finally, this review puts forward some perspectives that require further investigation. PMID:24039404

  2. Poly(lactic-co-glycolic) acid drug delivery systems through transdermal pathway: an overview

    OpenAIRE

    Naves, Lucas; Dhand, Chetna; Almeida, Luis; Rajamani, Lakshminarayanan; Ramakrishna, Seeram; Soares, Gra?a

    2017-01-01

    In past few decades, scientists have made tremendous advancement in the field of drug delivery systems (DDS), through transdermal pathway, as the skin represents a ready and large surface area for delivering drugs. Efforts are in progress to design efficient transdermal DDS that support sustained drug release at the targeted area for longer duration in the recommended therapeutic window without producing side-effects. Poly(lactic-co-glycolic acid) (PLGA) is one of the most promising Food and ...

  3. Ultrasound in Biomedical Engineering: Ultrasound Microbubble Contrast Agents Promote Transdermal Permeation of Drugs

    OpenAIRE

    Ai-Ho Liao

    2016-01-01

    This report discusses a new development in the use of ultrasound microbubble contrast agents on transdermal drug delivery. The medium surrounding the microbubbles at the optimum concentration from liquid to gel can be modified and it can still achieve the same enhancement for transdermal drug permeation as liquid medium. It was also found that under the same ultrasound power density, microbubbles of larger particle sizes can extend the penetration depths of dye at the phantom surface.

  4. Crystallographic characterization of the radixin FERM domain bound to the cytoplasmic tail of membrane-type 1 matrix metalloproteinase (MT1-MMP)

    International Nuclear Information System (INIS)

    Terawaki, Shin-ichi; Kitano, Ken; Aoyama, Miki; Hakoshima, Toshio

    2008-01-01

    The radixin FERM domain was shown to bind the MT1-MMP cytoplasmic peptide and crystals of the complex were obtained. ERM proteins play a role in the cross-linking found between plasma membranes and actin filaments. The N-terminal FERM domains of ERM proteins are responsible for membrane association through direct interaction with the cytoplasmic tails of integral membrane proteins. During cell migration and movement, membrane-type 1 matrix metalloproteinase (MT1-MMP) on plasma membranes sheds adhesion molecule CD44 in addition to degrading the extracellular matrix. Here, the interaction between the radixin FERM domain and the MT1-MMP cytoplasmic tail is reported and preliminary crystallographic characterization of crystals of the radixin FERM domain bound to the cytoplasmic tail of MT1-MMP is presented. The crystals belong to space group P6 1 22, with unit-cell parameters a = b = 122.7, c = 128.3 Å, and contain one complex in the crystallographic asymmetric unit. The diffraction data were collected to a resolution of 2.4 Å

  5. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry: a new possibility for the identification and typing of anaerobic bacteria.

    Science.gov (United States)

    Nagy, Elizabeth

    2014-01-01

    Anaerobic bacteria predominate in the normal flora of humans and are important, often life-threatening pathogens in mixed infections originating from the indigenous microbiota. The isolation and identification of anaerobes by phenotypic and DNA-based molecular methods at a species level is time-consuming and laborious. Following the successful adaptation of the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for the routine laboratory identification of bacteria, the extensive development of a database has been initiated to use this method for the identification of anaerobic bacteria. Not only frequently isolated anaerobic species, but also newly recognized and taxonomically rearranged genera and species can be identified using direct smear samples or whole-cell protein extraction, and even phylogenetically closely related species can be identified correctly by means of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Typing of anaerobic bacteria on a subspecies level, determination of antibiotic resistance and direct identification of blood culture isolates will revolutionize anaerobe bacteriology in the near future.

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

    Science.gov (United States)

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

    2015-12-01

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

  7. Pharmacokinetics of 2 Formulations of Transdermal Fentanyl in Cynomolgus Macaques (Macaca fascicularis)

    Science.gov (United States)

    Carlson, Amy M; Kelly, Richard; Fetterer, David P; Rico, Pedro J; Bailey, Emily J

    2016-01-01

    Fentanyl is a μ-opioid agonist that often is used as the analgesic component for balanced anesthesia in both human and veterinary patients. Minimal information has been published regarding appropriate dosing, and the pharmacokinetics of fentanyl are unknown in NHP. The pharmacokinetic properties of 2 transdermal fentanyl delivery methods, a solution (2.6 and 1.95 mg/kg) and a patch (25 µg/h), were determined when applied topically to the dorsal scapular area of cynomolgus macaques (Macaca fascicularis). Serum fentanyl concentrations were analyzed by using liquid chromatography–mass spectrometry. Compared with the patch, the transdermal fentanyl solution generated higher drug concentrations over longer time. Adverse reactions occurred in the macaques that received the transdermal fentanyl solution at 2.6 mg/kg. Both preparations showed significant interanimal variability in the maximal serum drug levels, time to achieve maximal fentanyl levels, elimination half-life, and AUC values. Both the maximal concentration and the time at which this concentration occurred were increased in macaques compared with most other species after application of the transdermal fentanyl patch and compared with dogs after application of the transdermal fentanyl solution. The pharmacokinetic properties of transdermal fentanyl in macaques are markedly different from those in other veterinary species and preclude its use as a long-acting analgesic drug in NHP. PMID:27423151

  8. Engineering approaches to transdermal drug delivery: a tribute to contributions of prof. Robert Langer.

    Science.gov (United States)

    Mitragotri, S

    2013-01-01

    Transdermal drug delivery continues to provide an advantageous route of drug administration over injections. While the number of drugs delivered by passive transdermal patches has increased over the years, no macromolecule is currently delivered by the transdermal route. Substantial research efforts have been dedicated by a large number of researchers representing varied disciplines including biology, chemistry, pharmaceutics and engineering to understand, model and overcome the skin's barrier properties. This article focuses on engineering contributions to the field of transdermal drug delivery. The article pays tribute to Prof. Robert Langer, who pioneered the engineering approach towards transdermal drug delivery. Over a period spanning nearly 25 years since his first publication in the field of transdermal drug delivery, Bob Langer has deeply impacted the field by quantitative analysis and innovative engineering. At the same time, he has inspired several generations of engineers by collaborations and mentorship. His scientific insights, innovative technologies, translational efforts and dedicated mentorship have transformed the field. © 2013 S. Karger AG, Basel.

  9. Enhancement of In Vitro Skin Transport and In Vivo Hypoglycemic ...

    African Journals Online (AJOL)

    ... (PVP) for the enhancement of the transdermal delivery of glimepiride (GMD). Methods: Matrix-type transdermal patches containing GMD, drug coprecipitate ... evaluation of the formulations was conducted using automated diffusion system.

  10. Calcitonin directly attenuates collagen type II degradation by inhibition of matrix metalloproteinase expression and activity in articular chondrocytes

    DEFF Research Database (Denmark)

    Sondergaard, B C; Wulf, H; Henriksen, K

    2006-01-01

    OBJECTIVE: Calcitonin was recently reported to counter progression of cartilage degradation in an experimental model of osteoarthritis, and the effects were primarily suggested to be mediated by inhibition of subchondral bone resorption. We investigated direct effects of calcitonin on chondrocytes...... by assessing expression of the receptor and pharmacological effects on collagen type II degradation under ex vivo and in vivo conditions. METHODS: Localization of the calcitonin receptor on articular chondrocytes was investigated by immunohistochemistry, and the expression by reverse transcriptase polymerase.......0001-1 microM]. In vivo, cartilage degradation was investigated in ovariectomized (OVX) rats administered with oral calcitonin [2 mg/kg calcitonin] for 9 weeks. RESULTS: The calcitonin receptor was identified in articular chondrocytes by immunohistochemistry and RT-PCR. Calcitonin concentration...

  11. Predictors of time to relapse in amphetamine-type substance users in the matrix treatment program in Iran: a Cox proportional hazard model application.

    Science.gov (United States)

    Moeeni, Maryam; Razaghi, Emran M; Ponnet, Koen; Torabi, Fatemeh; Shafiee, Seyed Ali; Pashaei, Tahereh

    2016-07-26

    The aim of this study was to determine which predictors influence the risk of relapse among a cohort of amphetamine-type substance (ATS) users in Iran. A Cox proportional hazards model was conducted to determine factors associated with the relapse time in the Matrix treatment program provided by the Iranian National Center of Addiction Studies (INCAS) between March 2010 and October 2011. Participating in more treatment sessions was associated with a lower probability of relapse. On the other hand, patients with less family support, longer dependence on ATS, and those with an experience of casual sex and a history of criminal offenses were more likely to relapse. This study broadens our understanding of factors influencing the risk of relapse in ATS use among an Iranian sample. The findings can guide practitioners during the treatment program.

  12. Thermal Response of Whipox-Type All-Oxide Ceramic Matrix Composites during Reentry Simulation in the Dlr-Lbk Arc-Heated Facility

    Science.gov (United States)

    Mechnich, P.; Braue, W.; Schneider, H.; Koch, U.; Esser, B.; Gülhan, A.

    2005-02-01

    All-oxide ceramic matrix composites (CMCs) such as WHIPOXTM (wound highly porous oxide) exhibit excellent damage tolerance and thermal stability up to 1400°C. Due to their low density and thermal conductivity these new ceramic materials are considered promising candidates for thermal protection systems (TPS) of spacecrafts. The performance of WHIPOX-type CMCs was evaluated during reentry simulations in the L2K leg of the arc-heated LBK facility of DLR, Cologne. The application of reaction-bonded alumina (RBAO) coatings provides significant CMC surface protection and decreased gas permeability, which are key issues for reentry applications. Since emittance and catalycity of the RBAO-coatings limit the performance of CMCs in a reentry environment, binary SiC/RBAO coatings providing higher emittance and/or lower catalycity proved to be a promising approach.

  13. CopA3 Peptide Prevents Ultraviolet-Induced Inhibition of Type-I Procollagen and Induction of Matrix Metalloproteinase-1 in Human Skin Fibroblasts

    Directory of Open Access Journals (Sweden)

    Dong-Hee Kim

    2014-05-01

    Full Text Available Ultraviolet (UV exposure is well-known to induce premature aging, which is mediated by matrix metalloproteinase-1 (MMP-1 activity. A 9-mer peptide, CopA3 (CopA3 was synthesized from a natural peptide, coprisin, which is isolated from the dung beetle Copris tripartitus. As part of our continuing search for novel bioactive natural products, CopA3 was investigated for its in vitro anti-skin photoaging activity. UV-induced inhibition of type-I procollagen and induction of MMP-1 were partially prevented in human skin fibroblasts by CopA3 peptide in a dose-dependent manner. At a concentration of 25 μM, CopA3 nearly completely inhibited MMP-1 expression. These results suggest that CopA3, an insect peptide, is a potential candidate for the prevention and treatment of skin aging.

  14. Increased levels of the calcification marker matrix Gla Protein and the inflammatory markers YKL-40 and CRP in patients with type 2 diabetes and ischemic heart disease

    DEFF Research Database (Denmark)

    Thomsen, Stine B; Rathcke, Camilla N; Zerahn, Bo

    2010-01-01

    . In the present study levels of markers of calcification (MGP) and inflammation (YKL-40, hsCRP) were evaluated in patients with T2 D and/or ischemic heart disease (IHD). MATERIALS AND METHODS: The study population consisted of 1) patients with T2D (n = 45); 2) patients with IHD (n = 37); patients with both T2D......OBJECTIVE AND DESIGN: Low grade inflammation is of pathogenic importance in atherosclerosis and in the development of cardiovascular disease (CVD) and type 2 diabetes (T2D). Matrix GLA protein (MGP), an inhibitor of medial calcification of arteries, is increased in patients with atherosclerosis...... and IHD (n = 20) and 4) healthy controls (n = 20). Biochemical parameters were measured in venous blood samples. RESULTS: Levels of MGP, YKL-40 and hsCRP were increased in patients with IHD and/or T2D (p T2D and IHD had higher MGP levels (p

  15. Brian Barry: innovative contributions to transdermal and topical drug delivery.

    Science.gov (United States)

    Williams, A C

    2013-01-01

    Brian Barry published over 300 research articles across topics ranging from colloid science, vasoconstriction and the importance of thermodynamics in dermal drug delivery to exploring the structure and organisation of the stratum corneum barrier lipids and numerous strategies for improving topical and transdermal drug delivery, including penetration enhancers, supersaturation, coacervation, eutectic formation and the use of varied liposomes. As research in the area blossomed in the early 1980s, Brian wrote the book that became essential reading for both new and established dermal delivery scientists, explaining the background mathematics and principles through to formulation design. Brian also worked with numerous scientists, as collaborators and students, who have themselves taken his rigorous approach to scientific investigation into their own research groups. This paper can only describe a small fraction of the many significant contributions that Brian made to the field during his 40-year academic career.

  16. Solid‐in‐oil nanodispersions for transdermal drug delivery systems

    Science.gov (United States)

    Kitaoka, Momoko; Wakabayashi, Rie; Kamiya, Noriho

    2016-01-01

    Abstract Transdermal administration of drugs has advantages over conventional oral administration or administration using injection equipment. The route of administration reduces the opportunity for drug evacuation before systemic circulation, and enables long‐lasting drug administration at a modest body concentration. In addition, the skin is an attractive route for vaccination, because there are many immune cells in the skin. Recently, solid‐in‐oil nanodisperison (S/O) technique has demonstrated to deliver cosmetic and pharmaceutical bioactives efficiently through the skin. S/O nanodispersions are nanosized drug carriers designed to overcome the skin barrier. This review discusses the rationale for preparation of efficient and stable S/O nanodispersions, as well as application examples in cosmetic and pharmaceutical materials including vaccines. Drug administration using a patch is user‐friendly, and may improve patient compliance. The technique is a potent transcutaneous immunization method without needles. PMID:27529824

  17. Current and future technological advances in transdermal gene delivery.

    Science.gov (United States)

    Chen, Xianfeng

    2017-12-19

    Transdermal gene delivery holds significant advantages as it is able to minimize the problems of systemic administration such as enzymatic degradation, systemic toxicity, and poor delivery to target tissues. This technology has the potential to transform the treatment and prevention of a range of diseases. However, the skin poses a great barrier for gene delivery because of the "bricks-and-mortar" structure of the stratum corneum and the tight junctions between keratinocytes in the epidermis. This review systematically summarizes the typical physical and chemical approaches to overcome these barriers and facilitate gene delivery via skin for applications in vaccination, wound healing, skin cancers and skin diseases. Next, the advantages and disadvantages of different approaches are discussed and the insights for future development are provided. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Efficacy of transdermal nitroglycerine in idiopathic pre-term labour.

    Science.gov (United States)

    Shaikh, Shahida; Shaikh, Abdul Hameed; Akhter, Saleem; Isran, Basma

    2012-01-01

    To determine the efficacy of transdermal Nitroglycerine patch in idiopathic pre-term labour and foetomaternal outcome. This quasi-experimental study was conducted at the Obstetrics Unit-II of Shaikh Zayed Hospital for Women, Chandka Medical College, Shaheed Mohtarma Benazir Bhutto Medical University, Larkana, from Jan 1 to June 30, 2010. Sixtyfive pregnant women at 28-34 weeks of gestation were recruited after they met the selection criteria based on non-probability consecutive sampling. Initially, 73 patients were selected, but 65 of them completed the treatment, while 8 patients refused to continue. Patients diagnosed with pre-term labour were given glyceryl trinitrate (GTN) 5 mg/12 hours transdermal patch which was applied on the anterior abdominal wall. The second patch of same dose was given after 12 hours. Arrest of labour, prolongation of pregnancy in days or weeks along with side effects of the agent were monitored. Patients were followed till delivery to know the foeto-maternal outcome. Dramatic effects were seen in around 60 (92.3%), of the total patients who had felt relief from premature labour pains within the first hour and only 5 (7.6%) patients could not go beyond 24 hours, as among them 3 (4.61%) had previous uterine scar and 2 (3.07%) developed ruptured membranes after 12 hours of admission and their babies also could not survive. Mean pregnancy prolongation was 15.35 +/- 9.45 days (min: 4 max: 35), so delivery was deferred up to 48 hours, 3 to 7 days and more than 7 days in 4 (6.15%), 6 (9.23%) and 50 (76.92%) respectively. Glyceryl trinitrate, trans dermal patch is effective and safe tocolytic in idiopathic preterm labour. By prolonging pregnancy it improves neonatal outcome.

  19. Modeling of transdermal drug delivery with a microneedle array

    Science.gov (United States)

    Lv, Y.-G.; Liu, J.; Gao, Y.-H.; Xu, B.

    2006-11-01

    Transdermal drug delivery is generally limited by the extraordinary barrier properties of the stratum corneum, the outer 10-15 µm layer of skin. A conventional needle inserted across this barrier and into deeper tissues could effectively deliver drugs. However, it would lead to infection and cause pain, thereby reducing patient compliance. In order to administer a frequent injection of insulin and other therapeutic agents more efficiently, integrated arrays with very short microneedles were recently proposed as very good candidates for painless injection or extraction. A variety of microneedle designs have thus been made available by employing the fabrication tools of the microelectronics industry and using materials such as silicon, metals, polymers and glass with feature sizes ranging from sub-micron to nanometers. At the same time, experiments were also made to test the capability of the microneedles to inject drugs into tissues. However, due to the difficulty encountered in measurement, a detailed understanding of the spatial and transient drug delivery process still remains unclear up to now. To better grasp the mechanisms involved, quantitative theoretical models were developed in this paper to simultaneously characterize the flow and drug transport, and numerical solutions were performed to predict the kinetics of dispersed drugs injected into the skin from a microneedle array. Calculations indicated that increasing the initial injection velocity and accelerating the blood circulation in skin tissue with high porosity are helpful to enhance the transdermal drug delivery. This study provides the first quantitative simulation of fluid injection through a microneedle array and drug species transport inside the skin. The modeling strategy can also possibly be extended to deal with a wider range of clinical issues such as targeted nanoparticle delivery for therapeutics or molecular imaging.

  20. Dysregulated miR-127-5p contributes to type II collagen degradation by targeting matrix metalloproteinase-13 in human intervertebral disc degeneration.

    Science.gov (United States)

    Hua, Wen-Bin; Wu, Xing-Huo; Zhang, Yu-Kun; Song, Yu; Tu, Ji; Kang, Liang; Zhao, Kang-Cheng; Li, Shuai; Wang, Kun; Liu, Wei; Shao, Zeng-Wu; Yang, Shu-Hua; Yang, Cao

    2017-08-01

    Intervertebral disc degeneration (IDD) is a chronic disease associated with the degradation of extracellular matrix (ECM). Matrix metalloproteinase (MMP)-13 is a major enzyme that mediates the degradation of ECM components. MMP-13 has been predicted to be a potential target of miR-127-5p. However, the exact function of miR-127-5p in IDD is still unclear. We designed this study to evaluate the correlation between miR-127-5p level and the degeneration of human intervertebral discs and explore the potential mechanisms. miR-127-5p levels and MMP-13 mRNA levels were detected by quantitative real-time polymerase chain reaction (qPCR). To determine whether MMP-13 is a target of miR-127-5p, dual luciferase reporter assays were performed. miR-127-5p mimic and miR-127-5p inhibitor were used to overexpress or downregulate miR-127-5p expression in human NP cells, respectively. Small interfering RNA (siRNA) was used to knock down MMP-13 expression in human NP cells. Type II collagen expression in human NP cells was detected by qPCR, western blotting, and immunofluorescence staining. We confirmed that miR-127-5p was significantly downregulated in nucleus pulposus (NP) tissue of degenerative discs and its expression was inversely correlated with MMP-13 mRNA levels. We reveal that MMP-13 may act as a target of miR-127-5p. Expression of miR-127-5p was inversely correlated with type II collagen expression in human NP cells. Moreover, suppression of MMP-13 expression by siRNA blocked downstream signaling and increased type II collagen expression. Dysregulated miR-127-5p contributed to the degradation of type II collagen by targeting MMP-13 in human IDD. Our findings highlight that miR-127-5p may serve as a new therapeutic target in IDD. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  1. Fuzzy risk matrix

    International Nuclear Information System (INIS)

    Markowski, Adam S.; Mannan, M. Sam

    2008-01-01

    A risk matrix is a mechanism to characterize and rank process risks that are typically identified through one or more multifunctional reviews (e.g., process hazard analysis, audits, or incident investigation). This paper describes a procedure for developing a fuzzy risk matrix that may be used for emerging fuzzy logic applications in different safety analyses (e.g., LOPA). The fuzzification of frequency and severity of the consequences of the incident scenario are described which are basic inputs for fuzzy risk matrix. Subsequently using different design of risk matrix, fuzzy rules are established enabling the development of fuzzy risk matrices. Three types of fuzzy risk matrix have been developed (low-cost, standard, and high-cost), and using a distillation column case study, the effect of the design on final defuzzified risk index is demonstrated

  2. Mutations in matrix and SP1 repair the packaging specificity of a Human Immunodeficiency Virus Type 1 mutant by reducing the association of Gag with spliced viral RNA

    Directory of Open Access Journals (Sweden)

    Ristic Natalia

    2010-09-01

    Full Text Available Abstract Background The viral genome of HIV-1 contains several secondary structures that are important for regulating viral replication. The stem-loop 1 (SL1 sequence in the 5' untranslated region directs HIV-1 genomic RNA dimerization and packaging into the virion. Without SL1, HIV-1 cannot replicate in human T cell lines. The replication restriction phenotype in the SL1 deletion mutant appears to be multifactorial, with defects in viral RNA dimerization and packaging in producer cells as well as in reverse transcription of the viral RNA in infected cells. In this study, we sought to characterize SL1 mutant replication restrictions and provide insights into the underlying mechanisms of compensation in revertants. Results HIV-1 lacking SL1 (NLΔSL1 did not replicate in PM-1 cells until two independent non-synonymous mutations emerged: G913A in the matrix domain (E42K on day 18 postinfection and C1907T in the SP1 domain (P10L on day 11 postinfection. NLΔSL1 revertants carrying either compensatory mutation showed enhanced infectivity in PM-1 cells. The SL1 revertants produced significantly more infectious particles per nanogram of p24 than did NLΔSL1. The SL1 deletion mutant packaged less HIV-1 genomic RNA and more cellular RNA, particularly signal recognition particle RNA, in the virion than the wild-type. NLΔSL1 also packaged 3- to 4-fold more spliced HIV mRNA into the virion, potentially interfering with infectious virus production. In contrast, both revertants encapsidated 2.5- to 5-fold less of these HIV-1 mRNA species. Quantitative RT-PCR analysis of RNA cross-linked with Gag in formaldehyde-fixed cells demonstrated that the compensatory mutations reduced the association between Gag and spliced HIV-1 RNA, thereby effectively preventing these RNAs from being packaged into the virion. The reduction of spliced viral RNA in the virion may have a major role in facilitating infectious virus production, thus restoring the infectivity of NLΔSL1

  3. Effects of macelignan isolated from Myristica fragrans (nutmeg) on expression of matrix metalloproteinase-1 and type I procollagen in UVB-irradiated human skin fibroblasts

    International Nuclear Information System (INIS)

    Lee, Kyung-Eun; Mun, Sukyeong; Pyun, Hee-Bong; Kim, Myung-Suk; Hwang, Jae-Kwan

    2012-01-01

    Exposure to ultraviolet (UV) light causes premature skin aging that is associated with upregulated matrix metalloproteinases (MMPs) and decreased collagen synthesis. Macelignan, a natural lignan compound isolated from Myristica fragrans HOUTT. (nutmeg), has been reported to possess antioxidant and antiinflammatory activities. This study assessed the effects of macelignan on photoaging and investigated its mechanisms of action in UV-irradiated human skin fibroblasts (Hs68) by reverse transcription-polymerase chain reaction, Western blot analysis, 2', 7'-dichlorofluorescein diacetate assay, and enzyme-linked immunosorbent assay. Our results show that macelignan attenuated UV-induced MMP-1 expression by suppressing phosphorylation of mitogen-activated protein kinases (MAPKs) induced by reactive oxygen species. Macelignan also increased type I procollagen expression and secretion through transforming growth factor β (TGF-β)/Smad signaling. These findings indicate that macelignan regulates the expression of MMP-1 and type I procollagen in UV-irradiated human skin fibroblasts by modulating MAPK and TGF-β/Smad signaling, suggesting its potential as an efficacious antiphotoaging agent. (author)

  4. A Computational Procedure for Assessing the Dynamic Performance of Diffusion-Controlled Transdermal Delivery Devices

    Directory of Open Access Journals (Sweden)

    Laurent Simon

    2011-08-01

    Full Text Available Abstract: The dynamic performances of two different controlled-release systems were analyzed. In a reservoir-type drug-delivery patch, the transdermal flux is influenced by the properties of the membrane. A constant thermodynamic drug activity is preserved in the donor compartment. Monolithic matrices are among the most inexpensive systems used to direct drug delivery. In these structures, the active pharmaceutical ingredients are encapsulated within a polymeric material. Despite the popularity of these two devices, to tailor the properties of the polymer and additives to specific transient behaviors can be challenging and time-consuming. The heuristic approaches often considered to select the vehicle formulation provide limited insight into key permeation mechanisms making it difficult to predict the device performance. In this contribution, a method to calculate the flux response time in a system consisting of a reservoir and a polymeric membrane was proposed and confirmed. Nearly 8.60 h passed before the metoprolol delivery rate reached ninety-eight percent of its final value. An expression was derived for the time it took to transport the active pharmaceutical ingredient out of the polymer. Ninety-eight percent of alpha-tocopherol acetate was released in 461.4 h following application to the skin. The effective time constant can be computed to help develop optimum design strategies.

  5. Formulation and in vitro/in vivo evaluation of levodopa transdermal delivery systems.

    Science.gov (United States)

    Lee, Kyung Eun; Choi, Yun Jung; Oh, Byu Ree; Chun, In Koo; Gwak, Hye Sun

    2013-11-18

    This study aims to investigate the feasibility of Levodopa transdermal delivery systems (TDSs). Levodopa TDSs were formulated using various vehicles and permeation enhancers, and in vitro permeation and in vivo pharmacokinetic studies were carried out. In the in vitro study, ester-type vehicles showed relatively high enhancing effects; propylene glycol monocaprylate and propylene glycol monolaurate showed the highest permeation fluxes from both solution and pressure sensitive adhesive (PSA) TDS formulations. Lag time was dramatically shortened with PSA TDS formulations as compared with solution formulations. In the in vivo study, the addition of fatty acids increased blood drug concentrations regardless of the kind or concentration of fatty acid; the AUCinf increased up to 8.7 times as compared with propylene glycol (PG) alone. PSA TDS containing 10% linoleic acid exhibited prolonged Tmax as compared with oral form. Total clearance of L-dopa from PSA TDSs was significantly lower than from oral form (up to 86.8 times). Especially, PSA TDS containing 10% linoleic acid (LOA) revealed 76.2 fold higher AUCinf than oral administration. Based on our results, the L-dopa PSA TDS containing PG with 10% LOA could be used as a good adjuvant therapy for Parkinson's disease patients who experience symptom fluctuation by L-dopa oral administration. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Evaluation of skin absorption of drugs from topical and transdermal formulations

    Directory of Open Access Journals (Sweden)

    André Luís Morais Ruela

    Full Text Available ABSTRACT The skin barrier function has been attributed to the stratum corneum and represents a major challenge in clinical practice pertaining to cutaneous administration of drugs. Despite this, a large number of bioactive compounds have been successfully administered via cutaneous administration because of advances in the design of topical and transdermal formulations. In vitro and in vivo evaluations of these novel drug delivery systems are necessary to characterize their quality and efficacy. This review covers the most well-known methods for assessing the cutaneous absorption of drugs as an auxiliary tool for pharmaceutical formulation scientists in the design of drug delivery systems. In vitro methods as skin permeation assays using Franz-type diffusion cells, cutaneous retention and tape-stripping methods to study the cutaneous penetration of drugs, and in vivo evaluations as pre-clinical pharmacokinetic studies in animal models are discussed. Alternative approaches to cutaneous microdialysis are also covered. Recent advances in research on skin absorption of drugs and the effect of skin absorption enhancers, as investigated using confocal laser scanning microscopy, Raman confocal microscopy, and attenuated total reflectance Fourier-transform infrared spectroscopy, are reviewed.

  7. Matrix calculus

    CERN Document Server

    Bodewig, E

    1959-01-01

    Matrix Calculus, Second Revised and Enlarged Edition focuses on systematic calculation with the building blocks of a matrix and rows and columns, shunning the use of individual elements. The publication first offers information on vectors, matrices, further applications, measures of the magnitude of a matrix, and forms. The text then examines eigenvalues and exact solutions, including the characteristic equation, eigenrows, extremum properties of the eigenvalues, bounds for the eigenvalues, elementary divisors, and bounds for the determinant. The text ponders on approximate solutions, as well

  8. Innate Immune Signalling Genetics of Pain, Cognitive Dysfunction and Sickness Symptoms in Cancer Pain Patients Treated with Transdermal Fentanyl

    Science.gov (United States)

    Barratt, Daniel T.; Klepstad, Pål; Dale, Ola; Kaasa, Stein; Somogyi, Andrew A.

    2015-01-01

    Common adverse symptoms of cancer and chemotherapy are a major health burden; chief among these is pain, with opioids including transdermal fentanyl the mainstay of treatment. Innate immune activation has been implicated generally in pain, opioid analgesia, cognitive dysfunction, and sickness type symptoms reported by cancer patients. We aimed to determine if genetic polymorphisms in neuroimmune activation pathways alter the serum fentanyl concentration-response relationships for pain control, cognitive dysfunction, and other adverse symptoms, in cancer pain patients. Cancer pain patients (468) receiving transdermal fentanyl were genotyped for 31 single nucleotide polymorphisms in 19 genes: CASP1, BDNF, CRP, LY96, IL6, IL1B, TGFB1, TNF, IL10, IL2, TLR2, TLR4, MYD88, IL6R, OPRM1, ARRB2, COMT, STAT6 and ABCB1. Lasso and backward stepwise generalised linear regression were used to identify non-genetic and genetic predictors, respectively, of pain control (average Brief Pain Inventory fentanyl concentrations did not predict between-patient variability in these outcomes, nor did genetic factors predict pain control, sickness response or opioid adverse event complaint. Carriers of the MYD88 rs6853 variant were half as likely to have cognitive dysfunction (11/111) than wild-type patients (69/325), with a relative risk of 0.45 (95% CI: 0.27 to 0.76) when accounting for major non-genetic predictors (age, Karnofsky functional score). This supports the involvement of innate immune signalling in cognitive dysfunction, and identifies MyD88 signalling pathways as a potential focus for predicting and reducing the burden of cognitive dysfunction in cancer pain patients. PMID:26332828

  9. Innate Immune Signalling Genetics of Pain, Cognitive Dysfunction and Sickness Symptoms in Cancer Pain Patients Treated with Transdermal Fentanyl.

    Directory of Open Access Journals (Sweden)

    Daniel T Barratt

    Full Text Available Common adverse symptoms of cancer and chemotherapy are a major health burden; chief among these is pain, with opioids including transdermal fentanyl the mainstay of treatment. Innate immune activation has been implicated generally in pain, opioid analgesia, cognitive dysfunction, and sickness type symptoms reported by cancer patients. We aimed to determine if genetic polymorphisms in neuroimmune activation pathways alter the serum fentanyl concentration-response relationships for pain control, cognitive dysfunction, and other adverse symptoms, in cancer pain patients. Cancer pain patients (468 receiving transdermal fentanyl were genotyped for 31 single nucleotide polymorphisms in 19 genes: CASP1, BDNF, CRP, LY96, IL6, IL1B, TGFB1, TNF, IL10, IL2, TLR2, TLR4, MYD88, IL6R, OPRM1, ARRB2, COMT, STAT6 and ABCB1. Lasso and backward stepwise generalised linear regression were used to identify non-genetic and genetic predictors, respectively, of pain control (average Brief Pain Inventory < 4, cognitive dysfunction (Mini-Mental State Examination ≤ 23, sickness response and opioid adverse event complaint. Serum fentanyl concentrations did not predict between-patient variability in these outcomes, nor did genetic factors predict pain control, sickness response or opioid adverse event complaint. Carriers of the MYD88 rs6853 variant were half as likely to have cognitive dysfunction (11/111 than wild-type patients (69/325, with a relative risk of 0.45 (95% CI: 0.27 to 0.76 when accounting for major non-genetic predictors (age, Karnofsky functional score. This supports the involvement of innate immune signalling in cognitive dysfunction, and identifies MyD88 signalling pathways as a potential focus for predicting and reducing the burden of cognitive dysfunction in cancer pain patients.

  10. Recent Advances in Skin Penetration Enhancers for Transdermal Gene and Drug Delivery.

    Science.gov (United States)

    Amjadi, Morteza; Mostaghaci, Babak; Sitti, Metin

    2017-01-01

    There is a growing interest in transdermal delivery systems because of their noninvasive, targeted, and on-demand delivery of gene and drugs. However, efficient penetration of therapeutic compounds into the skin is still challenging largely due to the impermeability of the outermost layer of the skin, known as stratum corneum. Recently, there have been major research activities to enhance the skin penetration depth of pharmacological agents. This article reviews recent advances in the development of various strategies for skin penetration enhancement. We show that approaches such as ultrasound waves, laser, and microneedle patches have successfully been employed to physically disrupt the stratum corneum structure for enhanced transdermal delivery. Rather than physical approaches, several non-physical route have also been utilized for efficient transdermal delivery across the skin barrier. Finally, we discuss some clinical applications of transdermal delivery systems for gene and drug delivery. This paper shows that transdermal delivery devices can potentially function for diverse healthcare and medical applications while further investigations are still necessary for more efficient skin penetration of gene and drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Systemic delivery of β-blockers via transdermal route for hypertension

    Science.gov (United States)

    Ahad, Abdul; Al-Jenoobi, Fahad I.; Al-Mohizea, Abdullah M.; Akhtar, Naseem; Raish, Mohammad; Aqil, Mohd.

    2014-01-01

    Hypertension is the most common cardiovascular disease worldwide. Moreover, management of hypertension requires long-term treatment that may result in poor patient compliance with conventional dosage forms due to greater frequency of drug administration. Although there is availability of a plethora of therapeutically effective antihypertensive molecules, inadequate patient welfare is observed; this arguably presents an opportunity to deliver antihypertensive agents through a different route. Ever since the transdermal drug delivery came into existence, it has offered great advantages including non-invasiveness, prolonged therapeutic effect, reduced side effects, improved bioavailability, better patient compliance and easy termination of drug therapy. Attempts were made to develop the transdermal therapeutic system for various antihypertensive agents, including β-blockers, an important antihypertensive class. β-blockers are potent, highly effective in the management of hypertension and other heart ailments by blocking the effects of normal amounts of adrenaline in the heart and blood vessels. The shortcomings associated with β-blockers such as more frequent dose administration, extensive first pass metabolism and variable bioavailability, make them an ideal candidate for transdermal therapeutic systems. The present article gives a brief view of different β-blockers formulated as transdermal therapeutic system in detail to enhance the bioavailability as well as to improve patient compliance. Constant improvement in this field holds promise for the long-term success in technologically advanced transdermal dosage forms being commercialized sooner rather than later. PMID:26702253

  12. Poly(lactic-co-glycolic) acid drug delivery systems through transdermal pathway: an overview.

    Science.gov (United States)

    Naves, Lucas; Dhand, Chetna; Almeida, Luis; Rajamani, Lakshminarayanan; Ramakrishna, Seeram; Soares, Graça

    2017-05-01

    In past few decades, scientists have made tremendous advancement in the field of drug delivery systems (DDS), through transdermal pathway, as the skin represents a ready and large surface area for delivering drugs. Efforts are in progress to design efficient transdermal DDS that support sustained drug release at the targeted area for longer duration in the recommended therapeutic window without producing side-effects. Poly(lactic-co-glycolic acid) (PLGA) is one of the most promising Food and Drug Administration approved synthetic polymers in designing versatile drug delivery carriers for different drug administration routes, including transdermal drug delivery. The present review provides a brief introduction over the transdermal drug delivery and PLGA as a material in context to its role in designing drug delivery vehicles. Attempts are made to compile literatures over PLGA-based drug delivery vehicles, including microneedles, nanoparticles, and nanofibers and their role in transdermal drug delivery of different therapeutic agents. Different nanostructure evaluation techniques with their working principles are briefly explained.

  13. Development, characterization & invivo evaluation of proniosomal based transdermal delivery system of Atenolol

    Directory of Open Access Journals (Sweden)

    S. Ramkanth

    2018-06-01

    Full Text Available The potential of proniosomes as a transdermal drug delivery system for Atenolol was investigated by encapsulating the drug in various formulations of proniosomal gel composed of various ratios of sorbitan fatty acid esters, cholesterol, lecithin prepared by Coacervation-phase separation method. The objectives of the present study were to define effects on the antihypertension activity and pharmacokinetics of a novel transdermal Proniosomal gel incorporating Atenolol. The formulated systems were characterized in vitro for size, drug entrapment, In vitro and in vivo drug permeation profiles and vesicular stability at different storage conditions. The optimized Atenolol proniosomes (AT8 showed nanometric vesicle size, high entrapment efficiency and marked enhancement in transdermal permeation. The prepared Proniosomal gel showed the relative bioavailability of 365.38 fold increased for AT8 than oral. The maximal concentrations (Cmax, of drug were significantly reduced while the areas under the plasma concentration–time curve (AUC, and mean residence times (MRT, t1/2 were evidently increased and extended, respectively. The results suggest that proniosomes can act as promising carrier which offers an alternative approach for transdermal delivery of Atenolol. Keywords: Proniosomes, Atenolol, Niosomes, Pharmacokinetic study, Transdermal delivery

  14. [Studies on transdermal delivery of ferulic acid through rat skin treated by microneedle arrays].

    Science.gov (United States)

    Yang, Bing; Du, Shou-ying; Bai, Jie; Shang, Ke-xin; Lu, Yang; Li, Peng-yue

    2014-12-01

    In order to investigate the characteristics of transdermal delivery of ferulic acid under the treated of microneedle arrays and the influence on permeability of rat skin capillaries, improved Franz-cells were used in the transdermal delivery experiment with the rat skin of abdominal wall and the length of microneedle arrays, different insertion forces, retention time were studied in the influence of characteristics of transdermal delivery of FA. The amount of FA was determined by HPLC system. Intravenous injection Evans blue and FA was added after microneedle arrays treated. Established inflammation model was built by daubing dimethylbenzene. The amount of Evans blue in the rat skin was read at 590 nm wavelength with a Multiskan Go microplate reader. Compared with passive diffusion group the skin pretreated with microneedle arrays had a remarkable enhancement of FA transport (P Microneedle arrays with different length had a remarkable enhancement of FA transport, but was not related to the increase of the length. The research of FA on the reduce of permeability of rat skin capillaries indicated that the skin pretreated with microneedle arrays could reduce the content of Evans blue in the skins of rat significantly compared with the untreated group. The permeation rate of ferulic acid transdermal delivery had remarkable increase under the treated of microneedle arrays and the length of microneedle arrays ,the retention time so as to the insertion force were important to the transdermal delivery of ferulic acid.

  15. Nanoemulsions as vehicles for transdermal delivery of glycyrrhizin

    Directory of Open Access Journals (Sweden)

    Ranjit Kumar Harwansh

    2011-12-01

    Full Text Available The present investigation aims to evaluate an isotropic and thermodynamically stable nanoemulsion formulation for transdermal delivery of glycyrrhizin (GZ, with minimum surfactant and cosurfactant (Smix concentrations that could improve its solubility, permeation enhancement, and stability. Pseudo-ternary phase diagrams were developed and various nanoemulsion formulations were prepared using soyabean oil as oil, Span 80, Brij 35 as a surfactant and isopropyl alcohol as a cosurfactant. Nanoemulsion formulations that passed the thermodynamic stability tests were characterized for pH, viscosity and droplet size using a transmission electron microscopy. The transdermal ability of glycyrrhizin through human cadaver skin was determined using Franz diffusion cells. The in vitro skin permeation profile of the optimized nanoemulsion formulation (NE2 was compared to that of conventional gel. A significant increase in permeability parameters such as steady-state flux (Jss and permeability coefficient (Kp was observed in the optimized nanoemulsion formulation (NE2, which consisted of 1% wt/wt of mono ammonium glycyrrhizinate (MAG, 32.4% Span 80, 3.7% Brij 35, 10% isopropyl alcohol, 46.5% soyabean oil and 6.4% distilled water. No obvious skin irritation was observed for the studied nanoemulsion formulation (NE2 or the gel. The results indicated that nanoemulsions are promising vehicles for transdermal delivery of glycyrrhizin through human cadaver skin, without the use of additional permeation enhancers, because excipients of nanoemulsions act as permeation enhancers themselves.O objetivo da investigação é avaliar uma nanoemulsão isotrópica termodinamicamente estável para a administração transdérmica da glicirrizina (GZ, com concentrações mínimas de tensoativo e co-tensoativo (Smix, que poderiam melhorar a sua solubilidade, a permeação e a estabilidade. Os diagramas pseudo-ternários de fase foram desenvolvidos e diversas nanoemulsões foram

  16. Promotion of the transdermal delivery of protein drugs by N-trimethyl chitosan nanoparticles combined with polypropylene electret.

    Science.gov (United States)

    Tu, Ye; Wang, Xinxia; Lu, Ying; Zhang, He; Yu, Yuan; Chen, Yan; Liu, Junjie; Sun, Zhiguo; Cui, Lili; Gao, Jing; Zhong, Yanqiang

    We recently reported that electret, which was prepared by a corona charging system with polypropylene film, could enhance the transdermal delivery of several drugs of low molecular weight. The aim of this study was to investigate whether electret could enhance the transdermal delivery of protein drugs by N -trimethyl chitosan nanoparticles (TMC NPs) prepared by an ionic gelation method. A series of experiments were performed, including in vitro skin permeation assays and anti-inflammatory effects, to evaluate the transdermal delivery of protein drugs by TMC NPs in the presence of electret. The results showed that in the presence of electret, the transdermal delivery of protein drugs in TMC NPs was significantly enhanced, as demonstrated by in vitro permeation studies and confocal laser scanning microscopy. Notably, superoxide dismutase-loaded TMC NPs combined with electret exhibited the best inhibitory effect on the edema of the mouse ear. TMC NPs combined with electret represent a novel platform for the transdermal delivery of protein drugs.

  17. Iontophoretic and Microneedle Mediated Transdermal Delivery of Glycopyrrolate

    Directory of Open Access Journals (Sweden)

    Meera Gujjar

    2014-12-01

    Full Text Available Purpose: The objective of this study was to investigate the use of iontophoresis, soluble microneedles and their combination for the transdermal delivery of glycopyrrolate. Methods: In vitro permeation was tested using full thickness porcine ear skin mounted onto Franz diffusion cells. Iontophoresis (0.5 mA/cm2 was done for 4 h using Ag/AgCl electrodes. For microneedles, three line array (27 needles/line of maltose microneedles were used to microporate the skin prior to mounting. Pore uniformity was determined by taking fluorescent images of distribution of calcein into pores and processing the images using an image analysis tool, which measured the fluorescent intensity in and around each pore to provide a pore permeability index (PPI. The donor chamber contained 500 µL of a 1 mg/mL solution of glycopyrrolate, and the receptor chamber contained 5 mL of 50 mM NaCl in deionized water. Samples were collected at predetermined time points over a period of 24 h and analyzed by HPLC. Skin irritation testing was performed with a 3D cell culture kit of human skin. MTT assay determined cell viability; viability less than 50% was considered irritant. Results: A control experiment which investigated passive permeation of glycopyrrolate delivered an average cumulative amount of 24.92 ± 1.77 µg/cm2 at 24 h, while microneedle pretreatment increased permeability to 46.54 ± 6.9 µg/cm2. Both iontophoresis (158.53 ± 17.50 µg/cm2 and a combination of iontophoresis and microneedles (182.43 ± 20.06 µg/ cm2 significantly increased delivery compared to passive and microneedles alone. Glycopyrrolate solution was found to be nonirritant with cell viability of 70.4% ± 5.03%. Conclusion: Iontophoresis and a combination of iontophoresis with microneedle pretreatment can be effectively used to enhance the transdermal delivery of glycopyrrolate. Glycopyrrolate was found to be non-irritant to skin.

  18. Validated RP-HPLC/DAD Method for the Quantification of Insect Repellent Ethyl 2-Aminobenzoate in Membrane-Moderated Matrix Type Monolithic Polymeric Device.

    Science.gov (United States)

    Islam, Johirul; Zaman, Kamaruz; Chakrabarti, Srijita; Sharma Bora, Nilutpal; Mandal, Santa; Pratim Pathak, Manash; Srinivas Raju, Pakalapati; Chattopadhyay, Pronobesh

    2017-07-01

    A simple, accurate and sensitive reversed-phase high-performance liquid chromatographic (RP-HPLC) method has been developed for the estimation of ethyl 2-aminobenzoate (EAB) in a matrix type monolithic polymeric device and validated as per the International Conference on Harmonization guidelines. The analysis was performed isocratically on a ZORBAX Eclipse plus C18 analytical column (250 × 4.4 mm, 5 μm) and a diode array detector (DAD) using acetonitrile and water (75:25 v/v) as the mobile phase by keeping the flow-rate constant at 1.0 mL/min. Determination of EAB was not interfered in the presence of excipients. Inter- and intra-day relative standard deviations were not higher than 2%. Mean recovery was between 98.7 and 101.3%. Calibration curve was linear in the concentration range of 0.5-10 µg/mL. Limits of detection and quantification were 0.19 and 0.60 µg/mL, respectively. Thus, the present report put forward a novel method for the estimation of EAB, an emerging insect repellent, by using RP-HPLC technique. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. Modular Study of the Type III Effector Repertoire in Pseudomonas syringae pv. tomato DC3000 Reveals a Matrix of Effector Interplay in Pathogenesis.

    Science.gov (United States)

    Wei, Hai-Lei; Zhang, Wei; Collmer, Alan

    2018-05-08

    The bacterial pathogen Pseudomonas syringae pv. tomato DC3000 suppresses the two-tiered innate immune system of Nicotiana benthamiana and other plants by injecting a complex repertoire of type III secretion effector (T3E) proteins. Effectorless polymutant DC3000D36E was used with a modularized system for native delivery of the 29 DC3000 T3Es singly and in pairs. Assays of the performance of this T3E library in N. benthamiana leaves revealed a matrix of T3E interplay, with six T3Es eliciting death and eight others variously suppressing the death activity of the six. The T3E library was also interrogated for effects on DC3000D36E elicitation of a reactive oxygen species burst, for growth in planta, and for T3Es that reversed these effects. Pseudomonas fluorescens and Agrobacterium tumefaciens heterologous delivery systems yielded notably different sets of death-T3Es. The DC3000D36E T3E library system highlights the importance of 13 T3Es and their interplay in interactions with N. benthamiana. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  20. Membrane-Type 1 Matrix Metal loproteinase Is Regulated by Sp1 through the Differential Activation of AKT, JNK, and ERK Pathways in Human Prostate Tumor Cells

    Directory of Open Access Journals (Sweden)

    Isis C. Sroka

    2007-05-01

    Full Text Available We and other investigators have previously shown that membrane-type 1 matrix metalloproteinase (MT1-MMP is overexpressed in invasive prostate cancer cells. However, the mechanism for this expression is not known. Here, we show that MT1-MMP is minimally expressed in nonmalignant primary prostate cells, moderately expressed in DU-145 cells, and highly expressed in invasive PC-3 and PC-3N cells. Using human MT1-MMP promoter reporter plasmids and mobility shift assays, we show that Spi regulates MT1-MMP expression in DU-145, PC-3, and PC-3N cells and in PC3-N cells using chromatin immunoprecipitation analysis and silencing RNA. Investigation of signaling pathway showed that DU-145 cells express constitutively phosphorylated extracellular stress-regulated kinase (ERK, whereas PC-3 and PC-3N cells express constitutively phosphorylated AKT/PKB and c-Jun NH2 terminal kinase (JNK. We show that MT1-MMP and Spi levels are decreased in PC-3 and PC-3N cells when phosphatidylinositol-3 kinase and JNK are inhibited, and that MT1-MMP levels are decreased in DU-145 cells when MEK is inhibited. Transient transfection of PC-3 and PC-3N cells with a dominant-negative JNK or p85, and of DU-145 cells with a dominant negative ERK, reduces MT1-MMP promoter activity. These results indicate differential signaling control of Spi-mediated transcriptional regulation of MT1-MMP in prostate cancer cell lines.

  1. Development and implementation of computational geometric model for simulation of plate type fuel fabrication process with microspheres dispersed in metallic matrix

    International Nuclear Information System (INIS)

    Lage, Aldo M.F.; Reis, Sergio C.; Braga, Daniel M.; Santos, Armindo; Ferraz, Wilmar B.

    2005-01-01

    In this report it is presented the development of a geometric model to simulate the plate type fuel fabrication process with fuels microspheres dispersed in metallic matrix, as well as its software implementation. The developed geometric model encloses the steps of pellets pressing and sintering, as well as the plate rolling passes. The model permits the simulation of structures, where the values of the various variables of the fabrication processes can be studied and modified. The following variables were analyzed: microspheres diameters, density of the powder/microspheres mixing, microspheres density, fuel volume fraction, sintering densification, and rolling passes number. In the model implementation, which was codified in DELPHI programming language, systems of structured analysis techniques were utilized. The structures simulated were visualized utilizing the AutoCAD applicative, what permitted to obtain planes sections in diverse directions. The objective of this model is to enable the analysis of the simulated structures and supply information that can help in the improvement of the dispersion microspheres fuel plates fabrication process, now in development at CDTN (Centro de Desenvolvimento da Tecnologia Nuclear) in cooperation with the CTMSP (Centro Tecnologico da Marinha em Sao Paulo). (author)

  2. Optimization of matrix solid-phase dispersion for the rapid determination of salicylate and benzophenone-type UV absorbing substances in marketed fish.

    Science.gov (United States)

    Tsai, Dung-Ying; Chen, Chien-Liang; Ding, Wang-Hsien

    2014-07-01

    A simple and effective method for the rapid determination of five salicylate and benzophenone-type UV absorbing substances in marketed fish is described. The method involves the use of matrix solid-phase dispersion (MSPD) prior to their determination by on-line silylation gas chromatography tandem mass spectrometry (GC-MS/MS). The parameters that affect the extraction efficiency were optimized using a Box-Behnken design method. The optimal extraction conditions involved dispersing 0.5g of freeze-dried powdered fish with 1.0g of Florisil using a mortar and pestle. This blend was then transferred to a solid-phase extraction (SPE) cartridge containing 1.0g of octadecyl bonded silica (C18), as the clean-up co-sorbent. The target analytes were then eluted with 7mL of acetonitrile. The extract was derivatized on-line in the GC injection-port by reaction with a trimethylsilylating (TMS) reagent. The TMS-derivatives were then identified and quantitated by GC-MS/MS. The limits of quantitation (LOQs) were less than 0.1ng/g. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. TISSUE INHIBITOR OF METALLOPROTEINASE 1, MATRIX METALLOPROTEINASE 9, ALPHA-1 ANTITRYPSIN, METALLOTHIONEIN AND UROKINASE TYPE PLASMINOGEN ACTIVATOR RECEPTOR IN SKIN BIOPSIES FROM PATIENTS AFFECTED BY AUTOIMMUNE BLISTERING DISEASES

    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu Velez

    2013-07-01

    Full Text Available Introduction: Proteinases and proteinase inhibitors have been described to play a role in autoimmune skin blistering diseases. We studied skin lesional biopsies from patients affected by several autoimmune skin blistering diseases for proteinases and proteinase inhibitors. Methods: We utilized immunohistochemistry to evaluate biopsies for alpha-1-antitrypsin, human matrix metalloproteinase 9 (MMP9, human tissue inhibitor of metalloproteinases 1 (TIMP-1, metallothionein and urokinase type plasminogen activator receptor (uPAR. We tested 30 patients affected by endemic pemphigus, 30 controls from the endemic area, and 15 normal controls. We also tested 30 biopsies from patients with bullous pemphigoid (BP, 20 with pemphigus vulgaris (PV, 8 with pemphigus foliaceus, and 14 with dermatitis herpetiformis (DH. Results: Contrary to findings in the current literature, most autoimmune skin blistering disease biopsies were negative for uPAR and MMP9. Only some chronic patients with El Bagre-EPF were positive to MMP9 in the dermis, in proximity to telocytes. TIMP-1 and metallothionein were positive in half of the biopsies from BP patients at the basement membrane of the skin, within several skin appendices, in areas of dermal blood vessel inflammation and within dermal mesenchymal-epithelial cell junctions.

  4. Matrix algebra for linear models

    CERN Document Server

    Gruber, Marvin H J

    2013-01-01

    Matrix methods have evolved from a tool for expressing statistical problems to an indispensable part of the development, understanding, and use of various types of complex statistical analyses. This evolution has made matrix methods a vital part of statistical education. Traditionally, matrix methods are taught in courses on everything from regression analysis to stochastic processes, thus creating a fractured view of the topic. Matrix Algebra for Linear Models offers readers a unique, unified view of matrix analysis theory (where and when necessary), methods, and their applications. Written f

  5. EXPERIMENTAL REPAIR OF DEEP CORNEAL DEFECTS USING A BIO-CONSTRUCT COMPRISING A COLLAGEN TYPE I MATRIX LOADED WITH BUCCAL EPITHELIAL CELLS

    Directory of Open Access Journals (Sweden)

    N. S. Egorova

    2017-01-01

    Full Text Available The  research  objective was  to study the  reparative effects of  the  collagen  type  I bio-construct loaded  with buccal epithelial cells, on the rabbit cornea after experimental keratectomy at various stages of treatment (on the 3rd, 7th, 14th, 3 0th days.Material  and methods.  The  experiments were  conducted on 20 rabbits  of  the  Chinchilla breed that  were  operated on cornea of both eyes aiming to inflict epithelial and stromal cornea defects. The collagen-based bio-construct bearing buccal epithelial cells was placed  over the cornea of the experimental eyes. The  cornea of the control  eyes was covered with smooth contact lens. After the surgery, a temporal blepharorrhaphy was performed and kept for 3 days. We studied macroand microscopic pattern of corneal regeneration at 3, 7, 14, and 30 days of experiment.Results. When  using the collaged-based bio-construct containing buccal epithelial cells, the complete epithelialization of the corneal defect occurred at mean 7 days earlier compared to that in the control eyes. Thus, the offered bio-construct stimulated the cell migration and proliferation at early stages of treatment (3–7 days reducing the inflammation activity.Conclusion. The bio-construct comprising a collagen type  I matrix loaded with buccal epithelial cells can provide an effective treatment option for corneal defects.

  6. Modular Study of the Type III Effector Repertoire in Pseudomonas syringae pv. tomato DC3000 Reveals a Matrix of Effector Interplay in Pathogenesis

    Directory of Open Access Journals (Sweden)

    Hai-Lei Wei

    2018-05-01

    Full Text Available Summary: The bacterial pathogen Pseudomonas syringae pv. tomato DC3000 suppresses the two-tiered innate immune system of Nicotiana benthamiana and other plants by injecting a complex repertoire of type III secretion effector (T3E proteins. Effectorless polymutant DC3000D36E was used with a modularized system for native delivery of the 29 DC3000 T3Es singly and in pairs. Assays of the performance of this T3E library in N. benthamiana leaves revealed a matrix of T3E interplay, with six T3Es eliciting death and eight others variously suppressing the death activity of the six. The T3E library was also interrogated for effects on DC3000D36E elicitation of a reactive oxygen species burst, for growth in planta, and for T3Es that reversed these effects. Pseudomonas fluorescens and Agrobacterium tumefaciens heterologous delivery systems yielded notably different sets of death-T3Es. The DC3000D36E T3E library system highlights the importance of 13 T3Es and their interplay in interactions with N. benthamiana. : Wei et al. used a Pseudomonas syringae strain lacking all known type III effectors with a modularized library expressing the 29 active effectors in the strain’s native repertoire, individually and in pairs, to comprehensively determine effector actions and interplay in inducing and suppressing responses associated with plant pathogenesis and immunity. Keywords: effector-triggered-immunity, pattern-triggered-immunity, Hop proteins, plant immunity, mini-Tn7

  7. Nanoparticle enabled transdermal drug delivery systems for enhanced dose control and tissue targeting

    Science.gov (United States)

    Palmer, Brian C.; DeLouise, Lisa A.

    2017-01-01

    Transdermal drug delivery systems have been around for decades, and current technologies (e.g. patches, ointments, and creams) enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases. PMID:27983701

  8. Nanoparticle-Enabled Transdermal Drug Delivery Systems for Enhanced Dose Control and Tissue Targeting.

    Science.gov (United States)

    Palmer, Brian C; DeLouise, Lisa A

    2016-12-15

    Transdermal drug delivery systems have been around for decades, and current technologies (e.g., patches, ointments, and creams) enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases.

  9. Transdermal and transbuccal drug delivery systems: enhancement using iontophoretic and chemical approaches.

    Science.gov (United States)

    Hu, Longsheng; Silva, Sérgio M C; Damaj, Bassam B; Martin, Richard; Michniak-Kohn, Bozena B

    2011-12-12

    We investigated the enhancement effect of chemical enhancers and iontophoresis on the in vitro transdermal and transbuccal delivery of lidocaine HCl (LHCl), nicotine hydrogen tartrate (NHT), and diltiazem HCl (DHCl) using porcine skin and buccal tissues. Dodecyl 2-(N,N-dimethylamino) propionate (DDAIP), dodecyl-2-(N,N-dimethylamino) propionate hydrochloride (DDAIP HCl), N-(4-bromobenzoyl)-S,S-dimethyliminosulfurane (Br-iminosulfurane), and azone (laurocapram) were used as chemical enhancers. The study results showed that the application of iontophoresis at either 0.1 mA or 0.3 mA significantly enhanced transdermal and transmucosal delivery of LHCl, NHT and DHCl. It was also demonstrated that iontophoresis had a more pronounced enhancement effect on transdermal delivery than on transbuccal delivery of LHCl, NHT and DHCl. In addition, DDAIP HCl was found to be the most effective enhancer for transbuccal delivery of LHCl and NHT. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Carbon Nanotube Membranes for use in the Transdermal Treatment of Nicotine Addiction and Opioid Withdrawal Symptoms

    Directory of Open Access Journals (Sweden)

    Audra L. Stinchcomb

    2009-01-01

    Full Text Available Transdermal systems are attractive methods of drug administration specifically when treating patients for drug addiction. Current systems however are deficient in therapies that allow variable flux values of drug, such as nicotine for smoking cessation or complex dosing regimens using clonidine when treating opioid withdrawal symptoms. Through the use of functionalized carbon nanotube (CNT membranes, drug delivery to the skin can be controlled by applying a small electrical bias to create a programmable drug delivery system. Clearly, a transdermal patch system that can be tailored to an individual’s needs will increase patient compliance as well as provide much more efficient therapy. The purpose of this paper is to discuss the applicability of using carbon nanotube membranes in transdermal systems for treatment of drug abuse.

  11. Biomaterials as novel penetration enhancers for transdermal and dermal drug delivery systems.

    Science.gov (United States)

    Chen, Yang; Wang, Manli; Fang, Liang

    2013-01-01

    The highly organized structure of the stratum corneum provides an effective barrier to the drug delivery into or across the skin. To overcome this barrier function, penetration enhancers are always used in the transdermal and dermal drug delivery systems. However, the conventional chemical enhancers are often limited by their inability to delivery large and hydrophilic molecules, and few to date have been routinely incorporated into the transdermal formulations due to their incompatibility and local irritation issues. Therefore, there has been a search for the compounds that exhibit broad enhancing activity for more drugs without producing much irritation. More recently, the use of biomaterials has emerged as a novel method to increase the skin permeability. In this paper, we present an overview of the investigations on the feasibility and application of biomaterials as penetration enhancers for transdermal or dermal drug delivery systems.

  12. Carbon Nanotube Membranes for use in the Transdermal Treatment of Nicotine Addiction and Opioid Withdrawal Symptoms

    Directory of Open Access Journals (Sweden)

    Caroline L. Strasinger

    2009-01-01

    Full Text Available Transdermal systems are attractive methods of drug administration specifically when treating patients for drug addiction. Current systems however are deficient in therapies that allow variable flux values of drug, such as nicotine for smoking cessation or complex dosing regimens using clonidine when treating opioid withdrawal symptoms. Through the use of functionalized carbon nanotube (CNT membranes, drug delivery to the skin can be controlled by applying a small electrical bias to create a programmable drug delivery system. Clearly, a transdermal patch system that can be tailored to an individual's needs will increase patient compliance as well as provide much more efficient therapy. The purpose of this paper is to discuss the applicability of using carbon nanotube membranes in transdermal systems for treatment of drug abuse.

  13. Nanoparticle-Enabled Transdermal Drug Delivery Systems for Enhanced Dose Control and Tissue Targeting

    Directory of Open Access Journals (Sweden)

    Brian C. Palmer

    2016-12-01

    Full Text Available Transdermal drug delivery systems have been around for decades, and current technologies (e.g., patches, ointments, and creams enhance the skin permeation of low molecular weight, lipophilic drugs that are efficacious at low doses. The objective of current transdermal drug delivery research is to discover ways to enhance skin penetration of larger, hydrophilic drugs and macromolecules for disease treatment and vaccination. Nanocarriers made of lipids, metals, or polymers have been successfully used to increase penetration of drugs or vaccines, control drug release, and target drugs to specific areas of skin in vivo. While more research is needed to identify the safety of nanocarriers, this technology has the potential to expand the use of transdermal routes of administration to a wide array of therapeutics. Here, we review the current state of nanoparticle skin delivery systems with special emphasis on targeting skin diseases.

  14. Computational and experimental model of transdermal iontophorethic drug delivery system.

    Science.gov (United States)

    Filipovic, Nenad; Saveljic, Igor; Rac, Vladislav; Graells, Beatriz Olalde; Bijelic, Goran

    2017-11-30

    The concept of iontophoresis is often applied to increase the transdermal transport of drugs and other bioactive agents into the skin or other tissues. It is a non-invasive drug delivery method which involves electromigration and electroosmosis in addition to diffusion and is shown to be a viable alternative to conventional administration routs such as oral, hypodermic and intravenous injection. In this study we investigated, experimentally and numerically, in vitro drug delivery of dexamethasone sodium phosphate to porcine skin. Different current densities, delivery durations and drug loads were investigated experimentally and introduced as boundary conditions for numerical simulations. Nernst-Planck equation was used for calculation of active substance flux through equivalent model of homogeneous hydrogel and skin layers. The obtained numerical results were in good agreement with experimental observations. A comprehensive in-silico platform, which includes appropriate numerical tools for fitting, could contribute to iontophoretic drug-delivery devices design and correct dosage and drug clearance profiles as well as to perform much faster in-silico experiments to better determine parameters and performance criteria of iontophoretic drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Iontophoresis: A Potential Emergence of a Transdermal Drug Delivery System

    Science.gov (United States)

    Dhote, Vinod; Bhatnagar, Punit; Mishra, Pradyumna K.; Mahajan, Suresh C.; Mishra, Dinesh K.

    2012-01-01

    The delivery of drugs into systemic circulation via skin has generated much attention during the last decade. Transdermal therapeutic systems propound controlled release of active ingredients through the skin and into the systemic circulation in a predictive manner. Drugs administered through these systems escape first-pass metabolism and maintain a steady state scenario similar to a continuous intravenous infusion for up to several days. However, the excellent impervious nature of the skin offers the greatest challenge for successful delivery of drug molecules by utilizing the concepts of iontophoresis. The present review deals with the principles and the recent innovations in the field of iontophoretic drug delivery system together with factors affecting the system. This delivery system utilizes electric current as a driving force for permeation of ionic and non-ionic medications. The rationale behind using this technique is to reversibly alter the barrier properties of skin, which could possibly improve the penetration of drugs such as proteins, peptides and other macromolecules to increase the systemic delivery of high molecular weight compounds with controlled input kinetics and minimum inter-subject variability. Although iontophoresis seems to be an ideal candidate to overcome the limitations associated with the delivery of ionic drugs, further extrapolation of this technique is imperative for translational utility and mass human application. PMID:22396901

  16. Solid-in-oil nanodispersions for transdermal drug delivery systems.

    Science.gov (United States)

    Kitaoka, Momoko; Wakabayashi, Rie; Kamiya, Noriho; Goto, Masahiro

    2016-11-01

    Transdermal administration of drugs has advantages over conventional oral administration or administration using injection equipment. The route of administration reduces the opportunity for drug evacuation before systemic circulation, and enables long-lasting drug administration at a modest body concentration. In addition, the skin is an attractive route for vaccination, because there are many immune cells in the skin. Recently, solid-in-oil nanodisperison (S/O) technique has demonstrated to deliver cosmetic and pharmaceutical bioactives efficiently through the skin. S/O nanodispersions are nanosized drug carriers designed to overcome the skin barrier. This review discusses the rationale for preparation of efficient and stable S/O nanodispersions, as well as application examples in cosmetic and pharmaceutical materials including vaccines. Drug administration using a patch is user-friendly, and may improve patient compliance. The technique is a potent transcutaneous immunization method without needles. © 2016 The Authors. Biotechnology Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Photoinduced disaggregation of TiO₂ nanoparticles enables transdermal penetration.

    Directory of Open Access Journals (Sweden)

    Samuel W Bennett

    Full Text Available Under many aqueous conditions, metal oxide nanoparticles attract other nanoparticles and grow into fractal aggregates as the result of a balance between electrostatic and Van Der Waals interactions. Although particle coagulation has been studied for over a century, the effect of light on the state of aggregation is not well understood. Since nanoparticle mobility and toxicity have been shown to be a function of aggregate size, and generally increase as size decreases, photo-induced disaggregation may have significant effects. We show that ambient light and other light sources can partially disaggregate nanoparticles from the aggregates and increase the dermal transport of nanoparticles, such that small nanoparticle clusters can readily diffuse into and through the dermal profile, likely via the interstitial spaces. The discovery of photoinduced disaggregation presents a new phenomenon that has not been previously reported or considered in coagulation theory or transdermal toxicological paradigms. Our results show that after just a few minutes of light, the hydrodynamic diameter of TiO(2 aggregates is reduced from ∼280 nm to ∼230 nm. We exposed pigskin to the nanoparticle suspension and found 200 mg kg(-1 of TiO(2 for skin that was exposed to nanoparticles in the presence of natural sunlight and only 75 mg kg(-1 for skin exposed to dark conditions, indicating the influence of light on NP penetration. These results suggest that photoinduced disaggregation may have important health implications.

  18. Biodegradable 3D printed polymer microneedles for transdermal drug delivery.

    Science.gov (United States)

    Luzuriaga, Michael A; Berry, Danielle R; Reagan, John C; Smaldone, Ronald A; Gassensmith, Jeremiah J

    2018-04-17

    Biodegradable polymer microneedle (MN) arrays are an emerging class of transdermal drug delivery devices that promise a painless and sanitary alternative to syringes; however, prototyping bespoke needle architectures is expensive and requires production of new master templates. Here, we present a new microfabrication technique for MNs using fused deposition modeling (FDM) 3D printing using polylactic acid, an FDA approved, renewable, biodegradable, thermoplastic material. We show how this natural degradability can be exploited to overcome a key challenge of FDM 3D printing, in particular the low resolution of these printers. We improved the feature size of the printed parts significantly by developing a post fabrication chemical etching protocol, which allowed us to access tip sizes as small as 1 μm. With 3D modeling software, various MN shapes were designed and printed rapidly with custom needle density, length, and shape. Scanning electron microscopy confirmed that our method resulted in needle tip sizes in the range of 1-55 μm, which could successfully penetrate and break off into porcine skin. We have also shown that these MNs have comparable mechanical strengths to currently fabricated MNs and we further demonstrated how the swellability of PLA can be exploited to load small molecule drugs and how its degradability in skin can release those small molecules over time.

  19. Rapidly Dissolving Microneedle Patches for Transdermal Iron Replenishment Therapy.

    Science.gov (United States)

    Maurya, Abhijeet; Nanjappa, Shivakumar H; Honnavar, Swati; Salwa, M; Murthy, S Narasimha

    2018-02-17

    The prevalence of iron deficiency anemia (IDA) is predominant in women and children especially in developing countries. The disorder affects cognitive functions and physical activity. Although oral iron supplementation and parenteral therapy remains the preferred choice of treatment, gastric side effects and risk of iron overload decreases adherence to therapy. Transdermal route is an established approach, which circumvents the side effects associated with conventional therapy. In this project, an attempt was made to investigate the use of rapidly dissolving microneedles loaded with ferric pyrophosphate (FPP) as a potential therapeutic approach for management of IDA. Microneedle array patches were made using the micromolding technique and tested in vitro using rat skin to check the duration required for dissolution/disappearance of needles. The ability of FPP-loaded microneedles to replenish iron was investigated in anemic rats. Rats were fed iron-deficient diet for 5 weeks to induce IDA following which microneedle treatment was initiated. Recovery of rats from anemic state was monitored by measuring hematological and biochemical parameters. Results from in vivo study displayed significant improvements in hemoglobin and serum iron levels after 2-week treatment with FPP-loaded microneedles. The study effectively demonstrated the potential of microneedle-mediated iron replenishment for treatment of IDA. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  20. Expression of the dendritic cell-associated C-type lectin DC-SIGN by inflammatory matrix metalloproteinase-producing macrophages in rheumatoid arthritis synovium and interaction with intercellular adhesion molecule 3-positive T cells.

    NARCIS (Netherlands)

    Lent, P.L.E.M. van; Figdor, C.G.; Barrera Rico, P.; Ginkel, K. van; Sloetjes, A.W.; Berg, W.B. van den; Torensma, R.

    2003-01-01

    OBJECTIVE: To determine whether matrix metalloproteinase (MMP)-producing inflammatory macrophages in the synovium of rheumatoid arthritis (RA) patients express the novel dendritic cell (DC)-specific C-type lectin DC-SIGN and whether this expression is associated with the presence of naive T cells

  1. A novel marker for assessment of liver matrix remodeling: An enzyme-linked immunosorbent assay (ELISA) detecting a MMP generated type I collagen neo-epitope (C1M)

    DEFF Research Database (Denmark)

    Leeming, Diana Julie; He, Y.; Veidal, S. S.

    2011-01-01

    A competitive enzyme-linked immunosorbent assay (ELISA) for detection of a type I collagen fragment generated by matrix metalloproteinases (MMP) -2, -9 and -13, was developed (CO1-764 or C1M). The biomarker was evaluated in two preclinical rat models of liver fibrosis: bile duct ligation (BDL) an...

  2. Transdermal nitroglycerine enhances postoperative analgesia of intrathecal neostigmine following abdominal hysterectomies

    Directory of Open Access Journals (Sweden)

    Fareed Ahmed

    2010-01-01

    Full Text Available This study was carried out to assess the effect of nitroglycerine (transdermal on intrathecal neostigmine with bupivacaine on postoperative analgesia and note the incidence of adverse effects, if any. After taking informed consent, 120 patients of ASA Grade I and II were systematically randomised into four groups of 30 each. Patients were premedicated with midazolam 0.05 mg/kg intravenously and hydration with Ringer′s lactate solution 10ml/kg preoperatively in the holding room. Group I patients received Intrathecal injection of 15 mg bupivacaine with 1ml of normal saline and transdermal placebo patch. Group II patients received Intrathecal injection of 15 mg bupivacaine with 5 mcg of neostigmine and transdermal placebo patch. Group III patients received Intrathecal injection of 15 mg bupivacaine with 1ml of normal saline with transdermal nitroglycerine patch (5 mg/24 hours. Group IV patients received Intrathecal injection of 15 mg bupivacaine with 5mcg of neostigmine and transdermal nitroglycerine patch (5 mg/24 hours, applied on a non anaesthetised area after 20 minutes. Groups were demographically similar and did not differ in intraoperative characteristics like sensory block, motor block, haemodynamic parameters and SpO 2 . The mean duration of analgesia was 202.17 minutes, 407.20 minutes, 207.53 minutes and 581.63 minutes in control group (I, neostigmine group (II, nitroglycerine group (III and nitroglycerine neostigmine group (IV respectively (P< 0.01. To conclude, our results show that transdermal nitroglycerine itself does not show any analgesic potential but it enhances the analgesic potential of intrathecal neostigmine.

  3. Modular reservoir concept for MEMS-based transdermal drug delivery systems

    International Nuclear Information System (INIS)

    Cantwell, Cara T; Wei, Pinghung; Ziaie, Babak; Rao, Masaru P

    2014-01-01

    While MEMS-based transdermal drug delivery device development efforts have typically focused on tightly-integrated solutions, we propose an alternate conception based upon a novel, modular drug reservoir approach. By decoupling the drug storage functionality from the rest of the delivery system, this approach seeks to minimize cold chain storage volume, enhance compatibility with conventional pharmaceutical practices, and allow independent optimization of reservoir device design, materials, and fabrication. Herein, we report the design, fabrication, and preliminary characterization of modular reservoirs that demonstrate the virtue of this approach within the application context of transdermal insulin administration for diabetes management. (technical note)

  4. Modular reservoir concept for MEMS-based transdermal drug delivery systems

    Science.gov (United States)

    Cantwell, Cara T.; Wei, Pinghung; Ziaie, Babak; Rao, Masaru P.

    2014-11-01

    While MEMS-based transdermal drug delivery device development efforts have typically focused on tightly-integrated solutions, we propose an alternate conception based upon a novel, modular drug reservoir approach. By decoupling the drug storage functionality from the rest of the delivery system, this approach seeks to minimize cold chain storage volume, enhance compatibility with conventional pharmaceutical practices, and allow independent optimization of reservoir device design, materials, and fabrication. Herein, we report the design, fabrication, and preliminary characterization of modular reservoirs that demonstrate the virtue of this approach within the application context of transdermal insulin administration for diabetes management.

  5. Matrix thermalization

    International Nuclear Information System (INIS)

    Craps, Ben; Evnin, Oleg; Nguyen, Kévin

    2017-01-01

    Matrix quantum mechanics offers an attractive environment for discussing gravitational holography, in which both sides of the holographic duality are well-defined. Similarly to higher-dimensional implementations of holography, collapsing shell solutions in the gravitational bulk correspond in this setting to thermalization processes in the dual quantum mechanical theory. We construct an explicit, fully nonlinear supergravity solution describing a generic collapsing dilaton shell, specify the holographic renormalization prescriptions necessary for computing the relevant boundary observables, and apply them to evaluating thermalizing two-point correlation functions in the dual matrix theory.

  6. Matrix thermalization

    Science.gov (United States)

    Craps, Ben; Evnin, Oleg; Nguyen, Kévin

    2017-02-01

    Matrix quantum mechanics offers an attractive environment for discussing gravitational holography, in which both sides of the holographic duality are well-defined. Similarly to higher-dimensional implementations of holography, collapsing shell solutions in the gravitational bulk correspond in this setting to thermalization processes in the dual quantum mechanical theory. We construct an explicit, fully nonlinear supergravity solution describing a generic collapsing dilaton shell, specify the holographic renormalization prescriptions necessary for computing the relevant boundary observables, and apply them to evaluating thermalizing two-point correlation functions in the dual matrix theory.

  7. Matrix thermalization

    Energy Technology Data Exchange (ETDEWEB)

    Craps, Ben [Theoretische Natuurkunde, Vrije Universiteit Brussel (VUB), and International Solvay Institutes, Pleinlaan 2, B-1050 Brussels (Belgium); Evnin, Oleg [Department of Physics, Faculty of Science, Chulalongkorn University, Thanon Phayathai, Pathumwan, Bangkok 10330 (Thailand); Theoretische Natuurkunde, Vrije Universiteit Brussel (VUB), and International Solvay Institutes, Pleinlaan 2, B-1050 Brussels (Belgium); Nguyen, Kévin [Theoretische Natuurkunde, Vrije Universiteit Brussel (VUB), and International Solvay Institutes, Pleinlaan 2, B-1050 Brussels (Belgium)

    2017-02-08

    Matrix quantum mechanics offers an attractive environment for discussing gravitational holography, in which both sides of the holographic duality are well-defined. Similarly to higher-dimensional implementations of holography, collapsing shell solutions in the gravitational bulk correspond in this setting to thermalization processes in the dual quantum mechanical theory. We construct an explicit, fully nonlinear supergravity solution describing a generic collapsing dilaton shell, specify the holographic renormalization prescriptions necessary for computing the relevant boundary observables, and apply them to evaluating thermalizing two-point correlation functions in the dual matrix theory.

  8. Tumor cell invasion of collagen matrices requires coordinate lipid agonist-induced G-protein and membrane-type matrix metalloproteinase-1-dependent signaling

    Directory of Open Access Journals (Sweden)

    Anthis Nicholas J

    2006-12-01

    Full Text Available Abstract Background Lysophosphatidic acid (LPA and sphingosine 1-phosphate (S1P are bioactive lipid signaling molecules implicated in tumor dissemination. Membrane-type matrix metalloproteinase 1 (MT1-MMP is a membrane-tethered collagenase thought to be involved in tumor invasion via extracellular matrix degradation. In this study, we investigated the molecular requirements for LPA- and S1P-regulated tumor cell migration in two dimensions (2D and invasion of three-dimensional (3D collagen matrices and, in particular, evaluated the role of MT1-MMP in this process. Results LPA stimulated while S1P inhibited migration of most tumor lines in Boyden chamber assays. Conversely, HT1080 fibrosarcoma cells migrated in response to both lipids. HT1080 cells also markedly invaded 3D collagen matrices (~700 μm over 48 hours in response to either lipid. siRNA targeting of LPA1 and Rac1, or S1P1, Rac1, and Cdc42 specifically inhibited LPA- or S1P-induced HT1080 invasion, respectively. Analysis of LPA-induced HT1080 motility on 2D substrates vs. 3D matrices revealed that synthetic MMP inhibitors markedly reduced the distance (~125 μm vs. ~45 μm and velocity of invasion (~0.09 μm/min vs. ~0.03 μm/min only when cells navigated 3D matrices signifying a role for MMPs exclusively in invasion. Additionally, tissue inhibitors of metalloproteinases (TIMPs-2, -3, and -4, but not TIMP-1, blocked lipid agonist-induced invasion indicating a role for membrane-type (MT-MMPs. Furthermore, MT1-MMP expression in several tumor lines directly correlated with LPA-induced invasion. HEK293s, which neither express MT1-MMP nor invade in the presence of LPA, were transfected with MT1-MMP cDNA, and subsequently invaded in response to LPA. When HT1080 cells were seeded on top of or within collagen matrices, siRNA targeting of MT1-MMP, but not other MMPs, inhibited lipid agonist-induced invasion establishing a requisite role for MT1-MMP in this process. Conclusion LPA is a

  9. Multi types DG expansion dynamic planning in distribution system under stochastic conditions using Covariance Matrix Adaptation Evolutionary Strategy and Monte-Carlo simulation

    International Nuclear Information System (INIS)

    Sadeghi, Mahmood; Kalantar, Mohsen

    2014-01-01

    Highlights: • Defining a DG dynamic planning problem. • Applying a new evolutionary algorithm called “CMAES” in planning process. • Considering electricity price and fuel price variation stochastic conditions. • Scenario generation and reduction with MCS and backward reduction programs. • Considering approximately all of the costs of the distribution system. - Abstract: This paper presents a dynamic DG planning problem considering uncertainties related to the intermittent nature of the DG technologies such as wind turbines and solar units in addition to the stochastic economic conditions. The stochastic economic situation includes the uncertainties related to the fuel and electricity price of each year. The Monte Carlo simulation is used to generate the possible scenarios of uncertain situations and the produced scenarios are reduced through backward reduction program. The aim of this paper is to maximize the revenue of the distribution system through the benefit cost analysis alongside the encouraging and punishment functions. In order to close to reality, the different growth rates for the planning period are selected. In this paper the Covariance Matrix Adaptation Evolutionary Strategy is introduced and is used to find the best planning scheme of the DG units. The different DG types are considered in the planning problem. The main assumption of this paper is that the DISCO is the owner of the distribution system and the DG units. The proposed method is tested on a 9 bus test distribution system and the results are compared with the known genetic algorithm and PSO methods to show the applicability of the CMAES method in this problem

  10. Retroviral gene transfer of an antisense construct against membrane type 1 matrix metalloproteinase reduces the invasiveness of rheumatoid arthritis synovial fibroblasts.

    Science.gov (United States)

    Rutkauskaite, Edita; Volkmer, Dagmar; Shigeyama, Yukio; Schedel, Jörg; Pap, Geza; Müller-Ladner, Ulf; Meinecke, Ingmar; Alexander, Dorothea; Gay, Renate E; Drynda, Susanne; Neumann, Wolfram; Michel, Beat A; Aicher, Wilhelm K; Gay, Steffen; Pap, Thomas

    2005-07-01

    Membrane type 1 matrix metalloproteinase (MT1-MMP) is expressed prominently in rheumatoid arthritis synovial fibroblasts (RASFs), but the specific contribution of MT1-MMP to fibroblast-mediated destruction of articular cartilage is incompletely understood. This study used gene transfer of an antisense expression construct to assess the effects of MT1-MMP inhibition on the invasiveness of RASFs. Retroviral gene transfer of a pLXIN vector-based antisense RNA expression construct (MT1-MMPalphaS) to MT1-MMP was used to stably transduce RASFs. Levels of MT1-MMP RNA and protein were determined by quantitative polymerase chain reaction, Western blotting, and immunocytochemistry in MT1-MMPalphaS-transduced RASFs as well as in control cells, with monitoring for 60 days. The effects of MT1-MMPalphaS on the invasiveness of RASFs were analyzed in the SCID mouse co-implantation model of RA. MT1-MMPalphaS-transduced RASFs produced high levels of antisense RNA that exceeded endogenous levels of MT1-MMP messenger RNA by 15-fold and resulted in a down-regulation of MT1-MMP at the protein level. Inhibition of MT1-MMP production was maintained for 60 days and significantly reduced the invasiveness of RASFs in the SCID mouse model. Whereas prominent invasion into cartilage by non-transduced and mock-transduced RASFs was observed (mean invasion scores 3.0 and 3.1, respectively), MT1-MMPalphaS-transduced cells showed only moderate invasiveness (mean invasion score 1.8; P < 0.05). The data demonstrate that an antisense RNA expression construct against MT1-MMP can be generated and expressed in RASFs for at least 60 days. Inhibition of MT1-MMP significantly reduces the cartilage degradation by RASFs.

  11. Membrane Type 1–Matrix Metalloproteinase/Akt Signaling Axis Modulates TNF-α-Induced Procoagulant Activity and Apoptosis in Endothelial Cells

    Science.gov (United States)

    Ohkawara, Hiroshi; Ishibashi, Toshiyuki; Sugimoto, Koichi; Ikeda, Kazuhiko; Ogawa, Kazuei; Takeishi, Yasuchika

    2014-01-01

    Membrane type 1–matrix metalloproteinase (MT1-MMP) functions as a signaling molecule in addition to a proteolytic enzyme. Our hypothesis was that MT1-MMP cooperates with protein kinase B (Akt) in tumor necrosis factor (TNF)-α-induced signaling pathways of vascular responses, including tissue factor (TF) procoagulant activity and endothelial apoptosis, in cultured human aortic endothelial cells (ECs). TNF-α (10 ng/mL) induced a decrease in Akt phosphorylation within 60 minutes in ECs. A chemical inhibitor of MMP, TIMP-2 and selective small interfering RNA (siRNA)-mediated suppression of MT1-MMP reversed TNF-α-triggered transient decrease of Akt phosphorylation within 60 minutes, suggesting that MT1-MMP may be a key regulator of Akt phosphorylation in TNF-α-stimulated ECs. In the downstream events, TNF-α increased TF antigen and activity, and suppressed the expression of thrombomodulin (TM) antigen. Inhibition of Akt markedly enhanced TNF-α-induced expression of TF antigen and activity, and further reduced the expression of TM antigen. Silencing of MT1-MMP by siRNA also reversed the changed expression of TF and TM induced by TNF-α. Moreover, TNF-α induced apoptosis of ECs through Akt- and forkhead box protein O1 (FoxO1)-dependent signaling pathway and nuclear factor-kB (NF-kB) activation. Knockdown of MT1-MMP by siRNA reversed apoptosis of ECs by inhibiting TNF-α-induced Akt-dependent regulation of FoxO1 in TNF-α-stimulated ECs. Immunoprecipitation demonstrated that TNF-α induced the changes in the associations between the cytoplasmic fraction of MT1-MMP and Akt in ECs. In conclusion, we show new evidence that MT1-MMP/Akt signaling axis is a key modifier for TNF-α-induced signaling pathways for modulation of procoagulant activity and apoptosis of ECs. PMID:25162582

  12. Conversion of Stationary to Invasive Tumor Initiating Cells (TICs): Role of Hypoxia in Membrane Type 1-Matrix Metalloproteinase (MT1-MMP) Trafficking

    Science.gov (United States)

    Li, Jian; Zucker, Stanley; Pulkoski-Gross, Ashleigh; Kuscu, Cem; Karaayvaz, Mihriban; Ju, Jingfang; Yao, Herui; Song, Erwei; Cao, Jian

    2012-01-01

    Emerging evidence has implicated the role of tumor initiating cells (TICs) in the process of cancer metastasis. The mechanism underlying the conversion of TICs from stationary to invasive remains to be characterized. In this report, we employed less invasive breast cancer TICs, SK-3rd, that displays CD44high/CD24low with high mammosphere-forming and tumorigenic capacities, to investigate the mechanism by which stationary TICs are converted to invasive TICs. Invasive ability of SK-3rd TICs was markedly enhanced when the cells were cultured under hypoxic conditions. Given the role of membrane type 1-matrix metalloproteinase (MT1-MMP) in cancer invasion/metastasis, we explored a possible involvement of MT1-MMP in hypoxia-induced TIC invasion. Silencing of MT1-MMP by a shRNA approach resulted in diminution of hypoxia-induced cell invasion in vitro and metastasis in vivo. Under hypoxic conditions, MT1-MMP redistributed from cytoplasmic storage pools to the cell surface of TICs, which coincides with the increased cell invasion. In addition, CD44, a cancer stem-like cell marker, inversely correlated with increased cell surface MT1-MMP. Interestingly, cell surface MT1-MMP gradually disappeared when the hypoxia-treated cells were switched to normoxia, suggesting the plasticity of TICs in response to oxygen content. Furthermore, we dissected the pathways leading to upregulated MT1-MMP in cytoplasmic storage pools under normoxic conditions, by demonstrating a cascade involving Twist1-miR10b-HoxD10 leading to enhanced MT1-MMP expression in SK-3rd TICs. These observations suggest that MT1-MMP is a key molecule capable of executing conversion of stationary TICs to invasive TICs under hypoxic conditions and thereby controlling metastasis. PMID:22679501

  13. Membrane type 1-matrix metalloproteinase/Akt signaling axis modulates TNF-α-induced procoagulant activity and apoptosis in endothelial cells.

    Directory of Open Access Journals (Sweden)

    Hiroshi Ohkawara

    Full Text Available Membrane type 1-matrix metalloproteinase (MT1-MMP functions as a signaling molecule in addition to a proteolytic enzyme. Our hypothesis was that MT1-MMP cooperates with protein kinase B (Akt in tumor necrosis factor (TNF-α-induced signaling pathways of vascular responses, including tissue factor (TF procoagulant activity and endothelial apoptosis, in cultured human aortic endothelial cells (ECs. TNF-α (10 ng/mL induced a decrease in Akt phosphorylation within 60 minutes in ECs. A chemical inhibitor of MMP, TIMP-2 and selective small interfering RNA (siRNA-mediated suppression of MT1-MMP reversed TNF-α-triggered transient decrease of Akt phosphorylation within 60 minutes, suggesting that MT1-MMP may be a key regulator of Akt phosphorylation in TNF-α-stimulated ECs. In the downstream events, TNF-α increased TF antigen and activity, and suppressed the expression of thrombomodulin (TM antigen. Inhibition of Akt markedly enhanced TNF-α-induced expression of TF antigen and activity, and further reduced the expression of TM antigen. Silencing of MT1-MMP by siRNA also reversed the changed expression of TF and TM induced by TNF-α. Moreover, TNF-α induced apoptosis of ECs through Akt- and forkhead box protein O1 (FoxO1-dependent signaling pathway and nuclear factor-kB (NF-kB activation. Knockdown of MT1-MMP by siRNA reversed apoptosis of ECs by inhibiting TNF-α-induced Akt-dependent regulation of FoxO1 in TNF-α-stimulated ECs. Immunoprecipitation demonstrated that TNF-α induced the changes in the associations between the cytoplasmic fraction of MT1-MMP and Akt in ECs. In conclusion, we show new evidence that MT1-MMP/Akt signaling axis is a key modifier for TNF-α-induced signaling pathways for modulation of procoagulant activity and apoptosis of ECs.

  14. Development of Carrageenan Hydrogel as a Sustained Release Matrix Containing Tocotrienol-Rich Palm-Based Vitamin E

    International Nuclear Information System (INIS)

    Yee, C.M.; Zafarizal Aldrin Azizul Hasan; Norashikin Ahmad; Hazimah, A.H.

    2016-01-01

    Topically applied hydrogel system as a general therapeutic mask for transdermal delivery of hydrophobic actives is not efficient due to the differences in polarity between the actives and the polymer network. This work presents a study on developing hydrogels based on carrageenan as a matrix for the delivery of a hydrophobic type of active, i.e. tocotrienol-rich palm-based vitamin E (TRPE) into the skin. The strength and flexibility of the hydrogel were increased by the inclusion of guar gum, potassium citrate and glycerine. The thermogravimetric analysis (TGA) results indicated a higher quantity of water in the hydrogel with glycerine while differential scanning calorimetry (DSC) showed three types of water molecules existed in the hydrogel. The hydrogel was non-irritating according to OECD Test Guideline No. 439 for in vitro skin irritation test. The hydrogel with TRPE fluids was able to permeate the polysulfone membrane and bioavailability of TRPE improved with the inclusion of PEG-40 hydrogenated castor oil mixture. Therefore, a carrageenan-based hydrogel with locust bean, guar gum, glycerine, potassium citrate and TRPE was successfully developed with good strength and flexibility and without any potential irritancy. The good bioavailability of TRPE-loaded in the hydrogel can be used for skin care application. (author)

  15. Characterization of polymeric microneedle arrays for transdermal drug delivery.

    Directory of Open Access Journals (Sweden)

    Yusuf K Demir

    Full Text Available Microfabrication of dissolvable, swellable, and biodegradable polymeric microneedle arrays (MNs were extensively investigated based in a nano sensitive fabrication style known as micromilling that is then combined with conventional micromolding technique. The aim of this study was to describe the polymer selection, and optimize formulation compounding parameters for various polymeric MNs. Inverse replication of micromilled master MNs reproduced with polydimethylsiloxane (PDMS, where solid out of plane polymeric MNs were subsequently assembled, and physicochemically characterized. Dissolvable, swellable, and biodegradable MNs were constructed to depth of less than 1 mm with an aspect ratio of 3.6, and 1/2 mm of both inter needle tip and base spacing. Micromolding step also enabled to replicate the MNs very precisely and accurate. Polymeric microneedles (MN precision was ranging from ± 0.18 to ± 1.82% for microneedle height, ± 0.45 to ± 1.42% for base diameter, and ± 0.22 to ± 0.95% for interbase spacing. Although dissolvable sodium alginate MN showed less physical robustness than biodegradable polylactic-co-glycolic acid MN, their thermogravimetric analysis is of promise for constructing these polymeric types of matrix devices.

  16. Concentration of Endogenous Secretory Receptor for Advanced Glycation End Products and Matrix Gla Protein in Controlled and Uncontrolled Type 2 Diabetes Mellitus Patients

    Directory of Open Access Journals (Sweden)

    Dwi Yuniati Daulay

    2013-04-01

    Full Text Available BACKGROUND: Advanced glycation end products (AGE and their receptor (RAGE system play an important role in the development of diabetic vascular complications. Recently, an endogenous secretory RAGE (esRAGE has been identified as a novel splice variant, which lacks the transmembrane domain and is secreted in human sera. Interestingly, it was reported that esRAGE binds AGE ligands and neutralizes AGE actions. Many studies have reported that diabetes mellitus correlates with vascular calcification event and increases progressively in uncontrolled diabetes. Matrix Gla Protein (MGP is known to act as an inhibitor in vascular calcification. The aim of this study was to observe progress of vascular calcification in uncontrolled diabetes patient by biochemical markers MGP as inhibitor in vascular calcification, via mechanism of AGEs. METHODS: This study was an observational study with cross sectional design on adult type 2 diabetic male patients who were defined by the 2011 Indonesian diabetes mellitus consensus criteria. RESULTS: The results of this study showed that there was a positive significant correlation between esRAGE and HbA1C (r=0.651, p=0.009, and negative correlation between MGP and HbA1C (r=-0.465, p=0.081 in controlled diabetes group. In uncontrolled diabetes group there was a positive significant correlation between MGP and HbA1C (r=0.350, p=0.023, despite the fact esRAGE showed no significant correlation with HbA1C. There was no significant difference in level of esRAGE and MGP in controlled and uncontrolled diabetes group, but MGP showed lower level in uncontrolled diabetes group, contrary to esRAGE that had higher concentration. CONCLUSIONS: In diabetes condition, complications of vascular calcification are caused by the mechanism of increased AGE formation represented by esRAGE. In diabetes control it is very important to keep the blood vessels from complications caused by vascular calcification. KEYWORDS: type 2 diabetes mellitus

  17. Association of cardiovascular complications with circulating levels of tribbles 3 human homolog and matrix metalloproteinases in Indian type 2 diabetic patients, with or without hypertension

    Directory of Open Access Journals (Sweden)

    Prashant Shirish Ratnaparkhi

    2018-01-01

    Full Text Available Aim and Objective: Matrix metalloproteinases (MMPs and Tribbles 3 (Trb3 human homologue have been reported to induce atherosclerosis. We wanted to evaluate the association of circulating levels of Trb3 human homologue and MMPs (MMP2 and MMP9, with possible cardiovascular complications in Indian type 2 diabetic patients (type 2 diabetes mellitus [T2DM], with or without hypertension (HT. Materials and Methods: Serum from 144 individuals, classified as follows: Group A1= (DM + HT; T2DM> 5 years + HT (n = 55; Group A2 = DM; T2DM <2 years, (n = 28; Group B1 = HT; (n = 31 and Group B2 = HC; (n = 30 age- and sex-matched healthy controls. Anthropometric measurements, biochemical profiles of sugar and lipids were established using auto analyser. MMP2, MMP9, Trb3, oxidised low-density lipoprotein cholesterol, and proinsulin were measured in the serum using ELISA. Results: Using Bonferroni correction, we found that MMP2 levels were increased in (DM + HT, when compared to individuals with DM and HT (P = 0.006 and 0.000. HT group had reduced levels of MMP2, as compared to HC, (P = 0.000. The Mann–Whitney U-test for MMP9 revealed that DM group had elevated levels of MMP9 compared to (DM + HT, HT and HC group, (P = 0.011, 0.000, and 0.001. (DM + HT had elevated levels of MMP9 when compared to HT group, (P = 0.012.. Levels of MMP9 in HT were lower than the HC group, although not significant. Levels of Trb3 were found to be elevated in (DM + HT when compared to DM, (P = 0.032. The levels of Trb3 were higher in the HT, when compared to HC group, although not statistically significant. Multiple linear regression model for Framingham Risk Score, weighted with post prandial blood sugar yielded R2 = 0.338; F = 7.602 (df = 9, P = 0.000. Trb3 (β = −0.179, P = 0.019; MMP2 (β =0.021, P = 0.787 and MMP9 (β = −0.03, P = 0.684. Conclusion: Trb3 is a useful marker for evaluating the association of cardiovascular risk in diabetic patients.

  18. Pharmacokinetics and repolarization effects of intravenous and transdermal granisetron.

    Science.gov (United States)

    Mason, Jay W; Selness, Daniel S; Moon, Thomas E; O'Mahony, Bridget; Donachie, Peter; Howell, Julian

    2012-05-15

    The need for greater clarity about the effects of 5-HT(3) receptor antagonists on cardiac repolarization is apparent in the changing product labeling across this therapeutic class. This study assessed the repolarization effects of granisetron, a 5-HT(3) receptor antagonist antiemetic, administered intravenously and by a granisetron transdermal system (GTDS). In a parallel four-arm study, healthy subjects were randomized to receive intravenous granisetron, GTDS, placebo, or oral moxifloxacin (active control). The primary endpoint was difference in change from baseline in mean Fridericia-corrected QT interval (QTcF) between GTDS and placebo (ddQTcF) on days 3 and 5. A total of 240 subjects were enrolled, 60 in each group. Adequate sensitivity for detection of QTc change was shown by a 5.75 ms lower bound of the 90% confidence interval (CI) for moxifloxacin versus placebo at 2 hours postdose on day 3. Day 3 ddQTcF values varied between 0.2 and 1.9 ms for GTDS (maximum upper bound of 90% CI, 6.88 ms), between -1.2 and 1.6 ms for i.v. granisetron (maximum upper bound of 90% CI, 5.86 ms), and between -3.4 and 4.7 ms for moxifloxacin (maximum upper bound of 90% CI, 13.45 ms). Day 5 findings were similar. Pharmacokinetic-ddQTcF modeling showed a minimally positive slope of 0.157 ms/(ng/mL), but a very low correlation (r = 0.090). GTDS was not associated with statistically or clinically significant effects on QTcF or other electrocardiographic variables. This study provides useful clarification on the effect of granisetron delivered by GTDS on cardiac repolarization. ©2012 AACR.

  19. Granisetron transdermal system improves refractory nausea and vomiting in gastroparesis.

    Science.gov (United States)

    Simmons, Kellie; Parkman, Henry P

    2014-06-01

    Symptoms of gastroparesis include nausea and vomiting, which can markedly diminish quality of life. Nausea and vomiting can also make treatment with oral antiemetics problematic. Our aim was to determine whether treatment-resistant nausea and vomiting in patients with gastroparesis improve after granisetron transdermal patch (GTP) therapy. In an open-label pilot study, patients with gastroparesis and symptoms of nausea and vomiting refractory to conventional treatment were treated with GTP. After 2 weeks, patients were asked to assess their therapeutic response using the Clinical Patient Grading Assessment Scale (CPGAS; +7 = completely better; 0 = no change; -7 = very considerably worse). Responders were defined as CPGAS score >0, non-responders as ≤0. Patients (n = 36) were treated with GTP. Of these 36 patients, one patient discontinued treatment due to the GTP not adhering to the skin. Of the remaining 35 patients, 18 improved, 15 remained the same, and two worsened. The average CPGAS score was +1.8 ± 0.4 (SEM) (P < 0.05 vs 0). Of the 18 patients with improvement, the average CPGAS score was +3.7 ± 0.3 (SEM), corresponding to "somewhat" to "moderately better" improvement in nausea/vomiting. Side effects occurred in nine patients: four developed constipation, three patients had skin rash, and two reported headaches. GTP was moderately effective in reducing refractory symptoms of nausea and/or vomiting from gastroparesis in 50% of patients. Mild side effects were reported by 25% of patients. GTP may be an effective treatment for nausea and vomiting in gastroparesis, and further study is warranted.

  20. Transdermal nicotine absorption handling e-cigarette refill liquids.

    Science.gov (United States)

    Maina, Giovanni; Castagnoli, Carlotta; Passini, Valter; Crosera, Matteo; Adami, Gianpiero; Mauro, Marcella; Filon, Francesca Larese

    2016-02-01

    The concentrated nicotine in e-cigarette refill liquids can be toxic if inadvertently ingested or absorbed through the skin. Reports of poisonings due to accidental ingestion of nicotine on refill liquids are rapidly increasing, while the evaluation of nicotine dermally absorbed still lacks. For that reason we studied transdermal nicotine absorption after the skin contamination with e-liquid. Donor chambers of eight Franz diffusion cells were filled with 1 mL of 0.8 mg/mL nicotine e-liquid for 24 h. The concentration of nicotine in the receiving phase was determined by high-performance liquid chromatography (LOD:0.1 μg/mL). Nicotine was detectable in receiving solution 2 h after the start of exposure and increased progressively. The medium flux calculated was 4.82 ± 1.05 μg/cm(2)/h with a lag time of 3.9 ± 0.1 h. After 24 h, the nicotine concentration in the receiving compartment was 101.02 ± 22.35 μg/cm(2) corresponding to 3.04 mg of absorbed nicotine after contamination of a skin surface of 100 cm(2). Skin contamination with e-liquid can cause nicotine skin absorption: caution must be paid when handling refill e-liquids. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Transdermal influenza immunization with vaccine-coated microneedle arrays.

    Directory of Open Access Journals (Sweden)

    Dimitrios G Koutsonanos

    Full Text Available Influenza is a contagious disease caused by a pathogenic virus, with outbreaks all over the world and thousands of hospitalizations and deaths every year. Due to virus antigenic drift and short-lived immune responses, annual vaccination is required. However, vaccine coverage is incomplete, and improvement in immunization is needed. The objective of this study is to investigate a novel method for transdermal delivery using metal microneedle arrays (MN coated with inactivated influenza virus to determine whether this route is a simpler and safer approach than the conventional immunization, capable to induce robust immune responses and confer protection against lethal virus challenge.Inactivated A/Aichi/2/68 (H3N2 influenza virus was coated on metal microneedle arrays and applied to mice as a vaccine in the caudal dorsal skin area. Substantial antibody titers with hemagglutination inhibition activity were detected in sera collected two and four weeks after a single vaccine dose. Challenge studies in mice with 5 x LD(50 of mouse adapted Aichi virus demonstrated complete protection. Microneedle vaccination induced a broad spectrum of immune responses including CD4+ and CD8+ responses in the spleen and draining lymph node, a high frequency of antigen-secreting cells in the lung and induction of virus-specific memory B-cells. In addition, the use of MN showed a dose-sparing effect and a strong Th2 bias when compared to an intramuscular (IM reference immunization.The present results show that delivery of inactivated influenza virus through the skin using metal microneedle arrays induced strong humoral and cellular immune responses capable of conferring protection against virus challenge as efficiently as intramuscular immunization, which is the standard vaccination route. In view of the convenience of delivery and the potential for self-administration, vaccine-coated metal microneedles may provide a novel and highly effective immunization method.

  2. Dodecyl Amino Glucoside Enhances Transdermal and Topical Drug Delivery via Reversible Interaction with Skin Barrier Lipids

    Czech Academy of Sciences Publication Activity Database

    Kopečná, M.; Macháček, M.; Prchalová, Eva; Štěpánek, P.; Drašar, P.; Kotora, Martin; Vávrová, K.

    2017-01-01

    Roč. 34, č. 3 (2017), s. 640-653 ISSN 0724-8741 Institutional support: RVO:61388963 Keywords : penetration enhancers * sugar * topical drug delivery * transdermal drug delivery Subject RIV: FR - Pharmacology ; Medidal Chemistry OBOR OECD: Pharmacology and pharmacy Impact factor: 3.002, year: 2016

  3. Use and cardiovascular safety of transdermal and other granisetron preparations in cancer management

    International Nuclear Information System (INIS)

    Mason, Jay W; Moon, Thomas E

    2013-01-01

    5-HT 3 antagonists have been available as oral and intravenous preparations for decades. The availability more recently of transdermal granisetron and the anticipated availability of a subcutaneous granisetron preparation have provided helpful alternatives to patients, and these preparations have been shown to have less potential to prolong QT than other drugs in the class

  4. Anti-cancer vaccination by transdermal delivery of antigen peptide-loaded nanogels via iontophoresis.

    Science.gov (United States)

    Toyoda, Mao; Hama, Susumu; Ikeda, Yutaka; Nagasaki, Yukio; Kogure, Kentaro

    2015-04-10

    Transdermal vaccination with cancer antigens is expected to become a useful anti-cancer therapy. However, it is difficult to accumulate enough antigen in the epidermis for effective exposure to Langerhans cells because of diffusion into the skin and muscle. Carriers, such as liposomes and nanoparticles, may be useful for the prevention of antigen diffusion. Iontophoresis, via application of a small electric current, is a noninvasive and efficient technology for transdermal drug delivery. Previously, we succeeded in the iontophoretic transdermal delivery of liposomes encapsulating insulin, and accumulation of polymer-based nanoparticle nanogels in the stratum corneum of the skin. Therefore, in the present study, we examined the use of iontophoresis with cancer antigen gp-100 peptide KVPRNQDWL-loaded nanogels for anti-cancer vaccination. Iontophoresis resulted in the accumulation of gp-100 peptide and nanogels in the epidermis, and subsequent increase in the number of Langerhans cells in the epidermis. Moreover, tumor growth was significantly suppressed by iontophoresis of the antigen peptide-loaded nanogels. Thus, iontophoresis of the antigen peptide-loaded nanogels may serve as an effective transdermal delivery system for anti-cancer vaccination. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Inefficacy of high-dose transdermal fentanyl in a patient with neuropathic pain, a case report.

    NARCIS (Netherlands)

    Bleeker, C.P.; Bremer, R.; Dongelmans, D.A.; Dongen, R.T.M. van; Crul, B.J.P.

    2001-01-01

    Pain partially responsive to opioids can lead to rapid escalating dosages due to tolerance development. In this report the case of a 58-year-old female with neuropathic pain using increasing transdermal (TTS) fentanyl dosages to a maximum dose of 3400 microg/h resulting in fentanyl plasma levels of

  6. Treatment with subcutaneous and transdermal fentanyl: results from a population pharmacokinetic study in cancer patients

    NARCIS (Netherlands)

    Oosten, A.W.; Abrantes, J.A.; Jonsson, S.; Bruijn, P. de; Kuip, E.J.M.; Falcao, A.; Rijt, C.C. van der; Mathijssen, R.H.

    2016-01-01

    PURPOSE: Transdermal fentanyl is effective for the treatment of moderate to severe cancer-related pain but is unsuitable for fast titration. In this setting, continuous subcutaneous fentanyl may be used. As data on the pharmacokinetics of continuous subcutaneous fentanyl are lacking, we studied the

  7. Treatment with subcutaneous and transdermal fentanyl: Results from a population pharmacokinetic study in cancer patients

    NARCIS (Netherlands)

    A.W. Oosten (Astrid); J.A. Abrantes (João A.); S. Jönsson (Siv); P. de Bruijn (Peter); E.J.M. Kuip (Evelien); A. Falcão (Amílcar); C.C.D. van der Rijt (Carin); A.H.J. Mathijssen (Ron)

    2016-01-01

    textabstractPurpose: Transdermal fentanyl is effective for the treatment of moderate to severe cancer-related pain but is unsuitable for fast titration. In this setting, continuous subcutaneous fentanyl may be used. As data on the pharmacokinetics of continuous subcutaneous fentanyl are lacking, we

  8. Methylphenidate Transdermal System in Adults with Past Stimulant Misuse: An Open-Label Trial

    Science.gov (United States)

    McRae-Clark, Aimee L.; Brady, Kathleen T.; Hartwell, Karen J.; White, Kathleen; Carter, Rickey E.

    2011-01-01

    Objective: This 8-week, open-label trial assessed the efficacy of methylphenidate transdermal system (MTS) in 14 adult individuals diagnosed with ADHD and with a history of stimulant misuse, abuse, or dependence. Method: The primary efficacy endpoint was the Wender-Reimherr Adult ADHD Scale (WRAADS), and secondary efficacy endpoints included the…

  9. Alfuzosin hydrochloride transdermal films: evaluation of physicochemical, in vitro human cadaver skin permeation and thermodynamic parameters

    Directory of Open Access Journals (Sweden)

    Satyanarayan Pattnaik

    2009-12-01

    Full Text Available Purpose: The main objective of the investigation was to develop a transdermal therapeutic system for alfuzosin hydrochloride and to study the effects of polymeric system and loading dose on the in vitro skin permeation pattern. Materials and methods: Principles of experimental design have been exploited to develop the dosage form. Ratio of ethyl cellulose (EC and polyvinyl pyrrolidone (PVP and loading dose were selected as independent variables and their influence on the cumulative amount of alfuzosin hydrochloride permeated per cm2 of human cadaver skin at 24 h (Q24, permeation flux (J and steady state permeability coefficient (P SS were studied using experimental design. Various physicochemical parameters of the transdermal films were also evaluated. Activation energy for in vitro transdermal permeation has been estimated. Results: Ratio of EC and PVP was found to be the main influential factor for all the dependent variables studied. Drug loading dose was also found to influence the dependent variables but to a lesser extent. Physicochemical parameters of the prepared films were evaluated and found satisfactory. Activation energy for alfuzosin permeation has also been estimated and reported. Conclusion: The therapeutic system was found to be dermatologically non-irritant and hence, a therapeutically effective amount of alfuzosin hydrochloride can be delivered via a transdermal route.

  10. Efficacy of a single dose of a transdermal diclofenac patch as pre ...

    African Journals Online (AJOL)

    2012-01-25

    Jan 25, 2012 ... When the side-effects were compared between the groups using a test of proportions, it was not significant. Discussion. The results of our study suggest that when applied at the beginning of surgery, a transdermal patch of diclofenac is as effective as intramuscular diclofenac in prolonging the requirement ...

  11. Functionalization of Cotton Fabrics with Polycaprolactone Nanoparticles for Transdermal Release of Melatonin

    Directory of Open Access Journals (Sweden)

    Daniele Massella

    2017-12-01

    Full Text Available Drug delivery by means of transdermal patches raised great interest as a non-invasive and sustained therapy. The present research aimed to design a patch for transdermal delivery of melatonin, which was encapsulated in polycaprolactone (PCL nanoparticles (NPs by employing flash nanoprecipitation (FNP technique. Melatonin-loaded PCL nanoparticles were successfully prepared with precise control of the particle size by effectively tuning process parameters. The effect of process parameters on the particle size was assessed by dynamic light scattering for producing particles with suitable size for transdermal applications. Quantification of encapsulated melatonin was performed by mean of UV spectrophotometry, obtaining the estimation of encapsulation efficiency (EE% and loading capacity (LC%. An EE% higher than 80% was obtained. Differential scanning calorimetry (DSC analysis of NPs was performed to confirm effective encapsulation in the solid phase. Cotton fabrics, functionalized by imbibition with the nano-suspension, were analyzed by scanning electron microscopy to check morphology, adhesion and distribution of the NPs on the surface; melatonin transdermal release from the functionalized fabric was performed via Franz’s cells by using a synthetic membrane. NPs were uniformly distributed on cotton fibres, as confirmed by SEM observations; the release test showed a continuous and controlled release whose kinetics were satisfactorily described by Baker–Lonsdale model.

  12. Transdermal uptake of diethyl phthalate and di(n-butyl) phthalate directly from air: Experimental verification

    DEFF Research Database (Denmark)

    Weschler, Charles J.; Bekö, Gabriel; Koch, Holger M.

    2015-01-01

    of phthalate esters. Objectives: This study investigated transdermal uptake, directly from air, of diethyl phthalate (DEP) and di(n-butyl) phthalate (DnBP) in humans. Methods: In a series of experiments, six human participants were exposed for 6 hr in a chamber containing deliberately elevated air...

  13. Transdermal Delivery and Cutaneous Targeting of Antivirals using a Penetration Enhancer and Lysolipid Prodrugs

    Czech Academy of Sciences Publication Activity Database

    Diblíková, D.; Kopečná, M.; Školová, B.; Krečmerová, Marcela; Roh, J.; Hrabálek, A.; Vávrová, K.

    2014-01-01

    Roč. 31, č. 4 (2014), s. 1071-1081 ISSN 0724-8741 Grant - others:GA ČR(CZ) GAP207/11/0365 Institutional support: RVO:61388963 Keywords : acyclic nucleoside phosphonate antivirals * lysolipid prodrug * penetration enhancer * skin absorption * transdermal drug delivery Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 3.420, year: 2014

  14. Novel diffusion cell for in vitro transdermal permeation, compatible with automated dynamic sampling

    NARCIS (Netherlands)

    Bosman, I.J; Lawant, A.L; Avegaart, S.R.; Ensing, K; de Zeeuw, R.A

    The development of a new diffusion cell for in vitro transdermal permeation is described. The so-called Kelder cells were used in combination with the ASPEC system (Automatic Sample Preparation with Extraction Columns), which is designed for the automation of solid-phase extractions (SPE). Instead

  15. Methylphenidate Transdermal System in Adult ADHD and Impact on Emotional and Oppositional Symptoms

    Science.gov (United States)

    Marchant, Barrie K.; Reimherr, Frederick W.; Robison, Reid J.; Olsen, John L.; Kondo, Douglas G.

    2011-01-01

    Objective: This trial evaluated the effect of methylphenidate transdermal system (MTS) on the full spectrum of adult symptoms (attention-disorganization, hyperactivity-impulsivity, emotional dysregulation [ED], and oppositional-defiant disorder [ODD]) found in this disorder. Method: This placebo-controlled, double-blind, flexible-dose, crossover…

  16. Improvement of Transdermal Delivery of Exendin-4 Using Novel Tip-Loaded Microneedle Arrays Fabricated from Hyaluronic Acid.

    Science.gov (United States)

    Liu, Shu; Wu, Dan; Quan, Ying-Shu; Kamiyama, Fumio; Kusamori, Kosuke; Katsumi, Hidemasa; Sakane, Toshiyasu; Yamamoto, Akira

    2016-01-04

    The purpose of this study was to evaluate the characteristics of exendin-4 tip-loaded microneedle arrays and to compare their acute efficacy with subcutaneous injections in type 2 diabetic GK/Slc rats. Fluorescein isothiocyanate labeled dextran with an average molecular weight of 4,000 (FD4) was selected as a model drug, and FD4 tip-loaded microneedle arrays were prepared in this study. In addition, intraperitoneal glucose tolerance tests after application of exendin-4 tip-loaded microneedle arrays were also compared with those after subcutaneous injection in type 2 diabetic GK/Slc rats. The release of FD4 from the tip-loaded microneedle arrays was very rapid, particularly in the initial 30 s, and most of the FD4 was released within 5 min. In addition, glucose tolerance was improved and the insulin secretion was enhanced after application of exendin-4 tip-loaded microneedle arrays, and these effects were comparable to those after subcutaneous injection of exendin-4. Similar plasma concentration profiles were seen after application of exendin-4 tip-loaded microneedle arrays, as was the case with subcutaneous injection in type 2 diabetic GK/Slc rats. These findings indicate that exendin-4 tip-loaded microneedle arrays can be used as an alternative to achieve sufficient delivery of exendin-4 for treatment of type 2 diabetes. To our knowledge, this is the first report of transdermal exendin-4 delivery using tip-loaded microneedle arrays.

  17. Matrix inequalities

    CERN Document Server

    Zhan, Xingzhi

    2002-01-01

    The main purpose of this monograph is to report on recent developments in the field of matrix inequalities, with emphasis on useful techniques and ingenious ideas. Among other results this book contains the affirmative solutions of eight conjectures. Many theorems unify or sharpen previous inequalities. The author's aim is to streamline the ideas in the literature. The book can be read by research workers, graduate students and advanced undergraduates.

  18. Transdermal delivery and cutaneous targeting of antivirals using a penetration enhancer and lysolipid prodrugs.

    Science.gov (United States)

    Diblíková, Denisa; Kopečná, Monika; Školová, Barbora; Krečmerová, Marcela; Roh, Jaroslav; Hrabálek, Alexandr; Vávrová, Kateřina

    2014-04-01

    In this work, we investigate prodrug and enhancer approaches for transdermal and topical delivery of antiviral drugs belonging to the 2,6-diaminopurine acyclic nucleoside phosphonate (ANP) group. Our question was whether we can differentiate between transdermal and topical delivery, i.e., to control the delivery of a given drug towards either systemic absorption or retention in the skin. The in vitro transdermal delivery and skin concentrations of seven antivirals, including (R)- and (S)-9-[2-(phosphonomethoxy)propyl]-2,6-diaminopurine (PMPDAP), (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]-2,6-diaminopurine ((S)-HPMPDAP), its 8-aza analog, and their cyclic and hexadecyloxypropyl (HDP) prodrugs, was investigated with and without the penetration enhancer dodecyl-6-(dimethylamino)hexanoate (DDAK) using human skin. The ability of ANPs to cross the human skin barrier was very low (0.5-1.4 nmol/cm(2)/h), and the majority of the compounds were found in the stratum corneum, the uppermost skin layer. The combination of antivirals and the penetration enhancer DDAK proved to be a viable approach for transdermal delivery, especially in case of (R)-PMPDAP, an anti-HIV effective drug (30.2 ± 2.3 nmol/cm(2)/h). On the other hand, lysophospholipid-like HDP prodrugs, e.g., HDP-(S)-HPMPDAP, reached high concentrations in viable epidermis without significant systemic absorption. By using penetration enhancers or lysolipid prodrugs, it is possible to effectively target systemic diseases by the transdermal route or to target cutaneous pathologies by topical delivery.

  19. Transdermal delivery of isoniazid and rifampin in guinea pigs by electro-phonophoresis.

    Science.gov (United States)

    Chen, Suting; Han, Yi; Yu, Daping; Huo, Fengmin; Wang, Fen; Li, Yunxu; Dong, Lingling; Liu, Zhidong; Huang, Hairong

    2017-11-01

    Electro-phonophoresis (EP) has been used as a drug delivery approach in clinical fields. The objective of the present study is to evaluate the skin permeability of isoniazid and rifampin in guinea pigs by EP to provide reference basis for clinical applications of such transdermal delivery system in the treatment of patients with superficial tuberculosis. Isoniazid and rifampin solutions were delivered transdermally with or without EP in health guinea pigs for 0.5 h. Local skin and blood samples were collected serially at 0, 1/2, 1, 2, 4, 6 and 24 h after dosing. Drug concentrations in local skin and blood were evaluated by high-performance liquid chromatography. Isoniazid concentrations in local skin of guinea pigs receiving isoniazid through EP transdermal delivery were significantly higher than in animals receiving only isoniazid with transdermal patch. However, for rifampin, patches alone group presented almost uniform concentration versus time curve with that of EP group, and both groups had concentrations much higher than the therapeutic concentration of the drug over sustainable time. After EP transdermal delivery, the mean peak concentrations of isoniazid and rifampin in skin were 771.0 ± 163.4 μg/mL and 81.2 ± 17.3 μg/mL respectively. Neither isoniazid nor rifampin concentration in blood could be detected (below the lower detection limit of 1 μg/mL) at any time point. The present study showed that application of EP significantly enhanced INH penetration through skin in guinea pigs, while RIF patch alone obtained therapeutic concentration in local skin. Our work suggests several possible medication approaches for efficient treatment of superficial tuberculosis.

  20. Contingency management for alcohol use reduction: a pilot study using a transdermal alcohol sensor.

    Science.gov (United States)

    Barnett, Nancy P; Tidey, Jennifer; Murphy, James G; Swift, Robert; Colby, Suzanne M

    2011-11-01

    Contingency management (CM) has not been thoroughly evaluated as a treatment for alcohol abuse or dependence, in part because verification of alcohol use reduction requires frequent in-person breath tests. Transdermal alcohol sensors detect alcohol regularly throughout the day, providing remote monitoring and allowing for rapid reinforcement of reductions in use. The purpose of this study was to evaluate the efficacy of CM for reduction in alcohol use, using a transdermal alcohol sensor to provide a continuous measure of alcohol use. Participants were 13 heavy drinking adults who wore the Secure Continuous Remote Alcohol Monitoring (SCRAM) bracelet for three weeks and provided reports of alcohol and drug use using daily web-based surveys. In Week 1, participants were asked to drink as usual; in Weeks 2 and 3, they were reinforced on an escalating schedule with values ranging from $5 to $17 per day on days when alcohol use was not reported or detected by the SCRAM. Self-reports of percent days abstinent and drinks per week, and transdermal measures of average and peak transdermal alcohol concentration and area under the curve declined significantly in Weeks 2-3. A nonsignificant but large effect size for reduction in days of tobacco use also was found. An adjustment to the SCRAM criteria for detecting alcohol use provided an accurate but less conservative method for use with non-mandated clients. Results support the efficacy of CM for alcohol use reductions and the feasibility of using transdermal monitoring of alcohol use for clinical purposes. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  1. Contingency Management for Alcohol Use Reduction: A Pilot Study using a Transdermal Alcohol Sensor*

    Science.gov (United States)

    Barnett, Nancy P.; Tidey, Jennifer; Murphy, James G.; Swift, Robert; Colby, Suzanne M.

    2011-01-01

    Background Contingency management (CM) has not been thoroughly evaluated as a treatment for alcohol abuse or dependence, in part because verification of alcohol use reduction requires frequent in-person breath tests. Transdermal alcohol sensors detect alcohol regularly throughout the day, providing remote monitoring and allowing for rapid reinforcement of reductions in use. Methods The purpose of this study was to evaluate the efficacy of CM for reduction in alcohol use, using a transdermal alcohol sensor to provide a continuous measure of alcohol use. Participants were 13 heavy drinking adults who wore the Secure Continuous Remote Alcohol Monitoring (SCRAM) bracelet for three weeks and provided reports of alcohol and drug use using daily web-based surveys. In Week 1, participants were asked to drink as usual; in Weeks 2 and 3, they were reinforced on an escalating schedule with values ranging from $5-$17 per day on days when alcohol use was not reported or detected by the SCRAM. Results Self-reports of percent days abstinent and drinks per week, and transdermal measures of average and peak transdermal alcohol concentration and area under the curve declined significantly in Weeks 2-3. A nonsignificant but large effect size for reduction in days of tobacco use also was found. An adjustment to the SCRAM criteria for detecting alcohol use provided an accurate but less conservative method for use with non-mandated clients. Conclusion Results support the efficacy of CM for alcohol use reductions and the feasibility of using transdermal monitoring of alcohol use for clinical purposes. PMID:21665385

  2. Therapeutic serum phenobarbital concentrations obtained using chronic transdermal administration of phenobarbital in healthy cats.

    Science.gov (United States)

    Delamaide Gasper, Joy A; Barnes Heller, Heidi L; Robertson, Michelle; Trepanier, Lauren A

    2015-04-01

    Seizures are a common cause of neurologic disease, and phenobarbital (PB) is the most commonly used antiepileptic drug. Chronic oral dosing can be challenging for cat owners, leading to poor compliance. The purpose of this study was to determine if the transdermal administration of PB could achieve serum PB concentrations of between 15 and 45 μg/ml in healthy cats. Nineteen healthy cats were enrolled in three groups. Transdermal PB in pluronic lecithin organogel (PLO) was applied to the pinnae for 14 days at a dosage of 3 mg/kg q12h in group 1 (n = 6 cats) and 9 mg/kg q12h in group 2 (n = 7 cats). Transdermal PB in Lipoderm Activemax was similarly applied at 9 mg/kg q12h for 14 days in group 3 (n = 6 cats). Steady-state serum PB concentrations were measured at trough, and at 2, 4 and 6 h after the morning dose on day 15. In group 1, median concentrations ranged from 6.0-7.5 μg/ml throughout the day (observed range 0-11 μg/ml). Group 2 median concentrations were 26.0 μg/ml (observed range 18.0-37.0 μg/ml). For group 3, median concentrations ranged from 15.0-17.0 μg/ml throughout the day (range 5-29 μg/ml). Side effects were mild. One cat was withdrawn from group 2 owing to ataxia and sedation. These results show therapeutic serum PB concentrations can be achieved in cats following chronic transdermal administration of PB in PLO at a dosage of 9 mg/kg q12h. More individual variation was noted using Lipoderm Activemax. Transdermal administration may be an alternative for cats that are difficult to medicate orally. © ISFM and AAFP 2014.

  3. Genetic, pathological and physiological determinants of transdermal fentanyl pharmacokinetics in 620 cancer patients of the EPOS study

    DEFF Research Database (Denmark)

    Barratt, Daniel T; Bandak, Benedikte; Klepstad, Pål

    2014-01-01

    This study aimed to investigate whether CYP3A4/5 genetic variants, together with clinical and patient factors, influence serum fentanyl and norfentanyl concentrations and their ratio in cancer pain patients receiving transdermal fentanyl....

  4. A new scheme for strain typing of methicillin-resistant Staphylococcus aureus on the basis of matrix-assisted laser desorption ionization time-of-flight mass spectrometry by using machine learning approach.

    Science.gov (United States)

    Wang, Hsin-Yao; Lee, Tzong-Yi; Tseng, Yi-Ju; Liu, Tsui-Ping; Huang, Kai-Yao; Chang, Yung-Ta; Chen, Chun-Hsien; Lu, Jang-Jih

    2018-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA), one of the most important clinical pathogens, conducts an increasing number of morbidity and mortality in the world. Rapid and accurate strain typing of bacteria would facilitate epidemiological investigation and infection control in near real time. Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry is a rapid and cost-effective tool for presumptive strain typing. To develop robust method for strain typing based on MALDI-TOF spectrum, machine learning (ML) is a promising algorithm for the construction of predictive model. In this study, a strategy of building templates of specific types was used to facilitate generating predictive models of methicillin-resistant Staphylococcus aureus (MRSA) strain typing through various ML methods. The strain types of the isolates were determined through multilocus sequence typing (MLST). The area under the receiver operating characteristic curve (AUC) and the predictive accuracy of the models were compared. ST5, ST59, and ST239 were the major MLST types, and ST45 was the minor type. For binary classification, the AUC values of various ML methods ranged from 0.76 to 0.99 for ST5, ST59, and ST239 types. In multiclass classification, the predictive accuracy of all generated models was more than 0.83. This study has demonstrated that ML methods can serve as a cost-effective and promising tool that provides preliminary strain typing information about major MRSA lineages on the basis of MALDI-TOF spectra.

  5. Matrix analysis

    CERN Document Server

    Bhatia, Rajendra

    1997-01-01

    A good part of matrix theory is functional analytic in spirit. This statement can be turned around. There are many problems in operator theory, where most of the complexities and subtleties are present in the finite-dimensional case. My purpose in writing this book is to present a systematic treatment of methods that are useful in the study of such problems. This book is intended for use as a text for upper division and gradu­ ate courses. Courses based on parts of the material have been given by me at the Indian Statistical Institute and at the University of Toronto (in collaboration with Chandler Davis). The book should also be useful as a reference for research workers in linear algebra, operator theory, mathe­ matical physics and numerical analysis. A possible subtitle of this book could be Matrix Inequalities. A reader who works through the book should expect to become proficient in the art of deriving such inequalities. Other authors have compared this art to that of cutting diamonds. One first has to...

  6. Prophylaxis of Postoperative Nausea and Vomiting in Adolescent Patients: A Review with Emphasis on Combination of Fixed-Dose Ondansetron and Transdermal Scopolamine

    Directory of Open Access Journals (Sweden)

    Joseph V. Pergolizzi

    2011-01-01

    Full Text Available Postoperative nausea and vomiting (PONV is a relatively common occurrence (20–30% that delays discharge and, if persistent, can lead to serious complications. The incidence of PONV is a function of patient characteristics, the type and duration of surgery, the type of anesthesia, and the choice of pre-, intra-, and postoperative pharmacotherapy. There are no completely effective antiemetic agents for this condition, but recommendations for treatment strategies are separately available for pediatric and adult patients. Left unclear is whether adolescents should be guided by the pediatric or the adult recommendations. We review the developmental physiology of the relevant physiological factors (absorption, distribution, metabolism, and elimination. We also review the clinical evidence regarding the safety and efficacy of a fixed-dose combination of ondansetron (4 mg, i.v. and transdermal scopolamine (1.5 mg.

  7. Tumor necrosis factor-α-accelerated degradation of type I collagen in human skin is associated with elevated matrix metalloproteinase (MMP)-1 and MMP-3 ex vivo

    DEFF Research Database (Denmark)

    Ågren, Magnus S; Schnabel, Reinhild; Christensen, Lise H

    2015-01-01

    Tumor necrosis factor (TNF)-α induces matrix metalloproteinases (MMPs) that may disrupt skin integrity. We have investigated the effects and mechanisms of exogenous TNF-α on collagen degradation by incubating human skin explants in defined serum-free media with or without TNF-α (10ng/ml) in the a......Tumor necrosis factor (TNF)-α induces matrix metalloproteinases (MMPs) that may disrupt skin integrity. We have investigated the effects and mechanisms of exogenous TNF-α on collagen degradation by incubating human skin explants in defined serum-free media with or without TNF-α (10ng...... tissue-derived collagenolytic activity with TNF-α exposure was blocked by neutralizing MMP-1 monoclonal antibody and was not due to down-regulation of tissue inhibitor of metalloproteinase-1. TNF-α increased production (pendogenous MMP-1...

  8. Matrix String Theory

    CERN Document Server

    Dijkgraaf, R; Verlinde, Herman L

    1997-01-01

    Via compactification on a circle, the matrix model of M-theory proposed by Banks et al suggests a concrete identification between the large N limit of two-dimensional N=8 supersymmetric Yang-Mills theory and type IIA string theory. In this paper we collect evidence that supports this identification. We explicitly identify the perturbative string states and their interactions, and describe the appearance of D-particle and D-membrane states.

  9. Development and in vitro evaluation of potential electromodulated transdermal drug delivery systems based on carbon nanotube buckypapers.

    Science.gov (United States)

    Schwengber, Alex; Prado, Héctor J; Bonelli, Pablo R; Cukierman, Ana L

    2017-07-01

    Buckypapers based on different types of carbon nanotubes with and without the addition of four model drugs, two of basic nature (clonidine hydrochloride, selegiline hydrochloride) and the others of acidic character (flurbiprofen, ketorolac tromethamine) were prepared and characterized. The influence of the conditions employed in the preparation of the buckypapers (dispersion time and solvents used in the preparation, as well as the type of carbon nanotubes used and the characteristics of the drug involved) on their conductivity was especially examined. The in vitro performance of the drug loaded buckypapers as passive and active transdermal drug release systems, the latter being modulated by means of the application of electric voltages, was studied. Passive drug loaded buckypapers presented characteristic release profiles, also depending on the drug used, which indicate differences in the drug-carbon nanotubes non-covalent interactions. Application of electrical biases of appropriate polarities enabled the modulation of the drug release profiles in any desired direction. Different mathematical models were fitted to passive and electromodulated experimental release data for the four model drugs. Among these models, the most appropriate for data description was a two-compartment pseudo-second-order one. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Matrix pentagons

    Science.gov (United States)

    Belitsky, A. V.

    2017-10-01

    The Operator Product Expansion for null polygonal Wilson loop in planar maximally supersymmetric Yang-Mills theory runs systematically in terms of multi-particle pentagon transitions which encode the physics of excitations propagating on the color flux tube ending on the sides of the four-dimensional contour. Their dynamics was unraveled in the past several years and culminated in a complete description of pentagons as an exact function of the 't Hooft coupling. In this paper we provide a solution for the last building block in this program, the SU(4) matrix structure arising from internal symmetry indices of scalars and fermions. This is achieved by a recursive solution of the Mirror and Watson equations obeyed by the so-called singlet pentagons and fixing the form of the twisted component in their tensor decomposition. The non-singlet, or charged, pentagons are deduced from these by a limiting procedure.

  11. Matrix pentagons

    Directory of Open Access Journals (Sweden)

    A.V. Belitsky

    2017-10-01

    Full Text Available The Operator Product Expansion for null polygonal Wilson loop in planar maximally supersymmetric Yang–Mills theory runs systematically in terms of multi-particle pentagon transitions which encode the physics of excitations propagating on the color flux tube ending on the sides of the four-dimensional contour. Their dynamics was unraveled in the past several years and culminated in a complete description of pentagons as an exact function of the 't Hooft coupling. In this paper we provide a solution for the last building block in this program, the SU(4 matrix structure arising from internal symmetry indices of scalars and fermions. This is achieved by a recursive solution of the Mirror and Watson equations obeyed by the so-called singlet pentagons and fixing the form of the twisted component in their tensor decomposition. The non-singlet, or charged, pentagons are deduced from these by a limiting procedure.

  12. Overexpression of interleukin-1β and interferon-γ in type I thoracic aortic dissections and ascending thoracic aortic aneurysms: possible correlation with matrix metalloproteinase-9 expression and apoptosis of aortic media cells.

    Science.gov (United States)

    Zhang, Lei; Liao, Ming-fang; Tian, Lei; Zou, Si-li; Lu, Qing-sheng; Bao, Jun-min; Pei, Yi-fei; Jing, Zai-ping

    2011-07-01

    To examine the expression of interleukin-1β and interferon-γ and their possible roles in aortic dissections and aneurysms. Aortic specimens were obtained from patients with type I thoracic aortic dissection, ascending thoracic aortic aneurysms, and control organ donors. The expression of interleukin-1β, interferon-γ, matrix metalloproteinase-9, and signal transduction factors phospho-p38 and phosphorylated c-jun N-terminal kinase (phospho-JNK) were detected by real time reverse transcription-polymerase chain reaction (real time RT-PCR), Western blot, and immunohistochemistry, respectively. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining was performed to detect apoptosis of media cells. The correlation of these factors and apoptosis was also studied. Apoptosis in the media of thoracic aortic dissection and in ascending thoracic aortic aneurysms was dramatically higher than in the control group. The expression of interleukin-1β gradually increased from the control group, thoracic aortic dissection to ascending thoracic aortic aneurysms (p matrix metalloproteinase-9 was significantly increased in the media of thoracic aortic dissection and ascending thoracic aortic aneurysms compared with the control group (p correlations between interleukin-1β versus matrix metalloproteinase-9, interleukin-1β versus phospho-p38 in thoracic aortic dissection (p matrix metalloproteinase-9, interferon-γ versus phospho-JNK, interferon-γ versus apoptosis, and interleukin-1β versus apoptosis in ascending thoracic aortic aneurysms (p = 0.02, 0.02, p matrix metalloproteinase-9 and the apoptosis of media cells in humans. Copyright © 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

  13. Random matrix theory

    CERN Document Server

    Deift, Percy

    2009-01-01

    This book features a unified derivation of the mathematical theory of the three classical types of invariant random matrix ensembles-orthogonal, unitary, and symplectic. The authors follow the approach of Tracy and Widom, but the exposition here contains a substantial amount of additional material, in particular, facts from functional analysis and the theory of Pfaffians. The main result in the book is a proof of universality for orthogonal and symplectic ensembles corresponding to generalized Gaussian type weights following the authors' prior work. New, quantitative error estimates are derive

  14. Diclofenac Potassium Transdermal Patches Using Natural Rubber Latex Biomembranes as Carrier

    Directory of Open Access Journals (Sweden)

    Natan Roberto de Barros

    2015-01-01

    Full Text Available The aim of this study was to design a compound transdermal patch containing diclofenac potassium (Dic-K using natural rubber latex (NRL biomembrane. The NRL from Hevea brasiliensis is easily manipulated and low cost and presents high mechanical resistance. It is a biocompatible material which can stimulate natural angiogenesis and is capable of adhering cells on its surface. Recent researches have used the NRL for Transdermal Drug Delivery Systems (TDDSs. Dic-K is used for the treatment of rheumatoid arthritis and osteoarthritis and pain relief for postoperative and posttraumatic cases, as well as inflammation and edema. Results showed that the biomembrane can release Dic-K for up to 216 hours. The kinetics of the Dic-K release could be fitted with double exponential function. X-ray diffraction and Fourier Transform Infrared (FTIR spectroscopy show some interaction by hydrogen bound. The results indicated the potential of the compound patch.

  15. Expanding the domain of drug delivery for HIV prevention: exploration of the transdermal route.

    Science.gov (United States)

    Puri, Ashana; Sivaraman, Arunprasad; Zhang, Wei; Clark, Meredith R; Banga, Ajay K

    2017-01-01

    Constant efforts for HIV prevention using antiretroviral drugs, pre- and postexposure prophylactic agents, and microbicides are being made by researchers. Drug-delivery systems such as oral tablets and coitally dependent vaginal gels are short acting, require daily application, and are associated with user adherence issues, whereas the coitally independent systems such as injectables and biodegradable implants are long acting, lasting several months, during which time the termination of prophylaxis is impractical in case of adverse effects. An effective drug-delivery system to be used for an intermediate duration, if available, would be an attractive alternative option for users in terms of adherence. Transdermal delivery systems, overcoming most of the limitations of the other routes of administration and aiming to provide sustained delivery of drugs through skin, may be explored for HIV prevention. Passive and physical enhancement techniques may be designed strategically to improve the transdermal delivery of HIV preventive agents.

  16. Current and emerging lipid-based systems for transdermal drug delivery.

    Science.gov (United States)

    Singla, Sumeet K; Sachdeva, Vishal

    2015-01-01

    Developing a transdermal drug delivery system is a challenging task considering the selective permeability of the skin and the physicochemical properties the drug must possess to permeate through the skin. Lipid-based drug delivery systems have contributed a great deal in this direction in the last few decades, and thereby have helped to expand the range of therapeutic molecules that can be delivered through the skin in a safe and effective manner. Additionally, vesicular delivery systems such as nanoparticles and emulsions have also played important roles in providing alternative novel approaches for drug delivery. In this article, we will discuss some of the current and future lipid-based systems for transdermal drug delivery along with the associated challenges.

  17. Acute Intoxication by Transdermal Opium Application in Infants: Two Case Reports

    Directory of Open Access Journals (Sweden)

    Iraj Sedighi

    2012-05-01

    Full Text Available Background: Acute opium intoxication is one of the most common causes of poisoning in children in Iran. Although most cases are accidental, traditional misuse of opium for symptomatic therapy of various childhood diseases also contributes to high rate of opium intoxication in Iran. Cases: Here, we report two cases of opium intoxication in infants resulted from transdermal application of opium on burned skin. To our knowledge this is the first case report of intoxication from transdermal misuse of opium. Conclusion: Health care providers should be aware about signs and symptoms of opium intoxication in children. Opium intoxication should be suspected in each child with history of a recent burn injury that presented with decreased level of consciousness.

  18. Drug profile: transdermal rivastigmine patch in the treatment of Alzheimer disease.

    Science.gov (United States)

    Emre, Murat; Bernabei, Roberto; Blesa, Rafael; Bullock, Roger; Cunha, Luis; Daniëls, Hugo; Dziadulewicz, Edward; Förstl, Hans; Frölich, Lutz; Gabryelewicz, Tomasz; Levin, Oleg; Lindesay, James; Martínez-Lage, Pablo; Monsch, Andreas; Tsolaki, Magda; van Laar, Teus

    2010-08-01

    Cholinesterase inhibitors constitute one of the mainstays of treatment of Alzheimer disease (AD). Gastrointestinal side effects, difficulty accessing therapeutic doses and poor patient compliance have been identified as barriers to effective treatment with these substances. The rivastigmine transdermal patch provides continuous delivery of drug through the skin into the bloodstream, avoiding the fluctuations in plasma concentration associated with oral administration. This pharmacokinetic profile is associated with reduced side effects, resulting in easier access to expected target doses. These benefits, along with other practical advantages of the transdermal patch, may contribute to enhanced patient compliance. Here, we present a review of the current literature on rivastigmine patch, and offer advice based on our own collective clinical experience. Rivastigmine patch provides an efficient option for managing patients with AD, to be considered among the first line therapies for the disease.

  19. Flexible and Stretchable Microneedle Patches with Integrated Rigid Stainless Steel Microneedles for Transdermal Biointerfacing.

    Science.gov (United States)

    Rajabi, Mina; Roxhed, Niclas; Shafagh, Reza Zandi; Haraldson, Tommy; Fischer, Andreas Christin; Wijngaart, Wouter van der; Stemme, Göran; Niklaus, Frank

    2016-01-01

    This paper demonstrates flexible and stretchable microneedle patches that combine soft and flexible base substrates with hard and sharp stainless steel microneedles. An elastomeric polymer base enables conformal contact between the microneedle patch and the complex topography and texture of the underlying skin, while robust and sharp stainless steel microneedles reliably pierce the outer layers of the skin. The flexible microneedle patches have been realized by magnetically assembling short stainless steel microneedles into a flexible polymer supporting base. In our experimental investigation, the microneedle patches were applied to human skin and an excellent adaptation of the patch to the wrinkles and deformations of the skin was verified, while at the same time the microneedles reliably penetrate the surface of the skin. The unobtrusive flexible and stretchable microneedle patches have great potential for transdermal biointerfacing in a variety of emerging applications such as transdermal drug delivery, bioelectric treatments and wearable bio-electronics for health and fitness monitoring.

  20. A comparative study on the transdermal penetration effect of gaseous and aqueous plasma reactive species

    Science.gov (United States)

    Liu, Xin; Gan, Lu; Ma, Mingyu; Zhang, Song; Liu, Jingjing; Chen, Hongxiang; Liu, Dawei; Lu, Xinpei

    2018-02-01

    To improve the depth of plasma active species in the skin, it is very important to develop skin disease treatment using plasma. In this article, an air plasma source was used to work directly with the skin of a mouse. A tortuous pathway, hair follicles, electroporation and a microneedle do not aid the transdermal delivery of gaseous plasma active species, therefore these gaseous plasma active species cannot penetrate mouse skin with a thickness of ~0.75 mm. The plasma activated water (PAW) produced by the air plasma source was used to study the transdermal penetration of the aqueous plasma activated species. This aqueous plasma activated species can penetrate the skin through hair follicles, intercellular and transcellular routes. The pH of the PAW did not affect the penetration efficiency of the aqueous plasma active species.

  1. In vivo studies of transdermal nanoparticle delivery with microneedles using photoacoustic microscopy

    Science.gov (United States)

    Moothanchery, Mohesh; Seeni, Razina Z.; Xu, Chenjie; Pramanik, Manojit

    2017-01-01

    Microneedle technology allows micron-sized conduits to be formed within the outermost skin layers for both localized and systemic delivery of therapeutics including nanoparticles. Histological methods are often employed for characterization, and unfortunately do not allow for the in vivo visualization of the delivery process. This study presents the utilization of optical resolution-photoacoustic microscopy to characterize the transdermal delivery of nanoparticles using microneedles. Specifically, we observe the in vivo transdermal delivery of gold nanoparticles using microneedles in mice ear and study the penetration, diffusion, and spatial distribution of the nanoparticles in the tissue. The promising results reveal that photoacoustic microscopy can be used as a potential imaging modality for the in vivo characterization of microneedles based drug delivery. PMID:29296482

  2. Lipid Nanocapsule-Based Gels for Enhancement of Transdermal Delivery of Ketorolac Tromethamine

    Directory of Open Access Journals (Sweden)

    Jaleh Varshosaz

    2011-01-01

    Full Text Available Previous reports show ineffective transdermal delivery of ketorolac by nanostructured lipid carriers (NLCs. The aim of the present work was enhancement of transdermal delivery of ketorolac by another colloidal carriers, lipid nanocapsules (LNCs. LNCs were prepared by emulsification with phase transition method and mixed in a Carbomer 934P gel base with oleic acid or propylene glycol as penetration enhancers. Permeation studies were performed by Franz diffusion cell using excised rat abdominal skin. Aerosil-induced rat paw edema model was used to investigate the in vivo performance. LNCs containing polyethylene glycol hydroxyl stearate, lecithin in Labrafac as the oily phase, and dilution of the primary emulsion with 3.5-fold volume of cold water produced the optimized nanoparticles. The 1% Carbomer gel base containing 10% oleic acid loaded with nanoparticles enhanced and prolonged the anti-inflammatory effects of this drug to more than 12 h in Aerosil-induced rat paw edema model.

  3. Odontogenic Differentiation of Human Dental Pulp Stem Cells on Hydrogel Scaffolds Derived from Decellularized Bone Extracellular Matrix and Collagen Type I.

    Science.gov (United States)

    Paduano, Francesco; Marrelli, Massimo; White, Lisa J; Shakesheff, Kevin M; Tatullo, Marco

    2016-01-01

    The aim of this study was to evaluate the level of odontogenic differentiation of dental pulp stem cells (DPSCs) on hydrogel scaffolds derived from bone extracellular matrix (bECM) in comparison to those seeded on collagen I (Col-I), one of the main components of dental pulp ECM. DPSCs isolated from human third molars were characterized for surface marker expression and odontogenic potential prior to seeding into bECM or Col-I hydrogel scaffolds. The cells were then seeded onto bECM and Col-I hydrogel scaffolds and cultured under basal conditions or with odontogenic and growth factor (GF) supplements. DPSCs cultivated on tissue culture polystyrene (TCPS) with and without supplements were used as controls. Gene expression of dentin sialophosphoprotein (DSPP), dentin matrix protein 1 (DMP-1) and matrix extracellular phosphoglycoprotein (MEPE) was evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and mineral deposition was observed by Von Kossa staining. When DPSCs were cultured on bECM hydrogels, the mRNA expression levels of DSPP, DMP-1 and MEPE genes were significantly upregulated with respect to those cultured on Col-I scaffolds or TCPS in the absence of extra odontogenic inducers. In addition, more mineral deposition was observed on bECM hydrogel scaffolds as demonstrated by Von Kossa staining. Moreover, DSPP, DMP-1 and MEPE mRNA expressions of DPSCs cultured on bECM hydrogels were further upregulated by the addition of GFs or osteo/odontogenic medium compared to Col-I treated cells in the same culture conditions. These results demonstrate the potential of the bECM hydrogel scaffolds to stimulate odontogenic differentiation of DPSCs.

  4. A novel type of matrix for surface-assisted laser desorption-ionization mass spectrometric detection of biomolecules using metal-organic frameworks.

    Science.gov (United States)

    Fu, Chien-Ping; Lirio, Stephen; Liu, Wan-Ling; Lin, Chia-Her; Huang, Hsi-Ya

    2015-08-12

    A 3D metal-organic framework (MOF) nanomaterial as matrix for surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) and tandem mass spectrometry (MS/MS) was developed for the analysis of complex biomolecules. Unlike other nanoparticle matrices, this MOF nanomaterial does not need chemical modification prior to use. An exceptional signal reproducibility as well as very low background interferences in analyzing mono-/di-saccharides, peptides and complex starch digests demonstrate its high potential for biomolecule assays, especially for small molecules. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. TRANSDERMAL PERMEABILITY OF ESTRADIOL THROUGH THE HUMAN SKIN OF DIFFERENT BODY REGIONS IN VITRO

    Institute of Scientific and Technical Information of China (English)

    CHENGuo-Shen; GONGSai-Jun; DUJie; MARun-Zhen; ZHOURong-Rong; LIULiang-Chu

    1989-01-01

    Transdermal permeability of estradiol was carried out by using Valia-Chien double compartment permeation cells for the following regions of intact skin and skin without stratum corncum: chest, abdomen, hip, upper arm, thigh and back. The estradiol permeation rates and accumulative amounts within 72h in vitro were examined by HPLC. The results showed that the permeation rates of intact skin from different regions of the body

  6. A Transdermal Drug Delivery System Based on LIGA Technology and Soft Lithography

    Science.gov (United States)

    Matteucci, Marco; Perennes, Frederic; Marmiroli, Benedetta; Di Fabrizio, Enzo

    2007-01-01

    This report presents a transdermal drug delivery system based on LIGA fabricated microparts. It is a portable device combining a magnetically actuated micro gear pump with a microneedle array. The fluidic behaviour of the system is analyzed in order to predict its performance according to the dimension of the microparts and then compared to experimental data. The manufacturing process of both micropump and microneedle array are described.

  7. Effect of electron beam irradiation on bacterial cellulose membranes used as transdermal drug delivery systems

    Energy Technology Data Exchange (ETDEWEB)

    Stoica-Guzun, Anicuta [Department of Chemical Engineering, ' Politehnica' University Bucharest, 313 Splaiul Independentei, 060042 Bucharest (Romania)], E-mail: astoica@mt.pub.ro; Stroescu, Marta; Tache, Florin [Department of Chemical Engineering, ' Politehnica' University Bucharest, 313 Splaiul Independentei, 060042 Bucharest (Romania); Zaharescu, Traian [Advanced Research Institute for Electrical Engineering, 313 Splaiul Unirii, 030138 Bucharest (Romania)], E-mail: zaharescut@icpe-ca.ro; Grosu, Elena [Department of Chemical Engineering, ' Politehnica' University Bucharest, 313 Splaiul Independentei, 060042 Bucharest (Romania)

    2007-12-15

    Ionizing radiation is an effective energetic source for polymer surfaces modification in order to obtain transdermal systems with different controlled release properties. In this work, gamma rays have been applied to induce changes in bacterial cellulose membranes. Permeation of drug (tetracycline) was theoretically and experimentally investigated starting from the effect of {gamma}-irradiation on membranes permeability. Release and permeation of drug from irradiated and non-irradiated membranes have been performed using a diffusion cell.

  8. Effect of electron beam irradiation on bacterial cellulose membranes used as transdermal drug delivery systems

    International Nuclear Information System (INIS)

    Stoica-Guzun, Anicuta; Stroescu, Marta; Tache, Florin; Zaharescu, Traian; Grosu, Elena

    2007-01-01

    Ionizing radiation is an effective energetic source for polymer surfaces modification in order to obtain transdermal systems with different controlled release properties. In this work, gamma rays have been applied to induce changes in bacterial cellulose membranes. Permeation of drug (tetracycline) was theoretically and experimentally investigated starting from the effect of γ-irradiation on membranes permeability. Release and permeation of drug from irradiated and non-irradiated membranes have been performed using a diffusion cell

  9. Effect of electron beam irradiation on bacterial cellulose membranes used as transdermal drug delivery systems

    Science.gov (United States)

    Stoica-Guzun, Anicuta; Stroescu, Marta; Tache, Florin; Zaharescu, Traian; Grosu, Elena

    2007-12-01

    Ionizing radiation is an effective energetic source for polymer surfaces modification in order to obtain transdermal systems with different controlled release properties. In this work, gamma rays have been applied to induce changes in bacterial cellulose membranes. Permeation of drug (tetracycline) was theoretically and experimentally investigated starting from the effect of γ-irradiation on membranes permeability. Release and permeation of drug from irradiated and non-irradiated membranes have been performed using a diffusion cell.

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

    Directory of Open Access Journals (Sweden)

    Fahmy UA

    2015-11-01

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

  11. Preparation and the in vitro evaluation of nanoemulsion system for the transdermal delivery of granisetron hydrochloride.

    Science.gov (United States)

    Zheng, Wen-wu; Zhao, Ling; Wei, Yu-meng; Ye, Yun; Xiao, Shun-han

    2010-08-01

    The objective of this study was to develop and evaluate nanoemulsion system for transdermal delivery of granisetron hydrochloride. Pseudo-ternary phase diagram was constructed to ascertain the concentration range of components of nanoemulsion composed of isopropyl myristate (IPM) as an oil phase, tween 85 as surfactant, ethanol as cosurfactant, water as aqueous phase. The effects of the content of IPM as an oil phase and n-methyl pyrrolidone (NMP) as transdermal enhancer on rat skin permeation of granisetron hydrochloride nanoemulsion were studied in vitro. The results showed that the mean particle size of nanoemulsion ranged from 50.4+/-1.5 to 82.4+/-0.9 nm with homogeneous size distribution. The resulted optimum formulation composed of 2.5% granisetron hydrochloride, 4% IPM, 40% tween 85/ethanol (1 : 1) and 10% NMP showed that the skin permeation rate was the highest (85.39+/-2.90 microg/cm(2)/h) and enhancement of drug permeability was 4.1-fold for transdermal delivery of granisetron hydrochloridein comparison with the control group (20% of tween 85 and 20% of ethanol micelle solution containing 2.5% of granisetron hydrochloride without IPM), and cumulative permeation amount was the highest (891.8+/-2.86 microg/cm(2)) with the shortest lag time (0.11+/-0.02 h) and was stable for at least 12 months. Therefore, the nanoemulsion system developed in this study offers a promising vehicle for the transdermal delivery system of granisetron hydrochloride, which may be as effective as oral or intravenous dosage forms and avoid some difficulties associated with these dosage forms.

  12. Use and cardiovascular safety of transdermal and other granisetron preparations in cancer management

    OpenAIRE

    Mason, Jay W; Moon, Thomas E

    2013-01-01

    Jay W Mason,1 Thomas E Moon2 1School of Medicine, University of Utah, Salt Lake City, UT, 2Tarizona eHealth Services, Inc, Emeryville, CA, USA Abstract: 5-HT3 antagonists have been available as oral and intravenous preparations for decades. The availability more recently of transdermal granisetron and the anticipated availability of a subcutaneous granisetron preparation have provided helpful alternatives to patients, and these preparations have been shown to have less potential to prolong Q...

  13. Microdose transdermal estrogen therapy for relief of vulvovaginal symptoms in postmenopausal women.

    Science.gov (United States)

    Bachmann, Gloria A; Schaefers, Matthias; Uddin, Alkaz; Utian, Wulf H

    2009-01-01

    The aim of this study was to investigate the effectiveness of microdose transdermal 17beta-estradiol (E2) therapy in postmenopausal women with moderate to severe vulvovaginal symptoms. This report is based on a subset of 121 women who reported most bothersome moderate or severe vulvovaginal symptoms at baseline, from a previous randomized, double-blind, placebo-controlled, multicenter study of 425 healthy, symptomatic, postmenopausal women. Recruits had experienced at least 7 moderate or severe hot flushes daily for at least 1 week or at least 50 moderate or severe hot flushes per week for at least 1 week. Effects on coprimary efficacy variables have been reported previously. Participants received low-dose transdermal E2 plus levonorgestrel (n = 43; nominal delivery 0.023 mg/d E2/0.0075 mg/d levonorgestrel), microdose E2 (n = 42; nominal delivery 0.014 mg/d), or placebo (n = 36) for 12 weeks. Secondary efficacy variables reported herein include mean change from baseline in vaginal pH and vaginal maturation index, the proportion of women with symptoms of vulvar and vaginal atrophy at baseline and week 12, and the proportion of women with moderate-to-severe symptoms of vulvar and vaginal atrophy. Microdose transdermal E2 treatment was associated with a consistent benefit versus placebo in women with vulvovaginal atrophy. There was a statistically significant difference between both E2 versus placebo for changes in vaginal pH and vaginal maturation index. Microdose transdermal E2 offers a useful addition to the therapeutic armamentarium for postmenopausal women in whom vulvovaginal symptoms are particularly troublesome.

  14. Enhanced Topical and Transdermal Delivery of Antineoplastic and Antiviral Acyclic Nucleoside Phosphonate cPr-PMEDAP

    Czech Academy of Sciences Publication Activity Database

    Vávrová, K.; Kovaříková, P.; Školová, B.; Líbalová, M.; Roh, J.; Čáp, R.; Holý, Antonín; Hrabálek, A.

    2011-01-01

    Roč. 28, č. 12 (2011), s. 3105-3115 ISSN 0724-8741 R&D Projects: GA MŠk 1M0508 Grant - others:GA ČR(CZ) GAP207/11/0365 Institutional research plan: CEZ:AV0Z40550506 Keywords : acyclic nucleoside phosphonates * antivirals * antineoplastics * permeation enhancer * topical skin application * transdermal delivery Subject RIV: CC - Organic Chemistry Impact factor: 4.093, year: 2011

  15. Sustained transdermal release of diltiazem hydrochloride through electron beam irradiated different PVA hydrogel membranes

    Energy Technology Data Exchange (ETDEWEB)

    Bhunia, Tridib [Department of Polymer Science and Technology, University of Calcutta, 92 A.P.C. Road, Calcutta 700009 (India); Goswami, Luna [KIIT School of Biotechnology, KIIT University Campus XI, Patia, Bhubaneswar 751024, Orissa (India); Chattopadhyay, Dipankar [Department of Polymer Science and Technology, University of Calcutta, 92 A.P.C. Road, Calcutta 700009 (India); Bandyopadhyay, Abhijit, E-mail: abpoly@caluniv.ac.in [Department of Polymer Science and Technology, University of Calcutta, 92 A.P.C. Road, Calcutta 700009 (India)

    2011-08-15

    Extremely fast release of diltiazem hydrochloride (water soluble, anti anginal drug used to treat chest pain) together with its faster erosion has been the primary problem in conventional oral therapy. It has been addressed in this paper by encapsulating the drug in electron beam irradiated various poly (vinyl alcohol) hydrogel membranes and delivering it through transdermal route. Results show excellent control over the release of diltiazem hydrochloride through these membranes subject to their physico-mechanicals.

  16. Sustained transdermal release of diltiazem hydrochloride through electron beam irradiated different PVA hydrogel membranes

    Science.gov (United States)

    Bhunia, Tridib; Goswami, Luna; Chattopadhyay, Dipankar; Bandyopadhyay, Abhijit

    2011-08-01

    Extremely fast release of diltiazem hydrochloride (water soluble, anti anginal drug used to treat chest pain) together with its faster erosion has been the primary problem in conventional oral therapy. It has been addressed in this paper by encapsulating the drug in electron beam irradiated various poly (vinyl alcohol) hydrogel membranes and delivering it through transdermal route. Results show excellent control over the release of diltiazem hydrochloride through these membranes subject to their physico-mechanicals.

  17. Sustained transdermal release of diltiazem hydrochloride through electron beam irradiated different PVA hydrogel membranes

    International Nuclear Information System (INIS)

    Bhunia, Tridib; Goswami, Luna; Chattopadhyay, Dipankar; Bandyopadhyay, Abhijit

    2011-01-01

    Extremely fast release of diltiazem hydrochloride (water soluble, anti anginal drug used to treat chest pain) together with its faster erosion has been the primary problem in conventional oral therapy. It has been addressed in this paper by encapsulating the drug in electron beam irradiated various poly (vinyl alcohol) hydrogel membranes and delivering it through transdermal route. Results show excellent control over the release of diltiazem hydrochloride through these membranes subject to their physico-mechanicals.

  18. Development of Tat-Conjugated Dendrimer for Transdermal DNA Vaccine Delivery.

    Science.gov (United States)

    Bahadoran, Azadeh; Moeini, Hassan; Bejo, Mohd Hair; Hussein, Mohd Zobir; Omar, Abdul Rahman

    In order to enhance cellular uptake and to facilitate transdermal delivery of DNA vaccine, polyamidoamine (PAMAM) dendrimers conjugated with HIV transactivator of transcription (TAT) was developed. First, the plasmid DNA (pIRES-H5/GFP) nanoparticle was formulated using PAMAM dendrimer and TAT peptide and then characterized for surface charge, particle size, DNA encapsulation and protection of the pIRES-H5/GFP DNA plasmid to enzymatic digestion. Subsequently, the potency of the TAT-conjugated dendrimer for gene delivery was evaluated through in vitro transfection into Vero cells followed by gene expression analysis including western blotting, fluorescent microscopy and PCR. The effect of the TAT peptide on cellular uptake of DNA vaccine was studied by qRT-PCR and flow cytometry. Finally, the ability of TAT-conjugated PAMAM dendrimer for transdermal delivery of the DNA plasmid was assessed through artificial membranes followed by qRT-PCR and flow cytometry. TAT-conjugated PAMAM dendrimer showed the ability to form a compact and nanometre-sized polyplexes with the plasmid DNA, having the size range of 105 to 115 nm and a positive charge of +42 to +45 mV over the N/P ratio of 6:1(+/-).  In vitro transfection analysis into Vero cells confirms the high potency of TAT-conjugated PAMAM dendrimer to enhance the cellular uptake of DNA vaccine.  The permeability value assay through artificial membranes reveals that TAT-conjugated PAMAM has more capacity for transdermal delivery of the DNA compared to unmodified PAMAM dendrimer (Pdendrimer is a promising non-viral vector for transdermal use.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.

  19. Physical, chemical and biological studies of gelatin/chitosan based transdermal fims with embedded silver nanoparticles

    Directory of Open Access Journals (Sweden)

    Sneha Paul

    2015-12-01

    Full Text Available Objective: To study the physical, chemical and biological properties of composite chitosangelatin transdermal film along with silver nanoparticles as binding agent and determine the compatibility of the prepared amalgamation towards wound management. Methods: Transdermal film preparations were done by solvent casting method containing different concentrations of biological synthesized silver nanoparticles. The films were characterized by using scanning electron microscope for their morphology and the determination of silver metal was done by using inductively coupled plasma atomic emission spectroscopy. Then a quantity of silver nanoparticles was further proceeded by physiochemical parameters (weight, thickness, temperature, solubility, absorption, tensile strength, in vitro drug release and skin permeation and biological parameters studies (anti-microbial, cytotoxicity and reactive oxygen species. Results: The film prepared by utilizing 2 g of gelatin and 0.5 g of chitosan exhibited better results. The physiochemical parameters studies revealed higher concentration of silver nanoparticles would give better results. In vitro drug release studies through dialysis and skin permeation showed the release of drug versus time (h. These films had shown excellent inhibition against Streptococcus and Escherichia coli species. Cytotoxicity study by MTT indicated the mild toxicity existed as the concentration of silver nanoparticles increased. Reactive oxygen species generation studies of transdermal film by using 2'7'-dichlorofluorescein diacetate assay demonstrated that the fluorescent cells were found in the higher concentration, which indicated cell damage (reactive oxygen species generated. Conclusions: Based on these observations, in vitro performances against various characteristics of transdermal film, would be utilized as a distinct dressing material and patches accessible in market.

  20. The Influence of Solid Microneedles on the Transdermal Delivery of Selected Antiepileptic Drugs

    Directory of Open Access Journals (Sweden)

    Julia Nguyen

    2016-11-01

    Full Text Available The aim of this project was to examine the effect of microneedle rollers on the percutaneous penetration of tiagabine hydrochloride and carbamazepine across porcine skin in vitro. Liquid chromatography-mass spectrometric analysis was carried out using an Agilent 1200 Series HPLC system coupled to an Agilent G1969A TOF-MS system. Transdermal flux values of the drugs were determined from the steady-state portion of the cumulative amount versus time curves. Following twelve hours of microneedle roller application, there was a 6.74-fold increase in the percutaneous penetration of tiagabine hydrochloride (86.42 ± 25.66 µg/cm2/h compared to passive delivery (12.83 ± 6.30 µg/cm2/h. For carbamazepine in 20% ethanol, passive transdermal flux of 7.85 ± 0.60 µg/cm2/h was observed compared to 10.85 ± 0.11 µg/cm2/h after microneedle treatment. Carbamazepine reconstituted in 30% ethanol resulted in only a 1.19-fold increase in drug permeation across porcine skin (36.73 ± 1.83 µg/cm2/h versus 30.74 ± 1.32 µg/cm2/h. Differences in flux values of untreated and microneedle-treated porcine skin using solid microneedles for the transdermal delivery of tiagabine were statistically significant. Although there were 1.38- and 1.19-fold increases in transdermal flux values of carbamazepine when applied as 20% and 30% ethanol solutions across microneedle-treated porcine skin, respectively, the increases were not statistically significant.

  1. Transdermal delivery of scopolamine by natural submicron injectors: in-vivo study in pig.

    Directory of Open Access Journals (Sweden)

    Esther Shaoul

    Full Text Available Transdermal drug delivery has made a notable contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. While transdermal delivery systems would appear to provide an attractive solution for local and systemic drug delivery, only a limited number of drugs can be delivered through the outer layer of the skin. The most difficult to deliver in this way are hydrophilic drugs. The aquatic phylum Cnidaria, which includes sea anemones, corals, jellyfish and hydra, is one of the most ancient multicellular phyla that possess stinging cells containing organelles (cnidocysts, comprising a sophisticated injection system. The apparatus is folded within collagenous microcapsules and upon activation injects a thin tubule that immediately penetrates the prey and delivers its contents. Here we show that this natural microscopic injection system can be adapted for systemic transdermal drug delivery once it is isolated from the cells and uploaded with the drug. Using a topically applied gel containing isolated natural sea anemone injectors and the muscarinic receptor antagonist scopolamine, we found that the formulated injectors could penetrate porcine skin and immediately deliver this hydrophilic drug. An in-vivo study in pigs demonstrated, for the first time, rapid systemic delivery of scopolamine, with T(max of 30 minutes and C(max 5 times higher than in controls treated topically with a scopolamine-containing gel without cnidocysts. The ability of the formulated natural injection system to penetrate a barrier as thick as the skin and systemically deliver an exogenous compound presents an intriguing and attractive alternative for hydrophilic transdermal drug delivery.

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

    OpenAIRE

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

    2010-01-01

    Controlled-release delivery of 6-β-naltrexol (NTXOL), the major active metabolite of naltrexone, via a transdermal patch is desirable for treatment of alcoholism. Unfortunately, NTXOL does not diffuse across skin at a therapeutic rate. Therefore, the focus of this study was to evaluate microneedle (MN) skin permeation enhancement of NTXOL's hydrochloride salt in hairless guinea pigs. Specifically, these studies were designed to determine the lifetime of MN-created aqueous pore pathways. Micro...

  3. The Effect of Transdermal Scopolamine for the Prevention of Postoperative Nausea and Vomiting

    Directory of Open Access Journals (Sweden)

    Maria A. Antor

    2014-04-01

    Full Text Available Postoperative nausea and vomiting is one of the most common and undesirable complaints recorded in as many as 70%-80% of high-risk surgical patients. The current prophylactic therapy recommendations for PONV management stated in the Society of Ambulatory Anesthesia guidelines should start with monotherapy and patients at moderate to high risk, a combination of antiemetic medication should be considered. Consequently, if rescue medication is required, the antiemetic drug chosen should be from a different therapeutic class and administration mode than the drug used for prophylaxis. The guidelines restrict the use of dexamethasone, transdermal scopolamine, aprepitant, and palonosetron as rescue medication 6 hours after surgery. In an effort to find a safer and reliable therapy for postoperative nausea and vomiting, new drugs with antiemetic properties and minimal side effects are needed, and scopolamine may be considered an effective alternative. Scopolamine is a belladonna alkaloid, α-(hydroxymethyl benzene acetic acid 9-methyl-3-oxa-9-azatricyclo non-7-yl ester, acting as a nonselective muscarinic antagonist and producing both peripheral antimuscarinic and central sedative, antiemetic, and amnestic effects. The empirical formula is C17H21NO4 and its structural formula is a tertiary amine L-(2-scopolamine (tropic acid ester with scopine; MW = 303.4. Scopolamine became the first drug commercially available as a transdermal therapeutic system used for extended continuous drug delivery during 72 hours. Clinical trials with transdermal scopolamine have consistently demonstrated its safety and efficacy in postoperative nausea and vomiting. Thus, scopolamine is a promising candidate for the management of postoperative nausea and vomiting in adults as a first line monotherapy or in combination with other drugs. In addition, transdermal scopolamine might be helpful in preventing postoperative discharge nausea and vomiting owing to its long

  4. ‘tripleint_cc’: A program for 2-centre variational leptonic Coulomb potential matrix elements using Hylleraas-type trial functions, with a performance optimization study

    Science.gov (United States)

    Plummer, M.; Armour, E. A. G.; Todd, A. C.; Franklin, C. P.; Cooper, J. N.

    2009-12-01

    We present a program used to calculate intricate three-particle integrals for variational calculations of solutions to the leptonic Schrödinger equation with two nuclear centres in which inter-leptonic distances (electron-electron and positron-electron) are included directly in the trial functions. The program has been used so far in calculations of He-H¯ interactions and positron H 2 scattering, however the precisely defined integrals are applicable to other situations. We include a summary discussion of how the program has been optimized from a 'legacy'-type code to a more modern high-performance code with a performance improvement factor of up to 1000. Program summaryProgram title: tripleint.cc Catalogue identifier: AEEV_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEEV_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 12 829 No. of bytes in distributed program, including test data, etc.: 91 798 Distribution format: tar.gz Programming language: Fortran 95 (fixed format) Computer: Modern PC (tested on AMD processor) [1], IBM Power5 [2] Cray XT4 [3], similar Operating system: Red Hat Linux [1], IBM AIX [2], UNICOS [3] Has the code been vectorized or parallelized?: Serial (multi-core shared memory may be needed for some large jobs) RAM: Dependent on parameter sizes and option to use intermediate I/O. Estimates for practical use: 0.5-2 GBytes (with intermediate I/O); 1-4 GBytes (all-memory: the preferred option). Classification: 2.4, 2.6, 2.7, 2.9, 16.5, 16.10, 20 Nature of problem: The 'tripleint.cc' code evaluates three-particle integrals needed in certain variational (in particular: Rayleigh-Ritz and generalized-Kohn) matrix elements for solution of the Schrödinger equation with two fixed centres (the solutions may then be used in subsequent dynamic

  5. Nonaqueous gel for the transdermal delivery of a DTPA penta-ethyl ester prodrug.

    Science.gov (United States)

    Zhang, Yong; Sadgrove, Matthew P; Sueda, Katsuhiko; Yang, Yu-Tsai; Pacyniak, Erik K; Kagel, John R; Braun, Brenda A; Zamboni, William C; Mumper, Russell J; Jay, Michael

    2013-04-01

    Diethylenetriamine pentaacetic acid penta-ethyl ester, designated as C2E5, was successfully incorporated into a nonaqueous gel for transdermal delivery. The thermal and rheological properties of a formulation containing 40% C2E5, 20% ethyl cellulose, and 40% Miglyol 840® prepared using the solvent evaporation method demonstrated that the gel had acceptable content uniformity and flow properties. In vitro studies showed that C2E5 was steadily released from the gel at a rate suitable for transdermal delivery. Topical application of the gel at a 200 mg C2E5/kg dose level in rats achieved significantly higher plasma exposures of several active metabolites compared with neat C2E5 oil at the same dose level. The results suggest that transdermal delivery of a chelator prodrug is an effective radionuclide decorporation strategy by delivering chelators to the circulation with a pharmacokinetic profile that is more consistent with the biokinetic profile of transuranic elements in contaminated individuals.

  6. Formulation Design and Development of a Unani Transdermal Patch for Antiemetic Therapy and Its Pharmaceutical Evaluation

    Directory of Open Access Journals (Sweden)

    Mohd Nauman Saleem

    2016-01-01

    Full Text Available The Transdermal Drug Delivery System (TDDS is one of the novel routes for systemic delivery of drugs through intact skin. A transdermal patch (TP is a medicated patch that is placed on skin for delivery of medication through skin into the blood stream. The aim of present study was to formulate and evaluate a Unani transdermal patch that could be used for antiemetic therapy. The incorporation of Unani ingredients, namely, Khardal (Brassica nigra, Zanjabeel (Zingiber officinale, Podina (Mentha arvensis, and Sirka (Vinegar were envisaged. The TP was prepared by solvent evaporation technique and was evaluated for organoleptic characteristics and other physicochemical properties, such as thickness, weight uniformity, folding endurance, moisture content, drug content, and tolerability and acceptability of patch. The in vitro permeation study of the patch was carried out through Franz diffusion cell using egg shell membrane as barrier membrane. Phosphate buffer pH 7.4 was used as dissolution medium and the temperature was maintained at 37 ± 1°C. The in vitro permeation study of the prepared TP indicated a time dependent increase in drug release throughout the study. The percentage of cumulative drug release was found to be 77.38% in 24 hours. The study shows a new approach to work in Unani pharmaceutics.

  7. Microemulsion for simultaneous transdermal delivery of benzocaine and indomethacin: in vitro and in vivo evaluation.

    Science.gov (United States)

    El Maghraby, Gamal M; Arafa, Mona F; Osman, Mohamed A

    2014-12-01

    This study investigated simultaneous transdermal delivery of indomethacin and benzocaine from microemulsion. Eucalyptus oil based microemulsion was used with Tween 80 and ethanol being employed as surfactant and cosurfactant, respectively. A microemulsion formulation comprising eucalyptus oil, polyoxyethylene sorbitan momooleate (Tween 80), ethanol and water (20:30:30:20) was selected. Indomethacin (1% w/w) and benzocaine (20% w/w) were incorporated separately or combined into this formulation before in vitro and in vivo evaluation. Application of indomethacin microemulsion enhanced the transdermal flux and reduced the lag time compared to saturated aqueous control. The same trend was evident for benzocaine microemulsion. Simultaneous application of the two drugs in microemulsion provided similar enhancement pattern. The in vivo evaluation employed the pinprick method and revealed rapid anesthesia after application of benzocaine microemulsion with the onset being 10 min and the action lasting for 50 min. For indomethacin microemulsion, the analgesic effect was recorded after 34.5 min and lasted for 70.5 min. Simultaneous application of benzocaine and indomethacin provided synergistic effect. The onset of action was achieved after 10 min and lasted for 95 min. The study highlighted the potential of microemulsion formulation in simultaneous transdermal delivery of two drugs.

  8. In vitro evaluation of transdermal nicotine delivery systems commercially available in Brazil

    Directory of Open Access Journals (Sweden)

    André Luís Morais Ruela

    2013-09-01

    Full Text Available The aim of this study was to develop and validate a method for evaluating the release and skin permeation from transdermal nicotine patches using the vertical diffusion cell (VDC. The VDC is an experimental apparatus employed in research, development, and the pharmaceutical field because it can simulate conditions closest to those established in clinical trials. Two transdermal nicotine delivery systems marketed in Brazil to release 14 mg over 24 hours were evaluated. Release studies were carried out using a regenerated cellulose dialysis membrane and permeation studies were carried out using excised porcine ear skin. The results indicated that nicotine release from both evaluated patches follows Higuchi's release kinetics, while skin permeation studies indicated zero-order release kinetics. Nicotine release rates were different between both evaluated patches, but drug permeation rates were not significantly different. According to validation studies, the method was appropriate for evaluating in vitro performance of nicotine patches. The proposed method can be applied to in vitro comparative studies between different commercial nicotine patches and may be used as an auxiliary tool in the design of new transdermal nicotine delivery systems.

  9. Thermoresponsive Hydrogels and Their Biomedical Applications: Special Insight into Their Applications in Textile Based Transdermal Therapy

    Directory of Open Access Journals (Sweden)

    Sudipta Chatterjee

    2018-04-01

    Full Text Available Various natural and synthetic polymers are capable of showing thermoresponsive properties and their hydrogels are finding a wide range of biomedical applications including drug delivery, tissue engineering and wound healing. Thermoresponsive hydrogels use temperature as external stimulus to show sol-gel transition and most of the thermoresponsive polymers can form hydrogels around body temperature. The availability of natural thermoresponsive polymers and multiple preparation methods of synthetic polymers, simple preparation method and high functionality of thermoresponsive hydrogels offer many advantages for developing drug delivery systems based on thermoresponsive hydrogels. In textile field applications of thermoresponsive hydrogels, textile based transdermal therapy is currently being applied using drug loaded thermoresponsive hydrogels. The current review focuses on the preparation, physico-chemical properties and various biomedical applications of thermoresponsive hydrogels based on natural and synthetic polymers and especially, their applications in developing functionalized textiles for transdermal therapies. Finally, future prospects of dual responsive (pH/temperature hydrogels made by these polymers for textile based transdermal treatments are mentioned in this review.

  10. Dendrimer-coupled sonophoresis-mediated transdermal drug-delivery system for diclofenac.

    Science.gov (United States)

    Huang, Bin; Dong, Wei-Jiang; Yang, Gao-Yi; Wang, Wei; Ji, Cong-Hua; Zhou, Fei-Ni

    2015-01-01

    The purpose of the present study was to develop a novel transdermal drug-delivery system comprising a polyamidoamine dendrimer coupled with sonophoresis to enhance the permeation of diclofenac (DF) through the skin. The novel transdermal drug-delivery system was developed by using a statistical Plackett-Burman design. Hairless male Wistar rat skin was used for the DF-permeation study. Coupling media concentration, ultrasound-application time, duty cycle, distance from probe to skin, and a third-generation polyamidoamine-dendrimer concentration were selected as independent variables, while in vitro drug release was selected as a dependent variable. Independent variables were found to be statistically significant (Pdelivery, run 13) showed 56.69 µg/cm(2) cumulative drug permeated through the skin, while the DF-dendrimer gel without sonophoresis treatment (run 14) showed 257.3 µg/cm(2) cumulative drug permeated through the skin after 24 hours. However, when the same gel was applied to sonophoresis-treated skin, drastic permeation enhancement was observed. In the case of run 3, the cumulative drug that permeated through the skin was 935.21 µg/cm(2). It was concluded that dendrimer-coupled sonophoresis-mediated transdermal drug delivery system has the potential to enhance the permeation of DF through the skin.

  11. Preparation and the Biopharmaceutical Evaluation for the Metered Dose Transdermal Spray of Dexketoprofen

    Science.gov (United States)

    Luo, Huafei; Zhu, Zhuangzhi; Wu, Yubo; Luo, Jing; Wang, Hao

    2014-01-01

    The objective of the present work was to develop a metered dose transdermal spray (MDTS) formulation for transdermal delivery of dexketoprofen (DE). DE release from a series of formulations was assessed in vitro. Various qualitative and quantitative parameters like spray pattern, pump seal efficiency test, average weight per metered dose, and dose uniformity were evaluated. The optimized formulation with good skin permeation and an appropriate drug concentration and permeation enhancer (PE) content was developed incorporating 7% (w/w, %) DE, 7% (v/v, %) isopropyl myristate (IPM), and 93% (v/v, %) ethanol. In vivo pharmacokinetic study indicated that the optimized formulation showed a more sustainable plasma-concentration profile compared with the Fenli group. The antiinflammatory effect of DE MDTS was evaluated by experiments involving egg-albumin-induced paw edema in rats and xylene-induced ear swelling in mice. Acetic acid-induced abdominal constriction was used to evaluate the anti-nociceptive actions of DE MDTS. Pharmacodynamic studies indicated that the DE MDTS has good anti-inflammatory and anti-nociceptive activities. Besides, skin irritation studies were performed using rat as an animal model. The results obtained show that the MDTS can be a promising and innovative therapeutic system used in transdermal drug delivery for DE. PMID:24660066

  12. Nanostructured transdermal hormone replacement therapy for relieving menopausal symptoms: a confocal Raman spectroscopy study

    Directory of Open Access Journals (Sweden)

    Marco Antonio Botelho

    2014-02-01

    Full Text Available OBJECTIVE: To determine the safety and efficacy of a transdermal nanostructured formulation of progesterone (10% combined with estriol (0.1% + estradiol (0.25% for relieving postmenopausal symptoms. METHODS: A total of 66 postmenopausal Brazilian women with climacteric symptoms of natural menopause received transdermal nanostructured formulations of progesterone and estrogens in the forearm daily for 60 months to mimic the normal ovarian secretory pattern. Confocal Raman spectroscopy of hormones in skin layers was performed. Clinical parameters, serum concentrations of estradiol and follicle-stimulating hormone, blood pressure, BI-RADS classification from bilateral mammography, and symptomatic relief were compared between baseline and 60 months post-treatment. Clinicaltrials.gov: NCT02033512. RESULTS: An improvement in climacteric symptoms was reported in 92.5% of women evaluated before and after 60 months of treatment. The serum concentrations of estradiol and follicle-stimulating hormone changed significantly (p<0.05 after treatment; the values of serum follicle-stimulating hormone decreased after 60 months from 82.04±4.9 to 57.12±4.1 IU/mL. A bilateral mammography assessment of the breasts revealed normal results in all women. No adverse health-related events were attributed to this hormone replacement therapy protocol. CONCLUSION: The nanostructured formulation is safe and effective in re-establishing optimal serum levels of estradiol and follicle-stimulating hormone and relieving the symptoms of menopause. This transdermal hormone replacement therapy may alleviate climacteric symptoms in postmenopausal women.

  13. A New Combination of Testosterone and Nestorone Transdermal Gels for Male Hormonal Contraception

    Science.gov (United States)

    Ilani, Niloufar; Roth, Mara Y.; Amory, John K.; Swerdloff, Ronald S.; Dart, Clint; Page, Stephanie T.; Bremner, William J.; Sitruk-Ware, Regine; Kumar, Narender; Blithe, Diana L.

    2012-01-01

    Context: Combinations of testosterone (T) and nestorone (NES; a nonandrogenic progestin) transdermal gels may suppress spermatogenesis and prove appealing to men for contraception. Objective: The objective of the study was to determine the effectiveness of T gel alone or combined with NES gel in suppressing spermatogenesis. Design and Setting: This was a randomized, double-blind, comparator clinical trial conducted at two academic medical centers. Participants: Ninety-nine healthy male volunteers participated in the study. Interventions: Volunteers were randomized to one of three treatment groups applying daily transdermal gels (group 1: T gel 10 g + NES 0 mg/placebo gel; group 2: T gel 10 g + NES gel 8 mg; group 3: T gel 10 g + NES gel 12 mg). Main Outcome Variable: The main outcome variable of the study was the percentage of men whose sperm concentration was suppressed to 1 million/ml or less by 20–24 wk of treatment. Results: Efficacy data analyses were performed on 56 subjects who adhered to the protocol and completed at least 20 wk of treatment. The percentage of men whose sperm concentration was 1 million/ml or less was significantly higher for T + NES 8 mg (89%, P male range throughout the treatment period. Adverse effects were minimal in all groups. Conclusion: A combination of daily NES + T gels suppressed sperm concentration to 1 million/ml or less in 88.5% of men, with minimal adverse effects, and may be further studied as a male transdermal hormonal contraceptive. PMID:22791756

  14. [{sup 11}C]diclofenac sodium: synthesis and PET assessment of transdermal penetration

    Energy Technology Data Exchange (ETDEWEB)

    Petroni, Debora, E-mail: debora.petroni@ifc.cnr.i [CNR Institute of Clinical Physiology, Via Moruzzi 1, 56124 Pisa (Italy); Menichetti, Luca; Sorace, Oreste; Poli, Michela [CNR Institute of Clinical Physiology, Via Moruzzi 1, 56124 Pisa (Italy); Vanasia, Massimo [Gienne Pharma, Via Lorenteggio 270/A, 20152 Milan (Italy); Salvadori, Piero A. [CNR Institute of Clinical Physiology, Via Moruzzi 1, 56124 Pisa (Italy)

    2011-02-15

    The aim of this work was to study the feasibility of using Positron Emission Tomography (PET) imaging as a new tool to detect transdermal penetration of topical drugs in human subjects. The compound used in the study is sodium 2-[(2,6-dichlorophenyl)amino]phenyl]acetate, better known as diclofenac sodium. This molecule belongs to the family of non-steroidal anti-inflammatory drugs and is considered one of the first choices among non-steroidal anti-inflammatory drugs for the treatment of inflammatory diseases; it is widely used and commercially present in a large number of pharmaceutical forms and formulations. {sup 11}C-labeled diclofenac has been synthesized and coformulated, as an internal indicator, with a proprietary preparation based on the use of a sprayer. The radiolabeled preparation was topically administered to healthy volunteers, and PET imaging was used to evaluate transdermal penetration. Results obtained have demonstrated the efficacy of PET and radiolabeled tracers for the evaluation of transdermal penetration of active pharmaceutical ingredients as topical formulations.

  15. [11C]diclofenac sodium: synthesis and PET assessment of transdermal penetration

    International Nuclear Information System (INIS)

    Petroni, Debora; Menichetti, Luca; Sorace, Oreste; Poli, Michela; Vanasia, Massimo; Salvadori, Piero A.

    2011-01-01

    The aim of this work was to study the feasibility of using Positron Emission Tomography (PET) imaging as a new tool to detect transdermal penetration of topical drugs in human subjects. The compound used in the study is sodium 2-[(2,6-dichlorophenyl)amino]phenyl]acetate, better known as diclofenac sodium. This molecule belongs to the family of non-steroidal anti-inflammatory drugs and is considered one of the first choices among non-steroidal anti-inflammatory drugs for the treatment of inflammatory diseases; it is widely used and commercially present in a large number of pharmaceutical forms and formulations. 11 C-labeled diclofenac has been synthesized and coformulated, as an internal indicator, with a proprietary preparation based on the use of a sprayer. The radiolabeled preparation was topically administered to healthy volunteers, and PET imaging was used to evaluate transdermal penetration. Results obtained have demonstrated the efficacy of PET and radiolabeled tracers for the evaluation of transdermal penetration of active pharmaceutical ingredients as topical formulations.

  16. Deformable Nanovesicles Synthesized through an Adaptable Microfluidic Platform for Enhanced Localized Transdermal Drug Delivery

    Directory of Open Access Journals (Sweden)

    Naren Subbiah

    2017-01-01

    Full Text Available Phospholipid-based deformable nanovesicles (DNVs that have flexibility in shape offer an adaptable and facile method to encapsulate diverse classes of therapeutics and facilitate localized transdermal delivery while minimizing systemic exposure. Here we report the use of a microfluidic reactor for the synthesis of DNVs and show that alteration of input parameters such as flow speeds as well as molar and flow rate ratios increases entrapment efficiency of drugs and allows fine-tuning of DNV size, elasticity, and surface charge. To determine the ability of DNV-encapsulated drug to be delivered transdermally to a local site, we synthesized, characterized, and tested DNVs carrying the fluorescently labeled hydrophilic bisphosphonate drug AF-647 zoledronate (AF647-Zol. AF647-Zol DNVs were lyophilized, resuspended, and applied topically as a paste to the calvarial skin of mice. High-resolution fluorescent imaging and confocal microscopy revealed significant increase of encapsulated payload delivery to the target tissue—cranial bone—by DNVs as compared to nondeformable nanovesicles (NVs or aqueous drug solutions. Interestingly, NV delivery was not superior to aqueous drug solution. Our studies show that microfluidic reactor-synthesized DNVs can be produced in good yield, with high encapsulation efficiency, reproducibility, and stability after storage, and represent a useful vehicle for localized transdermal drug delivery.

  17. Protection against soman and sarin exposure by transdermal physostigmine and scopolamine

    Energy Technology Data Exchange (ETDEWEB)

    Meshulam, Y.; Davidovici, R.; Levy, A.

    1993-05-13

    The purpose of this study was to evaluate the prophylactic efficacy of physostigmine (physo), administered via sustained release (SR) methods, with and without scopolamine, against soman and sarin exposure in guinea-pigs. Transdermal physo pad (3 sq cm/kg; 60-80 ug/sq cm), containing a vehicle based on propionic acid, was applied onto the dorsal back of the animals, 24 hours before exposure to the cholinesterase (ChE) inhibitors. At the time of exposure, physo concentrations in brain and plasma were 3.6 ng/g and 4.1 ng/ml respectively. Brain and whole blood ChE activity were inhibited to 70% and 57% of their original activity. Transdermal physo by itself protected up to 70% of the animals exposed to 1.5 LD(50) of soman or sarin (100% mortality was recorded in the control group). Combining transdermal physo with Scopoderm (by Ciba Geigy Inc.) provided full protection against 1.5 LD(50).

  18. Exposure to Fentanyl After Transdermal Patch Administration for Cancer Pain Management.

    Science.gov (United States)

    Bista, Sudeep R; Haywood, Alison; Hardy, Janet; Norris, Ross; Hennig, Stefanie

    2016-06-01

    This study aimed to describe exposure after fentanyl transdermal patch administration in patients with advanced cancer to quantify variability around the exposure. Patients (n  =  56) with advanced cancer who received transdermal fentanyl (Durogesic®; median dose, 50 μg/h; range, 12-200 μg/h) provided venous blood samples (n  =  163) at various times (0.5-72 hours) during several patch application intervals. Plasma fentanyl concentration was determined (median, 0.9 μg/L; range, 0.04-9.7 μg/L) by high-performance liquid chromatography coupled to tandem mass spectrometry. Pharmacokinetic analysis was performed using nonlinear mixed-effects modeling with NONMEM. A 1-compartment distribution model with first-order absorption and elimination described fentanyl exposure after transdermal patch administration. Fentanyl apparent clearance (between-subject variability [BSV], %) was estimated at 122 L/h/70 kg and 38.5%, respectively. The absorption rate constant was 0.013 h(-1) . Between-occasion variability on apparent clearance was 22.0%, which was lower than BSV, suggesting predictable exposure within the same patient and justifying therapeutic drug monitoring. Except for weight-based dosing, no other patient characteristic could be identified to guide initial fentanyl dose selection in patients with advanced cancer. © 2015, The American College of Clinical Pharmacology.

  19. Nanostructured transdermal hormone replacement therapy for relieving menopausal symptoms: a confocal Raman spectroscopy study

    International Nuclear Information System (INIS)

    Botelho, Marco Antonio; Queiroz, Dinalva Brito; Barros, Gisele; Guerreiro, Stela; Umbelino, Sonia; Lyra, Arao; Borges, Boniek; Freitas, Allan; Almeida, Jackson Guedes; Quintans Junior, Lucindo

    2014-01-01

    Objective:to determine the safety and efficacy of a transdermal nanostructured formulation of progesterone (10%) combined with estriol (0.1%) + estradiol (0.25%) for relieving postmenopausal symptoms. Methods: a total of 66 postmenopausal Brazilian women with climacteric symptoms of natural menopause received transdermal nanostructured formulations of progesterone and estrogens in the forearm daily for 60 months to mimic the normal ovarian secretory pattern. Confocal Raman spectroscopy of hormones in skin layers was performed. Clinical parameters, serum concentrations of estradiol and follicle-stimulating hormone, blood pressure, BI-RADS classification from bilateral mammography, and symptomatic relief were compared between baseline and 60 months post-treatment. Clinicaltrials.gov: NCT02033512. Results: an improvement in climacteric symptoms was reported in 92.5% of women evaluated before and after 60 months of treatment. The serum concentrations of estradiol and follicle-stimulating hormone changed significantly (p<0.05) after treatment; the values of serum follicle-stimulating hormone decreased after 60 months from 82.04 ± 4.9 to 57.12 ± 4.1 IU/mL. A bilateral mammography assessment of the breasts revealed normal results in all women. No adverse health-related events were attributed to this hormone replacement therapy protocol. Conclusion: the nanostructured formulation is safe and effective in re-establishing optimal serum levels of estradiol and follicle-stimulating hormone and relieving the symptoms of menopause. This transdermal hormone replacement therapy may alleviate climacteric symptoms in postmenopausal women. (author)

  20. A self-adherent, bullet-shaped microneedle patch for controlled transdermal delivery of insulin.

    Science.gov (United States)

    Seong, Keum-Yong; Seo, Min-Soo; Hwang, Dae Youn; O'Cearbhaill, Eoin D; Sreenan, Seamus; Karp, Jeffrey M; Yang, Seung Yun

    2017-11-10

    Proteins are important biologic therapeutics used for the treatment of various diseases. However, owing to low bioavailability and poor skin permeability, transdermal delivery of protein therapeutics poses a significant challenge. Here, we present a new approach for transdermal protein delivery using bullet-shaped double-layered microneedle (MN) arrays with water-swellable tips. This design enabled the MNs to mechanically interlock with soft tissues by selective distal swelling after skin insertion. Additionally, prolonged release of loaded proteins by passive diffusion through the swollen tips was obtained. The bullet-shaped MNs provided an optimal geometry for mechanical interlocking, thereby achieving significant adhesion strength (~1.6Ncm -2 ) with rat skin. By harnessing the MN's reversible swelling/deswelling property, insulin, a model protein drug, was loaded in the swellable tips using a mild drop/dry procedure. The insulin-loaded MN patch released 60% of insulin when immersed in saline over the course of 12h and approximately 70% of the released insulin appeared to have preserved structural integrity. An in vivo pilot study showed a prolonged release of insulin from swellable MN patches, leading to a gradual decrease in blood glucose levels. This self-adherent transdermal MN platform can be applied to a variety of protein drugs requiring sustained release kinetics. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Microneedle-mediated transdermal delivery of nanostructured lipid carriers for alkaloids from Aconitum sinomontanum.

    Science.gov (United States)

    Guo, Teng; Zhang, Yongtai; Li, Zhe; Zhao, Jihui; Feng, Nianping

    2017-09-12

    A combination method using microneedle (MN) pretreatment and nanostructured lipid carriers (NLCs) was developed to improve the transdermal delivery of therapeutics. The MN treatment of the skin and co-administration of NLCs loaded with total alkaloids isolated from Aconitum sinomontanum (AAS-NLCs) significantly increased the skin permeation of the drugs. Fluorescence imaging confirmed that MNs could provide microchannels penetrating the stratum corneum, and delivery of NLCs through the channels led to their deeper permeation. In vivo studies showed that combination of AAS-NLCs with MNs (AAS-NLCs-MN) in transdermal delivery could improve the bioavailability and maintain stable drug concentrations in the blood. Moreover, AAS-NLCs-MN showed benefits in eliminating paw swelling, decreasing inflammation and pain, and regulating immune function in adjuvant arthritis rats. After administration of AAS-NLCs-MN, no skin irritation was observed in rabbits, and electrocardiograms of rats showed improved arrhythmia. These results indicated that the dual approach combining MN insertion and NLCs has the potential to provide safe transdermal delivery and to improve the therapeutic efficacy through sustained release of AAS.

  2. Nanostructured transdermal hormone replacement therapy for relieving menopausal symptoms: a confocal Raman spectroscopy study

    Energy Technology Data Exchange (ETDEWEB)

    Botelho, Marco Antonio; Queiroz, Dinalva Brito; Barros, Gisele; Guerreiro, Stela; Umbelino, Sonia; Lyra, Arao; Borges, Boniek; Freitas, Allan, E-mail: marcobotelho@pq.cnpq.br [Universidade Potiguar, Natal, RN (Brazil). Lab. de Nanotecnologia; Fechine, Pierre [Universidade Federal do Ceara (GQMAT/UFCE), Fortaleza, CE (Brazil). Dept. de Quimica Analitica. Grupo Avancado de Biomateriais em Quimica; Queiroz, Danilo Caldas de [Instituto Federal de Ciencia e Tecnologia (IFCT), Fortaleza, CE (Brazil). Lab. de Biotecnologia; Ruela, Ronaldo [Instituto de Biotecnologia Aplicada (INBIOS), Fortaleza, CE (Brazil); Almeida, Jackson Guedes [Universidade Federal do Vale de Sao Francisco (UNIVALE), Petrolina, PE (Brazil). Fac. de Ciencias Farmaceuticas; Quintans Junior, Lucindo [Universidade Federal de Sergipe (UFSE), Sao Cristovao, SE (Brazil). Dept. de Fisiologia

    2014-06-01

    Objective:to determine the safety and efficacy of a transdermal nanostructured formulation of progesterone (10%) combined with estriol (0.1%) + estradiol (0.25%) for relieving postmenopausal symptoms. Methods: a total of 66 postmenopausal Brazilian women with climacteric symptoms of natural menopause received transdermal nanostructured formulations of progesterone and estrogens in the forearm daily for 60 months to mimic the normal ovarian secretory pattern. Confocal Raman spectroscopy of hormones in skin layers was performed. Clinical parameters, serum concentrations of estradiol and follicle-stimulating hormone, blood pressure, BI-RADS classification from bilateral mammography, and symptomatic relief were compared between baseline and 60 months post-treatment. Clinicaltrials.gov: NCT02033512. Results: an improvement in climacteric symptoms was reported in 92.5% of women evaluated before and after 60 months of treatment. The serum concentrations of estradiol and follicle-stimulating hormone changed significantly (p<0.05) after treatment; the values of serum follicle-stimulating hormone decreased after 60 months from 82.04 ± 4.9 to 57.12 ± 4.1 IU/mL. A bilateral mammography assessment of the breasts revealed normal results in all women. No adverse health-related events were attributed to this hormone replacement therapy protocol. Conclusion: the nanostructured formulation is safe and effective in re-establishing optimal serum levels of estradiol and follicle-stimulating hormone and relieving the symptoms of menopause. This transdermal hormone replacement therapy may alleviate climacteric symptoms in postmenopausal women. (author)

  3. Preparation and the Biopharmaceutical Evaluation for the Metered Dose Transdermal Spray of Dexketoprofen

    Directory of Open Access Journals (Sweden)

    Wangding Lu

    2014-01-01

    Full Text Available The objective of the present work was to develop a metered dose transdermal spray (MDTS formulation for transdermal delivery of dexketoprofen (DE. DE release from a series of formulations was assessed in vitro. Various qualitative and quantitative parameters like spray pattern, pump seal efficiency test, average weight per metered dose, and dose uniformity were evaluated. The optimized formulation with good skin permeation and an appropriate drug concentration and permeation enhancer (PE content was developed incorporating 7% (w/w, % DE, 7% (v/v, % isopropyl myristate (IPM, and 93% (v/v, % ethanol. In vivo pharmacokinetic study indicated that the optimized formulation showed a more sustainable plasma-concentration profile compared with the Fenli group. The antiinflammatory effect of DE MDTS was evaluated by experiments involving egg-albumin-induced paw edema in rats and xylene-induced ear swelling in mice. Acetic acid-induced abdominal constriction was used to evaluate the anti-nociceptive actions of DE MDTS. Pharmacodynamic studies indicated that the DE MDTS has good anti-inflammatory and anti-nociceptive activities. Besides, skin irritation studies were performed using rat as an animal model. The results obtained show that the MDTS can be a promising and innovative therapeutic system used in transdermal drug delivery for DE.

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

    Science.gov (United States)

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

    2010-07-01

    Controlled-release delivery of 6-beta-naltrexol (NTXOL), the major active metabolite of naltrexone, via a transdermal patch is desirable for treatment of alcoholism. Unfortunately, NTXOL does not diffuse across skin at a therapeutic rate. Therefore, the focus of this study was to evaluate microneedle (MN) skin permeation enhancement of NTXOL's hydrochloride salt in hairless guinea pigs. Specifically, these studies were designed to determine the lifetime of MN-created aqueous pore pathways. MN pore lifetime was estimated by pharmacokinetic evaluation, transepidermal water loss (TEWL) and visualization of MN-treated skin pore diameters using light microscopy. A 3.6-fold enhancement in steady-state plasma concentration was observed in vivo with MN treated skin with NTXOL.HCl, as compared to NTXOL base. TEWL measurements and microscopic evaluation of stained MN-treated guinea pig skin indicated the presence of pores, suggesting a feasible nonlipid bilayer pathway for enhanced transdermal delivery. Overall, MN-assisted transdermal delivery appears viable for at least 48 h after MN-application. (c) 2010 Wiley-Liss, Inc. and the American Pharmacists Association

  5. Human immunodeficiency virus type 1 KK26-27 matrix mutants display impaired infectivity, circularization and integration but not nuclear import

    International Nuclear Information System (INIS)

    Mannioui, Abdelkrim; Nelson, Elisabeth; Schiffer, Cecile

    2005-01-01

    We analyzed the role of human immunodeficiency virus (HIV)-1 matrix protein (MA) during the virus replication afferent phase. Single-round infection of H9 T lymphocytes showed that the combined mutation of MA Lys residues 26-27 in MA reported nuclear localization signal (NLS)-1 [Haffar, O.K., Popov, S., Dubrovsky, L., Agostini, I., Tang, H., Pushkarsky, T., Nadler, S.G., Bukrinsky, M., 2000. Two nuclear localization signals in the HIV-1 matrix protein regulate nuclear import of the HIV-1 pre-integration complex. J. Mol. Biol. 299 (2): 359-368] impaired infectivity, abrogated 2-LTR-circle formation and significantly reduced integration. However, the mutation did not affect viral DNA docking to chromatin in either interphasic or mitotic cells, indicating that MA N-terminal basic domain should not represent a major determinant of HIV-1 nuclear import in T lymphocytes. These data point to a previously unreported role of MA in the late, post-chromatin-binding, afferent phase of HIV-1 replication cycle

  6. Development of a Java Package for Matrix Programming

    OpenAIRE

    Lim, Ngee-Peng; Ling, Maurice HT; Lim, Shawn YC; Choi, Ji-Hee; Teo, Henry BK

    2003-01-01

    We had assembled a Java package, known as MatrixPak, of four classes for the purpose of numerical matrix computation. The classes are matrix, matrix_operations, StrToMatrix, and MatrixToStr; all of which are inherited from java.lang.Object class. Class matrix defines a matrix as a two-dimensional array of float types, and contains the following mathematical methods: transpose, adjoint, determinant, inverse, minor and cofactor. Class matrix_operations contains the following mathematical method...

  7. Ultradeformable Liposomes: a Novel Vesicular Carrier For Enhanced Transdermal Delivery of Procyanidins: Effect of Surfactants on the Formation, Stability, and Transdermal Delivery.

    Science.gov (United States)

    Chen, Rencai; Li, Rongli; Liu, Qian; Bai, Chao; Qin, Benlin; Ma, Yue; Han, Jing

    2017-07-01

    The aims of this work were to develop a novel vesicular carrier, procyanidins, ultradeformable liposomes (PUDLs), to expand the applications for procyanidins, and increase their stability and transdermal delivery. In this study, we prepared procyanidins ultradeformable liposomes using thin film hydration method and evaluated their encapsulation efficiency, vesicle deformability, storage stability, and skin permeation in vitro. The influence of different surfactants on the properties of PUDLs was also investigated. The results obtained showed that the PUDLs containing Tween 80 had a high entrapment efficiency (80.27 ± 0.99%), a small particle size (140.6 ± 19 nm), high elasticity, and prolonged drug release. Compared with procyanidins solution, the stability of procyanidins in PUDLs improved significantly when stored at 4, 25, and 30°C. The penetration rate of PUDLs was 6.25-fold greater than that of procyanidins solution. Finally, the results of our study suggested that PUDLs could increase the transdermal flux, prolong the release and improve the stability of procyanidins, and could serve as an effective dermal delivery system for procyanidins.

  8. Conductive polymer nanotube patch for fast and controlled in vivo transdermal drug delivery

    Science.gov (United States)

    Nguyen, Thao M.

    Transdermal drug delivery has created new applications for existing therapies and offered an alternative to the traditional oral route where drugs can prematurely metabolize in the liver causing adverse side effects. Opening the transdermal delivery route to large hydrophilic drugs is one of the greatest challenges due to the hydrophobicity of the skin. However, the ability to deliver hydrophilic drugs using a transdermal patch would provide a solution to problems of other delivery methods for hydrophilic drugs. The switching of conductive polymers (CP) between redox states cause simultaneous changes in the polymer charge, conductivity, and volume—properties that can all be exploited in the biomedical field of controlled drug delivery. Using the template synthesis method, poly(3,4-ethylenedioxythiophene (PEDOT) nanotubes were synthesized electrochemically and a transdermal drug delivery patch was successfully designed and developed. In vitro and in vivo uptake and release of hydrophilic drugs were investigated. The relationship between the strength of the applied potential and rate of drug release were also investigated. Results revealed that the strength of the applied potential is proportional to the rate of drug release; therefore one can control the rate of drug release by controlling the applied potential. The in vitro studies focused on the kinetics of the drug delivery system. It was determined that the drug released mainly followed zero-order kinetics. In addition, it was determined that applying a releasing potential to the transdermal drug delivery system lead to a higher release rate constant (up to 7 times greater) over an extended period of time (˜24h). In addition, over 24 hours, an average of 80% more model drug molecules were released with an applied potential than without. The in vivo study showed that the drug delivery system was capable of delivering model hydrophilic drugs molecules through the dermis layer of the skin within 30 minutes

  9. Pharmacodynamics of transdermal granisetron in women with nausea and vomiting of pregnancy.

    Science.gov (United States)

    Caritis, Steve; Zhao, Yang; Chen, Hui-Jun; Venkataramanan, Raman

    2016-07-01

    Limited options exist for women with nausea and vomiting of pregnancy (NVP) who cannot tolerate oral intake. Transdermal delivery of granisetron, a 5-hydroxytryptamine-3 receptor antagonist, provides an effective alternative for such patients. The objective of this study was to evaluate the pharmacodynamics of granisetron administered intravenously (IV) and as a sustained release transdermal patch in women with NVP. We recruited 16 women with singleton gestation between 12 0/7-18 6/7 weeks who were receiving treatment for NVP and had a Pregnancy Unique Quantification of Emesis and Nausea (PUQE) score of ≥6. All consenting subjects received 1 mg of granisetron as an IV infusion over 5 minutes and blood was obtained prior to the infusion and at 10, 20, 30, and 60 minutes and at 2, 4, 6, 8, 12, and 24 hours after the start of the infusion. After a minimum washout of 48 hours after initiation of IV granisetron, a 52-cm(2) granisetron patch (34.3 mg) was placed on the upper arm of all subjects for 7 days. Blood was drawn prior to patch placement and daily thereafter for 9 days. The subjects were evaluated daily. The PUQE score was obtained from these subjects prior to the IV infusion and daily for 2 days after and again prior to and daily for 9 days after patch placement. Complete data were available in 15 women after IV administration and 13 women after patch placement. One woman stopped participation during the IV infusion while data were not available in 2 additional women after patch placement due to noncompliance. Peak plasma granisetron concentrations after IV and transdermal administration were similar (∼10 ng/mL). Prior to IV administration of granisetron, the PUQE score was 8.6 ± 1.8 (mean ± SD). The PUQE scores were significantly reduced for the ensuing 2 days (P Granisetron significantly improved symptoms of nausea and vomiting as gauged by the PUQE score. After IV infusion the reduction in PUQE score was observed within 1 day. When granisetron was

  10. Experimental design and optimization of raloxifene hydrochloride loaded nanotransfersomes for transdermal application

    Directory of Open Access Journals (Sweden)

    Mahmood S

    2014-09-01

    Full Text Available Syed Mahmood, Muhammad Taher, Uttam Kumar Mandal Department of Pharmaceutical Technology, Kulliyyah of Pharmacy, International Islamic University Malaysia (IIUM, Pahang Darul Makmur, Malaysia Abstract: Raloxifene hydrochloride, a highly effective drug for the treatment of invasive breast cancer and osteoporosis in post-menopausal women, shows poor oral bioavailability of 2%. The aim of this study was to develop, statistically optimize, and characterize raloxifene hydrochloride-loaded transfersomes for transdermal delivery, in order to overcome the poor bioavailability issue with the drug. A response surface methodology experimental design was applied for the optimization of transfersomes, using Box-Behnken experimental design. Phospholipon® 90G, sodium deoxycholate, and sonication time, each at three levels, were selected as independent variables, while entrapment efficiency, vesicle size, and transdermal flux were identified as dependent variables. The formulation was characterized by surface morphology and shape, particle size, and zeta potential. Ex vivo transdermal flux was determined using a Hanson diffusion cell assembly, with rat skin as a barrier medium. Transfersomes from the optimized formulation were found to have spherical, unilamellar structures, with a ­homogeneous distribution and low polydispersity index (0.08. They had a particle size of 134±9 nM, with an entrapment efficiency of 91.00%±4.90%, and transdermal flux of 6.5±1.1 µg/cm2/hour. Raloxifene hydrochloride-loaded transfersomes proved significantly superior in terms of amount of drug permeated and deposited in the skin, with enhancement ratios of 6.25±1.50 and 9.25±2.40, respectively, when compared with drug-loaded conventional liposomes, and an ethanolic phosphate buffer saline. Differential scanning calorimetry study revealed a greater change in skin structure, compared with a control sample, during the ex vivo drug diffusion study. Further, confocal laser

  11. Use of granisetron transdermal system in the prevention of chemotherapy-induced nausea and vomiting: a review

    Directory of Open Access Journals (Sweden)

    Albert Tuca

    2009-12-01

    Full Text Available Albert TucaPalliative Care Hospital Team, Palliative Care Department, Institut Català d’Oncologia, L’Hospitalet de Llobregat, Barcelona, SpainAbstract: Until now only intravenous and oral formulations of 5HT3 receptor antagonists have been available. Recently a new formulation of a 5HT3 receptor antagonist, transdermal granisetron, has been developed, and approved by the FDA. Three phase I studies to evaluate its pharmacokinetic profile have shown that granisetron administered by a transdermal delivery system is absorbed by passive diffusion and maximal concentration is reached 48 hours after patch application. The patch of 52 cm2, which contains 34.3 mg of granisetron, releases 3.3 mg of the drug every day and maintains a stable average plasma concentration of 2.2 ng/mL over 6 days, similar to levels obtained with 2 mg of oral granisetron, administered every day during the same period of time. Two randomized as yet unpublished clinical trials (phase II/III have been conducted to evaluate the antiemetic efficacy of transdermal granisetron in chemotherapy-induced nausea and vomiting, in patients receiving moderately and highly emetogenic chemotherapy, compared with 2 mg of oral granisetron. More than 800 cancer patients were included in the trials. The rate of complete control of acute emesis was 49% for the phase II trial and 60% for the phase III trial. Neither trial showed a statistically significant difference between transdermal and oral granisetron. The control of delayed emesis was observed in 46% of patients, and there were no statistically significant differences between transdermal and oral granisetron. The most common adverse effects in both trials were constipation (<7% and headache (<1%; there were no statistically significant differences between transdermal and oral granisetron. These data show that transdermal granisetron is effective and safe in controlling acute emesis induced by chemotherapy with both moderate and high

  12. Use of granisetron transdermal system in the prevention of chemotherapy-induced nausea and vomiting: a review

    International Nuclear Information System (INIS)

    Tuca, Albert

    2009-01-01

    Until now only intravenous and oral formulations of 5HT 3 receptor antagonists have been available. Recently a new formulation of a 5HT 3 receptor antagonist, transdermal granisetron, has been developed, and approved by the FDA. Three phase I studies to evaluate its pharmacokinetic profile have shown that granisetron administered by a transdermal delivery system is absorbed by passive diffusion and maximal concentration is reached 48 hours after patch application. The patch of 52 cm 2 , which contains 34.3 mg of granisetron, releases 3.3 mg of the drug every day and maintains a stable average plasma concentration of 2.2 ng/mL over 6 days, similar to levels obtained with 2 mg of oral granisetron, administered every day during the same period of time. Two randomized as yet unpublished clinical trials (phase II/III) have been conducted to evaluate the antiemetic efficacy of transdermal granisetron in chemotherapy-induced nausea and vomiting, in patients receiving moderately and highly emetogenic chemotherapy, compared with 2 mg of oral granisetron. More than 800 cancer patients were included in the trials. The rate of complete control of acute emesis was 49% for the phase II trial and 60% for the phase III trial. Neither trial showed a statistically significant difference between transdermal and oral granisetron. The control of delayed emesis was observed in 46% of patients, and there were no statistically significant differences between transdermal and oral granisetron. The most common adverse effects in both trials were constipation (<7%) and headache (<1%); there were no statistically significant differences between transdermal and oral granisetron. These data show that transdermal granisetron is effective and safe in controlling acute emesis induced by chemotherapy with both moderate and high emetogenic potential. Efficacy and safety of transdermal granisetron are fully comparable with that of oral granisetron. More clinical trials using regimens of 2 or 3 drugs

  13. Three-Dimensional Coculture of Meniscal Cells and Mesenchymal Stem Cells in Collagen Type I Hydrogel on a Small Intestinal Matrix-A Pilot Study Toward Equine Meniscus Tissue Engineering.

    Science.gov (United States)

    Kremer, Antje; Ribitsch, Iris; Reboredo, Jenny; Dürr, Julia; Egerbacher, Monika; Jenner, Florien; Walles, Heike

    2017-05-01

    Meniscal injuries are the most frequently encountered soft tissue injuries in the equine stifle joint. Due to the inherent limited repair potential of meniscal tissue, meniscal injuries do not only affect the meniscus itself but also lead to impaired joint homeostasis and secondary osteoarthritis. The presented study compares 3D coculture constructs of primary equine mesenchymal stem cells (MSC) and meniscus cells (MC) seeded on three different scaffolds-a cell-laden collagen type I hydrogel (Col I gel), a tissue-derived small intestinal matrix scaffold (SIS-muc) and a combination thereof-for their qualification to be applied for meniscus tissue engineering. To investigate cell attachment of primary MC and MSC on SIS-muc matrix SEM pictures were performed. For molecular analysis, lyophilized samples of coculture constructs with different cell ratios (100% MC, 100% MSC, and 50% MC and 50% MSC, 20% MC, and 80% MSC) were digested and analyzed for DNA and GAG content. Active matrix remodeling of 3D coculture models was indicated by matrix metalloproteinases detection. For comparison of tissue-engineered constructs with the histologic architecture of natural equine menisci, paired lateral and medial menisci of 15 horses representing different age groups were examined. A meniscus phenotype with promising similarity to native meniscus tissue in its GAG/DNA expression in addition to Col I, Col II, and Aggrecan production was achieved using a scaffold composed of Col I gel on SIS-muc combined with a coculture of MC and MSC. The results encourage further development of this scaffold-cell combination for meniscus tissue engineering.

  14. Transdermal delivery of angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs) and others for management of hypertension.

    Science.gov (United States)

    Ahad, Abdul; Al-Mohizea, Abdullah Mohammed; Al-Jenoobi, Fahad Ibrahim; Aqil, Mohd

    2016-01-01

    Angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs) are some of the most commonly prescribed medications for hypertension. Most of all conventional dosage forms of ARBs and ACEIs undergo extensive first-pass metabolism, which significantly reduces bioavailability. Majority of ARBs and ACEIs are inherently short acting due to a rapid elimination half-life. In addition, oral dosage forms of ARBs and ACEIs have many high incidences of adverse effects due to variable absorption profiles, higher frequency of administration and poor patient compliance. Many attempts have been made globally at the laboratory level to investigate the skin permeation and to develop transdermal therapeutic systems of various ARBs, ACEIs and other anti-hypertensives, to circumvent the drawbacks associated with their conventional dosage form. This manuscript presents an outline of the transdermal research specifically in the area of ARBs, ACEIs and other anti-hypertensives reported in various pharmaceutical journals. The transdermal delivery has gained a significant importance for systemic treatment as it is able to avoid first-pass metabolism and major fluctuations of plasma levels typical of repeated oral administration. As we can experience from this review article that transdermal delivery of different ARBs and ACEIs improves bioavailability as well as patient compliance by many folds. In fact, the rationale development of some newer ARBs, ACEIs and other anti-hypertensives transdermal systems will provide new ways of treatment, circumventing current limitations for conventional dosage forms.

  15. Fabrication, appraisal, and transdermal permeation of sildenafil citrate-loaded nanostructured lipid carriers versus solid lipid nanoparticles

    Science.gov (United States)

    Elnaggar, Yosra SR; El-Massik, Magda A; Abdallah, Ossama Y

    2011-01-01

    Although sildenafil citrate (SC) is used extensively for erectile dysfunction, oral delivery of SC encounters many obstacles. Furthermore, the physicochemical characteristics of this amphoteric drug are challenging for delivery system formulation and transdermal permeation. This article concerns the assessment of the potential of nanomedicine for improving SC delivery and transdermal permeation. SC-loaded nanostructured lipid carriers (NLCs) and solid lipid nanoparticles (SLNs) were fabricated using a modified high-shear homogenization technique. Nanoparticle optimization steps included particle size analysis, entrapment efficiency (EE) determination, freeze-drying and reconstitution, differential scanning calorimetry, in vitro release, stability study and high-performance liquid chromatography analysis. Transdermal permeation of the nanocarriers compared with SC suspension across human skin was assessed using a modified Franz diffusion cell assembly. Results revealed that SLNs and NLCs could be optimized in the nanometric range (180 and 100 nm, respectively) with excellent EE (96.7% and 97.5%, respectively). Nanoparticles have significantly enhanced in vitro release and transdermal permeation of SC compared with its suspensions. Furthermore, transdermal permeation of SC exhibited higher initial release from both SLN and NLC formulations followed by controlled release, with promising implications for faster onset and longer drug duration. Nanomedicines prepared exhibited excellent physical stability for the study period. Solid nanoparticles optimized in this study successfully improved SC characteristics, paving the way for an efficient topical Viagra® product. PMID:22238508

  16. Advanced progress of microencapsulation technologies: in vivo and in vitro models for studying oral and transdermal drug deliveries.

    Science.gov (United States)

    Lam, P L; Gambari, R

    2014-03-28

    This review provides an overall discussion of microencapsulation systems for both oral and transdermal drug deliveries. Clinically, many drugs, especially proteins and peptides, are susceptible to the gastrointestinal tract and the first-pass metabolism after oral administration while some drugs exhibit low skin permeability through transdermal delivery route. Medicated microcapsules as oral and transdermal drug delivery vehicles are believed to offer an extended drug effect at a relatively low dose and provide a better patient compliance. The polymeric microcapsules can be produced by different microencapsulation methods and the drug microencapsulation technology provides the quality preservation for drug stabilization. The release of the entrapped drug is controlled and prolonged for specific usages. Some recent studies have focused on the evaluation of drug containing microcapsules on potential biological and therapeutic applications. For the oral delivery, in vivo animal models were used for evaluating possible treatment effects of drug containing microcapsules. For the transdermal drug delivery, skin delivery models were introduced to investigate the potential skin delivery of medicated microcapsules. Finally, the challenges and limitations of drug microencapsulation in real life are discussed and the commercially available drug formulations using microencapsulation technology for oral and transdermal applications are shown. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Information matrix estimation procedures for cognitive diagnostic models.

    Science.gov (United States)

    Liu, Yanlou; Xin, Tao; Andersson, Björn; Tian, Wei

    2018-03-06

    Two new methods to estimate the asymptotic covariance matrix for marginal maximum likelihood estimation of cognitive diagnosis models (CDMs), the inverse of the observed information matrix and the sandwich-type estimator, are introduced. Unlike several previous covariance matrix estimators, the new methods take into account both the item and structural parameters. The relationships between the observed information matrix, the empirical cross-product information matrix, the sandwich-type covariance matrix and the two approaches proposed by de la Torre (2009, J. Educ. Behav. Stat., 34, 115) are discussed. Simulation results show that, for a correctly specified CDM and Q-matrix or with a slightly misspecified probability model, the observed information matrix and the sandwich-type covariance matrix exhibit good performance with respect to providing consistent standard errors of item parameter estimates. However, with substantial model misspecification only the sandwich-type covariance matrix exhibits robust performance. © 2018 The British Psychological Society.

  18. Inhibition of microRNA-214-5p promotes cell survival and extracellular matrix formation by targeting collagen type IV alpha 1 in osteoblastic MC3T3-E1 cells.

    Science.gov (United States)

    Li, Q S; Meng, F Y; Zhao, Y H; Jin, C L; Tian, J; Yi, X J

    2017-08-01

    This study aimed to investigate the functional effects of microRNA (miR)-214-5p on osteoblastic cells, which might provide a potential role of miR-214-5p in bone fracture healing. Blood samples were obtained from patients with hand fracture or intra-articular calcaneal fracture and from healthy controls (HCs). Expression of miR-214-5p was monitored by qRT-PCR at day 7, 14 and 21 post-surgery. Mouse osteoblastic MC3T3-E1 cells were transfected with antisense oligonucleotides (ASO)-miR-214-5p, collagen type IV alpha 1 (COL4A1) vector or their controls; thereafter, cell viability, apoptotic rate, and the expression of collagen type I alpha 1 (COL1A1), type II collagen (COL-II), and type X collagen (COL-X) were determined. Luciferase reporter assay, qRT-PCR, and Western blot were performed to ascertain whether COL4A1 was a target of miR-214-5p. Plasma miR-214-5p was highly expressed in patients with bone fracture compared with HCs after fracture (p extracellular matrix (ECM) formation of osteoblastic MC3T3-E1 cells by targeting COL4A1. Cite this article: Q. S. Li, F. Y. Meng, Y. H. Zhao, C. L. Jin, J. Tian, X. J. Yi. Inhibition of microRNA-214-5p promotes cell survival and extracellular matrix formation by targeting collagen type IV alpha 1 in osteoblastic MC3T3-E1 cells. Bone Joint Res 2017;6:464-471. DOI: 10.1302/2046-3758.68.BJR-2016-0208.R2. © 2017 Yi et al.

  19. Use of Fentanyl Iontophoretic Transdermal System (ITS) (IONSYS®) in the Management of Patients with Acute Postoperative Pain: A Case Series.

    Science.gov (United States)

    Poplawski, Steven; Johnson, Matthew; Philips, Philip; Eberhart, Leopold H J; Koch, Tilo; Itri, Loretta M

    2016-12-01

    Fentanyl iontophoretic transdermal system (ITS) [IONSYS ® , The Medicines Company, Parsippany, NJ, USA] is a needle-free, patient-controlled, postoperative opioid pain management treatment. It is indicated for the short-term management of acute postoperative pain in adults requiring opioid analgesia in the hospital. The safety and effectiveness of fentanyl ITS for acute postoperative pain management has been demonstrated in a range of surgery and patient types studied in seven phase 3 trials (three placebo-controlled trials and four active-comparator trials). The majority of the patients in the phase 3 trials had undergone either abdominal/pelvic, orthopedic, or thoracic surgery. Consistent with the prescribing information, physicians in clinical practice may treat patients with this system following any type of surgery including those that may not have been included in the phase 3 trials. The purpose of this case series is to illustrate how fentanyl ITS is being utilized for postoperative pain management in real-world clinical practice following a variety of surgeries and in current pain management protocols that may have evolved since the completion of the phase 3 program. There are seven cases from three clinical centers described within this case series, each using fentanyl ITS according to the prescribing information. The surgery types included are bariatric (N = 3), prostate (N = 2), colorectal (N = 1), and perirectal abscess drainage (N = 1). A systematic review of each patient chart was conducted via a standardized retrospective assessment by the clinicians who managed each patient. Additionally, each healthcare professional was interviewed regarding their overall experience and key learnings using fentanyl ITS. Overall, fentanyl ITS was effective and well tolerated in these case reports in current-day clinical practice settings. These case studies are informative about fentanyl ITS use shortly after product approval and set the stage for

  20. Rapid identification and typing of Yersinia pestis and other Yersinia species by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry.

    Science.gov (United States)

    Ayyadurai, Saravanan; Flaudrops, Christophe; Raoult, Didier; Drancourt, Michel

    2010-11-12

    Accurate identification is necessary to discriminate harmless environmental Yersinia species from the food-borne pathogens Yersinia enterocolitica and Yersinia pseudotuberculosis and from the group A bioterrorism plague agent Yersinia pestis. In order to circumvent the limitations of current phenotypic and PCR-based identification methods, we aimed to assess the usefulness of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) protein profiling for accurate and rapid identification of Yersinia species. As a first step, we built a database of 39 different Yersinia strains representing 12 different Yersinia species, including 13 Y. pestis isolates representative of the Antiqua, Medievalis and Orientalis biotypes. The organisms were deposited on the MALDI-TOF plate after appropriate ethanol-based inactivation, and a protein profile was obtained within 6 minutes for each of the Yersinia species. When compared with a 3,025-profile database, every Yersinia species yielded a unique protein profile and was unambiguously identified. In the second step of analysis, environmental and clinical isolates of Y. pestis (n = 2) and Y. enterocolitica (n = 11) were compared to the database and correctly identified. In particular, Y. pestis was unambiguously identified at the species level, and MALDI-TOF was able to successfully differentiate the three biotypes. These data indicate that MALDI-TOF can be used as a rapid and accurate first-line method for the identification of Yersinia isolates.