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Sample records for vitro release behavior

  1. Fabrication, characterization and in vitro drug release behavior of electrospun PLGA/chitosan nanofibrous scaffold

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    Meng, Z.X.; Zheng, W.; Li, L. [Center for Biomedical Materials and Engineering, Harbin Engineering University, Harbin 150001 (China); Zheng, Y.F., E-mail: yfzheng@pku.edu.cn [Center for Biomedical Materials and Engineering, Harbin Engineering University, Harbin 150001 (China); Department of Advanced Materials and Nanotechnology, College of Engineering, Peking University, Beijing 100871 (China)

    2011-02-15

    Graphical abstract: The fenbufen loaded PLGA/chitosan nanofibrous scaffolds were fabricated by electrospinning. The hydrophilicity of nanofibrous scaffold was enhanced with the increase of chitosan content. The drug release also is accelerated with chitosan increasing because the higher hydrophilicity makes drug diffusing from scaffold more easily. Research highlights: {yields} The average diameter increased with the increase of chitosan content and then decreased. {yields} The release rate of fenbufen increased with the increase of chitosan. {yields} The aligned nanofibrous scaffold exhibits lower drug release rate. {yields} The drug release could be controlled by crosslinking in glutaraldehyde vapor. - Abstract: In this study both aligned and randomly oriented poly(D,L-lactide-co-glycolide) (PLGA)/chitosan nanofibrous scaffold have been prepared by electrospinning. The ratio of PLGA to chitosan was adjusted to get smooth nanofiber surface. Morphological characterization using scanning electron microscopy showed that the aligned nanofiber diameter distribution obtained by electrospinning of polymer blend increased with the increase of chitosan content which was similar to that of randomly oriented nanofibers. The release characteristic of model drug fenbufen (FBF) from the FBF-loaded aligned and randomly oriented PLGA and PLGA/chitosan nanofibrous scaffolds was investigated. The drug release rate increased with the increase of chitosan content because the addition of chitosan enhanced the hydrophilicity of the PLGA/chitosan composite scaffold. Moreover, for the aligned PLGA/chitosan nanofibrous scaffold the release rate was lower than that of randomly oriented PLGA/chitosan nanofibrous scaffold, which indicated that the nanofiber arrangement would influence the release behavior. In addition, crosslinking in glutaraldehyde vapor would decrease the burst release of FBF from FBF-loaded PLGA/chitosan nanofibrous scaffold with a PLGA/chitosan ratio less than 9/1, which

  2. The influence of spray-drying parameters on phase behavior, drug distribution, and in vitro release of injectable microspheres for sustained release.

    Science.gov (United States)

    Meeus, Joke; Lenaerts, Maité; Scurr, David J; Amssoms, Katie; Davies, Martyn C; Roberts, Clive J; Van Den Mooter, Guy

    2015-04-01

    For ternary solid dispersions, it is indispensable to characterize their structure, phase behavior, and the spatial distribution of the dispersed drug as this might influence the release profile and/or stability of these formulations. This study shows how formulation (feed concentration) and process (feed rate, inlet air temperature, and atomizing air pressure) parameters can influence the characteristics of ternary spray-dried solid dispersions. The microspheres considered here consist of a poly(lactic-co-glycolic acid) (PLGA) surface layer and an underlying polyvinylpyrrolidone (PVP) phase. A poorly soluble active pharmaceutical ingredient (API) was molecularly dispersed in this matrix. Differences were observed in component miscibility, phase heterogeneity, particle size, morphology, as well as API surface coverage for selected spray-drying parameters. Observed differences are likely because of changes in the droplet generation, evaporation, and thus particle formation processes. However, varying particle characteristics did not influence the drug release of the formulations studied, indicating the robustness of this approach to produce particles of consistent drug release characteristics. This is likely because of the fact that the release is dominated by diffusion from the PVP layer through pores in the PLGA surface layer and that observed differences in the latter have no influence on the release. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  3. Fabrication and in vitro release behavior of a novel antibacterial coating containing halogenated furanone-loaded poly(L-lactic acid) nanoparticles on microarc-oxidized titanium.

    Science.gov (United States)

    Cheng, Yicheng; Wu, Jiang; Gao, Bo; Zhao, Xianghui; Yao, Junyan; Mei, Shenglin; Zhang, Liang; Ren, Huifang

    2012-01-01

    Dental implants have become increasingly common for the management of missing teeth. However, peri-implant infection remains a problem, is usually difficult to treat, and may lead eventually to dental implant failure. The aim of this study was to fabricate a novel antibacterial coating containing a halogenated furanone compound, ie, (Z-)-4-bromo-5-(bromomethylene)-2(5H)-furanone (BBF)-loaded poly(L-lactic acid) (PLLA) nanoparticles on microarc-oxidized titanium and to evaluate its release behavior in vitro. BBF-loaded PLLA nanoparticles were prepared using the emulsion solvent-evaporation method, and the antibacterial coating was fabricated by cross-linking BBF-loaded PLLA nanoparticles with gelatin on microarc-oxidized titanium. The BBF-loaded PLLA nanoparticles had a small particle size (408 ± 14 nm), a low polydispersity index (0.140 ± 0.008), a high encapsulation efficiency (72.44% ± 1.27%), and a fine spherical shape with a smooth surface. The morphology of the fabricated antibacterial coating showed that the BBF-loaded PLLA nanoparticles were well distributed in the pores of the microarc oxidation coating, and were cross-linked with each other and the wall pores by gelatin. The release study indicated that the antibacterial coating could achieve sustained release of BBF for 60 days, with a slight initial burst release during the first 4 hours. The novel antibacterial coating fabricated in this study is a potentially promising method for prevention of early peri-implant infection.

  4. Polycaprolactone-coated 3D printed tricalcium phosphate scaffolds for bone tissue engineering: in vitro alendronate release behavior and local delivery effect on in vivo osteogenesis.

    Science.gov (United States)

    Tarafder, Solaiman; Bose, Susmita

    2014-07-09

    The aim of this work was to evaluate the effect of in vitro alendronate (AD) release behavior through polycaprolactone (PCL) coating on in vivo bone formation using PCL-coated 3D printed interconnected porous tricalcium phosphate (TCP) scaffolds. Higher AD and Ca(2+) ion release was observed at lower pH (5.0) than that at higher pH (7.4). AD and Ca(2+) release, surface morphology, and phase analysis after release indicated a matrix degradation dominated AD release caused by TCP dissolution. PCL coating showed its effectiveness for controlled and sustained AD release. Six different scaffold compositions, namely, (i) TCP (bare TCP), (ii) TCP + AD (AD-coated TCP), (iii) TCP + PCL (PCL-coated TCP), (iv) TCP + PCL + AD, (v) TCP + AD + PCL, and (vi) TCP + AD + PCL + AD were tested in the distal femoral defect of Sprague-Dawley rats for 6 and 10 weeks. An excellent bone formation inside the micro and macro pores of the scaffolds was observed from histomorphology. Histomorphometric analysis revealed maximum new bone formation in TCP + AD + PCL scaffolds after 6 weeks. No adverse effect of PCL on bioactivity of TCP and in vivo bone formation was observed. All scaffolds with AD showed higher bone formation and reduced TRAP (tartrate resistant acid phosphatase) positive cells activity compared to bare TCP and TCP coated with only PCL. Bare TCP scaffolds showed the highest TRAP positive cells activity followed by TCP + PCL scaffolds, whereas TCP + AD scaffolds showed the lowest TRAP activity. A higher TRAP positive cells activity was observed in TCP + AD + PCL compared to TCP + AD scaffolds after 6 weeks. Our results show that in vivo local AD delivery from PCL-coated 3DP TCP scaffolds could further induce increased early bone formation.

  5. Fabrication and in vitro release behavior of a novel antibacterial coating containing halogenated furanone-loaded poly(L-lactic acid) nanoparticles on microarc-oxidized titanium

    Science.gov (United States)

    Cheng, Yicheng; Wu, Jiang; Gao, Bo; Zhao, Xianghui; Yao, Junyan; Mei, Shenglin; Zhang, Liang; Ren, Huifang

    2012-01-01

    Background Dental implants have become increasingly common for the management of missing teeth. However, peri-implant infection remains a problem, is usually difficult to treat, and may lead eventually to dental implant failure. The aim of this study was to fabricate a novel antibacterial coating containing a halogenated furanone compound, ie, (Z-)-4-bromo-5-(bromomethylene)-2(5H)-furanone (BBF)-loaded poly(L-lactic acid) (PLLA) nanoparticles on microarc-oxidized titanium and to evaluate its release behavior in vitro. Methods BBF-loaded PLLA nanoparticles were prepared using the emulsion solvent-evaporation method, and the antibacterial coating was fabricated by cross-linking BBF-loaded PLLA nanoparticles with gelatin on microarc-oxidized titanium. Results The BBF-loaded PLLA nanoparticles had a small particle size (408 ± 14 nm), a low polydispersity index (0.140 ± 0.008), a high encapsulation efficiency (72.44% ± 1.27%), and a fine spherical shape with a smooth surface. The morphology of the fabricated antibacterial coating showed that the BBF-loaded PLLA nanoparticles were well distributed in the pores of the microarc oxidation coating, and were cross-linked with each other and the wall pores by gelatin. The release study indicated that the antibacterial coating could achieve sustained release of BBF for 60 days, with a slight initial burst release during the first 4 hours. Conclusion The novel antibacterial coating fabricated in this study is a potentially promising method for prevention of early peri-implant infection. PMID:23152682

  6. Research on the biological activity and doxorubicin release behavior in vitro of mesoporous bioactive SiO2-CaO-P2O5 glass nanospheres

    Science.gov (United States)

    Wang, Xiang; Wang, Gen; Zhang, Ying

    2017-10-01

    Mesoporous bioactive glass (MBG) nanospheres have been synthesized by a facile method of sacrificing template using cetyl trimethyl ammonium bromide (CTAB) as surfactant. The prepared MBG nanospheres possess high specific surface area (632 m2 g-1) as well as uniform size (∼100 nm). In addition, MBG nanospheres exhibited a quick in vitro bioactive response in simulated body fluids (SBF) and excellent bioactivity of inducing hydroxyapatite (HA) forming on the surface of MBG nanospheres. Furthermore, MBG nanospheres can sustain release of doxorubicin (DOX) with a higher encapsulation efficiency (63.6%) and show distinct degradation in PBS by releasing Si and Ca ions. The encapsulation efficiency and DOX release of MBG nanospheres could be controlled by mesoporous structure and local pH environment. The greater surface area and pore volumes of prepared MBG nanospheres are conducive to bioactive response and drug release in vitro. The amino groups in DOX can be easily protonated at acidic medium to become positively charged NH+3, which allow these drug molecules to be desorbed from the surface of MBG nanospheres via electrostatic effect. Therefore, the synthesized MBG nanospheres have a pH-sensitive drug release capability. In addition, the cytotoxicity of MBG nanospheres was assessed using a cell counting kit-8 (CCK-8), and results showed that the synthesized MBG nanospheres had no significant cytotoxicity to MC3T3 cells. These all indicated that as-prepared MBG nanospheres are promising candidates for bone tissue engineering.

  7. Regulating drug release behavior and kinetics from matrix tablets based on fine particle-sized ethyl cellulose ether derivatives: an in vitro and in vivo evaluation.

    Science.gov (United States)

    Shah, Kifayat Ullah; Khan, Gul Majid

    2012-01-01

    The design and fabrication of sustained/controlled release dosage forms, employing new excipients capable of extending/controlling the release of drugs from the dosage forms over prolonged periods, has worked well in achieving optimally enhanced therapeutic levels of the drugs. In this sense, the objective of this study was to investigate the suitability of selected cellulose ether derivatives for use in direct compression (DC) and as efficient drug release controlling agents. Controlled release matrix tablets of ciprofloxacin were prepared at different drug-to-polymer (D : P) ratios by direct compression using a fine particle sized ethylcellulose ether derivative (ETHOCEL Standard Premium 7FP) as rate controlling polymer. The tablets obtained were evaluated for various physico-chemical characteristics and in-vitro drug release studies were conducted in phosphate buffer (pH 7.4) using PharmaTest dissolution apparatus at constant temperature of 37 °C ± 0.1. Similarity factor f(2) was employed to the release profiles of test formulations and were compared with marketed ciprofloxacin conventional tablets. Drug release mechanism and the kinetics involved were investigated by fitting the release profile data to various kinetic models. It was found that with increasing the proportion of ethylcellulose ether derivative in the matrix, the drug release was significantly extended up to 24 hours. The tablets exhibited zero order or nearly zero order drug transport mechanism. In vivo drug release performance of the developed controlled release tablets and reference conventional tablets containing ciprofloxacin were determined in rabbit serum according to randomized two-way crossover study design using High Performance Liquid Chromatography. Several bioavailability parameters of both the test tablets and conventional tablets including C(max⁡), T(max⁡) and AUC(0-t) were compared which showed an optimized C(max⁡) and T(max⁡) (P < 0.05). A good correlation was obtained

  8. Regulating Drug Release Behavior and Kinetics from Matrix Tablets Based on Fine Particle-Sized Ethyl Cellulose Ether Derivatives: An In Vitro and In Vivo Evaluation

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    Kifayat Ullah Shah

    2012-01-01

    Full Text Available The design and fabrication of sustained/controlled release dosage forms, employing new excipients capable of extending/controlling the release of drugs from the dosage forms over prolonged periods, has worked well in achieving optimally enhanced therapeutic levels of the drugs. In this sense, the objective of this study was to investigate the suitability of selected cellulose ether derivatives for use in direct compression (DC and as efficient drug release controlling agents. Controlled release matrix tablets of ciprofloxacin were prepared at different drug-to-polymer (D : P ratios by direct compression using a fine particle sized ethylcellulose ether derivative (ETHOCEL Standard Premium 7FP as rate controlling polymer. The tablets obtained were evaluated for various physico-chemical characteristics and in-vitro drug release studies were conducted in phosphate buffer (pH 7.4 using PharmaTest dissolution apparatus at constant temperature of 37∘C±0.1. Similarity factor 2 was employed to the release profiles of test formulations and were compared with marketed ciprofloxacin conventional tablets. Drug release mechanism and the kinetics involved were investigated by fitting the release profile data to various kinetic models. It was found that with increasing the proportion of ethylcellulose ether derivative in the matrix, the drug release was significantly extended up to 24 hours. The tablets exhibited zero order or nearly zero order drug transport mechanism. In vivo drug release performance of the developed controlled release tablets and reference conventional tablets containing ciprofloxacin were determined in rabbit serum according to randomized two-way crossover study design using High Performance Liquid Chromatography. Several bioavailability parameters of both the test tablets and conventional tablets including max, max and AUC0- were compared which showed an optimized max and max (<0.05. A good correlation was obtained between in vitro

  9. Protein release from hippocampus in vitro.

    Science.gov (United States)

    Hesse, G W; Hofstein, R; Shashoua, V E

    1984-07-02

    Physiologically viable slices of rat hippocampus in vitro continuously release protein into the superfusion medium at a rate of about 2 micrograms/mg tissue/h. Assays of a cytoplasmic marker enzyme (lactate dehydrogenase) indicate that this material is not the result of cell lysis. Pulse-chase experiments using [3H]valine indicate that a substantial fraction of the newly synthesized proteins eventually appear in the incubation medium (18.7% +/- 3% of the total TCA precipitable radioactivity during a 6-h superfusion) and that the releasable protein pool has an apparent half-life of about 4 h. Simultaneous labeling of newly synthetized proteins with [3H]fucose and [14C]valine showed a 3-fold higher ratio of [3H]fucose to [14C]valine in the released protein fraction compared to the soluble cytoplasmic protein and to the crude membrane protein fraction, suggesting that the soluble released proteins are more highly glycosylated than the proteins retained in the tissue. Electrophoretic migration patterns on SDS-polyacrylamide gels with both labeled and unlabeled proteins show differences between the released proteins and the soluble cytoplasmic proteins of the tissue. Several molecular weights between 14 kdalton and 86 kdalton appear to be characteristic of the released protein fraction. These results suggest that a distinct group of proteins and glycoproteins exists in hippocampal tissue which is destined to be selectively released into the extracellular space.

  10. In vitro stress effect on degradation and drug release behaviors of basic fibroblast growth factor--poly(lactic-co-glycolic-acid) microsphere.

    Science.gov (United States)

    Xiong, Yan; Yu, Zeping; Lang, Yun; Hu, Juanyu; Li, Hong; Yan, Yonggang; Tu, Chongqi; Yang, Tianfu; Song, Yueming; Duan, Hong; Pei, Fuxing

    2016-01-01

    To study the degradation and basic fibroblast growth factor (bFGF) release activity of bFGF - poly(lactic-co-glycolic-acid) microsphere (bFGF-PLGA MS) under stress in vitro, including the static pressure and shearing force-simulating mechanical environment of the joint cavity. First, bFGF-PLGA MSs were created. Meanwhile, two self-made experimental instruments (static pressure and shearing force loading instruments) were initially explored to provide stress-simulating mechanical environment of the joint cavity. Then, bFGF-PLGA MSs were loaded into the two instruments respectively, to study microsphere degradation and drug release experiments. In the static pressure loading experiment, normal atmospheric pressure loading (approximately 0.1 MPa), 0.35 MPa, and 4.0 MPa pressure loading and shaking flask oscillation groups were designed to study bFGF-PLGA MS degradation and bFGF release. In the shearing force loading experiment, a pulsating pump was used to give the experimental group an output of 1,000 mL/min and the control group an output of 10 mL/min to carry out bFGF-PLGA MS degradation and drug release experiments. Changes of bFGF-PLGA MSs, including microsphere morphology, quality, weight-average molecular weight of polymer, and microsphere degradation and bFGF release, were analyzed respectively. In the static pressure loading experiment, bFGF-PLGA MSs at different pressure were stable initially. The trend of molecular weight change, quality loss, and bFGF release was consistent. Meanwhile, microsphere degradation and bFGF release rates in the 4.0 MPa pressure loading group were faster than those in the normal and 0.35 MPa pressure loading groups. It was the fastest in the shaking flask group, showing a statistically significant difference (P<0.0001). In the shearing force loading experiment, there were no distinctive differences in the rates of microsphere degradation and bFGF release between experimental and control group. Meanwhile, microsphere degradation

  11. Corrosion and ion release behavior of Cu/Ti film prepared via physical vapor deposition in vitro as potential biomaterials for cardiovascular devices

    Energy Technology Data Exchange (ETDEWEB)

    Liu Hengquan [Center of Research and Development, Lifetech Scientific (Shenzhen) Co., Ltd., Shenzhen 518057 (China); Department of Materials Science and Engineering, Shenzhen Graduate School, Harbin Institute of Technology, Shenzhen 518055 (China); Zhang Deyuan, E-mail: zhangdeyuan@lifetechmed.com [Center of Research and Development, Lifetech Scientific (Shenzhen) Co., Ltd., Shenzhen 518057 (China); Shen Feng [Center of Research and Development, Lifetech Scientific (Shenzhen) Co., Ltd., Shenzhen 518057 (China); Department of Materials Science and Engineering, Shenzhen Graduate School, Harbin Institute of Technology, Shenzhen 518055 (China); Zhang Gui [Center of Research and Development, Lifetech Scientific (Shenzhen) Co., Ltd., Shenzhen 518057 (China); Song Shenhua [Department of Materials Science and Engineering, Shenzhen Graduate School, Harbin Institute of Technology, Shenzhen 518055 (China)

    2012-07-15

    Cu/Ti films of various Cu/Ti ratios were prepared on a TiNi alloy via vacuum arc plasma deposition. The phase composition, structure, and concentration of elements were investigated via X-ray diffraction and X-photoelectron energy spectrum. The hemolysis ratio and platelet adhesion of the different films were characterized to evaluate blood compatibility. The corrosion and ion release behavior were investigated via a typical immersion test and electrochemical method. The growth of endothelial cells (ECs) was investigated, and methylthiazolyte-trazolium method was employed to evaluate the effect of Cu{sup 2+}. The sophisticated films showed good compatibility. However, with increasing quality ratio of Cu/Ti, the hemolysis ratio increased, and some platelets started to break slightly. The Cu{sup 2+} release was gradually stabilized. The open circuit potential of the Cu/Ti film-modified samples was lower than that of the TiNi substrate. The polarization test result indicates that the passivation stability performance of Cu/Ti film samples is less than the TiNi substrate, and is favorable to Cu{sup 2+} release. The adhesion and proliferation of ECs would be inhibited with 10 wt.% Cu concentration of the film, and ECs would undergo apoptosis at >50 wt.% concentration. A Cu/Ti film with good compatibility and anti-endothelialization has potential applications for special cardiovascular devices.

  12. In vitro drug release behavior from a novel thermosensitive composite hydrogel based on Pluronic f127 and poly(ethylene glycol-poly(ε-caprolactone-poly(ethylene glycol copolymer

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    Yang Jing

    2009-02-01

    Full Text Available Abstract Background Most conventional methods for delivering chemotherapeutic agents fail to achieve therapeutic concentrations of drugs, despite reaching toxic systemic levels. Novel controlled drug delivery systems are designed to deliver drugs at predetermined rates for predefined periods at the target organ and overcome the shortcomings of conventional drug formulations therefore could diminish the side effects and improve the life quality of the patients. Thus, a suitable controlled drug delivery system is extremely important for chemotherapy. Results A novel biodegradable thermosensitive composite hydrogel, based on poly(ethylene glycol-poly(ε-caprolactone-poly(ethylene glycol (PEG-PCL-PEG, PECE and Pluronic F127 copolymer, was successfully prepared in this work, which underwent thermosensitive sol-gel-sol transition. And it was flowing sol at ambient temperature but became non-flowing gel at body temperature. By varying the composition, sol-gel-sol transition and in vitro drug release behavior of the composite hydrogel could be adjusted. Cytotoxicity of the composite hydrogel was conducted by cell viability assay using human HEK293 cells. The 293 cell viability of composite hydrogel copolymers were yet higher than 71.4%, even when the input copolymers were 500 μg per well. Vitamin B12 (VB12, honokiol (HK, and bovine serum albumin (BSA were used as model drugs to investigate the in vitro release behavior of hydrophilic small molecular drug, hydrophobic small molecular drug, and protein drug from the composite hydrogel respectively. All the above-mentioned drugs in this work could be released slowly from composite hydrogel in an extended period. Chemical composition of composite hydrogel, initial drug loading, and hydrogel concentration substantially affected the drug release behavior. The higher Pluronic F127 content, lower initial drug loading amount, or lower hydrogel concentration resulted in higher cumulative release rate. Conclusion

  13. In-vitro Release Study of Carvedilol Phosphate Matrix Tablets ...

    African Journals Online (AJOL)

    The tablets were compressed using a compression force and compression time of 5 tons and 20 s, respectively. Prior to compression, the die and punch surfaces were sufficiently lubricated with magnesium stearate. In vitro release studies. In vitro drug release studies of the matrix tablets were carried out using a six-station.

  14. In Vitro Inhibition of Histamine Release Behavior of Cetirizine Intercalated into Zn/Al- and Mg/Al-Layered Double Hydroxides

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    Muhammad Nazrul Hakim

    2012-05-01

    Full Text Available The intercalation of cetirizine into two types of layered double hydroxides, Zn/Al and Mg/Al, has been investigated by the ion exchange method to form CTZAN and CTMAN nanocomposites, respectively. The basal spacing of the nanocomposites were expanded to 31.9 Å for CTZAN and 31.2 Å for CTMAN, suggesting that cetirizine anion was intercalated into Layered double hydroxides (LDHs and arranged in a tilted bilayer fashion. A Fourier transform infrared spectroscopy (FTIR study supported the formation of both the nanocomposites, and the intercalated cetirizine is thermally more stable than its counterpart in free state. The loading of cetirizine in the nanocomposite was estimated to be about 57.2% for CTZAN and 60.7% CTMAN. The cetirizine release from the nanocomposites show sustained release manner and the release rate of cetirizine from CTZAN and CTMAN nanocomposites at pH 7.4 is remarkably lower than that at pH 4.8, presumably due to the different release mechanism. The inhibition of histamine release from RBL2H3 cells by the free cetirizine is higher than the intercalated cetirizine both in CTZAN and CTMAN nanocomposites. The viability in human Chang liver cells at 1000 μg/mL for CTZAN and CTMAN nanocomposites are 74.5 and 91.9%, respectively.

  15. In Vitro Study of Release of Metronidazole Tablets Prepared from ...

    African Journals Online (AJOL)

    The aim of this study is to evaluate the ability of okra gum to release it\\'s medicament in bioadhesive polymer-based drug delivery system. Bioadhesive studies using the tensiometer were done to evaluate its bioadhesivenes. Conventional tablets were made with okra gum as binder and in-vitro release studies carried out ...

  16. Studies on renin release in vitro

    DEFF Research Database (Denmark)

    Skøtt, O

    1989-01-01

    1) Measurements of renin secretion from single arterioles at time intervals down to 20 seconds showed that the renin secretion is episodic, the amount of renin released during each episode corresponding to the estimated content of one secretory granule. 2) A decrease in osmolality elicits episodi...

  17. vitro Release of Saraca indica Caesalpiniaceae Bark Powder Tablets

    African Journals Online (AJOL)

    In-vitro dissolution study showed that more than a 90% of tannin was released within 30 and. 60 min from tablets prepared by wet ... Keywords: Saraca indica, Flowability, Powder, Tablets, Compressibility, Dissolution. Received: 16 September 2011 ... Talc and magnesium stearate (1. %w/w) were added and mixed for 4 min ...

  18. In vitro and in vivo metal ion release.

    Science.gov (United States)

    Brown, S A; Farnsworth, L J; Merritt, K; Crowe, T D

    1988-04-01

    A series of experiments was conducted to study in vitro and in vivo metal ion release and the urine excretion of metal ions. Metal salts were injected and urine analyzed. Anodic potentials were applied to stainless steel and cobalt-chromium-molybdenum (CCM) specimens to cause an acceleration of corrosion rates. Corrosion experiments were done in saline, 10% serum and in a subcutaneous space in hamsters. Corrosion rates were determined by measurements of weight loss and calculations of net charge transfer. Metal ion concentrations were determined with graphite furnace atomic absorption spectroscopy, and were calculated from total charge using Faraday's law. The results with stainless steel showed that the weight loss and metal ion release from stainless steel in vitro and in vivo can be calculated using Faraday's Law, assuming release in proportion to alloy composition. The results with CCM indicated that release rates in vitro can be used to determine the proportionality of release in vivo. All the nickel and most of the cobalt was rapidly excreted, while less than 50% of the chromium was excreted. The excretion of metals following salt injection or in vivo corrosion were very similar.

  19. Polymeric nanoparticles containing diazepam: preparation, optimization, characterization, in-vitro drug release and release kinetic study

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    Bohrey, Sarvesh; Chourasiya, Vibha; Pandey, Archna

    2016-03-01

    Nanoparticles formulated from biodegradable polymers like poly(lactic-co-glycolic acid) (PLGA) are being extensively investigated as drug delivery systems due to their two important properties such as biocompatibility and controlled drug release characteristics. The aim of this work to formulated diazepam loaded PLGA nanoparticles by using emulsion solvent evaporation technique. Polyvinyl alcohol (PVA) is used as stabilizing agent. Diazepam is a benzodiazepine derivative drug, and widely used as an anticonvulsant in the treatment of various types of epilepsy, insomnia and anxiety. This work investigates the effects of some preparation variables on the size and shape of nanoparticles prepared by emulsion solvent evaporation method. These nanoparticles were characterized by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM). Zeta potential study was also performed to understand the surface charge of nanoparticles. The drug release from drug loaded nanoparticles was studied by dialysis bag method and the in vitro drug release data was also studied by various kinetic models. The results show that sonication time, polymer content, surfactant concentration, ratio of organic to aqueous phase volume, and the amount of drug have an important effect on the size of nanoparticles. Hopefully we produced spherical shape Diazepam loaded PLGA nanoparticles with a size range under 250 nm with zeta potential -23.3 mV. The in vitro drug release analysis shows sustained release of drug from nanoparticles and follow Korsmeyer-Peppas model.

  20. Design, in vitro release characterization and pharmacokinetics of novel controlled release pellets containing levodropropizine.

    Science.gov (United States)

    Cao, Qing-Ri; Piao, Yong-Nan; Choi, Jae-Seung; Liu, Yan; Yang, Mingshi; Cui, Jing-Hao

    2014-05-01

    This study was performed to investigate the in vitro release characteristics of levodropropizine (LDP) from novel dual-coated sustained release (SR) pellets, and evaluate the pharmacokinetics of a novel controlled release (CR) preparation composed of the dual-coated SR pellets and immediate release (IR) LDP pellets. The dual-coated SR pellets composed of a drug-loaded nonpareil core, a sub-coating layer (HPMC 6cps) and an SR-coating layer (Aquacoat® ECD, Eudragit® RS 30D or Kollicoat® SR 30D) were prepared by a bottom-spray fluidized bed-coating method. The drug release from the dual-coated SR pellets coated with Aquacoat® ECD followed a zero-order profile in water, and the drug release was not affected by the coating level of the sub-coating layer and stable under the accelerated storage condition (40 °C, 75% RH) for 6 months. The CR preparation showed significantly decreased values of maximum drug concentration (Cmax) and elimination rate (K) than the reference product (LEVOTUS® SYR) but the similar bioavailability (F = 95.43%). The novel CR preparation presents promising delivery of LDP with an immediate and sustained release manner, with similar clinical effect as the commercial IR product.

  1. VEGF-releasing suture material for enhancement of vascularization: development, in vitro and in vivo study.

    Science.gov (United States)

    Bigalke, Christian; Luderer, Frank; Wulf, Katharina; Storm, Thilo; Löbler, Marian; Arbeiter, Daniela; Rau, Bettina M; Nizze, Horst; Vollmar, Brigitte; Schmitz, Klaus-Peter; Klar, Ernst; Sternberg, Katrin

    2014-12-01

    As it has been demonstrated that bioactive substances can be delivered locally using coated surgical suture materials, the authors developed a vascular endothelial growth factor (VEGF)-releasing suture material that should promote vascularization and potentially wound healing. In this context, the study focused on the characterization of the developed suture material and the verification of its biological activity, as well as establishing a coating process that allows reproducible and stable coating of a commercially available polydioxanone suture material with poly(l-lactide) (PLLA) and 0.1μg and 1.0μg VEGF. The in vitro VEGF release kinetics was studied using a Sandwich ELISA. The biological activity of the released VEGF was investigated in vitro using human umbilical vein endothelial cells. The potential of the VEGF-releasing suture material was also studied in vivo 5days after implantation in the hind limb of Wistar rats, when the histological findings were analyzed. The essential results, enhanced cell viability in vitro as well as significantly increased vascularization in vivo, were achieved using PLLA/1.0μg VEGF-coated suture material. Furthermore, ELISA measurements revealed a high reproducibility of the VEGF release behavior. Based on the results achieved regarding the dose-effect relationship of VEGF, the stability during its processing and the release behavior, it can be predicted that a bioactive suture material would be successful in later in vivo studies. Therefore, this knowledge could be the basis for future studies, where bioactive substances with different modes of action are combined for targeted, overall enhancement of wound healing. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  2. Preparation of Alprazolam Extended- Release Tablets and In vitro Characterization

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    Mohammad Reza Avadi

    2017-06-01

    Full Text Available The main aim of this study was to prepare and evaluate the extended - release system of an anxiolytic substance. Alprazolam is a short-acting benzodiazepine with general properties similar to those of diazepam. Our studies focused on the development of extended drug delivery system based on Hydroxy Propyl Methyl Cellulose (HPMC 4000cps as retard agent and polyvinylpyrrolidone (PVP k30 as binder using factorial design. All formulations were prepared according to wet granulation method and were compressed after lubrication using 7.0 mm dip concave punch with tablet weight of 100 mg. The humidity of granules was selected below 3 percent for obtaining to suitable flowability and compression process. Physical tests such as weight variation, friability, hardness, and thickness tests were carried out.The variables were studied based on 22 factorial design procedure. All prepared matrix tablets were evaluated for physicochemical evaluation and drug content. In vitro release study of matrix tablets for all formulations has shown that HPMC was the main component in retardation of alprazolam in the dissolution medium. The optimum formulation (30% HPMC 4000 and 10% PVP with suitable release profile according to criteria of United State Pharmacopoeia was selected for stability studies, according to ICH guidelines. For stability tests, the content of drugs did not show any change after 3 months during accelerated stability test. The release profile of this formulation was found acceptable as recommended by USP. The release studies have shown that swelling, swelling/erosion, and disentanglement/dissolution were the most important mechanisms that could affect the release profile.

  3. In vitro release properties of encapsulated blueberry (Vaccinium ashei) extracts.

    Science.gov (United States)

    Flores, Floirendo P; Singh, Rakesh K; Kerr, William L; Phillips, Dennis R; Kong, Fanbin

    2015-02-01

    We aimed to determine the effect of encapsulation on the release properties of blueberry extracts during simulated gastrointestinal digestion. An ethanolic pomace extract was microencapsulated with whey protein isolate via spray drying. The in vitro release of monomeric anthocyanins, phenolics and ferric reducing antioxidant activity of the microcapsules (W) were evaluated for the microcapsules and two non-encapsulated systems: ethanolic pomace extract (P) and freeze-dried juice (F). Concentrations of anthocyanin and phenolics were normalised prior to digestion. Results showed that antioxidant activity was in the order of: F>W>P. Regardless of encapsulation, more phenolics were released from W and P than F. Anthocyanin concentration decreased after intestinal digestion for W, but remained constant for P and F. MALDI-MS showed similar spectra for P and F but not for W. The spray-dried product has comparable release characteristics to freeze-dried juice, and may be investigated for food applications. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Formulation and in vitro, in vivo evaluation of effervescent floating sustained-release imatinib mesylate tablet.

    Directory of Open Access Journals (Sweden)

    Ali Kadivar

    Full Text Available Imatinib mesylate is an antineoplastic agent which has high absorption in the upper part of the gastrointestinal tract (GIT. Conventional imatinib mesylate (Gleevec tablets produce rapid and relatively high peak blood levels and requires frequent administration to keep the plasma drug level at an effective range. This might cause side effects, reduced effectiveness and poor therapeutic management. Therefore, floating sustained-release Imatinib tablets were developed to allow the tablets to be released in the upper part of the GIT and overcome the inadequacy of conventional tablets.Floating sustained-release Imatinib mesylate tablets were prepared using the wet granulation method. Tablets were formulated using Hydroxypropyl Methylcellulose (HPMC K4M, with Sodium alginate (SA and Carbomer 934P (CP as release-retarding polymers, sodium bicarbonate (NaHCO3 as the effervescent agent and lactose as a filler. Floating behavior, in vitro drug release, and swelling index studies were conducted. Initial and total drug release duration was compared with a commercial tablet (Gleevec in 0.1 N HCl (pH 1.2 at 37 ± 0.5°C for 24 hours. Tablets were then evaluated for various physical parameters, including weight variation, thickness, hardness, friability, and drug content. Consequently, 6 months of physical stability studies and in vitro gastro-retentive studies were conducted.Statistical data analysis revealed that tablets containing a composition of 14.67% w/w HPMC K4M, 10.67%, w/w Na alginate, 1.33%, w/w Carbomer 934P and 9.33%, w/w NaHCO3 produced the most favorable formulation to develop 24-hour sustained-release tablets with optimum floating behavior and satisfactory physicochemical characteristics. Furthermore, in vitro release study revealed that the formulated SR tablet had significantly lower Cmax and higher Tmax compared to the conventional tablet (Gleevec. Thus, formulated SR tablets preserved persistent concentration of plasma up to 24 hours

  5. Formulation and in vitro, in vivo evaluation of effervescent floating sustained-release imatinib mesylate tablet.

    Science.gov (United States)

    Kadivar, Ali; Kamalidehghan, Behnam; Javar, Hamid Akbari; Davoudi, Ehsan Taghizadeh; Zaharuddin, Nurul Dhania; Sabeti, Bahareh; Chung, Lip Yong; Noordin, Mohamed Ibrahim

    2015-01-01

    Imatinib mesylate is an antineoplastic agent which has high absorption in the upper part of the gastrointestinal tract (GIT). Conventional imatinib mesylate (Gleevec) tablets produce rapid and relatively high peak blood levels and requires frequent administration to keep the plasma drug level at an effective range. This might cause side effects, reduced effectiveness and poor therapeutic management. Therefore, floating sustained-release Imatinib tablets were developed to allow the tablets to be released in the upper part of the GIT and overcome the inadequacy of conventional tablets. Floating sustained-release Imatinib mesylate tablets were prepared using the wet granulation method. Tablets were formulated using Hydroxypropyl Methylcellulose (HPMC K4M), with Sodium alginate (SA) and Carbomer 934P (CP) as release-retarding polymers, sodium bicarbonate (NaHCO3) as the effervescent agent and lactose as a filler. Floating behavior, in vitro drug release, and swelling index studies were conducted. Initial and total drug release duration was compared with a commercial tablet (Gleevec) in 0.1 N HCl (pH 1.2) at 37 ± 0.5°C for 24 hours. Tablets were then evaluated for various physical parameters, including weight variation, thickness, hardness, friability, and drug content. Consequently, 6 months of physical stability studies and in vitro gastro-retentive studies were conducted. Statistical data analysis revealed that tablets containing a composition of 14.67% w/w HPMC K4M, 10.67%, w/w Na alginate, 1.33%, w/w Carbomer 934P and 9.33%, w/w NaHCO3 produced the most favorable formulation to develop 24-hour sustained-release tablets with optimum floating behavior and satisfactory physicochemical characteristics. Furthermore, in vitro release study revealed that the formulated SR tablet had significantly lower Cmax and higher Tmax compared to the conventional tablet (Gleevec). Thus, formulated SR tablets preserved persistent concentration of plasma up to 24 hours. In conclusion

  6. Preparation and in vitro/in vivo evaluation of esomeprazole magnesium-modified release pellets.

    Science.gov (United States)

    Kan, Shu-Ling; Lu, Jing; Liu, Jian-Ping; Zhao, Yi

    2016-01-01

    To reduce the drug plasma concentration fluctuation without being destroyed by gastric fluid, novel Esomeprazole magnesium modified-release pellets (EMZ-MRPs) with suitable in vitro release profiles and good in vitro and in vivo correlation (IVIVC) were developed. Fluid-bed was used to obtain EMZ-loaded pellets by spraying drug suspension onto blank sugar pellets. The drug-loaded pellets were subsequently coated with Eudragit® RS30D/RL30D (ERS/ERL) aqueous dispersion to achieve sustained-release (SR) characteristics. Furthermore, the SR pellets were coated with Eudragit® L30D-55 (EL-55) aqueous dispersion to achieve enteric properties. Besides, isolated coating film was necessary between drug layer and SR layer, as well as SR and enteric-coated layer to protect from their possible reaction. The resulting pellets were filled into the hard gelatin capsules for in vitro release processing and single-dose pharmacokinetic study in rats. The optimal formulation achieved good SR feature both in vitro and in vivo with a relative bioavailability of 103.50%. A good IVIVC was characterized by a high coefficient of determination (r = 0.9945) by deconvolution method. Compared to those of EMZ enteric-coated pellets (EMZ-ECPs, trade name NEXIUM), the in vivo study make known that the EMZ-MRPs with decreased maximum plasma concentration (Cmax), prolonged peak concentration time (Tmax) and mean residence time (MRT), and similar values both area under concentration-time curve from 0 to t (AUC0-t) and 0 to infinity (AUC0-∞). Collectively, these results manifested EMZ-MRPs had a satisfactory sustained-release behavior, a desired pharmacokinetic property, improved in vivo retention and decreased plasma drug concentration fluctuation.

  7. CONTROLLED-RELEASE OF PARACETAMOL FROM AMYLODEXTRIN TABLETS - IN-VITRO AND IN-VIVO RESULTS

    NARCIS (Netherlands)

    VANDERVEEN, J; EISSENS, AC; LERK, CF

    Amylodextrin is a suitable excipient for the design of solid controlled-release systems. The release of paracetamol from tablets containing 30% drug and 70% amylodextrin was studied in vitro and in vivo. In vitro dissolution profiles showed almost-constant drug release rates during 8 hr, when

  8. Sustained release donepezil loaded PLGA microspheres for injection: Preparation, in vitro and in vivo study

    Directory of Open Access Journals (Sweden)

    Wenjia Guo

    2015-10-01

    Full Text Available The purpose of this study was to develop a PLGA microspheres-based donepezil (DP formulation which was expected to sustain release of DP for one week with high encapsulation efficiency (EE. DP derived from donepezil hydrochloride was encapsulated in PLGA microspheres by the O/W emulsion-solvent evaporation method. The optimized formulation which avoided the crushing of microspheres during the preparation process was characterized in terms of particle size, morphology, drug loading and EE, physical state of DP in the matrix and in vitro and in vivo release behavior. DP microspheres were prepared successfully with average diameter of 30 µm, drug loading of 15.92 ± 0.31% and EE up to 78.79 ± 2.56%. Scanning electron microscope image showed it has integrated spherical shape with no drug crystal and porous on its surface. Differential scanning calorimetry and X-ray diffraction results suggested DP was in amorphous state or molecularly dispersed in microspheres. The Tg of PLGA was increased with the addition of DP. The release profile in vitro was characterized with slow but continuous release that lasted for about one week and fitted well with first-order model, which suggested the diffusion governing release mechanism. After single-dose administration of DP microspheres via subcutaneous injection in rats, the plasma concentration of DP reached peak concentration at 0.50 d, and then declined gradually, but was still detectable at 15 d. A good correlation between in vitro and in vivo data was obtained. The results suggest the potential use of DP microspheres for treatment of Alzheimer's disease over long periods.

  9. Gastroretentive Pulsatile Release Tablets of Lercanidipine HCl: Development, Statistical Optimization, and In Vitro and In Vivo Evaluation

    Directory of Open Access Journals (Sweden)

    Gagganapalli Santhoshi Reddy

    2014-01-01

    Full Text Available The present study was aimed at the development of gastroretentive floating pulsatile release tablets (FPRTs of lercanidipine HCl to enhance the bioavailability and treat early morning surge in blood pressure. Immediate release core tablets containing lercanidipine HCl were prepared and optimized core tablets were compression-coated using buoyant layer containing polyethylene oxide (PEO WSR coagulant, sodium bicarbonate, and directly compressible lactose. FPRTs were evaluated for various in vitro physicochemical parameters, drug-excipient compatibility, buoyancy, swelling, and release studies. The optimized FPRTs were tested in vivo in New Zealand white rabbits for buoyancy and pharmacokinetics. DoE optimization of data revealed FPRTs containing PEO (20% w/w with coat weight 480 mg were promising systems exhibiting good floating behavior and lag time in drug release. Abdominal X-ray imaging of rabbits after oral administration of the tablets, confirmed the floating behavior and lag time. A quadratic model was suggested for release at 7th and 12th h and a linear model was suggested for release lag time. The FPRT formulation improved pharmacokinetic parameters compared to immediate release tablet formulation in terms of extent of absorption in rabbits. As the formulation showed delay in drug release both in vitro and in vivo, nighttime administration could be beneficial to reduce the cardiovascular complications due to early morning surge in blood pressure.

  10. Effect of Permeation Enhancers on the Release Behavior and ...

    African Journals Online (AJOL)

    Purpose: The aim of this research work was to formulate, characterize and evaluate the in vitro permeation behavior of tramadol lotion containing propylene glycol (PG) and polyethylene glycol (PEG) as permeation enhancers. Methods: The permeation experiments were conducted in vitro using full thickness rabbit skin in ...

  11. In-vivo/in-vitro correlation of four extended release formulations of pseudoephedrine sulfate.

    Science.gov (United States)

    Mojaverian, P; Rosen, J; Vadino, W A; Liebowitz, S; Radwanski, E

    1997-01-01

    An in-vivo/in-vitro correlation was established for four formulations of pseudoephedrine sulfate modified release tablets exhibiting different in-vivo and in-vitro release rate and absorption characteristics. In-vitro release rate data were obtained for 12 individual tablets of each formulation using the USP Apparatus 2 paddle stirrer at 50 rev min-1 in 1000 ml 0.1 N hydrochloric acid for the first hour followed by 0.1 M phosphate buffer at pH 7.5 for hours 2-16. Inspection of the individual and mean release rate data indicated that the in-vitro release rate of pseudoephedrine sulfate was consistent with the intended design of the four extended release formulations. The in-vivo bioavailability and pharmacokinetics of these formulations were evaluated in 20 healthy volunteers under fasted conditions. Wagner-Nelson analyses of the in-vivo data revealed extended release absorption profiles for all four formulations. Linear regression analyses of the mean percentage of dose absorbed versus the mean in-vitro release resulted in statistically significant correlations (r2 > 0.99, p < 0.0001) for each formulation. Qualitative rank order correlations were observed among all combinations of in-vivo and in-vitro parameters. These data support a Level A correlation between in-vivo absorption profiles and in-vitro release rates of four pseudoephedrine sulfate extended release formulations determined in fasted healthy volunteers.

  12. In vitro modeling of repetitive motion injury and myofascial release.

    Science.gov (United States)

    Meltzer, Kate R; Cao, Thanh V; Schad, Joseph F; King, Hollis; Stoll, Scott T; Standley, Paul R

    2010-04-01

    In this study we modeled repetitive motion strain (RMS) and myofascial release (MFR) in vitro to investigate possible cellular and molecular mechanisms to potentially explain the immediate clinical outcomes associated with RMS and MFR. Cultured human fibroblasts were strained with 8h RMS, 60s MFR and combined treatment; RMS+MFR. Fibroblasts were immediately sampled upon cessation of strain and evaluated for cell morphology, cytokine secretions, proliferation, apoptosis, and potential changes to intracellular signaling molecules. RMS-induced fibroblast elongation of lameopodia, cellular decentralization, reduction of cell to cell contact and significant decreases in cell area to perimeter ratios compared to all other experimental groups (p<0.0001). Cellular proliferation indicated no change among any treatment group; however RMS resulted in a significant increase in apoptosis rate (p<0.05) along with increases in death-associated protein kinase (DAPK) and focal adhesion kinase (FAK) phosphorylation by 74% and 58% respectively, when compared to control. These responses were not observed in the MFR and RMS+MFR group. Of the 20 cytokines measured there was a significant increase in GRO secretion in the RMS+MFR group when compared to control and MFR alone. Our modeled injury (RMS) appropriately displayed enhanced apoptosis activity and loss of intercellular integrity that is consistent with pro-apoptotic dapk-2 and FAK signaling. Treatment with MFR following RMS resulted in normalization in apoptotic rate and cell morphology both consistent with changes observed in dapk-2. These in vitro studies build upon the cellular evidence base needed to fully explain clinical efficacy of manual manipulative therapies. Copyright 2010 Elsevier Ltd. All rights reserved.

  13. Superporous hybrid hydrogels based on polyacrylamide and chitosan: Characterization and in vitro drug release.

    Science.gov (United States)

    Nagpal, Manju; Singh, Shailendra Kumar; Mishra, Dinanath

    2013-04-01

    Current research was aimed at the development of the drug delivery systems based on the superporous hydrogels (SPH) with the desired swelling and the mechanical properties. Superporous hydrogel composites (SPHCs) and superporous hybrid hydrogels (SPHHs) based on the chitosan and the polyacrylamide were synthesized using the gas blowing technique. The prepared hydrogels were evaluated for swelling studies, mechanical strength and scanning electron microscopy. The selected hydrogels were loaded with the drug (verapamil hydrochloride) by aqueous loading method. Drug integrity with in polymeric network was evaluated via fourier transform infrared spectroscopy (FTIR), X-ray diffraction (X-RD), differential scanning calorimetry (DSC), proton nuclear magnetic resonance ((1)HNMR) studies. In vitro drug release studies were carried out using the united state pharmacopoeial (USP) dissolution apparatus (type II). The mechanical strength was observed to be higher in SPH hybrids in comparison to that in SPHCs while no significant difference was observed in swelling behavior. In situ crosslinking of chitosan with glutaraldehyde (GA) may be responsible for high mechanical strength. The equilibrium swelling time was slight higher in SPHH than in SPHCs. The integrity of pores was maintained in ethanol treated hydrogels as observed in scanning electron micrographs. Whereas, freeze dried SPH samples showed non-uniform pores. No drug polymer interaction was observed as indicated by DSC, FTIR, X-RD and NMR studies. However, the crosslinking of chitosan with GA was clearly indicated by these studies. The in vitro drug release studies from SPH hybrids indicated initial fast release (65%) with in first 2 h and then sustained release at the end of 24 h (95%). The addition of hydroxypropyl methyl cellulose with drug; however, leads to a significant decrease in drug release (56% at the end of 24 h). Superporous hybrid hydrogels can be promising devices for the sustained delivery of drug

  14. Promoter polymorphisms regulating corticotrophin-releasing hormone transcription in vitro.

    Science.gov (United States)

    Wagner, U; Wahle, M; Moritz, F; Wagner, U; Häntzschel, H; Baerwald, C G O

    2006-02-01

    To investigate whether polymorphisms in the corticotrophin-releasing hormone (CRH) promoter are associated with altered CRH gene regulation, we studied the reactivity of three recently described promoter variants in vitro. The 3625 bp variants A1B1, A2B1 and A2B2 of the human CRH promoter were cloned in the 5' region to a luciferase reporter gene and transiently transfected into both mouse anterior pituitary cells AtT-20D16vF2 and pheochromocytoma cells PC12. Incubation with 8-Br-cAMP alone or in combination with cytokines significantly enhanced the promoter activity in both cell lines studied by up to 22-fold. However, dexamethasone antagonised cAMP effects on CRH expression in AtT-20 cells while showing no effect on PC12 cells, indicating that tissue-specific factors play a crucial role. Among the haplotypes studied, A1B1 exhibited the greatest reactivity on various stimuli. Electric mobility shift assay (EMSA) was performed to study whether the described polymorphic nucleotide sequences in the 5' region of the hCRH gene interfere with binding of nuclear proteins. A specific DNA protein complex was detected at position -2353 bp for the wild type sequence only, possibly interfering with a binding site for the activating transcription factor 6 (ATF6). Taken together, this is the first study to demonstrate that CRH promoter reactivity varies between the compound promoter alleles.

  15. Mechanistic analysis of triamcinolone acetonide release from PLGA microspheres as a function of varying in vitro release conditions.

    Science.gov (United States)

    Doty, Amy C; Zhang, Ying; Weinstein, David G; Wang, Yan; Choi, Stephanie; Qu, Wen; Mittal, Sachin; Schwendeman, Steven P

    2017-04-01

    In vitro tests for controlled release PLGA microspheres in their current state often do not accurately predict in vivo performance of these products during formulation development. Here, we introduce a new mechanistic and multi-phase approach to more clearly understand in vitro-in vivo relationships, and describe the first "in vitro phase" with the model drug, triamcinolone acetonide (Tr-A). Two microsphere formulations encapsulating Tr-A were prepared from PLGAs of different molecular weights and end-capping (18kDa acid-capped and 54kDa ester-capped). In vitro release kinetics and the evidence for controlling mechanisms (i.e., erosion, diffusion, and water-mediated processes) were studied in four release media: PBST pH 7.4 (standard condition), PBST pH 6.5, PBS+1.0% triethyl citrate (TC), and HBST pH 7.4. The release mechanism in PBST was primarily polymer erosion-controlled as indicated by the similarity of release and mass loss kinetics. Release from the low MW PLGA was accelerated at low pH due to increased rate of hydrolysis and in the presence of the plasticizer TC due to slightly increased hydrolysis and much higher diffusion in the polymer matrix. TC also increased release from the high MW PLGA due to increased hydrolysis, erosion, and diffusion. This work demonstrates how in vitro conditions can be manipulated to change not only rates of drug release from PLGA microspheres but also the mechanism(s) by which release occurs. Follow-on studies in the next phases of this approach will utilize these results to compare the mechanistic data of the Tr-A/PLGA microsphere formulations developed here after recovery of microspheres in vivo. This new approach based on measuring mechanistic indicators of release in vitro and in vivo has the potential to design better, more predictive in vitro release tests for these formulations and potentially lead to mechanism-based in vitro-in vivo correlations. Copyright © 2016. Published by Elsevier B.V.

  16. In vitro biorelevant models for evaluating modified release mesalamine products to forecast the effect of formulation and meal intake on drug release.

    Science.gov (United States)

    Andreas, Cord J; Chen, Ying-Chen; Markopoulos, Constantinos; Reppas, Christos; Dressman, Jennifer

    2015-11-01

    Postprandial administration of solid oral dosage forms greatly changes the dissolution environment compared to fasted state administration. The aims of this study were to investigate and forecast the effect of co-administration of a meal on drug release for delayed and/or extended release mesalamine formulations as well as design of in vitro tests to distinguish among formulations in a biorelevant way. Five different mesalamine formulations (Asacol® 400 mg, Mezavant® 1200 mg, Pentasa® 500 mg and Salofalk® in the 250 mg and 500 mg strengths) were investigated with biorelevant dissolution methods using the USP apparatus III and USP apparatus IV (open loop mode) under both fasted and fed state conditions, as well as with the dissolution methods described in pharmacopeia for delayed and extended release mesalamine products. Using the biorelevant experimental conditions proposed in this study, changes in release in the proximal gut due to meal intake are forecast to be minimal for Asacol®, Mezavant®, Pentasa® and Salofalk® 500 mg, while for Salofalk® 250 mg release was predicted to occur much earlier under fed state conditions. The USP apparatus III generally tended to result in faster dissolution rates and forecast more pronounced food effects for Salofalk® 250 mg than the USP apparatus IV. The biorelevant dissolution gradients were also able to reflect the in vivo behavior of the formulations. In vitro biorelevant models can be useful in the comparison of the release behavior from different delayed and extended release mesalamine formulations as well as forecasting effects of concomitant meal intake on drug release. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Pharmacokinetics and correlation between in vitro release and in vivo absorption of bio-adhesive pellets of panax notoginseng saponins.

    Science.gov (United States)

    Li, Ying; Zhang, Yun; Zhu, Chun-Yan

    2017-02-01

    The present study was designed to prepare and compare bio-adhesive pellets of panax notoginseng saponins (PNS) with hydroxy propyl methyl cellulose (HPMC), chitosan, and chitosan : carbomer, explore the influence of different bio-adhesive materials on pharmacokinetics behaviors of PNSbio-adhesive pellets, and evaluate the correlation between in vivo absorption and in vitro release (IVIVC). In order to predict the in vivo concentration-time profile by the in vitro release data of bio-adhesive pellets, the release experiment was performed using the rotating basket method in pH 6.8 phosphate buffer. The PNS concentrations in rat plasma were analyzed by HPLC-MS-MS method and the relative bioavailability and other pharmacokinetic parameters were estimated using Kinetica4.4 pharmacokinetic software. Numerical deconvolution method was used to evaluate IVIVC. Our results indicated that, compared with ordinary pellets, PNS bio-adhesive pellets showed increased oral bioavailability by 1.45 to 3.20 times, increased Cmax, and extended MRT. What's more, the release behavior of drug in HPMC pellets was shown to follow a Fickian diffusion mechanism, a synergetic function of diffusion and skeleton corrosion. The in vitro release and the in vivo biological activity had a good correlation, demonstrating that the PNS bio-adhesive pellets had a better sustained release. Numerical deconvolution technique showed the advantage in evaluation of IVIVC for self-designed bio-adhesive pellets with HPMC. In conclusion, the in vitro release data of bio-adhesive pellets with HPMC can predict its concentration-time profile in vivo. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  18. A biorelevant in vitro release/permeation system for oral transmucosal dosage forms.

    Science.gov (United States)

    Delvadia, Poonam R; Barr, William H; Karnes, H Thomas

    2012-07-01

    This research describes the development and validation of a biorelevant in vitro release/permeation system to predict the in vivo performance of oral transmucosal dosage forms. The system is a biorelevant bidirectional transmucosal apparatus which allows better simulation of oral cavity physiological variables in comparison to compendial dissolution apparatuses and therefore may be a better predictor of in vivo behavior. The feasibility of the bidirectional apparatus was studied using smokeless tobacco (snus) as a model oral transmucosal product. In this research, nicotine release and permeation was investigated from commercially available snus using a modified USP IV flow-through apparatus, a commercially available vertical diffusion cell and a fabricated novel bidirectional transmucosal apparatus. The percent nicotine released/permeated was utilized as an input function for the prediction of in vivo plasma nicotine profiles by back calculation based on the Wagner-Nelson method. The prediction errors in C(max) and AUC(0-∞) with the USP IV flow-through device, vertical diffusion cell and novel apparatus were 4.03, 22.85 and 1.59 and -5.85, 5.85 and -9.27% respectively. This work demonstrated the suitability of the novel bidirectional transmucosal apparatus for predicting the in vivo behavior of oral transmucosal products. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. [Preparation and evaluation of sustained-release microsphere of Sanguis Draconis in vitro].

    Science.gov (United States)

    Ding, Li-Yu; Xia, Peng-Fei; Yang, Cai-Qin; Lin, Yu-Long; Wang, Jing

    2007-03-01

    To prepare sustained-release microsphere containing extract of Sanguis Draconis and to measure its dissolution in vitro. Sustained-release microsphere was prepared with polylactic acid (PLA) as carriers using the oil-in-water (O/W) emulsion solvent evaporation method. The powder particle's characteristics of sustainded-release microsphere were evaluated comprehensively, and its dissolution characteristics in vitro were studied. The microsphere was round and its surface was smooth, drug-loading rate was 21.97% and the entrapment rate was 55.76%, the accumulative release percentage was 76. 71% in 16 hours. The sustained release effect of Sanguis Draconis microspheres was formed with potentially wide applications.

  20. Formulation and In Vitro Evaluation of Release Retardant Diclofenac ...

    African Journals Online (AJOL)

    (F10) extended the drug release up to 24 h with initial burst effect. Upon modification, using ethyl cellulose as granulating agent (F11) extended drug release up to 24 h that followed zero order release kinetics (r2 = 0.9872). Model independent parameters such as t25%, t50%, t90%, DE720 and mean dissolution time (MDT) ...

  1. Influence of ethanol on swelling and release behaviors of Carbopol(®)-based tablets.

    Science.gov (United States)

    Rahim, Safwan Abdel; Al-Ghazawi, Mutasim; Al-Zoubi, Nizar

    2013-01-01

    The aim of this work was to investigate the effect of ethanol on the in vitro swelling and release behaviors of Carbopol(®)-based tablets. The swelling behavior of drug-free compacts and the release of model drugs (metformin HCl, caffeine and theophylline) from matrix tablets were evaluated in acidic and buffered media with 0, 20 and 40% (v/v) ethanol. Release data were analyzed by fitting to Higuchi and Peppas models and calculation of similarity factor (f2). ANOVA tests were performed to determine significant factors on swelling and release. It was found that ethanol affects swelling and erosion of drug-free Carbopol(®) compacts, and the effect was highly dependent on medium pH. For matrix tablets, no dose dumping due to ethanol was manifested. The release rate and mechanism, however, were significantly affected by ethanol concentration as indicated by ANOVA applied to the constant, KH, from Higuchi model and the exponent, n, from Peppas model, respectively. The effect of ethanol on release was further confirmed by similarity factor results, which indicated that ethanol led to different release profiles (f2 < 50) in seven of eight cases for matrices containing metformin HCl and in three of eight cases for matrices containing caffeine and theophylline.

  2. Investigation of In vitro Release Kinetics of Carbamazepine from ...

    African Journals Online (AJOL)

    Results: The hardness of batch series 'A' matrix tablet was >160 kg/cm2 while for batch series 'B', it was >170 kg/cm2. Carbamazepine tablets containing only Eudragit RS PO showed very slow release (less than 6% in 8 h) but when Eudragit RL PO was blended with Eudragit RS PO, the release rate improved significantly ...

  3. Chlorhexidine Salt-Loaded Polyurethane Orthodontic Chains: In Vitro Release and Antibacterial Activity Studies

    National Research Council Canada - National Science Library

    Padois, Karine; Bertholle, Valérie; Pirot, Fabrice; Hyunh, Truc Thanh Ngoc; Rossi, Alessandra; Colombo, Paolo; Falson, Françoise; Sonvico, Fabio

    2012-01-01

    .... The aim of the present study was to characterize the in vitro release of chlorhexidine from new polymeric orthodontic chains realized with polyurethane loaded with two different chlorhexidine salts...

  4. In vitro release of diclofenac diethylamine from gels: evaluation of generic semisolid drug products in Brazil

    National Research Council Canada - National Science Library

    Goebel, Karin; Sato, Mayumi Eliza Otsuka; Souza, Dayse Fernanda de; Murakami, Fábio Seigi; Andreazza, Itamar Francisco

    2013-01-01

    .... In this context, this aim of this study was to evaluate the in vitro release of commercial diclofenac diethylamine gel products available on the Brazilian pharmaceutical market, using the vertical diffusion cell method...

  5. In vitro study on tamsulosin release kinetics from biodegradable PLGA in situ implants

    National Research Council Canada - National Science Library

    Elias-Al-Mamun, Md; Khan, Humaira Afreen; Dewan, Irin; Jalil, Reza-Ul

    2009-01-01

    The objective of this study was to evaluate the effect of drug loading and the effect of excipients on the release pattern of tamsulosin tydrochloride from in situ PLGA implants formed in vitro in gelatin gel...

  6. Formulation and In vitro/In vivo Evaluation of Sustained Release ...

    African Journals Online (AJOL)

    HP

    2013-07-15

    Jul 15, 2013 ... Purpose: To develop and optimise sustained release (SR) matrix tablets of diltiazem hydrochloride (DHL). Methods: ... Keywords: Diltiazem, Matrix tablet, Hydroxypropyl methylcellulose Eudragit, In vitro/in vivo correlation, Optimization. Tropical ..... Makhija S, Vavia P. Once daily sustained release tablets.

  7. Peptide Drug Release Behavior from Biodegradable Temperature-Responsive Injectable Hydrogels Exhibiting Irreversible Gelation

    Directory of Open Access Journals (Sweden)

    Kazuyuki Takata

    2017-10-01

    Full Text Available We investigated the release behavior of glucagon-like peptide-1 (GLP-1 from a biodegradable injectable polymer (IP hydrogel. This hydrogel shows temperature-responsive irreversible gelation due to the covalent bond formation through a thiol-ene reaction. In vitro sustained release of GLP-1 from an irreversible IP formulation (F(P1/D+PA40 was observed compared with a reversible (physical gelation IP formulation (F(P1. Moreover, pharmaceutically active levels of GLP-1 were maintained in blood after subcutaneous injection of the irreversible IP formulation into rats. This system should be useful for the minimally invasive sustained drug release of peptide drugs and other water-soluble bioactive reagents.

  8. Mechanical, Rheological and Release Behaviors of a Poloxamer 407/ Poloxamer 188/Carbopol 940 Thermosensitive Composite Hydrogel

    Directory of Open Access Journals (Sweden)

    Jianyu Su

    2013-10-01

    Full Text Available The aims of this study were to prepare a thermosensitive composite hydrogel (TCH by mixing 24% (w/v poloxamer 407 (P407, 16% (w/v poloxamer 188 (P188 and 0.1% (w/v carbopol 940 (C940, and to determine the effect of natural borneol/ (2-hydroxypropyl-β-cyclodextrin (NB/HP-β-CD inclusion complex on the phase transition temperature, mechanical, rheological properties, and release behaviors of the TCH using the tube inversion method, a texture analyzer, a rheometer, and in vitro release , respectively. The results showed that as the concentration of NB/HP-β-CD increased, the phase transition temperature of the TCH was increased from 37.26 to 38.34 °C and the mechanical properties of the TCH showed that the hardness, cohesiveness, strength, and adhesiveness were increased from 0.025 to 0.064 kg, 0.022 to 0.064 kg, 0.110 to 0.307 kg and 0.036 to 0.105 kg, respectively, but the rheological properties of the TCH showed that G′, G′′ and η were decreased from 7,760 to 157.50 Pa, 1,274 to 36.28 Pa and 1,252 to 25.37 Pas, respectively. The in vitro release showed that an increasing NB/HP-β-CD concentration decreased the release rate of NB from the TCH, but the amount of NB released was more than 96% at 60 min, which showed the TCH had good release behavior.

  9. Mechanical, rheological and release behaviors of a poloxamer 407/ poloxamer 188/carbopol 940 thermosensitive composite hydrogel.

    Science.gov (United States)

    Chen, Jianping; Zhou, Rong; Li, Lin; Li, Bing; Zhang, Xia; Su, Jianyu

    2013-10-08

    The aims of this study were to prepare a thermosensitive composite hydrogel (TCH) by mixing 24% (w/v) poloxamer 407 (P407), 16% (w/v) poloxamer 188 (P188) and 0.1% (w/v) carbopol 940 (C940), and to determine the effect of natural borneol/ (2-hydroxypropyl)-β-cyclodextrin (NB/HP-β-CD) inclusion complex on the phase transition temperature, mechanical, rheological properties, and release behaviors of the TCH using the tube inversion method, a texture analyzer, a rheometer, and in vitro release , respectively. The results showed that as the concentration of NB/HP-β-CD increased, the phase transition temperature of the TCH was increased from 37.26 to 38.34 °C and the mechanical properties of the TCH showed that the hardness, cohesiveness, strength, and adhesiveness were increased from 0.025 to 0.064 kg, 0.022 to 0.064 kg, 0.110 to 0.307 kg and 0.036 to 0.105 kg, respectively, but the rheological properties of the TCH showed that G', G'' and η were decreased from 7,760 to 157.50 Pa, 1,274 to 36.28 Pa and 1,252 to 25.37 Pas, respectively. The in vitro release showed that an increasing NB/HP-β-CD concentration decreased the release rate of NB from the TCH, but the amount of NB released was more than 96% at 60 min, which showed the TCH had good release behavior.

  10. In Vitro Drug Release Studies of Metronidazole Topical ...

    African Journals Online (AJOL)

    Three different topical formulations namely gel, cream and ointment, each containing 1% w/w metronidazole, were prepared and in vitro permeation studies carried out. The permeation of metronidazole from each of the topical formulation was determined using dialyzing cellulose membrane in a dissolution tester. Glycerin ...

  11. In-vitro Release Study of Carvedilol Phosphate Matrix Tablets ...

    African Journals Online (AJOL)

    Methods: Matrix tablets containing carvedilol phosphate were prepared from 27 formulations in three batch series coded A, B and C, each containing 9 formulations. Each batch incorporated different ratios of two molecular weight grades of hydroxypropyl methylcellulose (Methocel® K4M CR and K15M CR) used as release ...

  12. Preparation, Characterization and In Vitro Drug Release Studies of 6 ...

    African Journals Online (AJOL)

    Oral thin films of 6-mercaptopurine were fabricated from mucoadhesive polymer, chitosan and polyvinylpyrrolidone for the purpose of prolonging drug release and improving its bioavailability. All fabricated film formulations prepared were smooth and translucent, with good flexibility. The weight and thickness of all the ...

  13. IN VITRO EVALUATION OF FLUORIDE RELEASE OF JELTRATE® DENTAL ALGINATE

    Directory of Open Access Journals (Sweden)

    Matheus Melo Pithon

    2009-04-01

    Full Text Available Objective: To evaluate of fluoride release from Jeltrate alginate®. Materials and Methods: Four Trademarks of alginate were divided in four groups: conventional Jeltrate®, Plus Jeltrate®, Chromatic Jeltrate® and Chromatic Ortho Jeltrate®. The alginates were handled following the guidelines of the manufacturers. After this was followed by the construction of evidence bodies using silicone molds of the dimensions of 4 mm in diameter and 4mm in height. After take prey, the evidence bodies were removed from the molds and placed in container with 10 ml of ultra purified water, for 2 min. The fluoride release was measured by selective ion electrode connected to an analyzer of ions. Results: The Plus Jeltrate® showed a higher releasing fluoride 247.85 µg/cm2 followed by Chromatic Ortho Jeltrate® (217.83 µg/cm2, Chromatic Jeltrate ® (138.21 µg/cm2 and Jeltrate® (79.61 µg/cm2. Conclusion: Plus Jeltrate® had the best performance in releasing fluoride, followed by Chromatic Ortho Jeltrate®, Chromatic Jeltrate® and conventional Jeltrate®..

  14. Drug Releasing Dental Cements: An In Vitro Study.

    African Journals Online (AJOL)

    reported that the strongest antibacterial activity was observed with a zinc oxide eugenol cement when compared to commercially available restorative dental biomaterials such as a fine-hybrid resin composite, an ion- releasing resin composite, a self-curing glass ionomer cement and a resin-modified glass ionomer cement.

  15. Stretch induces cytokine release by alveolar epithelial cells in vitro.

    Science.gov (United States)

    Vlahakis, N E; Schroeder, M A; Limper, A H; Hubmayr, R D

    1999-07-01

    Mechanical ventilation can injure the lung, causing edema and alveolar inflammation. Interleukin-8 (IL-8) plays an important role in this inflammatory response. We postulated that cyclic cell stretch upregulates the production and release of IL-8 by human alveolar epithelium in the absence of structural cell damage or paracrine stimulation. To test this hypothesis, alveolar epithelial cells (A549 cells) were cultured on a deformable silicoelastic membrane. When stretched by 30% for up to 48 h, the cells released 49 +/- 34% more IL-8 (P static controls. Smaller deformations (20% stretch) produced no consistent increase in IL-8. Stretch of 4 h duration increased IL-8 gene transcription fourfold above baseline. Stretch had no effect on cell proliferation, cell viability as assessed by (51)Cr release assay, or the release of granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-alpha. We conclude that deformation per se can trigger inflammatory signaling and that alveolar epithelial cells may be active participants in the alveolitis associated with ventilator-induced lung injury.

  16. Mydriatics release from solid and semi-solid ophthalmic formulations using different in vitro methods.

    Science.gov (United States)

    Pescina, Silvia; Macaluso, Claudio; Gioia, Gloria Antonia; Padula, Cristina; Santi, Patrizia; Nicoli, Sara

    2017-09-01

    The aim of the present paper was the development of semi-solid (hydrogels) and solid (film) ophthalmic formulations for the controlled release of two mydriatics: phenylephrine and tropicamide. The formulations - based on polyvinylalcohol and hyaluronic acid - were characterized, and release studies were performed with three different in vitro set-ups, i.e. Franz-type diffusion cell, vial method and inclined plane; for comparison, a solution and a commercial insert, both clinically used to induce mydriasis, were evaluated. Both gels and film allowed for a controlled release of drugs, appearing a useful alternative for mydriatics administration. However, the release kinetic was significantly influenced by the method used, highlighting the need for optimization and standardization of in vitro models for the evaluation of drug release from ophthalmic dosage forms.

  17. Alginate/quaternized carboxymethyl chitosan/clay nanocomposite microspheres: preparation and drug-controlled release behavior.

    Science.gov (United States)

    Liu, Bo; Luo, Jiwen; Wang, Xiaoying; Lu, Junxiang; Deng, Hongbing; Sun, Runcang

    2013-01-01

    Drug-delivery systems, using natural drug carriers, have become increasingly important because of their nontoxicity and biodegradability. In this study, firstly, quaternized carboxymethyl chitosan (QCMC) was intercalated into the interlayer of organic montmorillonite (OMMT) to obtain the QCMC/OMMT nanocomposites, their structure, morphology, and thermal stability were investigated. Next, crosslinked alginate/QCMC/OMMT (AQCOM) microsphere was obtained by crosslinking with CaCl2, and the drug-controlled release behavior was evaluated with bovine serum albumin (BSA) as model drug. The results suggested that, carboxyl groups in alginate and QCMC crosslinked with Ca(2+), quaternary ammonium groups in QCMC or OMMT electrostatically interacted with carboxyl groups in alginate, and there was stable three-dimensional network in AQCOM microsphere. The swelling ratio of AQCOM microspheres decreased with the increase of OMMT content, the lowest one was only about 45% compared to the microsphere without OMMT of 197%. Besides, the in vitro release results for BSA indicated that the AQCOM microsphere displayed more excellent encapsulation and controlled release capacities than the microsphere without OMMT. The in vitro active cutaneous anaphylaxis test was carried out on Guinea pigs, which revealed that AQCOM microsphere did not cause anaphylaxis. Therefore, QCMC/OMMT nanocomposites from natural materials are considerably suitable to apply as drug-controlled release carriers.

  18. Infuence of Microstructure in Drug Release Behavior of Silica Nanocapsules

    Directory of Open Access Journals (Sweden)

    Gema Gonzalez

    2013-01-01

    Full Text Available Meso- and nanoporous structures are adequate matrices for controlled drug delivery systems, due to their large surface areas and to their bioactive and biocompatibility properties. Mesoporous materials of type SBA-15, synthesized under different pH conditions, and zeolite beta were studied in order to compare the different intrinsic morphological characteristics as pore size, pore connectivity, and pore geometry on the drug loading and release process. These materials were characterized by X-ray diffraction, nitrogen adsorption, scanning and transmission electron microscopy, and calorimetric measurements. Ibuprofen (IBU was chosen as a model drug for the formulation of controlled-release dosage forms; it was impregnated into these two types of materials by a soaking procedure during different periods. Drug loading and release studies were followed by UV-Vis spectrophotometry. All nano- and mesostructured materials showed a similar loading behavior. It was found that the pore size and Al content strongly influenced the release process. These results suggest that the framework structure and architecture affect the drug adsorption and release properties of these materials. Both materials offer a good potential for a controlled delivery system of ibuprofen.

  19. Effect of pineal gland on testosterone release in vitro.

    Science.gov (United States)

    Jarrige, J F; Thieblot, P; Boucher, D

    1986-01-01

    We studied the effect of hCG, aminoglutethimide and pineal effluent on the basal testosterone secretion by superfused adult rat interstitial cells. The period used to determine the mean rates of release was 120-240 min. after the start of superfusion i.e. when basal secretory rate was stable. A 2 h administration of hCG (10 mUI/ml) induced a rapid increase in testosterone output while aminoglutethimide (100 microM) decreased it. Basal testosterone release was not modified when interstitial cells were superfused with effluent of a chamber containing 1, 2 or 4 pineal glands. These results suggest that pineal secretory products exert no direct acute action on testosterone biosynthesis by rat interstitial cells.

  20. Encapsulation and in vitro release of erythromycin using biopolymer micelle.

    Science.gov (United States)

    Huang, Y; Sun, Y; Wang, Q

    2015-11-20

    An amphiphilic block copolymer poly(ethylene glycol)-block-poly[2-(2-methoxyethoxy)ethyl methacrylate] (PEG-b-PMEO2MA) was prepared and the polymer micelle was applied to encapsulate erythromycin. The Critical Micelle Concentration (CMC) of PEG-b-PMEO2MA was determined by the fluorescent probe pyrene. The effects of addition of erythromycin on encapsulation efficiency and drug loading content were investigated. Drug release was also studied in a phosphate buffer solution with a pH of 7.5. The CMC of PEG-b-PMEO2MA is 0.065 mg/mL when the monomer ratio of the hydrophobic block PMEO2MA to the hydrophilic block PEG is equal to 6:4. The encapsulation efficiency and drug loading were 87.1% and 16.8%, respectively, as the loading content of erythromycin in polymeric micelle is equal to 28%. After erythromycin is loaded into the micelle, the size of PEG-b-PMEO2MA micelle becomes approximately thrice the size of unloaded micelle. The loading micelles stably release erythromycin within 180 hours in phosphate buffer, suggesting that the micelle loaded with erythromycin have a good sustained-release effect.

  1. Caprine Monocytes Release Extracellular Traps against Neospora caninum In Vitro

    Directory of Open Access Journals (Sweden)

    Zhengtao Yang

    2018-01-01

    Full Text Available Neospora caninum is an obligate intracellular apicomplexan parasite that causes reproductive loss and severe economic losses in dairy and goat industry. In the present study, we aim to investigate the effects of N. caninum tachyzoites on the release of extracellular traps (ETs in caprine monocytes and furthermore elucidated parts of its molecular mechanisms. N. caninum tachyzoite-induced monocytes-derived ETs formation was detected by scanning electron microscopy. H3 and myeloperoxidase (MPO within monocyte-ETs structures were examined using laser scanning confocal microscopy analyses. The results showed that N. caninum tachyzoites were not only able to trigger ETs formation in caprine monocytes, but also that monocyte-released ETs were capable of entrapping viable tachyzoites. Histones and MPO were found to be decorating the DNA within the monocytes derived-ETs structures thus proving the classical components of ETs. Furthermore, inhibitors of NADPH oxidase-, MPO-, ERK 1/2-, or p38 MAPK-signaling pathway significantly decreased N. caninum tachyzoite-triggered caprine monocyte-derived ETosis. This is the first report of ETs release extruded from caprine monocytes after N. caninum exposure and thus showing that this early innate immune effector mechanism might be relevant during the acute phase of caprine neosporosis.

  2. Extended Latanoprost Release from Commercial Contact Lenses: In Vitro Studies Using Corneal Models

    Science.gov (United States)

    Mohammadi, Saman; Jones, Lyndon; Gorbet, Maud

    2014-01-01

    In this study, we compared, for the first time, the release of a 432 kDa prostaglandin analogue drug, Latanoprost, from commercially available contact lenses using in vitro models with corneal epithelial cells. Conventional polyHEMA-based and silicone hydrogel soft contact lenses were soaked in drug solution ( solution in phosphate buffered saline). The drug release from the contact lens material and its diffusion through three in vitro models was studied. The three in vitro models consisted of a polyethylene terephthalate (PET) membrane without corneal epithelial cells, a PET membrane with a monolayer of human corneal epithelial cells (HCEC), and a PET membrane with stratified HCEC. In the cell-based in vitro corneal epithelium models, a zero order release was obtained with the silicone hydrogel materials (linear for the duration of the experiment) whereby, after 48 hours, between 4 to 6 of latanoprost (an amount well within the range of the prescribed daily dose for glaucoma patients) was released. In the absence of cells, a significantly lower amount of drug, between 0.3 to 0.5 , was released, (). The difference observed in release from the hydrogel lens materials in the presence and absence of cells emphasizes the importance of using an in vitro corneal model that is more representative of the physiological conditions in the eye to more adequately characterize ophthalmic drug delivery materials. Our results demonstrate how in vitro models with corneal epithelial cells may allow better prediction of in vivo release. It also highlights the potential of drug-soaked silicone hydrogel contact lens materials for drug delivery purposes. PMID:25207851

  3. Extended latanoprost release from commercial contact lenses: in vitro studies using corneal models.

    Directory of Open Access Journals (Sweden)

    Saman Mohammadi

    Full Text Available In this study, we compared, for the first time, the release of a 432 kDa prostaglandin F2a analogue drug, Latanoprost, from commercially available contact lenses using in vitro models with corneal epithelial cells. Conventional polyHEMA-based and silicone hydrogel soft contact lenses were soaked in drug solution (131 μg = ml solution in phosphate buffered saline. The drug release from the contact lens material and its diffusion through three in vitro models was studied. The three in vitro models consisted of a polyethylene terephthalate (PET membrane without corneal epithelial cells, a PET membrane with a monolayer of human corneal epithelial cells (HCEC, and a PET membrane with stratified HCEC. In the cell-based in vitro corneal epithelium models, a zero order release was obtained with the silicone hydrogel materials (linear for the duration of the experiment whereby, after 48 hours, between 4 to 6 μg of latanoprost (an amount well within the range of the prescribed daily dose for glaucoma patients was released. In the absence of cells, a significantly lower amount of drug, between 0.3 to 0.5 μg, was released, (p <0:001. The difference observed in release from the hydrogel lens materials in the presence and absence of cells emphasizes the importance of using an in vitro corneal model that is more representative of the physiological conditions in the eye to more adequately characterize ophthalmic drug delivery materials. Our results demonstrate how in vitro models with corneal epithelial cells may allow better prediction of in vivo release. It also highlights the potential of drug-soaked silicone hydrogel contact lens materials for drug delivery purposes.

  4. Accelerated in vitro release testing method for naltrexone loaded PLGA microspheres.

    Science.gov (United States)

    Andhariya, Janki V; Choi, Stephanie; Wang, Yan; Zou, Yuan; Burgess, Diane J; Shen, Jie

    2017-03-30

    The objective of the present study was to develop a discriminatory and reproducible accelerated release testing method for naltrexone loaded parenteral polymeric microspheres. The commercially available naltrexone microsphere product (Vivitrol ® ) was used as the testing formulation in the in vitro release method development, and both sample-and-separate and USP apparatus 4 methods were investigated. Following an in vitro drug stability study, frequent media replacement and addition of anti-oxidant in the release medium were used to prevent degradation of naltrexone during release testing at "real-time" (37°C) and "accelerated" (45°C), respectively. The USP apparatus 4 method was more reproducible than the sample-and-separate method. In addition, the accelerated release profile obtained using USP apparatus 4 had a shortened release duration (within seven days), and good correlation with the "real-time" release profile. Lastly, the discriminatory ability of the developed accelerated release method was assessed using compositionally equivalent naltrexone microspheres with different release characteristics. The developed accelerated USP apparatus 4 release method was able to detect differences in the release characteristics of the prepared naltrexone microspheres. Moreover, a linear correlation was observed between the "real-time" and accelerated release profiles of all the formulations investigated, suggesting that the release mechanism(s) may be similar under both conditions. These results indicate that the developed accelerated USP apparatus 4 method has the potential to be an appropriate fast quality control tool for long-acting naltrexone PLGA microspheres. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. In vitro cytotoxicity of metallic ions released from dental alloys

    NARCIS (Netherlands)

    Milheiro, A.; Nozaki, K.; Kleverlaan, C.J.; Muris, J.; Miura, H.; Feilzer, A.J.

    2016-01-01

    The cytotoxicity of a dental alloy depends on, but is not limited to, the extent of its corrosion behavior. Individual ions may have effects on cell viability that are different from metals interacting within the alloy structure. We aimed to investigate the cytotoxicity of individual metal ions in

  6. Slow-release amylase increases in vitro ruminal digestion of maize ...

    African Journals Online (AJOL)

    The objective of this study was to evaluate the effects of slow-release α-amylase in ruminal in vitro digestion of maize and sorghum grains. Digestibility was measured using an in vitro procedure with 40 mL of buffer and 10 mL of ruminal fluid, flushed with CO2 and incubated at 39 °C. The digestibility of sorghum and maize ...

  7. Impairment of the in vitro Release of Carbamazepine from Tablets

    Directory of Open Access Journals (Sweden)

    Alija Uzunović

    2010-08-01

    Full Text Available Carbamazepine belongs to the class II biopharmaceutical classification system (BCS which is characterized by a high per-oral dose, a low aqueous solubility and a high membrane permeability. The bioavailability of such a drug is limited by the dissolution rate. The present study deals with the formulations of immediate release tablets of poorly soluble carbamazepine. As model tablets for this investigation, two formulations (named “A” and “B” formulations of carbamazepine tablets labeled to contain 200 mg were evaluated. The aim of this study was to establish possible differences in dissolution profile of these two formulations purchased from the local market.The increased crystallinity together with enlarged particle size, enhanced aggregation and decreased wettability of the drug, resulted in insufficient dissolution rate for formulation “B’.’ From the dissolution point of view, this formulation was inferior to the formulation “A, due to the solubilization effect.

  8. In vivo release of bupivacaine from subcutaneously administered oily solution. Comparison with in vitro release

    DEFF Research Database (Denmark)

    Larsen, Dorrit Bjerg; Joergensen, Stig; Olsen, Niels Vidiendal

    2002-01-01

    administration of oily solution showed a prolonged bupivacaine release with lower peak plasma levels as compared to administration of an aqueous formulation applied in the same compartment. t(1/2), t(max), C(max) and AUC(0-infinity) for the aqueous solution were 63+/-8 min, 19+/-16 min, 194+/-46 ng x ml(-1...

  9. Effect of polymer type and drug dose on the in vitro and in vivo behavior of amorphous solid dispersions

    DEFF Research Database (Denmark)

    Knopp, Matthias Manne; Chourak, Nabil; Khan, Fauzan

    2016-01-01

    This study investigated the non-sink in vitro dissolution behavior and in vivo performance in rats of celecoxib (CCX) amorphous solid dispersions with polyvinyl acetate (PVA), polyvinylpyrrolidone (PVP) and hydroxypropyl methylcellulose (HPMC) at different drug doses. Both in vitro and in vivo...... showed a lower AUC both in vitro and in vivo than crystalline CCX. For crystalline CCX and CCX:PVA, the in vitro AUC was limited by the low solubility of the drug and the slow release of the drug from the hydrophobic polymer, respectively. For the supersaturating formulations, amorphous CCX, CCX...

  10. Novel semi-IPN based on crosslinked carboxymethyl starch and clay for the in vitro release of theophylline.

    Science.gov (United States)

    Anirudhan, T S; Parvathy, J

    2014-06-01

    A novel semi-interpenetrating polymer network (IPN) based on crosslinked carboxymethyl starch (CL-CMS) and montmorillonite (MMT) was prepared, where carboxymethylation occurs as a result of the reaction between native starch and monochloroacetic acid in isopropanol/water medium at 60°C. The carboxymethyl starch is further crosslinked and made into a semi-IPN with MMT for the release of theophylline. The drug carrier was characterized using FTIR, XRD and surface analysis using SEM. Studies including physio-chemical analysis, swelling behavior, encapsulation efficiency, effect of MMT content, effect of ionic strength and in vitro drug release were carried out. Theophylline encapsulation of up to 74% was achieved and drug release was monitored in SGF (pH 1.2) and SIF (pH 7.4). Results show that the matrix releases drug at a much faster rate in the basic medium than in the acidic medium, thereby holding the promise of developing the semi-IPN system as a potential candidate for the release of theophylline. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Studies on in vitro release of CPM from semi-interpenetrating ...

    Indian Academy of Sciences (India)

    Home; Journals; Bulletin of Materials Science; Volume 31; Issue 2. Studies on in vitro release of CPM from semi-interpenetrating polymer network (IPN) composed of chitosan and glutamic acid. K Kumari P P Kundu. Polymers Volume 31 Issue 2 April 2008 pp 159-167 ...

  12. PLGA microsphere/calcium phosphate cement composites for tissue engineering: in vitro release and degradation characteristics.

    NARCIS (Netherlands)

    Habraken, W.J.E.M.; Wolke, J.G.C.; Mikos, A.G.; Jansen, J.A.

    2008-01-01

    Bone cements with biodegradable poly(lactic-co-glycolic acid) (PLGA) microspheres have already been proven to provide a macroporous calcium phosphate cement (CPC) during in situ microsphere degradation. Furthermore, in vitro/in vivo release studies with these PLGA microsphere/CPC composites

  13. Modelling of Cr and Ni ions release during orthodontic treatment: in vitro and in vivo methods.

    Science.gov (United States)

    Chojnacka, Katarzyna; Mikulewicz, Marcin

    2014-11-01

    The kinetics of metal ions release from orthodontic appliances in in vitro, in in vivo on pigs, and in vivo trials on patients (where hair samples were taken) was discussed. We have evaluated (by means of ICP-OES and ISO 17025) and compared the mass of Cr and Ni ions released. Not all the metal ions released from the appliance were transferred to hair tissue. The transfer factor was expressed as coefficient ω and evaluated as: ωCr(patients) 33.0%, ωCr(pigs) 17.2%, ωNi(patients) 49.8%, ωNi(pigs) 0.553%. The kinetics was described by a power function. Coefficient ω was used to combine the models: the in vitro and in vivo on animals on the one hand and the in vitro and in vivo on human on the other, which enabled the extrapolation of in vitro and translation of the results into in vivo conditions. The dose of metal ions released during orthodontic treatment was estimated. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. In vitro release of doxycycline from bioabsorbable materials and acrylic strips

    DEFF Research Database (Denmark)

    Larsen, T

    1990-01-01

    Treatment of marginal periodontitis may include use of local antibiotics. In the present in vitro study the bioabsorbable materials Surgicel, Tissell, and CollaCote and acrylic strips were examined for release of doxycycline into liquids and residual antibacterial activity of the materials. Piece...

  15. Slow-release amylase increases in vitro ruminal digestion of maize ...

    African Journals Online (AJOL)

    p2492989

    Slow-release amylase increases in vitro ruminal digestion of maize and sorghum grain. M. Crosby. 1. , G.D. Mendoza. 2#. , I. Bonola. 2. , F.X. Plata. 2. , H. Sandoval. 2. & L.M. Melgoza. 2. 1 Colegio de Postgraduados, Campus Montecillo, México 56230. 2 Universidad Autónoma Metropolitana, Unidad Xochimilco, 04960 ...

  16. Direct and indirect effects of cannabinoids on in vitro GABA release in the rat arcuate nucleus.

    Science.gov (United States)

    Menzies, J R W; Ludwig, M; Leng, G

    2010-06-01

    Within the hypothalamic arcuate nucleus, two neuronal subpopulations play particularly important roles in energy balance; neurones expressing neuropeptide Y (NPY), agouti-related peptide (AgRP) and GABA are orexigenic, whereas neurones expressing pro-opiomelanocortin and CART are anorexigenic. The pivotal role of these neuropeptides in energy homeostasis is well-known, although GABA may also be an important signal because targeted knockout of the GABA transporter in NPY/AgRP/GABA neurones results in a lean, obesity-resistant phenotype. In the present study, we describe an in vitro model of K(+)-evoked GABA release from the hypothalamus and determine the effects of cannabinoid receptor activation. K(+)-evoked GABA release was sensitive to leptin, insulin and PYY(3-36), indicating that GABA was released by arcuate NPY/AgRP/GABA neurones. In the presence of tetrodotoxin (TTX), the cannabinoid CB1 receptor agonist WIN 55,212-2 inhibited K(+)-evoked GABA release. This was prevented by the CB1 receptor inverse agonist rimonabant. Rimonabant had no effect when applied alone. In the absence of TTX, however, the opposite effects were observed: WIN 55,212-2 had no effect while rimonabant inhibited GABA release. This indicates that GABA release can involve an indirect, TTX-sensitive mechanism. The most parsimonious explanation for the inhibition of GABA release by a CB receptor inverse agonist is via the disinhibition of an cannabinoid-sensitive inhibitory input onto GABAergic neurones. One local source of an inhibitory neurotransmitter is the opioidergic arcuate neurones. In our in vitro model, K(+)-evoked GABA release was inhibited by the endogenous opioid peptide beta-endorphin in a naloxone-sensitive manner. The inhibitory effect of rimonabant was also prevented by naloxone and a kappa-opioid receptor selective antagonist, suggesting that GABA release from arcuate NPY/AgRP/GABA neurones can be inhibited by endogenous opioid peptides, and that the release of opioid

  17. Comparison of in vitro release rates of acyclovir from cream formulations using vertical diffusion cells.

    Science.gov (United States)

    Nallagundla, Sumalatha; Patnala, Srinivas; Kanfer, Isadore

    2014-08-01

    Acyclovir, indicated in the treatment of herpes labialis ("cold sores"), is formulated as semisolid topical dosage forms and marketed in numerous countries. Since the formulations of the various acyclovir products may differ from country to country, this study was undertaken to compare the in vitro release of acyclovir from various generic cream products available on the South African and Indian markets using the respective brand/innovator product as the reference product. The in vitro studies were carried out using vertical diffusion cells with a diffusional surface area of 1.767 cm(2) and various commercially available membranes. Normal saline was used as receptor fluid and the temperature maintained at 32 ± 0.5°C. The in vitro release comparisons were based on the recommendations described in the US Food and Drug Administration Draft Guidance for acyclovir ointment and the SUPAC-SS Guidance for non-sterile semisolid dosage forms. The release rates (slope) of the test (T) and the relevant reference product (R) were monitored and compared. The comparative release of acyclovir from the various generic formulations compared with the reference product was found to be within the limits of 75-133.33% with a 90% confidence interval. These experiments indicate that the generic acyclovir cream formulations exhibited release rates that were comparable to the innovator product and could be considered to be bioequivalent.

  18. Adsorption and release of antibiotics from morselized cancellous bone. In vitro studies of 8 antibiotics.

    Science.gov (United States)

    Witsø, E; Persen, L; Løseth, K; Bergh, K

    1999-06-01

    We studied the basic release patterns of antibiotics from cancellous bone in vitro. Antibiotic-impregnated bone was compressed into a wire-mesh cylinder and the release of antibiotic was assessed by two different in vitro methods: agar diffusion and broth elution. The zones of inhibition were measured on seeded agar and the amounts of antibiotics released in elution tubes were assessed by a bioassay. The study continued for 21 days with daily transfer of the cylinders. The results indicated that benzylpenicillin, dicloxacillin, cephalotin, netilmicin, clindamycin, vancomycin, ciprofloxacin and rifampicin were adsorbed to cancellous bone in vitro. Compared to broth elution, agar diffusion showed a prolonged period of release, owing to the small amounts of antibiotic leaking out of the cylinder into the agar. The betalactams had antibacterial activity in broth for a shorter time than the other antibiotics. The release patterns of the betalactams were similar, in spite of their differences in thermal stability. Only rifampicin showed a concentration higher than MIC for longer than 21 days.

  19. An in situ synthesis of mesoporous SBA-16/hydroxyapatite for ciprofloxacin release: in vitro stability and cytocompatibility studies.

    Science.gov (United States)

    Andrade, Gracielle Ferreira; Gomide, Viviane Silva; da Silva Júnior, Armando Cunha; Goes, Alfredo Miranda; de Sousa, Edésia Martins Barros

    2014-11-01

    The present work developed a biomaterial (HA/SBA-16) based on the growth of calcium phosphate (HA) particles within an organized silica structure (SBA-16) to evaluate its application as a drug delivery system. The samples were charged with ciprofloxacin as a model drug and in vitro release assays were carried out. The samples were characterized by elemental analysis (CHN), Fourier transform infrared spectroscopy, nitrogen adsorption, scanning electron microscopy (SEM), transmission electron microscopy (TEM), small angle X-ray scattering (SAXS) and X-ray diffraction. The results obtained by TEM, SEM and SAXS reveal a well-defined cubic arrangement of a uniform spherical mesoporous structure, an intrinsic characteristic of these materials, which indicated that SBA-16 and HA/SBA-16 could potentially encapsulate bioactive molecules by means of ordered mesopores. It was found that both surface interaction and pore volume affect the rate and amount of ciprofloxacin released from the mesoporous materials. In vitro assays were performed to evaluate the adhesion, viability, and growth behavior of human adipose tissue-derived stem cells (hADSC) on SBA-16 and HA/SBA-16 nanocomposites to verify their potential as a scaffold for application in bone-tissue engineering using MTT assay and alkaline phosphatase activity tests. The results showed that the materials are promising systems for bone repair, providing a good environment for the adhesion and proliferation of rat mesenchymal stem cells and hADSC in vitro.

  20. Swelling and drug release behavior of poly(2-hydroxyethyl methacrylate/itaconic acid) copolymeric hydrogels obtained by gamma irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Tomic, S.Lj. [Faculty of Technology and Metallurgy, Karnegijeva 4/V, Belgrade (Serbia and Montenegro); Micic, M.M. [Vinca Institute of Nuclear Sciences, P.O. Box 522, 11001 Belgrade (Serbia and Montenegro); Filipovic, J.M. [Faculty of Technology and Metallurgy, Karnegijeva 4/V, Belgrade (Serbia and Montenegro); Suljovrujic, E.H. [Vinca Institute of Nuclear Sciences, P.O. Box 522, 11001 Belgrade (Serbia and Montenegro)]. E-mail: edin@vin.bg.ac.yu

    2007-05-15

    The new copolymeric hydrogels based on 2-hydroxyethyl methacrylate (HEMA) and itaconic acid (IA) were prepared by gamma irradiation, in order to examine the potential use of these hydrogels in controlled drug release systems. The influence of IA content in the gel on the swelling characteristics and the releasing behavior of hydrogels, and the effect of different drugs, theophylline (TPH) and fenethylline hydrochloride (FE), on the releasing behavior of P(HEMA/IA) matrix were investigated in vitro. The diffusion exponents for swelling and drug release indicate that the mechanisms of buffer uptake and drug release are governed by Fickian diffusion. The swelling kinetics and, therefore, the release rate depends on the matrix swelling degree. The drug release was faster for copolymeric hydrogels with a higher content of itaconic acid. Furthermore, the drug release for TPH as model drug was faster due to a smaller molecular size and a weaker interaction of the TPH molecules with(in) the P(HEMA/IA) copolymeric networks.

  1. In vitro and in silico characterisation of Tacrolimus released under biorelevant conditions.

    Science.gov (United States)

    Mercuri, A; Wu, S; Stranzinger, S; Mohr, S; Salar-Behzadi, S; Bresciani, M; Fröhlich, E

    2016-12-30

    This work aims to better understand the in vivo behaviour of modified release (MR) formulations (Envarsus® tablets and Advagraf® capsules) using in vitro properties of tacrolimus and in silico simulations. The in silico concentration profiles of tacrolimus released from the MR formulations were predicted after building a three compartments PK model with GastroPlus™, and using the experimentally determined in vitro physico-chemical properties as input parameters. In vitro-in vivo correlations (IVIVC) were obtained after deconvolution of in vivo data from a clinical trial. The IVIVC showed that the in vitro dissolution was faster than the in vivo deconvoluted dissolution for Advagraf®, while the in vitro dissolution was slightly slower than the in vivo deconvoluted dissolution for Envarsus®. Population PK simulation showed that variability in the simulation was lower for Envarsus® compared to Advagraf®. The in silico predicted preferential absorption sites were the proximal and distal tract for Advagraf® and Envarsus®, respectively. The integration of experimental in vitro solubility, permeability and biorelevant dissolution data allowed to generate in silico tacrolimus concentrations for two different MR formulations. This permitted to compare the two formulations in a single PK profile, in a simulated population PK study and with respect to their absorption sites. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. In vitro characterization and release study of Ambroxol hydrochloride matrix tablets prepared by direct compression.

    Science.gov (United States)

    Abd-Elbary, A; Haider, M; Sayed, S

    2012-01-01

    A series of either hydrophilic or hydrophobic polymers were used to prepare controlled release Ambroxol hydrochloride (AMX) matrix tablets by direct compression. Both the compatibility and flow properties of AMX/polymer mixtures were investigated. The effect of the amount and type of polymer on the physical properties and in vitro drug release was studied and compared to commercially available Ambroxol(®) SR capsules. A kinetic study of the release profile of AMX from the prepared matrix tablets was performed. All excipients used in the study were compatible with the model drug. AMX/drug mixtures containing sodium alginate (NA) and hydroxypropylmethyl cellulose (HPMC) showed better flow properties than other polymers used in the study. The in vitro drug release studies showed that matrix tablets formulae containing 10% HPMC (S7) or a combination of 30% NA and 5% HPMC (Ah) exhibited a higher ability to control the release of AMX. The kinetic study revealed that a diffusion controlled mechanism prevailed except when carbopol was used. Formula Ah followed a non-fickian diffusion mechanism similar to Ambroxol(®) SR capsules. Both formulae S7 and Ah could be considered as potential candidates for formulation of AMX controlled release matrix tablets.

  3. Controlled release of dutasteride from biodegradable microspheres: in vitro and in vivo studies.

    Directory of Open Access Journals (Sweden)

    Xiangyang Xie

    Full Text Available The aim of the present work was to study the in vitro/in vivo characteristics of dutasteride loaded biodegradable microspheres designed for sustained release of dutasteride over four weeks. An O/W emulsion-solvent evaporation method was used to incorporate dutasteride, which is of interest in the treatment of benign prostatic hyperplasia (BPH, into poly(lactide-co-glycolide (PLGA. A response surface method (RSM with central composite design (CCD was employed to optimize the formulation variables. A prolonged in vitro drug release profile was observed, with a complete release of the entrapped drug within 28 days. The pharmacokinetics study showed sustained plasma drug concentration-time profile of dutasteride loaded microspheres after subcutaneous injection into rats. The in vitro drug release in rats correlated well with the in vivo pharmacokinetics profile. The pharmacodynamics evaluated by determination of the BPH inhibition in the rat models also showed a prolonged pharmacological response. These results suggest the potential use of dutasteride loaded biodegradable microspheres for the management of BPH over long periods.

  4. Long-term release of fluoride from fissure sealants-In vitro study.

    Science.gov (United States)

    Kosior, Piotr; Dobrzyński, Maciej; Korczyński, Mariusz; Herman, Katarzyna; Czajczyńska-Waszkiewicz, Agnieszka; Kowalczyk-Zając, Małgorzata; Piesiak-Pańczyszyn, Dagmara; Fita, Katarzyna; Janeczek, Maciej

    2017-05-01

    The intensity of the cariostatic activity of fluoride ions can be attributed to their multidirectional influence on the caries process. They are an irreplaceable factor that helps sustain mineral balance of dental tissues, simultaneously demonstrating antibacterial properties. As a consequence, many manufacturers of fissure sealants include fluoride ions in their products. The aim of this in vitro study was to determine long-term fluoride release from four fissure sealants (Conseal F, Fissurit FX, Delton Fs+, Admira Seal). During a 14-week-long observation, all the materials showed a relatively constant level of F- release; however, it is crucial to mention that within the first 48h, the most significant increase in fluoride release was found for Fissurit and Delton sealants. Based on the overall assessment, the highest total amount of the released fluoride ions was observed for Delton, and the lowest level was reported for Admira Seal. Copyright © 2017 Elsevier GmbH. All rights reserved.

  5. Release Characteristics In Vitro and In Vivo of In Situ Gels for a Novel Peptide Compared with Low-Molecular-Weight Hydrophilic Drug.

    Science.gov (United States)

    Zhang, Guiying; Hu, Jie; Meng, Qingbin; Wang, Tao; Yang, Xi; Gao, Lijun; Quan, Dongqin

    2017-01-01

    The thermo-sensitive in situ gels based on copolymers are attractive as an injectable drug delivery carriers for sustained releasing of hydrophilic drugs. The purposes of this work are to investigate the release behavior in vitro and pharmacokinetic profiles in vivo of peptide and lowmolecular- weight hydrophilic drug loaded in the in situ gels. A triblock copolymer PLGA-PEG-PLGA (1402-1000-1402) 1115A (1115A) was synthesized and its rheological and gelatin properties were evaluated. The temperature-sensitive in situ gels based on 1115A of LXT-101, a polypeptide drug, were prepared and the release characteristics in vitro and pharmacokinetic behavior in vivo were investigated. Meanwhile, naltrexone hydrochloride (NTX), a water-soluble low-molecular-weight drug was chosen as the model drug and the in situ gels were also prepared and studied comparatively. Slow-release characteristics were observed in vitro with in situ gels of LXT-101 and NTX. The release profiles and the mechanisms were different manifested by that NTX was released from in situ gels faster and more completely than LXT-101. Otherwise, the release pattern of LXT-101 showed a biphasic mechanism, an initial Fickian diffusion followed by a combination of degradation and diffusion at a later stage. The results of pharmacokinetic study indicated that a sustained release behavior could be obtained with MRT0-t (30.34 ± 12.47) h for LXT-101 and MRT0-t (2.37 ± 0.876) h for NTX, about 10 and 4 times longer than those of aqueous solution respectively. The pharmacodynamics studies in vivo further showed that in situ gel formulations of LXT-101 could sustain efficacy 6 days compared with only 1 day for aqueous solutions. The results of release behavior in vitro and in vivo indicated that in situ gels with copolymer 1115A could be served as carriers for delay-released drug delivery systems and might be more suitable for polypeptide drugs compared to low-molecular-weight hydrophilic drugs. Copyright© Bentham

  6. An in vitro study of the release capacity of the local anaesthetics from siloxane matrices.

    Science.gov (United States)

    Preda, Gabriela; Rogobete, Alexandru Florin; Săndesc, Dorel; Bedreag, Ovidiu Horea; Cradigati, Carmen Alina; Sarandan, Mirela; Papurica, Marius; Popovici, Sonia Elena; Dragomirescu, Monica

    2016-10-01

    In the field of anaesthesia and intensive care, the controlled release systems capable of delivering constantly local anaesthetics are of interest because of the advantages brought to pain management. In this paper we presented the release profiles by usage of siloxane matrices of two common local anaesthetics, lidocaine and bupivacaine, analysed in vitro. The siloxane matrices were obtained in accordance with the methods described in the specialized literature, tetraethoxysilane (TEOS) and tetramethoxysilane (TMOS) were used as precursors. Lidocaine and bupivacaine were encapsulated in the synthesized gels. The controlled release was performed in vitro artificial systems in which temperature (30°C, 36.5°C, 40°C) and pH (6, 7, 8) have varied. Following the analysis of the artificial systems similar profiles were highlighted for both local anaesthetics. Statistically significant differences were identified (p < 0.05) for systems where the release occurred at temperatures above 36.5°C. There were no statistically significant differences regarding the influence of pH, the type of the entrapped anaesthetic or the type of the precursor used in the synthesis of siloxane matrices. According to this experimental study, the pH, the type of precursor or the type of anaesthetic does not statistically influence the release profile from the studied system. In conclusion, these systems are promising for obtaining pharmaceutical preparations which can be used in current clinical practice. Several studies on controlled release siloxane systems should be carried out both in vitro and in vivo in order to exclude possible toxicity and histopathological effects.

  7. In vitro release of diclofenac diethylamine from gels: evaluation of generic semisolid drug products in Brazil

    Directory of Open Access Journals (Sweden)

    Karin Goebel

    2013-06-01

    Full Text Available In order for the pharmacological action of a topical dermal drug product to occur, the drug must first be released from the vehicle to be available to penetrate the skin layers and reach the site of action. Drug release is mainly dependent on the characteristics of the formulation. Currently, to register a generic or a similar drug product in Brazil performance testing of topical drug products for local action is not required. In this context, this aim of this study was to evaluate the in vitro release of commercial diclofenac diethylamine gel products available on the Brazilian pharmaceutical market, using the vertical diffusion cell method. Factors which may influence the test, such as the type of membrane used, and the effect of the formulation characteristics on the diffusion rate were evaluated. Brazilian legislation currently allows generic drug products to contain excipients other than the reference drug, which may affect the drug release from the vehicle. Only one of the four generic drug products tested could be considered equivalent to the reference Cataflam Emulgel®. The cellulose acetate and polyethersulfone membranes tested were found to be interchangeable in the in vitro release studies carried out on this product.

  8. Dimorphic ejaculates and sperm release strategies associated with alternative mating behaviors in the squid.

    Science.gov (United States)

    Apostólico, Lígia H; Marian, José E A R

    2017-11-01

    Sperm competition is a powerful postcopulatory selective force influencing male adaptations associated with increasing fertilization success, and it is usually related to the evolution of different strategies of ejaculate expenditure between individuals. Ejaculates may also be influenced by additional selective pressures associated with sperm competition, such as timing between insemination and fertilization, female reproductive tract morphology, and fertilization environment. Also, males that adopt alternative mating tactics may face distinct sperm competition pressures, which may lead to the evolution of intraspecific diversity in ejaculates. In loliginid squids, males with alternative reproductive tactics (sneakers and consorts) differ not only in mating behavior, but also transfer spermatophores into two distinct sites within the female. Here, we compared structure and functioning of spermatophores between sneakers and consorts in the squid Doryteuthis plei applying microscopy techniques and in vitro experiments. Sneakers and consorts exhibit differences in spermatophore structure that lead to distinct spermatophoric reactions and spermatangium morphologies. Moreover, in sneakers, sperm release lasts longer and their sperm show an aggregative behavior not detected in consorts. Slow sperm release may be a strategy to guarantee longer sperm provision, given the wide interval between sneaker mating and egg release. For consorts, in turn, intense and quick sperm discharge may be advantageous, as timing between mating and egg-laying is relatively short. Within the complex squid mating system, factors such as (i) different fertilization sites and (ii) interval between mating and egg release may also influence sperm competition, and ultimately shape the evolution of divergent ejaculates between dimorphic males. © 2017 Wiley Periodicals, Inc.

  9. Studies on Flowability, Compressibility and In-vitro Release of Terminalia Chebula Fruit Powder Tablets

    Science.gov (United States)

    Satya Prakash, Singh; Patra, Ch Niranjan; Santanu, Chakraborty; Hemant Kumar, Pandit; Patro, V Jagannath; Devi, M Vimala

    2011-01-01

    The dried fruit of Terminalia chebula is widely used for its laxative properties. The objective of the present study was to examine the flowability and compressibility of Terminalia chebula fruit powder, subsequently developing its tablet formulations by utilizing wet granulation and direct compression technology. Initial studies on flowability and compressibility revealed that the fruit powder flows poorly, is poorly compressible and mucilaginous in nature. The consolidation behaviors of the fruit powder and of its tablet formulations were studied using the Kawakita, Heckel and Leuenberger equations. Kawakita analysis revealed reduced cohesiveness hence improved flowability was achieved in formulations prepared by direct compression and the wet granulation technique. The Heckel plot showed that the Terminalia chebula fruit powder when formulated using direct compression showed initial fragmentation followed by plastic deformation and that the granules exhibited plastic deformation without initial fragmentation. The compression susceptibility parameter obtained from the Leuenberger equation for compacts formed by using the direct compression and wet granulation techniques indicated that the maximum crushing strength is reached faster and at lower compression pressures. The Tannin content (with reference to standard tannin) in fruit powder and tablet formulations was determined by UV spectrophotometry at 273 nm. The in-vitro dissolution study in simulated SGF (without enzymes) showed more than a 90% release of tannin from the tablets with in 1 h. The brittle fracture index value revealed that tablets prepared from granules showed less fracture tendency in comparison to those formed by direct compression formulation. From this study, it was concluded that the desired flowability, compressibility and compactibility of Terminalia chebula fruit powder can be obtained by using the direct compression and wet granulation techniques. PMID:24250371

  10. Calcein release behavior from liposomal bilayer; influence of physicochemical/mechanical/structural properties of lipids.

    Science.gov (United States)

    Maherani, Behnoush; Arab-Tehrany, Elmira; Kheirolomoom, Azadeh; Geny, David; Linder, Michel

    2013-11-01

    The design of the drug delivery depends upon different parameters. One of the most noticeable factors in design of the drug delivery is drug-release profile which determines the site of action, the concentration of the drug at the time of administration, the period of time that the drug must remain at a therapeutic concentration. To get a better understanding of drug release, large unilamellar liposomes containing calcein were prepared using 1,2-dioleoyl-sn-glycero-3-phosphocholine, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine and 1,2-palmitoyl-sn-glycero-3-phosphocholine, and a mixture of them; calcein was chosen as a model of hydrophilic drug. The calcein permeability across liposomal membrane (with different compositions) was evaluated on the basis of the first-order kinetic by spectrofluorometer. Also, the effects of liposome composition/fluidity as well as the incubation temperature/pH were investigated. Furthermore, we simulated the digestion condition in the gastrointestinal tract in humans, to mimic human gastro-duodenal digestion to monitor calcein release during the course of the digestion process. In vitro digestion model ''pH stat'' was used to systematically examine the influence of pH/enzyme on phospholipid liposomes digestion under simulated gastro-duodenal digestion. The results revealed that calcein permeates across liposomal membrane without membrane disruption. The release rate of calcein from the liposomes depends on the number and fluidity of bilayers and its mechanical/physical properties such as permeability, bending elasticity. Chemo-structural properties of drugs like as partition coefficient (Log P), H-bonding, polar surface area (PSA) are also determinative parameter in release behavior. Finally, stimulated emission depletion (STED) microscopy was used to study calcein translocation through liposomal bilayers. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  11. Chlorhexidine Salt-Loaded Polyurethane Orthodontic Chains: In Vitro Release and Antibacterial Activity Studies

    OpenAIRE

    Padois, Karine; Bertholle, Valérie; Pirot, Fabrice; Hyunh, Truc Thanh Ngoc; De Rossi, Alessandra; Colombo, Paolo; Falson, Françoise; Sonvico, Fabio

    2012-01-01

    The widespread use of indwelling medical devices has enormously increased the interest in materials incorporating antibiotics and antimicrobial agents as a means to prevent dangerous device-related infections. Recently, chlorhexidine-loaded polyurethane has been proposed as a material suitable for the production of devices which are able to resist microbial contamination. The aim of the present study was to characterize the in vitro release of chlorhexidine from new polymeric orthodontic chai...

  12. Enteric-coated sustained-release nanoparticles by coaxial electrospray: preparation, characterization, and in vitro evaluation

    Science.gov (United States)

    Hao, Shilei; Wang, Bochu; Wang, Yazhou; Xu, Yingqian

    2014-02-01

    Enteric-coated formulations can delay the release of drugs until they have passed through the stomach. However, high concentration of drugs caused by rapidly released in the small intestine leads to the intestinal damage, and frequent administration would increase the probability of missing medication and reduce the patient compliance. To solve the above-mentioned problems, aspirin-loaded enteric-coated sustained-release nanoparticles with core-shell structure were prepared via one-step method using coaxial electrospray in this study. Eudragit L100-55 as pH-sensitive polymer and Eudragit RS as sustained-release polymer were used for the outer coating and inner core of the nanoparticles, respectively. The maximum loading capacity of nanoparticles was 23.66 % by changing the flow rate ratio of outer/inner solutions, and the entrapment efficiency was nearly 100 %. Nanoparticles with core-shell structure were observed via fluorescence microscope and transmission electron microscope. And pH-sensitive and sustained drug release profiles were observed in the media with different pH values (1.2 and 6.8). In addition, mild cytotoxicity in vitro was detected, and the nanoparticles could be taken up by Caco-2 cells within 1.0 h in cellular uptake study. These results indicate that prepared enteric-coated sustained-release nanoparticles would be a more safety and effective carrier for oral drug delivery.

  13. Inhibition of serotonin release by bombesin-like peptides in rat hypothalamus in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Saporito, M.S.; Warwick, R.O. Jr.

    1989-01-01

    We investigated the activity of bombesin (BN), neuromedin-C (NM-C) and neuromedin-B (NM-B) on serotonin (5-HT) release and reuptake in rat hypothalamus (HYP) in vitro. BN and NM-C but not NM-B decreased K/sup +/ evoked /sup 3/H-5-HT release from superfused HYP slices by 25%. Bacitracin, a nonspecific peptidase inhibitor, reversed the inhibitory effect of BN on K/sup +/ evoked /sup 3/H-5-HT release. Phosphoramidon (PAN, 10 /mu/M) an endopeptidase 24.11 inhibitor, abolished the inhibitory effect of BN, but not NM-C, on K/sup +/ evoked /sup 3/H-5-HT release. The peptidyl dipeptidase A inhibitor enalaprilat (ENP, 10 /mu/M), enhanced both BN and NM-C inhibition of /sup 3/H-5-HT release. Bestatin (BST, 10 /mu/M) had no effect on BN or NM-C inhibitory activity on /sup 3/H-5-HT release. Neither BN, NM-C nor NM-B affected reuptake of /sup 3/H-5-HT into HYP synaptosomes alone or in combination with any of the peptidase inhibitors, nor did these peptides alter the ability of fluoxetine to inhibit /sup 3/H-5-HT uptake.

  14. Dehydroepiandrosterone inhibits the spontaneous release of superoxide radical by alveolar macrophages in vitro in asbestosis

    Energy Technology Data Exchange (ETDEWEB)

    Rom, W.N.; Harkin, T. (New York Univ. Medical Center, New York (United States))

    1991-08-01

    Asbestosis is characterized by an alveolar macrophage alveolitis with injury and fibrosis of the lower respiratory tract. Alveolar macrophages recovered by bronchoalveolar lavage spontaneously release exaggerated amounts of oxidants including superoxide anion and hydrogen peroxide that may mediate alveolar epithelial cell injury. Dehydroepiandrosterone (DHEA) is a normally occurring adrenal androgen that inhibits glucose-6-phosphate dehydrogenase, the initial enzyme in the pentose phosphate shunt necessary for NADPH generation and superoxide anion formation. In this regard, the authors hypothesized that DHEA may reduce asbestos-induced oxidant release. DHEA added in vitro to alveolar macrophages lavaged from 11 nonsmoking asbestos workers significantly reduced superoxide anion release. DHEA is an antioxidant and potential anticarcinogenic agent that may have a therapeutic role in reducing the increased oxidant burden in asbestos-induced alveolitis of the lower respiratory tract.

  15. Preparation and In vitro Characterization of Alprazolam Extended- Release Tablets Using HPMC 4000cps

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Avadi

    2016-06-01

    Full Text Available The main aim of this study was preparation and evaluation of extended - release system of the anxiolytic substance. Alprazolam is a short-acting benzodiazepine with general properties similar to those of diazepam. Our studies focused on development of extended drug delivery system based on Hydroxy Propyl Methyl Cellulose (HPMC 4000cps as retard agent and Polyvinylpyrrolidone (PVP k30 as binder using factorial design. All prepared matrix tablets were considered for physicochemical evaluation and drug content. In vitro release study of matrix tablets for all formulations has shown that HPMC is the main component in retarding of alprazolam in dissolution medium. The optimum formulation (30% HPMC 4000 and 10% PVP with suitable release profile according to criteria of United State Pharmacopoeia has selected for stability studies according to ICH guidelines.

  16. In vitro release studies of insulin from lipid implants in solution and in a hydrogel matrix mimicking the subcutis

    DEFF Research Database (Denmark)

    Jensen, Sabrine S; Jensen, Henrik; Møller, Eva H

    2016-01-01

    Widely accepted in vitro methodologies for sustained release parenteral drug formulations remain to be established. Hydrogels have been proposed as a release matrix more closely resembling the in vivo conditions for formulations intended for subcutaneous administration. The perspective of the cur......Widely accepted in vitro methodologies for sustained release parenteral drug formulations remain to be established. Hydrogels have been proposed as a release matrix more closely resembling the in vivo conditions for formulations intended for subcutaneous administration. The perspective...... sustained release of the model protein insulin and investigate the release into 0.5% (w/v) agarose hydrogels, pH7.40, using UV imaging- and a gel sampling-based release testing method. These results were compared to insulin release into well agitated buffer solution. Irrespective of the applied in vitro...... solution was faster as compared to release into agarose hydrogel. This was ascribed to the additional mass transfer resistance provided by the agarose hydrogel. Interestingly, the release profiles of insulin from implants with an initial drug load of 20% (w/w) obtained by the three in vitro methods were...

  17. Sulfanilamide in solution and liposome vesicles; in vitro release and UV-stability studies

    Directory of Open Access Journals (Sweden)

    Sanja Petrović

    2017-12-01

    Full Text Available The main goal of this study was to develop a liposome formulation with sulfanilamide and to investigate the liposomes impact on its release and stability to the UV-A/UV-B and UV-C irradiation. Liposome dispersions with incorporated sulfanilamide were prepared by thin-film hydration method and liposomes role to the sulfanilamide release was investigated by using a dialysis method. Comparatively, sulfanilamide in phosphate buffer solution was subject to release study as well to the UV irradiation providing for the possibilities of kinetics analysis. In vitro drug release study demonstrated that 20% of sulfanilamide was released from liposomes within 1 h that is approximately twice as slower as in the case of dissolved sulfanilamide in phosphate buffer solution. The kinetic release process can be described by Korsmeyer–Peppas model and according to the value of diffusion release exponent it can be concluded that drug release mechanism is based on the phenomenon of diffusion. The sulfanilamide degradation in phosphate buffer solution and liposomes is related to the formation of UV-induced degradation products that are identified by UHPLC/MS analysis as: sulfanilic acid, aniline and benzidine. The UV-induced sulfanilamide degradation in the phosphate buffer solution and liposome vesicles fits the first- order kinetic model. The degradation rate constants are dependent on the involved UV photons energy input as well as sulfanilamide microenvironment. Liposome microenvironment provides better irradiation sulfanilamide stability. The obtained results suggest that liposomes might be promising carriers for delayed sulfanilamide delivery and may serve as a basis for further research.

  18. Development and in vitro evaluation of mesalamine delayed release pellets and tableted reservoir-type pellets.

    Science.gov (United States)

    Bendas, Ehab R; Christensen, J Mark; Ayres, James W

    2010-04-01

    The basic objective of this study was to develop a novel technique that aids in compaction of coated pellets into tablets and obtain a release pattern from compressed pellets resembling the same pattern before compression. Multi-unit dosage forms of mesalamine targeted to the colon were formulated by extrusion-spheronization, and then coated with Eudragit S (30%). These pellets were filled into gelatin capsules or further formulated and compressed into tablets. Tablets for colonic delivery of mesalamine were prepared by mixing the coated beads with cushioning agents like stearic acid and Explotab, or by applying an additional coat of gelatin (4% weight gain) onto the Eudragit S coated pellets, and then compressing into tablets (tableted reservoir-type pellets). Then additional coating of the tablets prepared by the coating technique was applied utilizing Eudragit L 100-55 (5% weight gain). This technique provides additive protection for the coated beads to withstand the compression force during tableting. Excellent in vitro dissolution results were obtained, which were comparable to the results of the release of mesalamine from uncompressed beads filled in capsules. Mesalamine release from the capsules was 0.3% after 2 hours in gastric pH, 0.37% was released after an additional 1 hour in pH 6, and 89% was released after 1.5 hours in colonic pH 7.2. Various formulation and process parameters have to be optimized in order to obtain tableted reservoir-type pellets having the same release properties as the uncompressed pellets. The coating technique delays the release of mesalamine until the beads reach the terminal ileum and colon. Once released in the colon, mesalamine is minimally absorbed and can act locally to treat ulcerative colitis.

  19. Potential inhibition of demineralization in vitro by fluoride-releasing sealants.

    Science.gov (United States)

    Salar, David V; García-Godoy, Franklin; Flaitz, Catherine M; Hicks, M John

    2007-04-01

    The incorporation of fluoride into sealants has been viewed as a viable way to prevent pit-and-fissure caries by potential inhibition of demineralization through the release of fluoride to enamel. The authors conducted a study to examine the effect of a recently introduced fluoride-releasing sealant (ProSeal, Reliance Orthodontic Products, Itasca, Ill.) on enamel demineralization in an in vitro artificial caries system. The authors randomly assigned 45 extracted human third molars to three treatment groups receiving either conventional sealant without fluoride (Group 1), fluoride-releasing sealant (Group 2) or glass ionomer sealant with high fluoride release (Group 3). They placed cavity preparations on the buccal surfaces of the molars and filled them with the assigned material. They placed acid-resistant varnish on the specimens' enamel surfaces to within 1 millimeter of the sealant, leaving a 1-mm rim of sound enamel available for in vitro enamel caries formation. They thermocycled the teeth (500 cycles) in artificial saliva. They subjected the teeth to an in vitro artificial caries challenge for six weeks to produce caries-like lesions in enamel adjacent to the sealant materials. The authors took longitudinal sections from each tooth, immersed them in water and examined them via polarized light microscopy to determine wall lesion frequencies. The mean (+/- standard deviation) lesion depths were 232 +/- 17 micrometers for Group 1, 144 +/- 21 mum for Group 2 and 128 +/- 15 mum for Group 3. The wall lesion frequency was 12 percent for Group 1 and 7 percent for both Groups 2 and 3. There was a significant difference (P sealant substantially reduces the amount of enamel demineralization adjacent to the material. ProSeal provided increased demineralization inhibition compared with a conventional sealant containing no fluoride, but less than that shown by a glass ionomer sealant. ProSeal's physical properties and cariostatic effects may allow for applications beyond

  20. Effect of methylcellulose on the formation and drug release behavior of silk fibroin hydrogel.

    Science.gov (United States)

    Park, Cho Hee; Jeong, Lim; Cho, Donghwan; Kwon, Oh Hyeong; Park, Won Ho

    2013-10-15

    In this study, methylcellulose (MC) was used to control the gelation time of silk fibroin (SF) aqueous solution. The gelation time was measured using a Vibro Viscometer at 50 °C. Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and a texture meter were used to investigate the effect of MC on the hydrogelation of SF solution. SF/MC hydrogels could be formed by the addition of MC, although their gelation time was increased with MC content. To examine the conformational change of SF/MC hydrogels, time-resolved FT-IR spectra were obtained at constant temperature using a custom-made IR chamber. From FT-IR spectra focused on the amide I peak position, the transition of SF molecules in SF/MC solution from a random coil to a β-sheet structure was inhibited in the presence of MC molecules. In addition, the drug release of SF/MC hydrogels loaded with 5-aminosalicylic acid was studied in 2-dimensional (2-D) and 3-dimensional (3-D) conditions in vitro. The drug release behavior of SF or SF/MC hydrogels was measured using UV-Vis spectroscopy. The release rate of 5-aminosalicylic acid in SF/MC hydrogel was lower than that of SF hydrogel, which may be closely associated with the hydrophilic interaction between MC and 5-aminosalicylic acid. This approach to controlling the sol-gel transition and the drug release of SF hydrogels by the addition of MC will be useful in the design and tailoring of novel materials for biomedical applications. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Sustained-release of caffeine from a polymeric tablet matrix: An in vitro and pharmacokinetic study

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Donna [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117597 (Singapore); Zhao Bin [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117597 (Singapore); Moochhala, Shabbir [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117597 (Singapore)]. E-mail: mshabbir@dso.org.sg; Yang Yiyan [Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, 04-01, The Nanos, Singapore 138669 (Singapore)

    2006-07-25

    Caffeine is utilized as a stimulant to impart a desired level of alertness during certain working hours. Usually, a single dose of caffeine induces 2-3 h of alertness coupled with side effects whereas a longer effect of 8-12 h is very useful for both daily life and military action. Thus, there is a need to deliver the stimulant continuously to an individual at one time to impart an increased level of alertness for the period stated after administration. This study aimed to design a polymeric microparticle system for sustained delivery of caffeine using a polymeric matrix. Poly(ethylene oxide) (PEO) was used as the erodible matrix material and the caffeine polymeric tablets were fabricated by compression using a Graseby Specac hydraulic press. In vitro release profiles as well as the pharmacokinetics studies data were obtained. Caffeine tablets fabricated using various polymers showed a high initial burst release type profile as compared to the caffeine-PEO-tablet. The PK studies showed sustained delivery of caffeine resulted in two expected phenomena: a reduction in the initial high rate of caffeine release (burst release) as well as a reduction in the change in caffeine concentration in the systemic circulation. A simple two-component system for sustained-release caffeine formulation therefore has been achieved.

  2. Synthesis, characterization and in vitro release performance of the pegylated valnemulin prodrug.

    Science.gov (United States)

    Dong, Xinrui; Shu, Xueye; Wang, Yingnan; Niu, Zhaohuan; Xu, Shixia; Zhang, Yue; Zhao, Shuchun

    2017-11-28

    Valnemulin, successfully developed by Sandoz in 1984, is a new generation derivative of pleuromutilin related to tiamulin. Valnemulin has low water-solubility, a short half-life period, low bioavailability, and instability. The application of valnemulin was restricted. Therefore, finding a more moderate delivery system is necessary to improve the shortcomings of valnemulin. The purpose of the study was to improve the strong stability and the irritation caused by of valnemulin hydrochloride power through pegylated-valnemulin prodrug mode. The prepared pegylated-valnemulin prodrug was characterized and evaluated by in vitro release performance under buffer solutions with pH levels of 7.4 and 3.6. The loading rate of valnemulin in PEG-succinic-valnemulin prodrug was determined by ultraviolet spectrophotometer and high performance liquid chromatography (HPLC). HPLC with evaporative light scattering detector was applied to determine the amount of PEG-succinic acid. The loading rate of valnemulin in PEG-succinic-valnemulin prodrug was 6.46%. PEG-succinic-valnemulin prodrug demonstrated a satisfactory solubility of valnemulin with 523 mg·ml-1 and excellent stability verified by the stability experiment. The result of the in vitro release test showed that the prepared PEG-valnemulin prodrug has controlled release ability and the release rate of valnemulin from PEG-valnemulin prodrug with a pH of 7.4 was 64.98%, which was higher than that of pH3.6 with release rate of 31.90%. Therefore, the prepared PEG-succinic-valnemulin prodrug has great application potential.

  3. Tapentadol inhibits calcitonin gene-related peptide release from rat brainstem in vitro.

    Science.gov (United States)

    Greco, Maria Cristina; Lisi, Lucia; Currò, Diego; Navarra, Pierluigi; Tringali, Giuseppe

    2014-06-01

    We have previously developed an in vitro model of rat brainstem explants. The latter release sizable amounts of calcitonin gene-related peptide (CGRP); basal release can be stimulated by such secretagogues as high KCl concentrations, veratridine or capsaicine. In this paradigm we investigated the activity of the analgesic agent tapentadol; the effects of tapentadol were compared to those of a classical opioid receptor agonist, morphine, and the selective noradrenaline reuptake inhibitor reboxetine. Morphine inhibited basal CGRP release, with statistical significance from 1 nM onward and maximal (-44%) inhibition at 100 μM. Morphine also inhibited K(+)-stimulated peptide release, with a significant effect from 1 μM and maximal (-39%) decrease at 100 μM, but failed to inhibit release stimulated by 10 μM capsaicin. At variance, reboxetine had no effect on baseline CGRP outflow, but was able to inhibit both K(+)-stimulated [significant inhibition from 1 μM onward and maximal (-37%) decrease at 100 μM], and capsaicin-stimulated release [significant effect from 1 μM and maximal (-31%) decrease at 100 μM]. Likewise, tapentadol had no effect on baseline CGRP release up to 100 μM, but decreased secretion stimulated by 56 mM KCl or capsaicin, with significant effects from 0.1 and 1 μM respectively; maximal inhibition over 56 mM KCl and capsaicin stimuli was -29% and -31%, respectively. Naloxone antagonized the effect of morphine, but not those of reboxetine and tapentadol, on K(+)-stimulated CGRP secretion. In conclusion the present study provides consistent pharmacological evidence that tapentadol acts as a noradrenaline reuptake inhibitor agent in this experimental model. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Minocycline-released hydroxyapatite-gelatin nanocomposite and its cytocompatibility in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Dou Xiaochen; Zhu Xiaopeng; Zhou Jian; Cai Huaqiong; Li Quanli [Key Laboratory of Oral Disease Research of Anhui Province, Stomatologic Hospital and Collage, Anhui Medical University, Hefei (China); Tang Jian, E-mail: ql-li@126.com [Department of Orthopedic Surgery, The First Hospital of Anhui Medical University, Hefei (China)

    2011-04-15

    The incorporation of antibacterial agents into biomaterials is extremely desirable for repairing bone defects. Minocycline, a semi-synthetic tetracycline antibiotic, is active against aerobic, anaerobic, Gram-positive and Gram-negative bacteria, and can enhance bone formation, decrease connective tissue breakdown and diminish bone resorption. In this study, a novel minocycline-releasing biomaterial was synthesized using a biomimetic method. A measured amount of an acidic hydroxyapatite and minocycline solution was respectively added to a gelatin solution and kept at 40 deg. C and pH 7-8 for 2 h. The mixture was aged overnight, lyophilized and a hydroxyapatite-gelatin-minocycline composite was obtained. The composite was co-cultured with rat bone marrow stromal cells (BMSCs) in vitro. Our results show that nanohydroxyapatite was distributed evenly in the fibrils of the gelatin. Minocycline was incorporated into the composite and could be released from the composite particles slowly over 2 weeks in vitro. The composite promoted BMSC adhesion, proliferation and differentiation in vitro. The approach described here may provide a basis for the preparation of an antibacterial biomaterial for bone regeneration.

  5. In vitro gentamicin release from commercially available calcium-phosphate bone substitutes influence of carrier type on duration of the release profile

    Directory of Open Access Journals (Sweden)

    Bronckers Antonius LJJ

    2006-02-01

    Full Text Available Abstract Background Polymethyl-methacrylate (PMMA beads releasing antibiotics are used extensively to treat osteomyelitis, but require surgical removal afterwards because they do not degrade. Methods As an alternative option, this report compares the in vitro gentamicin release profile from clinically used, biodegradable carrier-materials: six injectable cements and six granule-types. Cement cylinders and coated granules containing 3% gentamicin were submerged in dH2O and placed in a 48-sample parallel drug-release system. At regular intervals (30, 90, 180 min. and then every 24 h, for 21 days, the release fluid was exchanged and the gentamicin concentration was measured. The activity of released gentamicin was tested on Staphylococcus aureus. Results All combinations showed initial burst-release of active gentamicin, two cements had continuous-release (17 days. The relative release of all cements (36–85% and granules (30–62% was higher than previously reported for injectable PMMA-cements (up to 17% and comparable to other biodegradable carriers. From the cements residual gentamicin could be extracted, whereas the granules released all gentamicin that had adhered to the surface. Conclusion The high release achieved shows great promise for clinical application of these biodegradable drug-carriers. Using the appropriate combination, the required release profile (burst or sustained may be achieved.

  6. In-vitro/In-vivo comparison of leuprolide acetate release from an in-situ forming plga system.

    Science.gov (United States)

    Mashayekhi, Roya; Mobedi, Hamid; Najafi, Jamal; Enayati, Marjan

    2013-07-15

    A poly (lactide-co-glycolide) (PLGA) implant was used to control the release profile of leuprolide acetate (LA) drug. The system is an in-situ polymeric precipitation system. And the formulation consisted of PLGA polymer, LA drug and N-methyl-2-pyrrolidon solvent with no additives. First, the formulation was injected into PBS solution for in-vitro studies and then it was administered to the animal models (female rats) for in-vivo release studies. The release profiles of leuprolide acetate were measured by UV spectrophotometry for a period of 28 days. The initial burst release of LA was 14% in in-vitro whereas it was 7% in in-vivo. In-vitro and in-vivo release profiles of LA had similar trends after 72 hours. However, the rate of LA release was slower in-vivo. This might be attributed to the limited diffusion process of solvent and the drug molecules. This could be due to presence of an additional pressure caused by the surrounding tissue and also the presence of small amount of water between cells in the subcutaneous site. Cross-section and surface of the implants were studied via scanning electron microscopy. Morphology of both in-vitro and in-vivo implants confirmed the release behaviours. No toxicity effects were reported in the histopathological assay. Furthermore, the pharmacological analysis showed more inactive ovaries due to release of LA.

  7. In-vitro/In-vivo Comparison of Leuprolide Acetate Release from an in-situ Forming Plga System

    Directory of Open Access Journals (Sweden)

    Roya Mashayekhi

    2013-07-01

    Full Text Available A poly (lactide-co-glycolide (PLGA implant was used to control the release profile of leuprolide acetate (LA drug. The system is an in-situ polymeric precipitation system. And the formulation consisted of PLGA polymer, LA drug and N-methyl-2-pyrrolidon solvent with no additives. First, the formulation was injected into PBS solution for in-vitro studies and then it was administered to the animal models (female rats for in-vivo release studies. The release profiles of leuprolide acetate were measured by UV spectrophotometry for a period of 28 days. The initial burst release of LA was 14% in in-vitro whereas it was 7% in in-vivo. In-vitro and in-vivo release profiles of LA had similar trends after 72 hours. However, the rate of LA release was slower in-vivo. This might be attributed to the limited diffusion process of solvent and the drug molecules. This could be due to presence of an additional pressure caused by the surrounding tissue and also the presence of small amount of water between cells in the subcutaneous site. Cross-section and surface of the implants were studied via scanning electron microscopy. Morphology of both in-vitro and in-vivo implants confirmed the release behaviours. No toxicity effects were reported in the histopathological assay. Furthermore, the pharmacological analysis showed more inactive ovaries due to release of LA.

  8. In vitro release from oil injectables for intra-articular administration: Importance of interfacial area, diffusivity and partitioning.

    Science.gov (United States)

    Thing, Mette; Larsen, Claus; Østergaard, Jesper; Jensen, Henrik; Larsen, Susan Weng

    2012-02-14

    Most in vitro methods for evaluating parenteral oil based depots are focusing on intramuscular or subcutaneous injection. For intra-articular injection other mechanisms may control the overall drug release rate due to a relatively smaller interfacial area and longer transport distance of the drug substance in the oil to the oil-synovial fluid interface. In the current work, an in vitro model for testing drug release from oil solutions intended for intra-articular injection was evaluated. The release of the model drugs naproxen, piroxicam and ropivaciane from a well-defined surface area of the lipophilic solutions were followed using an in vitro model based on a modified USP II paddle apparatus with modest agitation (50rpm) of the oil formulation. By alteration of the viscosity of the oil, the oil-water interfacial area, the oil volume and the stirring efficiency of the release medium, it was shown that the drug release rate was dependent on the drug diffusivity in the oil and the degree of agitation generated in the oil vehicle. In addition, the partitioning of the drug between the oil vehicle and the release media was found to influence the release rate. In combination with an improved understanding of in vivo drug release and distribution, the present work may form a promising foundation for future in vivoin vitro correlations. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. In vitro release and biological activities of Carum copticum essential oil (CEO) loaded chitosan nanoparticles.

    Science.gov (United States)

    Esmaeili, Akbar; Asgari, Azadeh

    2015-11-01

    In recent years, the unparalleled and functional properties of essential oils have been extensively reported, but the sensitivity of essential oils to environmental factors and their poor aqueous solubility have limited their applications in industries. Hence, we encapsulated CEO in chitosan nanoparticles by an emulsion-ionic gelation with pantasodium tripolyphosphate (TPP) and sodium hexametaphosphte (HMP), separately, as crosslinkers. The nanoparticles were analyzed by Fourier transform infrared spectroscopy (FT-IR), Ultraviolet-visible spectroscopy (UV-vis), differential scanning calorimetry (DSC), scanning electron microscope (SEM) and dynamic light scattering (DLS). The encapsulation efficiency (EE) and loading capacity (LC) of CEO in chitosan nanoparticles increased with the increase of initial CEO amount. The nanoparticles displayed an average size of 30-80nm with a spherical shape and regular distribution. In vitro release profiles exhibited an initial burst release and followed by a sustained CEO release at different pH conditions. The amount of CEO release from chitosan nanoparticles was higher in acidic pH to basic or neutral pH, respectively. The biological properties of CEO, before and after the encapsulation process were evaluated by 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and agar disk diffusion method, respectively. The results indicated the encapsulation of CEO in chitosan nanoparticles could be protected the quality. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. In vitro chlorhexidine release from alginate based microbeads for periodontal therapy.

    Directory of Open Access Journals (Sweden)

    Malte Scholz

    Full Text Available Periodontitis is one of the most common infectious diseases globally that, if untreated, leads to destruction of the tooth supporting tissues and finally results in tooth loss. Evidence shows that standard procedures as mechanical root cleaning could be supported by further treatment options such as locally applied substances. Due to gingival crevicular fluid flow, substances are commonly washed out off the periodontal pockets. The evaluation of administration techniques and the development of local drug releasing devices is thus an important aspect in periodontal research. This study describes the development and examination of a new alginate based, biodegradable and easily applicable drug delivery system for chlorhexidine (CHX. Different micro beads were produced and loaded with CHX and the release profiles were investigated by high performance liquid chromatography (HPLC. The in vitro-demonstrated release of CHX from alginate based beads shows comparable releasing characteristics as clinically approved systems. Yet many characteristics of this new delivery system show to be favourable for periodontal therapy. Easy application by injection, low production costs and multifunctional adaptions to patient related specifics may improve the usage in routine care.

  11. Chitosan based hydrogel assisted spongelike calcium phosphate mineralization for in-vitro BSA release.

    Science.gov (United States)

    Salama, Ahmed

    2017-12-07

    New chitosan-g- poly (3-sulfopropyl methacrylate), CHI-g-P(SPMA), hydrogel was prepared by free radical polymerization process and investigated as a template for biomimetic spongelike calcium phosphate mineralization in a solution mimicking physiological condition. Infrared spectroscopy, scanning electron microscopy, X-ray diffraction and transmission electron microscopy confirmed the predominant formation of rod-like hydroxyapatite. The swelling behavior of the nanocomposite was evaluated at different pHs and different saline concentrations. Bovine serum albumin (BSA), as a model protein drug, was loaded in the CHI-g-P(SPMA)/calcium phosphate hybrid. The BSA release behavior was investigated and the results suggested CHI-g-P(SPMA)/calcium phosphate hybrid as controlled release carrier. These results suggest that next generation of polysaccharides based hybrid materials could be interesting for biomedical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Effect of Lipid Composition on In Vitro Release and Skin Deposition of Curcumin Encapsulated Liposomes

    Directory of Open Access Journals (Sweden)

    Geethi Pamunuwa

    2016-01-01

    Full Text Available Liposomal encapsulation improves numerous physiochemical and biological properties of curcumin. The aim of this work was to impart slow release and skin delivery of curcumin via liposomal encapsulation. Liposomes were made using egg yolk phosphatidylcholine as the staple lipid while incorporating polysorbate 80 and stearylamine to prepare hybrid liposomes and positively charged liposomes, respectively. Negatively charged liposomes exhibited the highest encapsulation efficiencies (87.8±4.3% and loading capacities (3.4±0.2%. The sizes of all formulations were about 250 nm, while stearylamine increased the polydispersity index. Positively charged liposomes showed lower degradation temperatures than negatively charged liposomes by 10–15°C, attributable to the presence of stearylamine. The melting temperatures of positively charged liposomes (40–50°C were much higher than those of negatively charged liposomes (14-15°C, which may have affected release and skin deposition behavior of liposomes. The positively charged liposomes exhibited the slowest release of curcumin in phosphate buffered saline (pH 6.8 and the release profiles of all liposomal formulations conformed to the Gompertz model. The negatively charged liposomes facilitated the highest skin deposition of curcumin as revealed by studies conducted using excised pig ear skin. Concisely, positively and negatively charged liposomes were optimal for slow release and skin deposition of curcumin, respectively.

  13. Sustained Release of Lidocaine from Solvent-Free Biodegradable Poly[(d,l-Lactide-co-Glycolide] (PLGA: In Vitro and In Vivo Study

    Directory of Open Access Journals (Sweden)

    Yi-Chuan Kau

    2014-09-01

    Full Text Available Local anesthetics are commonly used for pain relief by regional nerve blocking. In this study, we fabricated solvent-free biodegradable pellets to extend the duration of lidocaine release without any significant local or systemic toxicity levels. To manufacture the pellets, poly[(d,l-lactide-co-glycolide] (PLGA was first pre-mixed with lidocaine powder into different ratios. The powder mixture was then compressed with a mold (diameter of 1, 5, 8 or 10 mm and sintered at 65 °C to form pellets. The in vitro release study showed that the lidocaine/PLGA pellets exhibited a tri-phase release behavior (a burst, a diffusion-controlled release and a degradation-dominated release and reached completion around day 28. Scanning electron microscope (SEM photos show that small channels could be found on the surfaces of the pellets on day 2. Furthermore, the polymer matrix swelled and fell apart on day 7, while the pellets became viscous after 10 days of in vitro elution. Perineural administration of the lidocaine/PLGA pellets produced anti-hypersensitivity effects lasting for at least 24 h in rats, significant when compared to the control group (a pure PLGA was pellet administered. In addition, no inflammation was detected within the nerve and in the neighboring muscle by histopathology.

  14. Micro- and nano bio-based delivery systems for food applications: In vitro behavior.

    Science.gov (United States)

    de Souza Simões, Lívia; Madalena, Daniel A; Pinheiro, Ana C; Teixeira, José A; Vicente, António A; Ramos, Óscar L

    2017-05-01

    Micro- and nanoencapsulation is an emerging technology in the food field that potentially allows the improvement of food quality and human health. Bio-based delivery systems of bioactive compounds have a wide variety of morphologies that influence their stability and functional performance. The incorporation of bioactive compounds in food products using micro- and nano-delivery systems may offer extra health benefits, beyond basic nutrition, once their encapsulation may provide protection against undesired environmental conditions (e.g., heat, light and oxygen) along the food chain (including processing and storage), thus improving their bioavailability, while enabling their controlled release and target delivery. This review provides an overview of the bio-based materials currently used for encapsulation of bioactive compounds intended for food applications, as well as the main production techniques employed in the development of micro- and nanosystems. The behavior of such systems and of bioactive compounds entrapped into, throughout in vitro gastrointestinal systems, is also tracked in a critical manner. Comparisons between various in vitro digestion systems (including the main advantages and disadvantages) currently in use, as well as correlations between the behavior of micro- and nanosystems studied through in vitro and in vivo systems were highlighted and discussed here for the first time. Finally, examples of bioactive micro- and nanosystems added to food simulants or to real food matrices are provided, together with a revision of the main challenges for their safe commercialization, the regulatory issues involved and the main legislation aspects. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Chloroaluminium phthalocyanine polymeric nanoparticles as photosensitisers: photophysical and physicochemical characterisation, release and phototoxicity in vitro.

    Science.gov (United States)

    de Paula, Carina Silva; Tedesco, Antonio Cláudio; Primo, Fernando Lucas; Vilela, José Mário Carneiro; Andrade, Margareth Spangler; Mosqueira, Vanessa Carla Furtado

    2013-06-14

    Nanoparticles of poly(d,l-lactide-co-glycolide), poly(d,l-lactide) and polyethylene glycol-block-poly(d,l-lactide) were developed to encapsulate chloroaluminium phthalocyanine (AlClPc), a new hydrophobic photosensitiser used in photodynamic therapy (PDT). The mean nanoparticle size varied from 115 to 274 nm, and the encapsulation efficiency ranged from 57% to 96% due to drug precipitation induced by different types of polymer. All nanoparticle formulations presented negative zeta potential values (-37 mV to -59 mV), explaining their colloidal stability. The characteristic photophysical parameters were analysed: the absorption spectrum profile, fluorescence quantum yield and transient absorbance decay, with similar values for free and nanoparticles of AlClPc. The time-resolved spectroscopy measurements for AlClPc triplet excited state lifetimes indicate that encapsulation in nanocapsules increases triplet lifetime, which is advantageous for PDT efficiency. A sustained release profile over 168 h was obtained using external sink method. An in vitro phototoxic effect higher than 80% was observed in human fibroblasts at low laser light doses (3 J/cm(2)) with 10 μM of AlClPc. The AlClPc loaded within polymeric nanocapsules presented suitable physical stability, improved photophysical properties, sustained released profile and suitable activity in vitro to be considered a promising formulation for PDT. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Polyacrylamide-chitosan hydrogels: in vitro biocompatibility and sustained antibiotic release studies.

    Science.gov (United States)

    Risbud, M V; Bhonde, R R

    2000-01-01

    Controlled drug delivery is gaining importance over the conventional methods of drug administration because of its inherent benefits. Self-regulated release from the delivery vehicle may enhance drug potency with a sustained action. The present study describes a novel hydrogel blend of polyacrylamide with chitosan for controlled delivery of antibiotics. Hydrogel was synthesized by cross-linking acrylamide-chitosan mixture (8:2 v/v) with N,N' methylene bisacrylamide. Hydrogel was characterized for surface morphology, hydrophilicity, pH-dependent swelling properties, cytotoxicity, and control release properties. Scanning electron microscopy (SEM) revealed the macroporous surface morphology of the matrix with average pore size at 104 +/- 7.61 mu. Hydrogel was found to be highly hydrophilic as assessed by octane contact angle (154.5 + 0.572) measurement. Hydrogel showed no cytotoxic effects on NIH3T3 and HeLa cells up to 40% of extract concentrations as determined by MTT and neutral red assay. This showed hydrogel biocompatibility and thus absence of deleterious effects of the hydrogel on cell viability and functionality. Hydrogels did not show any pH-dependent swelling profile, and they swelled considerably to achieve a swelling ratio of approximately 16.0 at the end of 24 hr. Amoxicillin was incorporated in the hydrogel matrix as a candidate antibiotic for release studies. In vitro release studies of amoxicillin revealed the sustained nature of delivery and matrix released 56.47 + 1.12% and 77.096 + 1.72% of amoxicillin at the end of 24 and 75 hr, respectively. Although in vivo studies are awaited, the present study provides enough documentation to consider polyacrylamide-chiotsan hydrogel as a possible candidate for controlled delivery of antibiotics.

  17. In vitro effect of. Delta. sup 9 -tetrahydrocannabinol to stimulate somatostatin release and block that of luteinizing hormone-releasing hormone by suppression of the release of prostaglandin E sub 2

    Energy Technology Data Exchange (ETDEWEB)

    Rettori, V.; Aguila, M.C.; McCann, S.M. (Univ. of Texas Southwestern Medical Center at Dallas (United States)); Gimeno, M.F.; Franchi, A.M. (Centro de Estudios Farmacologicos y de Principios Naturales, Buenos Aires (Argentina))

    1990-12-01

    Previous in vivo studies have shown that {Delta}{sup 9}-tetrahydrocannabinol (THC), the principal active ingredient in marijuana, can suppress both luteinizing hormone (LH) and growth hormone (GH) secretion after its injection into the third ventricle of conscious male rats. The present studies were deigned to determine the mechanism of these effects. Various doses of THC were incubated with either stalk median eminence fragments (MEs) or mediobasal hypothalamic (MBH) fragments in vitro. Although THC (10 nM) did not alter basal release of LH-releasing hormone (LHRH) from MEs in vitro, it completely blocked the stimulatory action of dopamine or nonrepinephrine on LHRH release. The effective doses to block LHRH release were associated with a blockade of synthesis and release of prostaglandin E{sub 2} (PGE{sub 2}) from MBH in vitro. In contrast to the suppressive effect of THC on LHRH release, somatostatin release from MEs was enhanced in a dose-related manner with a minimal effective dose of 1 nM. Since PGE{sub 2} suppresses somatostatin release, this enhancement may also be related to the suppressive effect of THC on PGE{sub 2} synthesis and release. The authors speculate that these actions are mediated by the recently discovered THC receptors in the tissue. The results indicate that the suppressive effect of THC on LH release is mediated by a blockade of LHRH release, whereas the suppressive effect of the compound on growth hormone release is mediated, at least in part, by a stimulation of somatostatin release.

  18. Polyvinyl Alcohol/Lithospermum Erythrorhizon Nanofibrous Membrane: Characterizations, In Vitro Drug Release, and Cell Viability

    Directory of Open Access Journals (Sweden)

    Ching-Wen Lou

    2017-11-01

    Full Text Available This study proposes an optimization process of the Lithospermum erythrorhizon (LE extraction with a higher purity of shikonin (SK. The influence of extraction temperature on the concentration of SK is examined, and an in vitro cell viability assay is used to examine the optimal concentration of SK. Afterwards, polyvinyl alcohol (PVA/LE solutions at ratios of 90/10, 80/20, and 70/30 w/w are electrospun into LE electrospun nanofibrous membranes (LENMs. The optimal manufacture parameters of LENMs are evaluated based on the test results of in vitro drug release test and cell viability assay. The optimal concentration occurs when the extraction temperature is −10 °C. The purity of the LE extract reaches 53.8% and the concentration of SK is 1.07 mg/mL. Moreover, the cell viability of nanofibrous membranes significantly increases to 136.8% when 0.7 μM SK is used. The diameter of nanofibers of LENM is decreased by 43.9% when the ratio of PVA solution to LE extract is 70/30 (w/w. 80/20 (w/w LENM has the maximum amount of drug release of 79% for a continuous period of 48 h. In particular, 90/10 (w/w LENM can create the maximum cell proliferation of 157.5% in a 24-h in vitro cell viability assay. This suggests that LENM has great potential to be used in facilitating tissue regeneration and wound healing.

  19. Nanoemulsion containing dapsone for topical administration: a study of in vitro release and epidermal permeation.

    Science.gov (United States)

    Borges, Vinécius Raphael de Almeida; Simon, Alice; Sena, Adrian Ricardo Cuello; Cabral, Lúcio Mendes; de Sousa, Valéria Pereira

    2013-01-01

    Topical administration of dapsone can be an alternative route for treatment of leprosy and can also provide new therapeutic applications for an established drug. However, the physicochemical properties of dapsone make it difficult to incorporate into conventional formulations. The current study was directed toward developing a stable nanoemulsion that contains dapsone which can be adapted for topical use. Nanoemulsions were prepared using isopropyl myristate or n-methyl-pyrrolidone as the oil phase, and characterized according to their mean droplet size, conductivity, refractive index, pH, drug content, and stability. The in vitro release of dapsone and its ability to permeate the epidermis were also evaluated. Physicochemical characterization demonstrated that nanosystems were formed, which had a uniform droplet distribution and a pH compatible with the skin surface. Use of n-methyl-pyrrolidone provided a greater nanoemulsion region and higher solubilization of dapsone, and increased the in vitro release rate when compared with a nanoemulsion prepared using isopropyl myristate. However, use of isopropyl myristate promoted an increase in in vitro epidermal permeation that followed the Higuchi model. This demonstrates the ability of a nanosystem to influence permeation of dapsone through the skin barrier. Furthermore, the nanoemulsions developed and evaluated here had ideal physicochemical stability over a 3-month period. Incorporation of dapsone into a nanoemulsion may be a promising system for enabling topical delivery of dapsone, while minimizing skin permeation, for the treatment of acne. The method developed here used isopropyl myristate as the oil phase, and promoted permeation of dapsone through the skin barrier for the treatment of leprosy upon use of n-methyl-pyrrolidone as the oil phase.

  20. Nanoemulsion containing dapsone for topical administration: a study of in vitro release and epidermal permeation

    Science.gov (United States)

    de Almeida Borges, Vinécius Raphael; Simon, Alice; Sena, Adrian Ricardo Cuello; Cabral, Lúcio Mendes; de Sousa, Valéria Pereira

    2013-01-01

    Background Topical administration of dapsone can be an alternative route for treatment of leprosy and can also provide new therapeutic applications for an established drug. However, the physicochemical properties of dapsone make it difficult to incorporate into conventional formulations. The current study was directed toward developing a stable nanoemulsion that contains dapsone which can be adapted for topical use. Methods Nanoemulsions were prepared using isopropyl myristate or n-methyl-pyrrolidone as the oil phase, and characterized according to their mean droplet size, conductivity, refractive index, pH, drug content, and stability. The in vitro release of dapsone and its ability to permeate the epidermis were also evaluated. Results Physicochemical characterization demonstrated that nanosystems were formed, which had a uniform droplet distribution and a pH compatible with the skin surface. Use of n-methyl-pyrrolidone provided a greater nanoemulsion region and higher solubilization of dapsone, and increased the in vitro release rate when compared with a nanoemulsion prepared using isopropyl myristate. However, use of isopropyl myristate promoted an increase in in vitro epidermal permeation that followed the Higuchi model. This demonstrates the ability of a nanosystem to influence permeation of dapsone through the skin barrier. Furthermore, the nanoemulsions developed and evaluated here had ideal physicochemical stability over a 3-month period. Conclusion Incorporation of dapsone into a nanoemulsion may be a promising system for enabling topical delivery of dapsone, while minimizing skin permeation, for the treatment of acne. The method developed here used isopropyl myristate as the oil phase, and promoted permeation of dapsone through the skin barrier for the treatment of leprosy upon use of n-methyl-pyrrolidone as the oil phase. PMID:23411489

  1. Release of sICAM-1 in oocytes and in vitro fertilized human embryos.

    Directory of Open Access Journals (Sweden)

    Monica Borgatti

    Full Text Available During the last years, several studies have reported the significant relationship between the production of soluble HLA-G molecules (sHLA-G by 48-72 hours early embryos and an increased implantation rate in IVF protocols. As consequence, the detection of HLA-G modulation was suggested as a marker to identify the best embryos to be transferred. On the opposite, no suitable markers are available for the oocyte selection.The major finding of the present paper is that the release of ICAM-1 might be predictive of oocyte maturation. The results obtained are confirmed using three independent methodologies, such as ELISA, Bio-Plex assay and Western blotting. The sICAM-1 release is very high in immature oocytes, decrease in mature oocytes and become even lower in in vitro fertilized embryos. No significant differences were observed in the levels of sICAM-1 release between immature oocytes with different morphological characteristics. On the contrary, when the mature oocytes were subdivided accordingly to morphological criteria, the mean sICAM-I levels in grade 1 oocytes were significantly decreased when compared to grade 2 and 3 oocytes.The reduction of the number of fertilized oocytes and transferred embryos represents the main target of assisted reproductive medicine. We propose sICAM-1 as a biochemical marker for oocyte maturation and grading, with a possible interesting rebound in assisted reproduction techniques.

  2. In vitro release profiles of PLGA core-shell composite particles loaded with theophylline and budesonide.

    Science.gov (United States)

    Yeh, Hsi-Wei; Chen, Da-Ren

    2017-08-07

    We investigated the effects of drug loading location, matrix material and shell thickness on the in vitro release of combinational drugs from core-shell PLGA (i.e., poly(lactic-co-glycolic acid)) particles. Budesonide and Theophylline were selected as highly hydrophobic and hydrophilic model drugs, respectively. The dual-capillary electrospray (ES) technique, operated at the cone-jet mode, was used to produce samples of drug-loaded core-shell composite particles with selected overall sizes, polymer materials, and shell thicknesses. Theophylline and Budesonide were loaded at different locations in a PLGA composite particle. This study illustrated how the aforementioned factors affect the release rates of Budesonide and Theophylline loaded in core-shell PLGA composites. We further identified that core-shell composite particles with both model drugs loaded in the core and with matrix PLGA polymers of low molecular weights and low LA/GA ratios are the best formulation for the sustained release of highly hydrophilic and hydrophobic active pharmaceutical ingredients from PLGA composite particles. The formulation strategy obtained in this study can be in principle generalized for biopharmaceutical applications in fixed-dose combination therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Preparation and characterization of pH-sensitive methyl methacrylate-g-starch/hydroxypropylated starch hydrogels: in vitro and in vivo study on release of esomeprazole magnesium.

    Science.gov (United States)

    Kumar, Pankaj; Ganure, Ashok Laxmanrao; Subudhi, Bharat Bhushan; Shukla, Shubhanjali

    2015-06-01

    In the present study, novel hydrogels were prepared through graft copolymerization of methyl methacrylate onto starch and hydroxypropylated starch for intestinal drug delivery. The successful grafting has been confirmed by FTIR, NMR spectroscopy, and elemental analysis. Morphological examination of copolymeric hydrogels by scanning electron microscopy (SEM) confirms the macroporous nature of the copolymers. The high decomposition temperature was observed in thermograms indicating the thermal stability of the hydrogels. To attain a hydrogel with maximum percent graft yield, the impact of reaction variables like concentration of ceric ammonium nitrate as initiator and methyl methacrylate as monomer were consistently optimized. X-ray powder diffraction and differential scanning calorimetric analysis supported the successful entrapment of the drug moiety (esomeprazole magnesium; proton pump inhibitor) within the hydrogel network. Drug encapsulation efficiency of optimized hydrogels was found to be >78%. Furthermore, swelling capacity of copolymeric hydrogels exhibited a pH-responsive behavior which makes the synthesized hydrogels potential candidates for controlled delivery of medicinal agents. In vitro drug release was found to be sustained up to 14 h with 80-90% drug release in pH 6.8 solution; however, the cumulative release was 40-45% in pH 1.2. The gastrointestinal transit behavior of optimized hydrogel was determined by gamma scintigraphy, using (99m)Tc as marker. The amount of radioactive tracer released from the labeled hydrogel was minimal when the hydrogel was in the stomach, whereas it increased as hydrogel reached in intestine. Well-correlated results of in vitro and in vivo analysis proved their controlled release behavior with preferential delivery into alkaline pH environment.

  4. Effect of Permeation Enhancers on the Release Behavior and ...

    African Journals Online (AJOL)

    HP

    Methods: The permeation experiments were conducted in vitro using full thickness rabbit skin in Franz diffusion cells. The donor compartment was ... isopropyl alcohol (IPA) and sodium chloride. (NaCl) were purchased from Merck, Germany. ... ethanol (5 mL) and PBS (pH 7.4) added to make up the final volume to 100 mL.

  5. Theoretical Modeling of Mechanical Behavior and Release Properties of Microcapsules

    NARCIS (Netherlands)

    Sagis, L.M.C.

    2015-01-01

    Microcapsules in food often have a shell with a complex microstructure; the mechanical and structural properties of these shells affect the response of the capsules to deforming forces and the release kinetics of encapsulated components. In this chapter we will discuss a number of models which are

  6. [In vitro study of the antimicrobial properties of a silver ion-releasing polyurethane foam].

    Science.gov (United States)

    Arce, José Miguel Sahuquillo; Tatay, Agustín Iranzo; Luna, Martín Llácer; Boix, Yovana Sanchis; Deltell, Jorge Guitán; Barberá, Eva González; Heras, Joycelyna Beltrán; Serrano, Miguel Gobernado

    2011-10-01

    The antimicrobial properties of a silver ion (Ag+)-releasing polyurethane foam were evaluated using different microorganisms. The diffusion of Ag+ from the medium, as well as any possible cytotoxicity on human cells, was also studied. Silver release from V.A.C. GranuFoam Silver(®) was assessed by using inductively coupled plasma mass spectrometry (ICP-MS). An in vitro experimental study was designed to evaluate the bactericide capacity using lethal dose curves on A. baumannii, P. aeruginosa, S. maltophilia, K. pneumoniae, E. coli, P. mirabilis, methicillin resistant S. aureus, E. faecium, S. pyogenes and C. minutissimum. A cytotoxicity study was also performed on human fibroblasts. The silver release showed an exponential curve with a stable meseta phase after 3 hours, with levels of 0.22-0.24 mg/l. A reduction of 99.9% of all the gram-negatives was achieved at 3 hours. The reduction was greater than 99% at 2 hours in S. pyogenes and C. minutissimum, at 6h in S. aureus and at 14 h in E. faecium. In an in vivo simulation model, these reductions were achieved in 6 hours in the gram negatives and 24h in the gram positives. The silver concentrations were no cytotoxic to human fibroblasts, with no differences being observed between the cells exposed to Ag+ and the controls (p=.7) V.A.C. Granufoam Silver(®) releases bactericide concentrations of Ag+ that did not damage human fibroblasts. It appears to be a good alternative for the control and prevention of local infections. Copyright © 2010 AEC. Published by Elsevier Espana. All rights reserved.

  7. In vitro release of diclofenac diethylamine from caprylocaproyl macrogolglycerides based microemulsions.

    Science.gov (United States)

    Djordjevic, Ljiljana; Primorac, Marija; Stupar, Mirjana

    2005-05-30

    The purpose of the present study was to determine the influence of both formulation parameters and vehicle structure on in vitro release rate of amphiphilic drug diclofenac diethylamine (DDA) from microemulsion vehicles containing PEG-8 caprylic/capric glycerides (surfactant), polyglyceryl-6 dioleate (cosurfactant), isopropyl myristate and water. From the constructed pseudo-ternary phase diagram at surfactant-cosurfactant mass ratio (K(m) 1:1), the optimum oil-to-surfactant-cosurfactant mass ratio values (O/SC 0.67-1.64) for formulation of microemulsions with similar concentrations of hydrophilic, lipophilic and amphiphilic phases (balanced microemulsions) were found. The results of characterization experiments indicated bicontinuous or nonspherical water-continuous internal structure of the selected microemulsion vehicles. Low water/isopropyl myristate apparent partition coefficient for DDA as well as elevated electrical conductivity and apparent viscosity values for the investigated microemulsion formulations containing 1.16% (w/w) of DDA, suggested that the drug molecules was predominantly partitioned in the water phase and most likely selfaggregate and interact with interfacial film. Release of DDA from the selected water-continuous (W/O), oil-continuous (O/W) and balanced microemulsions was investigated using rotating paddle dissolution apparatus modified by addition of enhancer cell. A linear diffusion of DDA through regenerated cellulose membrane was observed for the W/O and O/W formulations with the low content of dispersed phase. Non-linearity of the drug release profile in the case of bicontinuous formulations was related to the more complex distribution of DDA including interactions between the drug and vehicle. The membrane flux value increases from 25.02 microgcm(-2)h(-1) (W/O microemulsion) to 117.94 microgcm(-2)h(-1) (O/W microemulsion) as the water phase concentration increases. Moreover, the obtained flux values for balanced microemulsions (29

  8. Extracorporeal Shockwave Therapy Increases Growth Factor Release from Equine Platelet-Rich Plasma In Vitro

    Directory of Open Access Journals (Sweden)

    Kathryn A. Seabaugh

    2017-12-01

    Full Text Available IntroductionExtracorporeal shockwave therapy (ESWT and platelet-rich plasma (PRP are common treatments for soft tissue injuries in horses. Shockwave triggers cell specific responses to promote healing. Growth factors released from PRP also promote healing. It has been hypothesized that greater growth factor release would amplify the healing process. The combination of ESWT and PRP could promote healing in injured tendons and ligaments in the horse. The objective of this study was to determine if application of shockwaves to PRP samples increases the concentration of transforming growth factor-β1 (TGF-β1 and platelet-derived growth factor ββ (PDGF-ββ released from the platelets in vitro.Materials and methodsPRP was produced from blood drawn from six horses. The PRP from each horse was exposed to the following treatments: (1 positive control (freeze-thaw cycle, (2 untreated negative control, or shockwaves with either (3 a “standard probe” (ESWT-S with a 2 cm focal width and medium energy density or (4 a “power probe” (ESWT-P with a 1 cm focal width and high energy density. After each treatment, the samples were centrifuged, and the supernatant was harvested. The supernatant was then used for growth factor quantification via commercially available ELISA kits for TGF-β1 and PDGF-ββ.ResultsConcentrations of TGF-β1 and PDGF-ββ in PRP that underwent a freeze-thaw cycle were significantly increased compared with all other treatments. Both ESWT-S and ESWT-P resulted in significantly increased TGF-β1 concentrations, 46 and 33%, respectively, when compared with the negative control. Both ESWT-S and ESWT-P resulted in significantly increased PDGF-ββ concentrations, 219 and 190%, respectively, when compared with the negative control.DiscussionThese data indicate that the application of ESWT to PRP increases the expression of growth factors in vitro. This suggests that the combination therapy of local PRP injection followed by ESWT

  9. Infection Spread and Virus Release in Vitro in Cell Populations as a System with Percolation

    Science.gov (United States)

    Ochoa, Juan G. Diaz

    The comprehension of the innate immune system of cell populations is not only of interest to understand systems in vivo but also in vitro, for example, in the control of the release of viral particles for the production of vaccines. In this report I introduce a model, based on dynamical networks, that simulates the cell signaling responsible for this innate immune response and its effect on the infection spread and virus production. The central motivation is to represent a cell population that is constantly mixed in a bio-reactor where there is a cell-to-cell signaling of cytokines (which are proteins responsible for the activation of the antiviral response inside the cell). Such signaling allows the definition of clusters of linked immune cells. Additionally, depending on the density of links, it is possible to identify critical threshold parameters associated to a percolation phase transition. I show that the control of this antiviral response is equivalent to a percolation process.

  10. The Acyclic Retinoid Peretinoin Inhibits Hepatitis C Virus Replication and Infectious Virus Release in Vitro

    Science.gov (United States)

    Shimakami, Tetsuro; Honda, Masao; Shirasaki, Takayoshi; Takabatake, Riuta; Liu, Fanwei; Murai, Kazuhisa; Shiomoto, Takayuki; Funaki, Masaya; Yamane, Daisuke; Murakami, Seishi; Lemon, Stanley M.; Kaneko, Shuichi

    2014-04-01

    Clinical studies suggest that the oral acyclic retinoid Peretinoin may reduce the recurrence of hepatocellular carcinoma (HCC) following surgical ablation of primary tumours. Since hepatitis C virus (HCV) infection is a major cause of HCC, we assessed whether Peretinoin and other retinoids have any effect on HCV infection. For this purpose, we measured the effects of several retinoids on the replication of genotype 1a, 1b, and 2a HCV in vitro. Peretinoin inhibited RNA replication for all genotypes and showed the strongest antiviral effect among the retinoids tested. Furthermore, it reduced infectious virus release by 80-90% without affecting virus assembly. These effects could be due to reduced signalling from lipid droplets, triglyceride abundance, and the expression of mature sterol regulatory element-binding protein 1c and fatty acid synthase. These negative effects of Peretinoin on HCV infection may be beneficial in addition to its potential for HCC chemoprevention in HCV-infected patients.

  11. Sustained-release study on Exenatide loaded into mesoporous silica nanoparticles: in vitro characterization and in vivo evaluation.

    Science.gov (United States)

    Chen, Cuiwei; Zheng, Hongyue; Xu, Junjun; Shi, Xiaowei; Li, Fanzhu; Wang, Xuanshen

    2017-09-04

    Exenatide (EXT), the first glucagon-like peptide-1 receptor agonist, has been approved as an adjunctive therapy for patients with type 2 diabetes. Due to EXT's short half-life, EXT must be administrated by continuous subcutaneous (s.c.) injection twice daily. In previous studies, many studies on EXT loaded into polymer materials carriers for sustained release had been reported. However, these carriers have some defects, such as hydrophobicity, low surface energy, low mechanical strength, and poor chemical stability. Therefore, this study aims to develop a novel drug delivery system, which is EXT loaded into well-ordered hexagonal mesoporous silica structures (EXT-SBA-15), to control the sustainability of EXT. SBA-15 was prepared by hydrothermal method with uniform size. Morphology of SBA-15 was employed by transmission electron microscopy. The pore size of SBA-15 was characterized by N2 adsorption-desorption isotherms. The in vitro drug release behavior and pharmacokinetics of EXT-SBA-15 were investigated. Furthermore, the blood glucose levels of diabetic mice were monitored after subcutaneous injection of EXT-Sol and EXT-SBA-15 to evaluate further the stable hypoglycemic effect of EXT-SBA-15. EXT-SBA-15 showed a higher drug loading efficiency (15.2 ± 2.0%) and sustained-release features in vitro. In addition, pharmacokinetic studies revealed that the EXT-SBA-15 treatment group extended the half-life t 1/2(β) to 14.53 ± 0.70 h compared with that of the EXT solution (EXT-Sol) treatment group (0.60 ± 0.08 h) in vivo. Results of the pharmacodynamics study show that the EXT-SBA-15 treatment group had inhibited blood glucose levels below 20 mmol/L for 25 days, and the lowest blood glucose level was 13 mmol/L on the 10th day. This study demonstrates that the EXT-SBA-15 delivery system can control the sustainability of EXT and contribute to improve EXT clinical use.

  12. IDENTIFICATION OF PHARMACEUTICAL EXCIPIENT BEHAVIOR OF CHICKPEA (CICER ARIETINUM) STARCH IN GLICLAZIDE IMMEDIATE RELEASE TABLETS.

    Science.gov (United States)

    Meka, Venkata Srikanth; Yee, Phung; Sheshala, Ravi

    2016-01-01

    In the past few years, there are number of researchers carrying out their research on the excipients derived from polysaccharides and some of these researches show that natural excipients are comparable and can serve as an alternative to the synthetic excipients. Hence, the objectives of this research are to characterize the naturally sourced chickpea starch powder and to study the pharmaceutical excipient behavior of chickpea starch in gliclazide immediate release (IR) tablets. In this research, the binding properties of chickpea starch were compared to that of povidone, whereas the disintegrant properties of chickpea starch were compared to those of crospovidone, croscarmellose sodium and sodium starch glycolate. Flow property of chickpea starch was assessed with the measurement of bulk density, tapped density, compressibility index and angle of repose. Calibration curve for gliclazide in phosphate buffer pH 7.4 was developed. Gliclazide IR tablets were then produced with direct compression method. Physicochemical characteristics of the tablets, including thickness, tablet weight uniformity, hardness, disintegration time and friability were evaluated. Then, in vitro dissolution studies were performed by following United States Pharmacopeia (USP) dissolution method. The dissolution results were analyzed and compared with t30, t50, dissolution efficiency (DE). Lastly, drug-excipient compatibility studies, including Fourier transform infrared (FTIR) spectroscopic analysis and differential scanning calorimetric (DSC) analysis were carried out. Fair flow property was observed in the chickpea starch powder. Furthermore, the tablets produced passed all the tests in physicochemical characteristics evaluation except hardness and disintegration test. Additionally, in vitro dissolution studies show that chickpea starch acted as a disintegrant instead of a binder in gliclazide IR tablets and its disintegrant properties were comparable to those of crospovidone, croscarmellose

  13. Capreomycin oleate microparticles for intramuscular administration: Preparation, in vitro release and preliminary in vivo evaluation.

    Science.gov (United States)

    Cambronero-Rojas, Adrián; Torres-Vergara, Pablo; Godoy, Ricardo; von Plessing, Carlos; Sepúlveda, Jacqueline; Gómez-Gaete, Carolina

    2015-07-10

    Capreomycin sulfate (CS) is a second-line drug used for the treatment of multidrug-resistant tuberculosis (MDR-TB). The adverse effects profile and uncomfortable administration scheme of CS has led to the development of formulations based on liposomes and polymeric microparticles. However, as CS is a water-soluble peptide that does not encapsulate properly into hydrophobic particulate matrices, it was necessary to reduce its aqueous solubility by forming the pharmacologically active capreomycin oleate (CO) ion pair. The aim of this research was to develop a new formulation of CO for intramuscular injection, based on biodegradable microparticles that encapsulate CO in order to provide a controlled release of the drug with reduced local and systemic adverse effects. The CO-loaded microparticles prepared by spray drying or solvent emulsion-evaporation were characterized in their morphology, encapsulation efficiency, in vitro/in vivo kinetics and tissue tolerance. Through scanning electron microscopy it was confirmed that the microparticles were monodisperse and spherical, with an optimal size for intramuscular administration. The interaction between CO and the components of the microparticle matrix was confirmed on both formulations by X-ray powder diffraction and differential scanning calorimetry analyses. The encapsulation efficiencies for the spray-dried and emulsion-evaporation microparticles were 92% and 56%, respectively. The in vitro kinetics performed on both formulations demonstrated a controlled and continuous release of CO from the microparticles, which was successfully reproduced on an in vivo rodent model. The results of the histological analysis demonstrated that none of the formulations produced significant tissue damage on the site of injection. Therefore, the results suggest that injectable CO microparticles obtained by spray drying and solvent emulsion-evaporation could represent an interesting therapeutic alternative for the treatment of MDR

  14. In vitro controlled release of clove essential oil in self-assembly of amphiphilic polyethylene glycol-block-polycaprolactone.

    Science.gov (United States)

    Thonggoom, O; Punrattanasin, N; Srisawang, N; Promawan, N; Thonggoom, R

    2016-05-01

    In this study, a micellar delivery system with an amphiphilic diblock copolymer of poly (ethylene glycol) and poly (ɛ-caprolactone) was synthesised and used to incorporate hydrophobic clove essential oil (CEO). To determine an optimal delivery system, the effects of the copolymer's hydrophobic block length and the CEO-loading content on the encapsulation of CEO were investigated. Percentages of entrapment efficiency (%EE), CEO loading (%CEO), and in vitro release profiles were determined. The size, size distribution, zeta potential, and morphology of the obtained micelles were determined by DLS, FE-SEM, and TEM. The %EE, %CEO, and in vitro release profiles of CEO incorporated in micelles were analysed by HPLC. The study revealed a sustained release profile of CEO from CEO-loaded micelles. The results indicate the successful formulation of CEO-loaded PEG-b-PCL micelle nanoparticles. It is suggested that this micelle system has considerably potential applications in the sustained release of CEO in intravascular drug delivery.

  15. Enhanced Oral Bioavailability of Efavirenz by Solid Lipid Nanoparticles: In Vitro Drug Release and Pharmacokinetics Studies

    Directory of Open Access Journals (Sweden)

    Praveen Kumar Gaur

    2014-01-01

    Full Text Available Solid lipid nanoparticle is an efficient lipid based drug delivery system which can enhance the bioavailability of poorly water soluble drugs. Efavirenz is a highly lipophilic drug from nonnucleoside inhibitor category for treatment of HIV. Present work illustrates development of an SLN formulation for Efavirenz with increased bioavailability. At first, suitable lipid component and surfactant were chosen. SLNs were prepared and analyzed for physical parameters, stability, and pharmacokinetic profile. Efavirenz loaded SLNs were formulated using Glyceryl monostearate as main lipid and Tween 80 as surfactant. ESLN-3 has shown mean particle size of 124.5±3.2 nm with a PDI value of 0.234, negative zeta potential, and 86% drug entrapment. In vitro drug release study has shown 60.6–98.22% drug release in 24 h by various SLN formulations. Optimized SLNs have shown good stability at 40°C ± 2°C and 75±5% relative humidity (RH for 180 days. ESLN-3 exhibited 5.32-fold increase in peak plasma concentration (Cmax⁡ and 10.98-fold increase in AUC in comparison to Efavirenz suspension (ES.

  16. Pharmaceutical suspension containing both immediate/sustained-release amoxicillin-loaded gelatin nanoparticles: preparation and in vitro characterization

    Science.gov (United States)

    Harsha, Sree

    2013-01-01

    Pharmaceutical suspension containing oral dosage forms delivering both immediate-release and sustained-release amoxicillin was developed as a new dosage form to eradicate Helicobacter pylori. Amoxicillin-loaded gelatin nanoparticles are able to bind with the mucosal membrane after delivery to the stomach and could escalate the effectiveness of a drug, providing dual release. The objective of this study was to develop amoxicillin nanoparticles using innovative new technology – the Büchi Nano Spray Dryer B-90 – and investigate such features as drug content, particle morphology, yield, in vitro release, flow properties, and stability. The nanoparticles had an average particle size of 571 nm. The drug content and percentage yield was 89.2% ± 0.5% and 93.3% ± 0.6%, respectively. Angle of repose of nanoparticle suspension was 26.3° and bulk density was 0.59 g/cm3. In vitro drug release of formulations was best fitted by first-order and Peppas models with R2 of 0.9841 and 0.9837 respectively; release profile was 15.9%, while; for the original drug, amoxicillin, under the same conditions, 90% was released in the first 30 minutes. The nanoparticles used in this study enabled sustained release of amoxicillin over an extended period of time, up to 12 hours, and were stable for 12 months under accelerated storage conditions of 25°C ± 2°C and 60% ± 5% relative humidity. PMID:24101859

  17. Design and in vitro and in vivo evaluation of mucoadhesive microcapsules of glipizide for oral controlled release: A technical note

    OpenAIRE

    Chowdary, K. P. R.; Rao, Y. Srinivasa

    2003-01-01

    Thus, large spherical microcapsules with a coat consisting of alginate and a mucoadhesive polymer (sodium CMC, methylcellulose, Carbopol, or HPMC) could be prepared by an orifice-ionic gelation process. The microcapsules exhibited good mucoadhesive properties in an in vitro test. Glipizide release from these mucoadhesive microcapsules was slow and extended over longer periods of time and depended on composition of the coat. Drug release was diffusion controlled and followed zero-order kinetic...

  18. PLA/CS/Nifedipine Nanocomposite Films: Properties and the In Vitro Release of Nifedipine

    Science.gov (United States)

    Trang, Nguyen Thi Thu; Chinh, Nguyen Thuy; Giang, Nguyen Vu; Thanh, Dinh Thi Mai; Lam, Tran Dai; Hoang, Thai

    2016-07-01

    The polylactic acid (PLA)/chitosan (CS) films containing a drug, nifedipine (NIF), in the presence of polyethylene oxide (PEO) as a compatibilizer were prepared by the solution method. This method has not been used to form films containing four components (PLA, CS, NIF, PEO) up to now. The CS, PEO, and NIF contents are 25 wt.%, 6-8 wt.%, and 10-50 wt.% in comparison with PLA weight, respectively. Fourier transform infrared spectroscopy (FTIR), thermo-gravimetric analysis (TGA), differential scanning calorimetry (DSC), and field emission scanning electron microscopy (FESEM) were used to characterize the interactions, properties, and morphology of the PLA/CS/PEO/NIF films. The FTIR, TGA, and DSC results show that NIF carried by PLA/CS/PEO films and PLA, CS, NIF had better interaction and were more compatible when using PEO. The surface morphology of PLA/CS/PEO/NIF films was similar to that of PLA/CS/PEO films. Moreover, this was the first time drug loading and NIF release content from PLA/CS/PEO films were determined by the ultraviolet-visible (UV-Vis) spectroscopy method. The drug loading of PLA/CS/PEO/NIF films was from 80.99% to 93.61%. The in vitro NIF release studies were carried out in pH 2, 6.8, and 7.4 solutions corresponding to the pH of stomach, colon, and duodenum regions in the human body, respectively. The NIF release content in different pH solutions is in the order: pH 2 > pH 6.8 > pH 7.4 and increases when there is increasing NIF loading. The PLA/CS/PEO films are potential materials to apply for long-circulating systems for NIF delivery.

  19. An in vitro comparison of nickel and chromium release from brackets

    Directory of Open Access Journals (Sweden)

    Ana Cristina Soares Santos Haddad

    2009-12-01

    Full Text Available This study aimed at comparing amounts of nickel (Ni and chromium (Cr released from brackets from different manufacturers in simulated oral environments. 280 brackets were equally divided into 7 groups according to manufacturer. 6 groups of brackets were stainless steel, and 1 group of brackets was made of a cobalt-chromium alloy with low Ni content (0.5%. International standard ISO 10271/2001 was applied to provide test methods. Each bracket was immersed in 0.5 ml of synthetic saliva (SS or artificial plaque fluid (PF over a period of 28 days at 37ºC. Solutions were replaced every 7 days, and were analyzed by spectrometry. The Kruskal-Wallis test was applied. Amounts of Ni release in SS (µg L-1 per week varied between groups from "bellow detection limits" to 694, and from 49 to 5,948.5 in PF. The group of brackets made of cobalt-chromium alloy, with the least nickel content, did not release the least amounts of Ni. Amounts of Cr detected in SS and in PF (µg L-1 per week were from 1 to 10.4 and from 50.5 to 8,225, respectively. It was therefore concluded that brackets from different manufacturers present different corrosion behavior. Further studies are necessary to determine clinical implications of the findings.

  20. Development and in vitro characterization of floating sustained-release drug delivery systems of polyphenols.

    Science.gov (United States)

    Rosenzweig, Ohad; Lavy, Eran; Gati, Irith; Kohen, Ron; Friedman, Michael

    2013-01-01

    The aim of this study was to develop and characterize floating stomach-retentive matrix tablets that will deliver polyphenols in a controlled release manner. The tablets were prepared by direct compression. A number of polymers were examined and egg albumin was chosen in light of a better performance in terms of floating behavior and decomposition time. Dissolution studies for three representative polyphenols loaded into a number of formulations were performed using the "f₂" factor in order to compare release profiles of different polyphenols and formulations. The release data showed a good fit into the power law equation and zero-order kinetics has been determined for some of the systems. Erosion and textural analysis studies revealed that higher concentration of egg albumin results in a higher gel strength that is less susceptible to erosion, potentially leading to a prolonged delivery time of drug. The ability of egg albumin-based tablets to resist high mechanical forces was also determined, while comparison to cellulose-derived polymers revealed that the latter have a much lower ability to resist the same forces. The developed delivery system has the potential to increase the efficacy of the therapy for various pathological stomach conditions and to improve patient compliance.

  1. Release of EPA and DHA from salmon oil - a comparison of in vitro digestion with human and porcine gastrointestinal enzymes.

    Science.gov (United States)

    Aarak, K E; Kirkhus, B; Holm, H; Vogt, G; Jacobsen, M; Vegarud, G E

    2013-10-01

    In the present study, we hypothesised whether in vitro digestion of salmon oil would release different amounts of PUFA depending on the origin of the lipolytic enzymes used. For this purpose, in vitro digestion of salmon oil (SO) was performed using human duodenal juice (HDJ) or a commercial enzyme preparation consisting of porcine pancreatin and bile (PB). The lipolytic effect was determined by measuring the release of fatty acids (FA) using solid-phase extraction and GC-flame ionisation detection, withdrawing samples every 20 min during digestion. The amount of FA released indicated that a plateau was reached after 80 min with approximately similar amounts of FA detected using both HDJ and PB (379 (sd 18) and 352 (sd 23) mg/g SO, respectively). However, the release of 18 : 2, EPA (20 : 5) and DHA (22 : 6) was significantly different during in vitro digestion. At 80 min, HDJ and PB released 43 and 33% of 18 : 2, 14 and 9% of EPA and 11 and 9% of DHA, respectively. Both enzyme preparations released approximately the same amounts of the other FA analysed. The effect of the addition of bile salts (BS) was significantly different in the two enzyme systems, where porcine pancreatin highly responded to the increase in BS concentration, in contrast to HDJ.

  2. The effects of captive rearing on the behavior of newly-released whooping cranes (Grus americana)

    Science.gov (United States)

    Kreger, M.D.; Hatfield, J.S.; Estevez, I.; Gee, G.F.; Clugston, D.A.

    2005-01-01

    Rearing treatments used in captivity to prepare animals for reintroduction to the wild may have a profound effect on behavior and, possibly, affect their survival after reintroduction. This study examined the behaviors of captive-reared whooping cranes (Grus americana) upon their release in Florida to determine if rearing treatments may affect the behavior of the birds and how these affect their chances of survival in the wild. Individually tagged birds were observed at the rearing facility, the U.S. Geological Survey Patuxent Wildlife Research Center in Maryland, from hatch to 20 weeks of age and at the release site in Central Florida for up to 6 weeks post release. The rearing treatments were parent reared (PR), hand reared (HR), and hand reared with exercise (HRE). Observations at the rearing facility are described in a previous paper. At the release site, each bird was observed for 5 min every morning (0700?1000 h) and late afternoon (1500?1800 h) during the 6-week study period. Our results indicated that most of the time, the n = 34 birds were foraging (46.03 ? 1.48%), followed by nonvigilant (20.89 ? 0.73%), vigilant (19.21 ? 0.72%), or performing comfort behaviors (11.61 ? 1.28%). Data were analyzed using mixed models repeated measures ANOVA. There were no significant behavioral differences between HR and HRE birds. PR birds were found in larger groups than HR birds during the first 2 weeks post release and greater than HR and HRE birds afterwards. This may be interpreted as an antipredator strategy for birds that relied on parental guidance during rearing. HR and HRE birds foraged more than PR birds during the first 2 weeks post release and PR birds were more vigilant during the first 2 weeks post release. Across rearing treatments, the percentages of time spent foraging and engaged in vigilant behaviors during rearing were positively correlated with their behavior upon release. If any of these behaviors can be demonstrated to have relevance for the

  3. Ultra-small and anionic starch nanospheres: formation and vitro thrombolytic behavior study.

    Science.gov (United States)

    Huang, Yinjuan; Ding, Shenglong; Liu, Mingzhu; Gao, Chunmei; Yang, Jinlong; Zhang, Xinjie; Ding, Bin

    2013-07-25

    This paper is considered as the first report on the investigation of nattokinase (NK) release from anionic starch nanospheres. The ultra-small and anionic starch nanospheres were prepared by the method of reverse micro-emulsion crosslinking in this work. Starch nanospheres were characterized through Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and dynamic light scattering (DLS). Effects of preparation conditions on particle size were studied. The cytotoxicity, biodegradable and vitro thrombolytic behaviors of nattokinase (NK) loaded anionic starch nanospheres were also studied. The results showed that the anionic starch nanospheres are non-toxic, biocompatible and biodegradable. Moreover, the anionic starch nanospheres can protect NK from fast biodegradation hence prolongs the circulation in vivo and can reduce the risk of acute hemorrhage complication by decreasing the thrombolysis rate. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. In vitro corrosion behavior and cellular response of thermally oxidized Zr-3Sn alloy

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, F.Y.; Wang, B.L.; Qiu, K.J. [Center for Biomedical Materials and Engineering, Harbin Engineering University, Harbin 150001 (China); Li, H.F. [Department of Materials Science and Engineering, College of Engineering, Peking University, Beijing 100871 (China); Li, L. [Center for Biomedical Materials and Engineering, Harbin Engineering University, Harbin 150001 (China); Zheng, Y.F., E-mail: yfzheng@pku.edu.cn [Center for Biomedical Materials and Engineering, Harbin Engineering University, Harbin 150001 (China); Department of Materials Science and Engineering, College of Engineering, Peking University, Beijing 100871 (China); Han, Y. [State Key Laboratory for Mechanical Behavior of Materials, Xian Jiaotong University, Xian 710049 (China)

    2013-01-15

    Highlights: Black-Right-Pointing-Pointer A main monoclinic ZrO{sub 2} layer formed on ZrSn alloy after thermal oxidation. Black-Right-Pointing-Pointer Corrosion resistance of ZrSn alloy was improved with thermal oxidation. Black-Right-Pointing-Pointer The oxide layer inhibited the release of the ions into the mediums. Black-Right-Pointing-Pointer Oxidized ZrSn alloy exhibited an excellent in vitro biocompatibility. - Abstract: In this study, ZrSn alloy was thermally oxidized at 600 Degree-Sign C for 3 h and its morphological and structural characteristics, corrosion behavior, ion release and in vitro cytocompatibility were studied to evaluate the feasibility of applying it as dental implant. After oxidation, a dense black oxide layer formed on ZrSn alloy surface, which consisted of predominant monoclinic zirconia and a few non-stoichiometric oxides. The scratching and water contact angle test results demonstrated that the oxide layer exhibited good adhesion strength and similar hydrophilicity to zirconia. The oxidized ZrSn alloy showed higher corrosion resistance, as indicated by far lower corrosion current density and passive current density compared to pure Ti and untreated ZrSn alloy in artificial saliva with and without H{sub 2}O{sub 2}. The amount of ions released from the oxidized ZrSn alloy was much lower than that dissolved from pure Ti in simulated corrosive oral mediums. Moreover, the oxidized ZrSn alloy did not present any significant toxic effect to both osteoblast-like cells and fibroblast cells, and osteoblast-like cells could adhere well onto the surface and exhibited a good proliferative pattern. The combination of improved surface properties, superior corrosion resistance and good biocompatibility made the oxidized ZrSn alloy promising for oral implantology application.

  5. The effect of difference in saliva pH against Hg release from amalgam restoration on in vitro research

    OpenAIRE

    Oksana Megasari

    2007-01-01

    Hg release from amalgam restoration is continuos as long as an amalgam in the mouth. The difference in saliva pH is one factor that influences Hg releasing from amalgam restoration. The purpose of this research was to find data the effect of the difference in saliva pH against Hg release from amalgam restoration. This research was a true experimental in vitro research. This research used 40 samples of premolar teeth of the maxilla, prepared in occlusal Class I, restored with amalgam and then ...

  6. Biodegradable Injectable In Situ Implants and Microparticles for Sustained Release of Montelukast: In Vitro Release, Pharmacokinetics, and Stability

    OpenAIRE

    Ahmed, Tarek A.; Ibrahim, Hany M.; Ahmed M Samy; Kaseem, Alaa; Nutan, Mohammad T. H.; Hussain, Muhammad Delwar

    2014-01-01

    The objective of this study was to investigate the sustained release of a hydrophilic drug, montelukast (MK), from two biodegradable polymeric drug delivery systems, in situ implant (ISI) and in situ microparticles (ISM). N-Methyl pyrrolidone (NMP), dimethyl sulfoxide (DMSO), triacetin, and ethyl acetate were selected as solvents. The release of 10% (w/v) MK from both systems containing poly-lactic-co-glycolic acid (PLGA) as the biodegradable polymer was compared. Upon contact with the aqueou...

  7. Release, partitioning and stability of isoflavones from enriched custards during mouth, stomach and intestine in vitro simulations

    NARCIS (Netherlands)

    Sanz, T.; Luyten, J.M.J.G.

    2006-01-01

    Custard desserts were enriched with a soy germ extract as source of isoflavones and the influence of the thickening agent (starch or carboxymethylcellulose (CMC)) and the presence of fat on the release, partitioning and stability of the isoflavones after mouth, stomach and small intestine in vitro

  8. Sleep-wake sensitive mechanisms of adenosine release in the basal forebrain of rodents: an in vitro study.

    Directory of Open Access Journals (Sweden)

    Robert Edward Sims

    Full Text Available Adenosine acting in the basal forebrain is a key mediator of sleep homeostasis. Extracellular adenosine concentrations increase during wakefulness, especially during prolonged wakefulness and lead to increased sleep pressure and subsequent rebound sleep. The release of endogenous adenosine during the sleep-wake cycle has mainly been studied in vivo with microdialysis techniques. The biochemical changes that accompany sleep-wake status may be preserved in vitro. We have therefore used adenosine-sensitive biosensors in slices of the basal forebrain (BFB to study both depolarization-evoked adenosine release and the steady state adenosine tone in rats, mice and hamsters. Adenosine release was evoked by high K(+, AMPA, NMDA and mGlu receptor agonists, but not by other transmitters associated with wakefulness such as orexin, histamine or neurotensin. Evoked and basal adenosine release in the BFB in vitro exhibited three key features: the magnitude of each varied systematically with the diurnal time at which the animal was sacrificed; sleep deprivation prior to sacrifice greatly increased both evoked adenosine release and the basal tone; and the enhancement of evoked adenosine release and basal tone resulting from sleep deprivation was reversed by the inducible nitric oxide synthase (iNOS inhibitor, 1400 W. These data indicate that characteristics of adenosine release recorded in the BFB in vitro reflect those that have been linked in vivo to the homeostatic control of sleep. Our results provide methodologically independent support for a key role for induction of iNOS as a trigger for enhanced adenosine release following sleep deprivation and suggest that this induction may constitute a biochemical memory of this state.

  9. Sleep-Wake Sensitive Mechanisms of Adenosine Release in the Basal Forebrain of Rodents: An In Vitro Study

    Science.gov (United States)

    Sims, Robert Edward; Wu, Houdini Ho Tin; Dale, Nicholas

    2013-01-01

    Adenosine acting in the basal forebrain is a key mediator of sleep homeostasis. Extracellular adenosine concentrations increase during wakefulness, especially during prolonged wakefulness and lead to increased sleep pressure and subsequent rebound sleep. The release of endogenous adenosine during the sleep-wake cycle has mainly been studied in vivo with microdialysis techniques. The biochemical changes that accompany sleep-wake status may be preserved in vitro. We have therefore used adenosine-sensitive biosensors in slices of the basal forebrain (BFB) to study both depolarization-evoked adenosine release and the steady state adenosine tone in rats, mice and hamsters. Adenosine release was evoked by high K+, AMPA, NMDA and mGlu receptor agonists, but not by other transmitters associated with wakefulness such as orexin, histamine or neurotensin. Evoked and basal adenosine release in the BFB in vitro exhibited three key features: the magnitude of each varied systematically with the diurnal time at which the animal was sacrificed; sleep deprivation prior to sacrifice greatly increased both evoked adenosine release and the basal tone; and the enhancement of evoked adenosine release and basal tone resulting from sleep deprivation was reversed by the inducible nitric oxide synthase (iNOS) inhibitor, 1400 W. These data indicate that characteristics of adenosine release recorded in the BFB in vitro reflect those that have been linked in vivo to the homeostatic control of sleep. Our results provide methodologically independent support for a key role for induction of iNOS as a trigger for enhanced adenosine release following sleep deprivation and suggest that this induction may constitute a biochemical memory of this state. PMID:23326515

  10. Silicone-Acyclovir Controlled Release Devices Suppress Primary Herpes Simplex Virus-2 and Varicella Zoster Virus Infections In Vitro

    Directory of Open Access Journals (Sweden)

    Carol L. Berkower

    2013-01-01

    Full Text Available Following initial infection, herpesviruses retreat into a permanent latent state with periodic reactivation resulting in an enhanced likelihood of transmission and clinical disease. The nucleoside analogue acyclovir reduces clinical symptoms of the three human alpha herpesviruses, HSV-1, HSV-2, and VZV. Long-term administration of acyclovir (ACV can reduce the frequency and severity of reactivation, but its low bioavailability and short half-life require a daily drug regimen. Our lab is working to develop a subcutaneous delivery system to provide long-lasting, sustained release of ACV. Previously, we demonstrated that an implantable silicone (MED-4050 device, impregnated with ACV protected against HSV-1 both in vitro and in vivo. Here, we extend our in vitro observations to include protection against both HSV-2 and VZV. We also demonstrate protection against HSV-2 in vitro using MED-4750, a silicone polymer designed for long-term use in humans. When release of ACV from MED-4750 is quantitated on a daily basis, an initial burst of 5 days is observed, followed by a long period of slow release with near-zero-order kinetics, with an average daily release of 1.3923 ± 0.5908 μg ACV over days 20–60. Development of a slow-release implant has the potential to significantly impact the treatment of human alpha herpesvirus infections.

  11. Amantadine Ameliorates Dopamine-Releasing Deficits and Behavioral Deficits in Rats after Fluid Percussion Injury

    Science.gov (United States)

    Huang, Eagle Yi-Kung; Tsui, Pi-Fen; Kuo, Tung-Tai; Tsai, Jing-Jr.; Chou, Yu-Ching; Ma, Hsin-I; Chiang, Yung-Hsiao; Chen, Yuan-Hao

    2014-01-01

    Aims To investigate the role of dopamine in cognitive and motor learning skill deficits after a traumatic brain injury (TBI), we investigated dopamine release and behavioral changes at a series of time points after fluid percussion injury, and explored the potential of amantadine hydrochloride as a chronic treatment to provide behavioral recovery. Materials and Methods In this study, we sequentially investigated dopamine release at the striatum and behavioral changes at 1, 2, 4, 6, and 8 weeks after fluid percussion injury. Rats subjected to 6-Pa cerebral cortical fluid percussion injury were treated by using subcutaneous infusion pumps filled with either saline (sham group) or amantadine hydrochloride, with a releasing rate of 3.6mg/kg/hour for 8 weeks. The dopamine-releasing conditions and metabolism were analyzed sequentially by fast scan cyclic voltammetry (FSCV) and high-pressure liquid chromatography (HPLC). Novel object recognition (NOR) and fixed-speed rotarod (FSRR) behavioral tests were used to determine treatment effects on cognitive and motor deficits after injury. Results Sequential dopamine-release deficits were revealed in 6-Pa-fluid-percussion cerebral cortical injured animals. The reuptake rate (tau value) of dopamine in injured animals was prolonged, but the tau value became close to the value for the control group after amantadine therapy. Cognitive and motor learning impairments were shown evidenced by the NOR and FSRR behavioral tests after injury. Chronic amantadine therapy reversed dopamine-release deficits, and behavioral impairment after fluid percussion injuries were ameliorated in the rats treated by using amantadine-pumping infusion. Conclusion Chronic treatment with amantadine hydrochloride can ameliorate dopamine-release deficits as well as cognitive and motor deficits caused by cerebral fluid-percussion injury. PMID:24497943

  12. Amantadine ameliorates dopamine-releasing deficits and behavioral deficits in rats after fluid percussion injury.

    Directory of Open Access Journals (Sweden)

    Eagle Yi-Kung Huang

    Full Text Available AIMS: To investigate the role of dopamine in cognitive and motor learning skill deficits after a traumatic brain injury (TBI, we investigated dopamine release and behavioral changes at a series of time points after fluid percussion injury, and explored the potential of amantadine hydrochloride as a chronic treatment to provide behavioral recovery. MATERIALS AND METHODS: In this study, we sequentially investigated dopamine release at the striatum and behavioral changes at 1, 2, 4, 6, and 8 weeks after fluid percussion injury. Rats subjected to 6-Pa cerebral cortical fluid percussion injury were treated by using subcutaneous infusion pumps filled with either saline (sham group or amantadine hydrochloride, with a releasing rate of 3.6 mg/kg/hour for 8 weeks. The dopamine-releasing conditions and metabolism were analyzed sequentially by fast scan cyclic voltammetry (FSCV and high-pressure liquid chromatography (HPLC. Novel object recognition (NOR and fixed-speed rotarod (FSRR behavioral tests were used to determine treatment effects on cognitive and motor deficits after injury. RESULTS: Sequential dopamine-release deficits were revealed in 6-Pa-fluid-percussion cerebral cortical injured animals. The reuptake rate (tau value of dopamine in injured animals was prolonged, but the tau value became close to the value for the control group after amantadine therapy. Cognitive and motor learning impairments were shown evidenced by the NOR and FSRR behavioral tests after injury. Chronic amantadine therapy reversed dopamine-release deficits, and behavioral impairment after fluid percussion injuries were ameliorated in the rats treated by using amantadine-pumping infusion. CONCLUSION: Chronic treatment with amantadine hydrochloride can ameliorate dopamine-release deficits as well as cognitive and motor deficits caused by cerebral fluid-percussion injury.

  13. Amantadine ameliorates dopamine-releasing deficits and behavioral deficits in rats after fluid percussion injury.

    Science.gov (United States)

    Huang, Eagle Yi-Kung; Tsui, Pi-Fen; Kuo, Tung-Tai; Tsai, Jing-Jr; Chou, Yu-Ching; Ma, Hsin-I; Chiang, Yung-Hsiao; Chen, Yuan-Hao

    2014-01-01

    To investigate the role of dopamine in cognitive and motor learning skill deficits after a traumatic brain injury (TBI), we investigated dopamine release and behavioral changes at a series of time points after fluid percussion injury, and explored the potential of amantadine hydrochloride as a chronic treatment to provide behavioral recovery. In this study, we sequentially investigated dopamine release at the striatum and behavioral changes at 1, 2, 4, 6, and 8 weeks after fluid percussion injury. Rats subjected to 6-Pa cerebral cortical fluid percussion injury were treated by using subcutaneous infusion pumps filled with either saline (sham group) or amantadine hydrochloride, with a releasing rate of 3.6 mg/kg/hour for 8 weeks. The dopamine-releasing conditions and metabolism were analyzed sequentially by fast scan cyclic voltammetry (FSCV) and high-pressure liquid chromatography (HPLC). Novel object recognition (NOR) and fixed-speed rotarod (FSRR) behavioral tests were used to determine treatment effects on cognitive and motor deficits after injury. Sequential dopamine-release deficits were revealed in 6-Pa-fluid-percussion cerebral cortical injured animals. The reuptake rate (tau value) of dopamine in injured animals was prolonged, but the tau value became close to the value for the control group after amantadine therapy. Cognitive and motor learning impairments were shown evidenced by the NOR and FSRR behavioral tests after injury. Chronic amantadine therapy reversed dopamine-release deficits, and behavioral impairment after fluid percussion injuries were ameliorated in the rats treated by using amantadine-pumping infusion. Chronic treatment with amantadine hydrochloride can ameliorate dopamine-release deficits as well as cognitive and motor deficits caused by cerebral fluid-percussion injury.

  14. Release and in vitro skin permeation of polyphenols from cosmetic emulsions.

    Science.gov (United States)

    Zillich, O V; Schweiggert-Weisz, U; Hasenkopf, K; Eisner, P; Kerscher, M

    2013-10-01

    Polyphenols are natural antioxidants, which can inhibit oxidative chain reactions in human skin and prevent therefore some skin diseases and premature ageing. A prerequisite of this behaviour is their permeation through the skin barrier, in particular the stratum corneum (SC). In this study, we investigated the skin permeation kinetic of polyphenols, incorporated to semisolid emulsions, and the release of polyphenols from the emulsions. Mixtures of model substances, consisting of catechin, epigallocatechin gallate (EGCG), resveratrol, quercetin, rutin and protocatechuic acid (PCA), were formulated into o/w emulsions with different oil phase content. The in vitro experiments were carried out in Franz-type diffusion cells by means of ex vivo pig skin and a cellulose membrane. The increased oil content in the emulsion led to a significant decrease in initial release coefficients (K(r)), diffusion coefficients within the formulation (D(v)) and skin permeation coefficients (K(p)), respectively. The study considered the dependence of K(r) on molecular weight and lipophilicity of polyphenolics. For both more hydrophilic and more lipophilic substance groups, the values for K(r) were inverse proportional to molecular weight. For catechin, quercetin, rutin, resveratrol and PCA, a good correlation between K(p) and K(r) parameters was obtained. The most permeable substance was PCA (K(p) = 1.2·10(-3) cm h(-1)), and the least permeable was quercetin (K(p) = 1.5·10(-5) cm h(-1)). All substances could pass the SC barrier and were found mostly in the epidermis and dermis, confirming the potential of polyphenols as anti-ageing active cosmetic ingredients. © 2013 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  15. Human pathogenic viruses are retained in and released by Candida albicans biofilm in vitro.

    Science.gov (United States)

    Mazaheritehrani, Elham; Sala, Arianna; Orsi, Carlotta Francesca; Neglia, Rachele Giovanna; Morace, Giulia; Blasi, Elisabetta; Cermelli, Claudio

    2014-01-22

    Candida albicans is the most prevalent human fungal pathogen associated with biofilm formation on indwelling medical devices. Under this form, Candida represents an infectious reservoir difficult to eradicate and possibly responsible for systemic, often lethal infections. Currently, no information is available on the occurrence and persistence of pathogenic viruses within C. albicans biofilm. Therefore, the aim of this study was to investigate whether Herpes Simplex Virus type 1 (HSV-1) and Coxsackievirus type B5 (CVB5) can be encompassed in Candida biofilm, retain their infectivity and then be released. Thus, cell-free virus inocula or HSV-1-infected cells were added to 24h-old fungal biofilm in tissue culture plates; 48 h later, the biofilm was detached by washing and energetic scratching and the presence of virus in the rescued material was end-point titrated on VERO cells. Planktonic Candida cultures and samples containing only medium were run in parallel as controls. We found that both HSV-1 and CVB5 free virus particles, as well as HSV-1 infected cells remain embedded in the biofilm retaining their infectivity. As a second step, the influence of biofilm on virus sensitivity to sodium hypochlorite and to specific neutralizing antibodies was investigated. The results showed that virus encompassment in fungal biofilm reduces virus sensitivity to chemical inactivation but does not affect antibody neutralization. Overall, these data provide the first in vitro evidence that viruses can be encompassed within Candida biofilm and then be released. Thus, it may be speculated that Candida biofilm can be a reservoir of viruses too, posing a further health risk. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. FORMULATION AND IN VITRO STUDY OF PROPRANOLOL HYDROCHLORIDE CONTROLLED RELEASE FROM CARBOXYMETHYL CHITOSAN-BASED MATRIX TABLETS

    Directory of Open Access Journals (Sweden)

    Hernawan Hernawan

    2013-12-01

    Full Text Available Formulation and in vitro study of propranolol hydrochloride controlled release from carboxymethyl chitosan-based matrix tablets have been conducted. Formulations with various concentrations of carboxymethyl chitosan 2% (F1, 4% (F2, 6% (F3 were done by wet granulation method. Compatibility test was conducted by XRD and FTIR spectroscopy to determine interaction between propranolol hydrochloride and polymer excipients. Dissolution profiles was obtained through in vitro tests release using simulated gastric fluid (without enzymes, pH 1.2 for the first 2 h and followed by simulated intestinal fluid (phosphate buffer solution without enzyme, pH 7.2 for 2 h remaining. The dissolution profile of each formulation was fitted with five kinetics modeling of drug release (zero order, first order, Higuchi, Peppas-Korsmeyer, and Hixson-Crowell. The compatibility test results showed that formulation caused physical interactions between propranolol hydrochloride and polymer excipient but doesn't make crystallinity nature of propranolol hydrochloride disturbed even after formulation. Dissolution profiles of each formulation showed that controlled release of propranolol hydrochloride from the tablet followed Peppas-Korsmeyer model. It is concluded that carboxymethyl chitosan in appropriate proportions is suitable for formulating propranolol hydrochloride controlled release tablets which exhibit Peppas-Korsmeyer release kinetics.

  17. Synthesis, characterization of dextran hydrogels and their in vitro release of gentamycin sulphate.

    Science.gov (United States)

    Guo, Rui; Chen, Peizhe; Mo, Yunfei; Lan, Yong; Xue, Wei; Zhang, Yuanming

    2015-10-16

    This study reports on the synthesis and characterization of biodegradable dextran-allyl isocyanate-ethylamine (Dex-AE)/polyethylene glycol-diacrylate (PEGDA) hydrogels for the controlled release of gentamycin sulphate (GS) and in vitro inhibition of organisms. The Dex-AE precursor was prepared through a 2-step chemical modification and characterized by Fourier transform infrared spectroscopy (FTIR). Scanning electron microscopy (SEM) results revealed that an increase in Dex-AE content led to an initial decrease in pore size of the Dex-AE/PEGDA hydrogels, but a further increase in Dex-AE content resulted in a slightly increase of pore size. The swelling data indicated that the swelling ratio depended on the precursor feed ratio. GS was incorporated into the hydrogels through 2 different methods, i.e., immersed and crosslinked. The crosslinked GS-Dex-AE/PEGDA hydorgels exhibited stronger antimicrobial activities against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. Finally, the viscoelastic properties of crosslinked GS-Dex-AE/PEGDA hydorgels were investigated.

  18. Dynamic Duos? Jamaican Fruit Bats (Artibeus jamaicensis) Do Not Show Prosocial Behavior in a Release Paradigm

    Science.gov (United States)

    Hoffmaster, Eric; Vonk, Jennifer

    2016-01-01

    Once thought to be uniquely human, prosocial behavior has been observed in a number of species, including vampire bats that engage in costly food-sharing. Another social chiropteran, Jamaican fruit bats (Artibeus jamaicensis), have been observed to engage in cooperative mate guarding, and thus might be expected to display prosocial behavior as well. However, frugivory and hematophagy diets may impose different selection pressures on prosocial preferences, given that prosocial preferences may depend upon cognitive abilities selected by different ecological constraints. Thus, we assessed whether Jamaican fruit bats would assist a conspecific in an escape paradigm in which a donor could opt to release a recipient from an enclosure. The test apparatus contained two compartments—one of which was equipped with a sensor that, once triggered, released the trap door of the adjacent compartment. Sixty-six exhaustive pairs of 12 bats were tested, with each bat in each role, twice when the recipient was present and twice when absent. Bats decreased their behavior of releasing the trapdoor in both conditions over time, decreasing the behavior slightly more rapidly in the recipient absent condition. Bats did not release the door more often when recipients were present, regardless of the recipient; thus, there was no clear evidence of prosocial behavior. PMID:27879623

  19. Dynamic Duos? Jamaican Fruit Bats (Artibeus jamaicensis Do Not Show Prosocial Behavior in a Release Paradigm

    Directory of Open Access Journals (Sweden)

    Eric Hoffmaster

    2016-11-01

    Full Text Available Once thought to be uniquely human, prosocial behavior has been observed in a number of species, including vampire bats that engage in costly food-sharing. Another social chiropteran, Jamaican fruit bats (Artibeus jamaicensis, have been observed to engage in cooperative mate guarding, and thus might be expected to display prosocial behavior as well. However, frugivory and hematophagy diets may impose different selection pressures on prosocial preferences, given that prosocial preferences may depend upon cognitive abilities selected by different ecological constraints. Thus, we assessed whether Jamaican fruit bats would assist a conspecific in an escape paradigm in which a donor could opt to release a recipient from an enclosure. The test apparatus contained two compartments—one of which was equipped with a sensor that, once triggered, released the trap door of the adjacent compartment. Sixty-six exhaustive pairs of 12 bats were tested, with each bat in each role, twice when the recipient was present and twice when absent. Bats decreased their behavior of releasing the trapdoor in both conditions over time, decreasing the behavior slightly more rapidly in the recipient absent condition. Bats did not release the door more often when recipients were present, regardless of the recipient; thus, there was no clear evidence of prosocial behavior.

  20. Gastro-floating bilayer tablets for the sustained release of metformin and immediate release of pioglitazone: preparation and in vitro/in vivo evaluation.

    Science.gov (United States)

    He, Wei; Li, Yongji; Zhang, Rao; Wu, Zhannan; Yin, Lifang

    2014-12-10

    Owing to the complementary mechanisms of action of metformin hydrochloride (MH) and pioglitazone hydrochloride (PG), combination therapy for type 2 diabetes mellitus using the two drugs is highly desired; on the other hand, MH is not well absorbed in lower gastrointestinal tract and has a short half-life, therefore compromising the therapeutic effects. Herein, the present study was to develop gastro-floating bilayer matrix tablets in which the two drugs were incorporated into two separate layers, aiming at sustaining MH release with enhanced absorption and achieving immediate release of PG. The tablets of the optimized formulation floated on the test medium for more than 24 h with 5 min of floating lag time, and sustained MH release for 12 h via a diffusion-dependent manner; and complete release of PG within 5 min were achieved. Moreover, a steady plasma concentration of MH with a 1.5-fold increase in bioavailability, decreased C(max) and reduced T(max) was obtained, and the in vivo behavior of PG was similar to the marked product. Summarily, sustained MH release with improved absorption and immediate release of PG were obtained simultaneously using the gastro-floating bilayer tablet, allowing strengthened combination therapy for diabetes mellitus. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. In vitro release kinetics of gentamycin from a sodium hyaluronate gel delivery system suitable for the treatment of peripheral vestibular disease.

    Science.gov (United States)

    Kelly, R M; Meyer, J D; Matsuura, J E; Shefter, E; Hart, M J; Malone, D J; Manning, M C

    1999-01-01

    For certain patients who experience intense vertigo arising from unilateral vestibular lesions, the primary therapy is a vestibular nerve section, an intracranial surgical procedure. One alternative to this treatment is therapeutic ablation of vestibular function on the unaffected side using an ototoxic agent. We prepared a biodegradable sustained-release gel delivery system using sodium hyaluronate that can be administered into the middle ear using only a local anesthetic. The gel contains gentamycin sulfate, the ototoxic agent of choice for treatment of unilateral vestibulopathy, and it exhibits diffusion-controlled release of the drug over a period of hours. The released gentamycin could then diffuse into the inner ear through the round membrane. This represents an important advance over previous formulations, which used only gentamycin sulfate solutions, in that it should allow more careful control of the dose, it should reduce loss of the drug from the middle ear site, and it should maintain intimate contact with the round membrane. By carefully controlling the dose, it should be possible to inhibit vestibular function while minimizing hearing loss. Herein we describe the in vitro release kinetics of gentamycin sulfate from sodium hyaluronate gels and find that the system obeys Fickian behavior.

  2. Gas retention and release behavior in Hanford single-shell waste tanks

    Energy Technology Data Exchange (ETDEWEB)

    Stewart, C.W.; Brewster, M.E.; Gauglitz, P.A.; Mahoney, L.A.; Meyer, P.A.; Recknagle, K.P.; Reid, H.C.

    1996-12-01

    This report describes the current understanding of flammable gas retention and release in Hanford single-shell waste tanks based on theory, experimental results, and observations of tank behavior. The single-shell tanks likely to pose a flammable gas hazard are listed and described, and photographs of core extrusions and the waste surface are included. The credible mechanisms for significant flammable gas releases are described, and release volumes and rates are quantified as much as possible. The only mechanism demonstrably capable of producing large ({approximately}100 m{sup 3}) spontaneous gas releases is the buoyant displacement, which occurs only in tanks with a relatively deep layer of supernatant liquid. Only the double-shell tanks currently satisfy this condition. All release mechanisms believed plausible in single-shell tanks have been investigated, and none have the potential for large spontaneous gas releases. Only small spontaneous gas releases of several cubic meters are likely by these mechanisms. The reasons several other postulated gas release mechanisms are implausible or incredible are also given.

  3. Once-daily propranolol extended-release tablet dosage form: formulation design and in vitro/in vivo investigation.

    Science.gov (United States)

    Huang, Yaw-Bin; Tsai, Yi-Hung; Yang, Wan-Chiech; Chang, Jui-Sheng; Wu, Pao-Chu; Takayama, Kozo

    2004-11-01

    The purpose of this study was to develop and optimize the propranolol once-daily extended release formulations containing HPMC, Microcrystalline cellulose (MCC) and lactose. In vitro studies, the response surface methodology and multiple response optimization utilizing the polynomial equation were used to search for the optimal formulation with specific release rate at different time intervals. The constrained mixture experimental design was used to prepare systematic model formulations, which were composed of three formulation variables: the content of HPMC (X(1)) MCC (X(2)) and lactose (X(3)). The drug release percent at 1.5, 4, 8, 14 and 24 h were the target responses and were restricted to 15-30, 35-55, 55-75, 75-90 and 90-110%, respectively. The results showed that the optimized formulation provided a dissolution pattern equivalent to the predicted curve, which indicated that the optimal formulation could be obtained using response surface methodology. The mechanism of drug release from HMPC matrix tablets followed non-Fickian diffusion. In the vivo study, the MRT was prolonged for matrix tablets when compared with commercial immediate release tablets. Furthermore, a linear relationship between in vitro dissolution and in vivo absorption was observed in the beagle dogs.

  4. In vitro controlled release of antihypertensive drugs intercalated into unmodified SBA-15 and MgO modified SBA-15 matrices.

    Science.gov (United States)

    Alexa, Iuliana Florentina; Ignat, Maria; Popovici, Roxana Florentina; Timpu, Daniel; Popovici, Eveline

    2012-10-15

    The use of nanotechnology in medicine and more specifically in drug delivery systems is set to spread rapidly. In order to broaden the range of matrices and implicitly to develop the class of drug delivery systems based on diffusion mechanism, in this study the starting materials, SBA-15 powder matrices, were engineered by MgO modification for antihypertensive drugs intercalation. Captopril and aliskiren were used as drug models. All powders, unmodified and MgO-modified silica matrices, and their corresponding drug-loaded samples were characterized by X-ray diffraction, N(2) adsorption and desorption, FTIR spectroscopy and scanning electron microscopy. The studied drug carriers were tested in the controlled drug release process and the influence of the silica pore morphology and geometry on drug release profiles was extensively studied. In order to analyze the data obtained from the in vitro release studies and to evaluate the kinetic release mechanism, the Korsmeyer and Peppas equation was used. The obtained drug delivery system based on MgO-SBA-15 matrix exhibits exciting structural features and is therefore promising for its use as antihypertensive drug delivery system, having potential therapeutic benefits resulting in safe and effective management of captopril and aliskiren adsorption and in vitro release. Published by Elsevier B.V.

  5. Controlled delivery of aspirin: effect of aspirin on polymer degradation and in vitro release from PLGA based phase sensitive systems.

    Science.gov (United States)

    Tang, Yu; Singh, Jagdish

    2008-06-05

    The objective of this study was to develop poly (d,l-lactide-co-glycolide) (PLGA) based injectable phase sensitive in situ gel forming delivery system for controlled delivery of aspirin, and to characterize the effect of drug/polymer interaction on the in vitro release of aspirin and polymer degradation. Aspirin was dissolved into PLGA solution in 1-methyl-2-pyrrolidone. Poly(ethylene glycol)400 was used as plasticizer to reduce initial burst release. The solution formulation was injected into aqueous release medium to form a gel depot. Released samples were withdrawn periodically and assayed for aspirin content by high performance liquid chromatography. The effect of aspirin on the degradation of PLGA matrix was evaluated using Proton Nuclear Magnetic Resonance and Gel Permeation Chromatography. PLGA based in situ gel forming formulations controlled the in vitro release of aspirin for 7 days only. Analysis of PLGA matrix residuals revealed that PLGA in aspirin loaded formulations exhibited a significantly (pdegradation compared to blank formulations. These findings suggest that aspirin causes an unusually faster degradation of PLGA. Such faster degradation of PLGA has not been noticed for any other drugs reported in the literature.

  6. Design and in vitro/in vivo evaluation of sustained-release floating tablets of itopride hydrochloride.

    Science.gov (United States)

    Ahmed, Sayed M; Ahmed Ali, Adel; Ali, Ahmed Ma; Hassan, Omiya A

    2016-01-01

    The aim of the present study was to improve the bioavailability of itopride (ITO) and sustain its action by formulating as a floating dosage form. Sustained-release floating tablets of ITO hydrochloride (HCl) were prepared by direct compression using different hydrocolloid polymers such as hydroxypropyl methylcellulose and ethylcellulose and/or methacrylic acid polymers Eudragit RSPM and Carbopol 934P. The floating property was achieved using an effervescent mixture of sodium bicarbonate and anhydrous citric acid (1:1 mol/mol). Hardness, friability, content uniformity, and dissolution rate of the prepared floating tablets were evaluated. The formulation F10 composed of 28.5% Eudragit RSPM, 3% NaHCO3, and 7% citric acid provided sustained drug release. In vitro results showed sustained release of F10 where the drug release percentage was 96.51%±1.75% after 24 hours (P=0.031). The pharmacokinetic results indicated that the area under the curve (AUC0-∞) of the prepared sustained-release floating tablets at infinity achieved 93.69 µg·h/mL compared to 49.89 µg·h/mL for the reference formulation (Ganaton(®)) and the relative bioavailability of the sustained-release formulation F10 increased to 187.80% (P=0.022). The prepared floating tablets of ITO HCl (F10) could be a promising drug delivery system with sustained-release action and enhanced drug bioavailability.

  7. In vitro evaluation of sustained released matrix tablets containing ibuprofen: a model poorly water-soluble drug

    Directory of Open Access Journals (Sweden)

    Wendy Leticia Guerra-Ponce

    Full Text Available ABSTRACT A matrix system was developed that releases ibuprofen (IB over a 12-hour period and the influence of the polymer type and concentration on the release rate of the drug was evaluated. Tablets containing different concentrations of Carbopol (CP, hydroxypropyl methylcellulose (HPMC, or ethyl cellulose (EC were prepared using direct compression and the drug content, content uniformity, hardness, friability, dissolution performance, and in vitro release kinetics were examined. Formulated tablets were found to be within acceptable limits for physical and chemical parameters. The release kinetics of the Carbopol(r971P 8% formulation showed the best linearity (r 2 =0.977 in fitting zero-order kinetics, suggesting the release rate was time independent. The drug release from tablets containing 8% CP was extended over approximately 18 hours and the release kinetics were nearly linear, suggesting that this system has the potential to maintain constant plasma drug concentrations over 12 hours, which could reduce the frequency of administration and the occurrence of adverse effects associated with repeated administration of conventional IB tablets.

  8. Electrochemical detection of catecholamine release from rat carotid body in vitro.

    Science.gov (United States)

    Donnelly, D F

    1993-05-01

    Neurotransmitter secretion from carotid body glomus cells is hypothesized to be an essential element of chemotransduction. To address one aspect of this hypothesis, catecholamine release in response to hypoxic hypoxia and histotoxic hypoxia was examined using electrically treated carbon-fiber microelectrodes placed in rat carotid bodies in vitro. Carotid bodies of mature rats were removed, along with a portion of the sinus nerve, and suspended in oxygenated (95% O2-5% CO2) Ringer saline at 35 degrees C. The microelectrode differential current after a 50-mV step was recorded over the potential range of -300 to +500 mV. In some preparations, a suction electrode applied to the sinus nerve recorded single-fiber chemoreceptor afferent activity. Stimulation by severe hypoxia (Po2 approximately 0-10 Torr for 3 min, n = 10) and cyanide (2 mM for 2 min) caused an increase in sinus nerve activity and an increase in the carbon-fiber electrode current at a potential corresponding to the oxidation potential of dopamine. As measured in the amperometric mode (constant voltage), tissue catecholamine was 0.35 +/- 0.05 microM (n = 6) and increased to 1.64 +/- 0.43 microM by 1 min of severe hypoxia or to 1.06 +/- 0.17 microM at 2 min of moderate hypoxia (Po2 approximately 50 Torr). Exposure to calcium-free Ringer saline before hypoxia ablated the increase in electrode current, and the response was restored after reperfusion with calcium-containing saline. Repeated exposures to hypoxia (3-min duration) every 15 min resulted in significantly smaller nerve and catecholamine responses. By the third hypoxia exposure, nerve and catecholamine responses were diminished by 30-50%.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Interleukin-6 infusion during human endotoxaemia inhibits in vitro release of the urokinase receptor from peripheral blood mononuclear cells

    DEFF Research Database (Denmark)

    Ostrowski, S R; Plomgaard, P; Fischer, C P

    2005-01-01

    in humans. Healthy subjects received intravenous endotoxin injection [high-dose, 2 ng/kg (n=8) and low-dose, 0.06 ng/kg (n=7)], coadministration of 0.06 ng/kg endotoxin and 3 h recombinant human (rh)IL-6 infusion (n=7) or 3 h infusion of rhIL-6 (n=6), rhTNF-alpha (n=6) or NaCl (n=5). Soluble uPAR (su...... that a systemic effect on the plasma suPAR level was detectable. Even subclinical doses of endotoxin in vivo enhance the capacity of PBMC to release uPAR after incubation in vitro. The inhibitory effect of IL-6 on endotoxin-mediated uPAR-release in vitro suggests that IL-6 has anti-inflammatory effects...

  10. Nanostructure of liquid crystalline matrix determines in vitro sustained release and in vivo oral absorption kinetics for hydrophilic model drugs.

    Science.gov (United States)

    Lee, Kathy W Y; Nguyen, Tri-Hung; Hanley, Tracey; Boyd, Ben J

    2009-01-05

    Nanostructured lipid-based liquid crystalline systems have been proposed as sustained oral drug delivery systems, but the interplay between their intrinsic release rates, susceptibility to digestive processes, and the manner in which these effects impact on their application in vivo, are not well understood. In this study, two different bicontinuous cubic phases, prepared from glyceryl monooleate and phytantriol, and a reversed hexagonal phase formed by addition of a small amount of vitamin E to phytantriol (Q(II GMO), Q(II PHYT) and H(II PHYT+VitEA), respectively) were prepared. The release kinetics for a number of model hydrophilic drugs with increasing molecular weights (glucose, Allura Red and FITC-dextrans) was determined in in vitro release experiments. Diffusion-controlled release was observed in all cases as anticipated from previous studies with liquid crystalline systems, and it was discovered that the release rates of each drug decreased as the matrix was changed from Q(II GMO) to Q(II PHYT) to H(II PHYT+VitEA). Formulations containing (14)C-glucose, utilized as a rapidly absorbed marker of drug release, were then orally administered to rats to determine the relative in vivo absorption rates from the different formulations. The results showed a trend by which the rate of absorption of (14)C-glucose followed that observed in the corresponding in vitro release studies, providing the first indication that the nanostructure of these materials may provide the ability to tailor the absorption kinetics of hydrophilic drugs in vivo, and hence form the basis of a new drug delivery system.

  11. In vivo and in vitro taste masking of ofloxacin and sustained release by forming interpenetrating polymer network beads.

    Science.gov (United States)

    Rajesh, A Michael; Popat, Kiritkumar Mangaldas

    2017-02-01

    Drug-resin complexes (DRCs) of ofloxacin and ion-exchange resins (IERs) were prepared in different ratios of drug/IERs, that is, 1:1, 1:2 and 1:4 (w/w) and investigated for taste masking by in vivo and in vitro release studies. Human volunteers graded AD1:4 (DRC) as tasteless with an average value of 0.3 ± 0.03 and in vitro study showed that AD 1:4 released only 1.70 ± 0.86% of drug at salivary pH within 30s. Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (P-XRD) and differential scanning calorimetry (DSC) studies of AD 1:4 showed the change in the morphology of the drug, that is, from crystalline phase to amorphous phase during complex formation. The release of drug from AD 1:4 was completed within 30 min at gastric pH 1.2 and to extend the release time of drug at gastric pH, it was entrapped with different biopolymers, such as sodium alginate (SA) and sodium carboxymethyl cellulose (SCMC), in the presence of ferric chloride and glutaraldehyde (GA) to form interpenetrating polymer network (IPN) beads. FTIR studies revealed that IPN beads were crosslinked with Fe3+ and GA. The release of drug at gastric and intestinal pH was 14.53 ± 1.52% and 65.86 ± 1.29%, respectively, for a contact time of 10 h. The kinetics release study shows fickian diffusion for ionically crosslinked beads and zero-order release for GA crosslinking beads.

  12. In Vitro – In Vivo Evaluation of Sustained – Release Lithium Carbonate Matrix Tablets: Influence of Hydrophilic Matrix Materials

    Directory of Open Access Journals (Sweden)

    J Emami

    2004-04-01

    Full Text Available Background: Conventional Lithium carbonate (LC tablets produce rapid and relatively high peak blood levels resulting in adverse effects. These drawbacks can be overcome by designing a suitable sustained or controlled-release LC preparation. Methods: Sustained-release matrix tablets were therefore developed using different types and ratios of polymers including carbomer (CP, Na carboxymethylcellulose (Na CMC and hydroxypropylmethylcellulose (HPMC, to assess the release profiles and in vivo performance of the formulations. The tablets were prepared by either direct compression (DC or wet granulation (WG. In the DC method, 69% (450 mg LC, 5, 10 or 15% CP or Na CMC (of total tablet weight, lactose and /or Avicel (to maintain constant tablet weight were mixed and directly compressed. In the WG method, 450 mg LC and 10, 20, or 30% HPMC were granulated with Eudragit S100 solution, dried, and then compressed to formulate the tablets. In vitro and in vivo, newly formulated sustained-release LC tablets were compared with sustained-release commercial tablets (Eskalith and Priadel. In vivo studies were conducted in nine healthy subjects in a cross-over design, with a 3x3 Latin square sequence, and pharmacokinetic parameters were estimated using classical methods. Results: The matrix tablets containing 15% CP exhibited suitable release kinetics and uniform absorption characteristics comparable to that of Eskalith. In vivo, this formulation produced a smooth and extended absorption phase very much similar to that of Eskalith with the identical elimination half-life and extent of absorption. Conclusion: The matrix tablets containing 15% CP reduces the incidence of side effects often associated with high serum concentration of Lithium and blood level variations. Direct correlation between the dissolution profiles and the relative bioavailability of the formulations could be observed. Keywords: Lithium carbonate, Matrix tablets, Sustained-release, In vitro

  13. Paclitaxel-loaded polymeric microparticles: Quantitative relationships between in vitro drug release rate and in vivo pharmacodynamics

    Science.gov (United States)

    Tsai, Max; Lu, Ze; Wientjes, M. Guillaume; Au, Jessie L.-S.

    2013-01-01

    Intraperitoneal therapy (IP) has demonstrated survival advantages in patients with peritoneal cancers, but has not become a widely practiced standard-of-care in part due to local toxicity and sub-optimal drug delivery. Paclitaxel-loaded, polymeric microparticles were developed to overcome these limitations. The present study evaluated the effects of microparticle properties on paclitaxel release (extent and rate) and in vivo pharmacodynamics. In vitro paclitaxel release from microparticles with varying physical characteristics (i.e., particle size, copolymer viscosity and composition) was evaluated. A method was developed to simulate the dosing rate and cumulative dose released in the peritoneal cavity based on the in vitro release data. The relationship between the simulated drug delivery and treatment outcomes of seven microparticle compositions was studied in mice bearing IP human pancreatic tumors, and compared to that of the intravenous Cremophor micellar paclitaxel solution used off-label in previous IP studies. Paclitaxel release from polymeric microparticles in vitro was multi-phasic; release was greater and more rapid from microparticles with lower polymer viscosities and smaller diameters (e.g., viscosity of 0.17 vs. 0.67 dl/g and diameter of 5–6 vs. 50–60 μm). The simulated drug release in the peritoneal cavity linearly correlated with treatment efficacy in mice (r2>0.8, pmicroparticles, which distribute more evenly in the peritoneal cavity compared to the large microparticles, showed greater dose efficiency. For single treatment, the microparticles demonstrated up to 2-times longer survival extension and 4-times higher dose efficiency, relative to the paclitaxel/Cremophor micellar solution. Upon repeated dosing, the paclitaxel/Cremophor micellar solution showed cumulative toxicity whereas the microparticle that yielded 2-times longer survival did not display cumulative toxicity. The efficacy of IP therapy depended on both temporal and spatial

  14. DESIGN AND IN-VITRO CHARACTERIZATION OF DELAYED RELEASE MULTI UNIT PARTICULATES USING WURSTER TECHNOLOGY

    OpenAIRE

    Dr . M. Sunitha Reddy*, Raju Eddagiri, S. Muhammad Fazal Hl Haq, Dr. V. Venkateswarlu

    2017-01-01

    The aim of the present research was to design and characterize delayed release Multi Unit Particles (MUPS). These were produced primarily for the purpose of oral modified release dosage forms having gastro resistant and delayed-release properties. During the development of MUPS agglomeration, generations of fines and twins formation are identified as critical issues. The delayed release multiple units were prepared by layering drug suspension using Wurster technology. The prepared multi unit ...

  15. How do culture media influence in vitro perivascular cell behavior?

    Science.gov (United States)

    Huber, Birgit; Volz, Ann-Cathrin; Kluger, Petra Juliane

    2015-12-01

    Perivascular cells are multilineage cells located around the vessel wall and important for wall stabilization. In this study, we evaluated a stem cell media and a perivascular cell-specific media for the culture of primary perivascular cells regarding their cell morphology, doubling time, stem cell properties, and expression of cell type-specific markers. When the two cell culture media were compared to each other, perivascular cells cultured in the stem cell medium had a more elongated morphology and a faster doubling rate and cells cultured in the pericyte medium had a more typical morphology, with several filopodia, and a slower doubling rate. To evaluate stem cell properties, perivascular cells, CD146(-) cells, and mesenchymal stem cells (MSCs) were differentiated into the adipogenic, osteogenic, and chondrogenic lineages. It was seen that perivascular cells, as well as CD146(-) cells and MSCs, cultured in stem cell medium showed greater differentiation than cells cultured in pericyte-specific medium. The expression of pericyte-specific markers CD146, neural/glial antigen 2 (NG2), platelet-derived growth factor receptor-β (PDGFR-β), myosin, and α-smooth muscle actin (α-SMA) could be found in both pericyte cultures, as well as to varying amounts in CD146(-) cells, MSCs, and endothelial cells. The here presented work shows that perivascular cells can adapt to their in vitro environment and cell culture conditions influence cell functionality, such as doubling rate or differentiation behavior. Pericyte-specific markers were shown to be expressed also from cells other than perivascular cells. We can further conclude that CD146(+) perivascular cells are inhomogeneous cell population probably containing stem cell subpopulations, which are located perivascular around capillaries. © 2015 International Federation for Cell Biology.

  16. Synthesis of polymeric derivatives of isoniazid: characterization and in vitro release from a water-soluble adduct with polysuccinimide.

    Science.gov (United States)

    Giammona, G; Giannola, L I; Carlisi, B

    1989-04-01

    Coupling of isoniazid with polysuccinimide afforded a water-insoluble polymeric pro-drug; by reaction with ethanolamine it was chemically transformed in a water-soluble adduct. The in vitro release of isoniazid from the drug-polymer adduct was studied by using an artificial stomach wall lipid membrane. The transfer rate constant from simulated gastric juice to simulated plasma was defined and compared with that of an equivalent dose of pure drug.

  17. Relationship between Surface Properties and In Vitro Drug Release from Compressed Matrix Containing Polymeric Materials with Different Hydrophobicity Degrees

    OpenAIRE

    Yarce, Cristhian J.; Echeverri, Juan D.; Palacio, Mario A.; Rivera, Carlos A.; Salamanca, Constain H.

    2017-01-01

    This work is the continuation of a study focused on establishing relations between surface thermodynamic properties and in vitro release mechanisms using a model drug (ampicillin trihydrate), besides analyzing the granulometric properties of new polymeric materials and thus establishing the potential to be used in the pharmaceutical field as modified delivery excipients. To do this, we used copolymeric materials derived from maleic anhydride with decreasing polarity corresponding to poly(isob...

  18. The release behavior and kinetic evaluation of tramadol HCl from chemically cross linked Ter polymeric hydrogels

    Directory of Open Access Journals (Sweden)

    Malana Muhammad A

    2013-01-01

    Full Text Available Abstract Background and the purpose of the study Hydrogels, being stimuli responsive are considered to be effective for targeted and sustained drug delivery. The main purpose for this work was to study the release behavior and kinetic evaluation of Tramadol HCl from chemically cross linked ter polymeric hydrogels. Methods Ter-polymers of methacrylate, vinyl acetate and acrylic acid cross linked with ethylene glycol dimethacrylate (EGDMA were prepared by free radical polymerization. The drug release rates, dynamic swelling behavior and pH sensitivity of hydrogels ranging in composition from 1-10 mol% EGDMA were studied. Tramadol HCl was used as model drug substance. The release behavior was investigated at pH 8 where all formulations exhibited non-Fickian diffusion mechanism. Results and major conclusion Absorbency was found to be more than 99% indicating good drug loading capability of these hydrogels towards the selected drug substance. Formulations designed with increasing amounts of EGDMA had a decreased equilibrium media content as well as media penetrating velocity and thus exhibited a slower drug release rate. Fitting of release data to different kinetic models indicate that the kinetic order shifts from the first to zero order as the concentration of drug was increased in the medium, showing gradual independency of drug release towards its concentration. Formulations with low drug content showed best fitness with Higuchi model whereas those with higher concentration of drug followed Hixson-Crowell model with better correlation values indicating that the drug release from these formulations depends more on change in surface area and diameter of tablets than that on concentration of the drug. Release exponent (n derived from Korse-Meyer Peppas equation implied that the release of Tramadol HCl from these formulations was generally non-Fickian (n > 0.5 > 1 showing swelling controlled mechanism. The mechanical strength and controlled

  19. The Release Behavior and Kinetic Evaluation of Tramadol HCl from Chemically Cross Linked Ter Polymeric Hydrogels

    Directory of Open Access Journals (Sweden)

    Muhammad A Malana

    2013-01-01

    Full Text Available Background and the purpose of the study: Hydrogels, being stimuli responsive are considered to be effective for targeted and sustained drug delivery. The main purpose for this work was to study the release behavior and kinetic evaluation of Tramadol HCl from chemically cross linked ter polymeric hydrogels.MethodsTer-polymers of methacrylate, vinyl acetate and acrylic acid cross linked with ethylene glycol dimethacrylate (EGDMA were prepared by free radical polymerization. The drug release rates, dynamic swelling behavior and pH sensitivity of hydrogels ranging in composition from 1-10 mol % EGDMA were studied. Tramadol HCl was used as model drug substance. The release behavior was investigated at pH 8 where all formulations exhibited non-Fickian diffusion mechanism.Results and major conclusion: Absorbency was found to be more than 99% indicating good drug loading capability of these hydrogels towards the selected drug substance. Formulations designed with increasing amounts of EGDMA had a decreased equilibrium media content as well as media penetrating velocity and thus exhibited a slower drug release rate. Fitting of release data to different kinetic models indicate that the kinetic order shifts from the first to zero order as the concentration of drug was increased in the medium, showing gradual independency of drug release towards its concentration. Formulations with low drug content showed best fitness with Higuchi model whereas those with higher concentration of drug followed Hixson-Crowell model with better correlation values indicating that the drug release from these formulations depends more on change in surface area and diameter of tablets than that on concentration of the drug. Release exponent (n derived from Korse-Meyer Peppas equation implied that the release of Tramadol HCl from these formulations was generally non-Fickian (n>0.5>1 showing swelling controlled mechanism. The mechanical strength and controlled release capability of

  20. Formulation and in vitro evaluation of mucoadhesive controlled release matrix tablets of flurbiprofen using response surface methodology

    Directory of Open Access Journals (Sweden)

    Ikrima Khalid

    2014-09-01

    Full Text Available The objective of the current study was to formulate mucoadhesive controlled release matrix tablets of flurbiprofen and to optimize its drug release profile and bioadhesion using response surface methodology. Tablets were prepared via a direct compression technique and evaluated for in vitro dissolution parameters and bioadhesive strength. A central composite design for two factors at five levels each was employed for the study. Carbopol 934 and sodium carboxymethylcellulose were taken as independent variables. Fourier transform infrared (FTIR spectroscopy studies were performed to observe the stability of the drug during direct compression and to check for a drug-polymer interaction. Various kinetic models were applied to evaluate drug release from the polymers. Contour and response surface plots were also drawn to portray the relationship between the independent and response variables. Mucoadhesive tablets of flurbiprofen exhibited non-Fickian drug release kinetics extending towards zero-order, with some formulations (F3, F8, and F9 reaching super case II transport, as the value of the release rate exponent (n varied between 0.584 and 1.104. Polynomial mathematical models, generated for various response variables, were found to be statistically significant (P<0.05. The study also helped to find the drug's optimum formulation with excellent bioadhesive strength. Suitable combinations of two polymers provided adequate release profile, while carbopol 934 produced more bioadhesion.

  1. In vitro release and diffusion studies of promethazine hydrochloride from polymeric dermatological bases using cellulose membrane and hairless mouse skin.

    Science.gov (United States)

    Babar, A; Ray, S D; Patel, N K; Plakogiannis, F M; Gogineni, P

    1999-02-01

    The study was designed to investigate the feasibility of developing a transdermal drug dosage form of promethazine hydrochloride (PMH). The in vitro release and diffusion characteristics of PMH from various dermatological polymeric bases were studied using cellulose membrane and hairless mouse skin as the diffusion barriers. These included polyethylene glycol (PEG), hydroxypropyl methylcellulose (HPMC), cross-linked microcrystalline cellulose, and carboxyl methyl cellulose sodium (Avicel CL-611), and a modified hydrophilic ointment USP. In addition, the effects of several additive ingredients known to enhance the drug release from topical formulations were evaluated. The general rank order for the drug release from these formulations using cellulose membrane was observed to be PEG > HMPC > Avicel CL-611 > hydrophilic ointment base. The inclusion of the additives had little or no effect on the drug diffusion from these bases, except for the hydrophilic ointment formulation containing 15% ethanol, which provided a significant increase in the drug release. However, when these formulations were studied for drug diffusion through the hairless mouse skin, the Avicel CL-611 base containing 15% ethanol exhibited the optimum drug release. The data also revealed that this formulation gave the highest steady-state flux, diffusion, and permeability coefficient values and correlated well with the amount of drug release.

  2. Montmorillonite-alginate nanocomposite as a drug delivery system--incorporation and in vitro release of irinotecan.

    Science.gov (United States)

    Iliescu, Ruxandra Irina; Andronescu, Ecaterina; Ghitulica, Cristina Daniela; Voicu, Georgeta; Ficai, Anton; Hoteteu, Mihai

    2014-03-25

    The scope of the present study was the preparation and characterization of irinotecan nanocomposite beads based on montmorillonite (Mt) and sodium alginate (AL) as drug carriers. After irinotecan (I) incorporation into Mt, the resulting hybrid was compounded with alginate, and I-Mt-AL nanocomposite beads were obtained by ionotropic gelation technique. The structure and surface morphology of the hybrid and composite materials were established by means of X-ray diffraction (XRD), IR spectroscopy (FT-IR), thermal analysis (TG-DTA) and scanning electron microscopy (SEM). Irinotecan incorporation efficiency in Mt and in alginate beads was determined both by UV-vis spectroscopy and thermal analysis and was found to be high. The hybrid and composite materials were tested in vitro in simulated intestinal fluid (pH 7.4, at 37 °C) in order to establish if upon administering the beads at the site of a resected colorectal tumor, the delivery of the drug is sustained and can represent an alternative to the existing systemic chemotherapy. The in vitro drug release test results clearly suggested that Mt, and Mt along with AL were able to control the release of irinotecan by making it sustained, without any burst effect, and by reducing the released amount and the release rate. The nanocomposite beads may be a promising drug delivery system in chemotherapy. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Evidence for lysosomal exocytosis and release of aggrecan-degrading hydrolases from hypertrophic chondrocytes, in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Edward R. Bastow

    2012-02-01

    The abundant proteoglycan, aggrecan, is resorbed from growth plate cartilage during endochondral bone ossification, yet mice with genetically-ablated aggrecan-degrading activity have no defects in bone formation. To account for this apparent anomaly, we propose that lysosomal hydrolases degrade extracellular, hyaluronan-bound aggrecan aggregates in growth plate cartilage, and that lysosomal hydrolases are released from hypertrophic chondrocytes into growth plate cartilage via Ca2+-dependent lysosomal exocytosis. In this study we confirm that hypertrophic chondrocytes release hydrolases via lysosomal exocytosis in vitro and we show in vivo evidence for lysosomal exocytosis in hypertrophic chondrocytes during skeletal development. We show that lysosome-associated membrane protein 1 (LAMP1 is detected at the cell surface following in vitro treatment of epiphyseal chondrocytes with the calcium ionophore, ionomycin. Furthermore, we show that in addition to the lysosomal exocytosis markers, cathepsin D and β-hexosaminidase, ionomycin induces release of aggrecan- and hyaluronan-degrading activity from cultured epiphyseal chondrocytes. We identify VAMP-8 and VAMP7 as v-SNARE proteins with potential roles in lysosomal exocytosis in hypertrophic chondrocytes, based on their colocalisation with LAMP1 at the cell surface in secondary ossification centers in mouse tibiae. We propose that resorbing growth plate cartilage involves release of destructive hydrolases from hypertrophic chondrocytes, via lysosomal exocytosis.

  4. Preventing false-negatives in the in vitro skin sensitization testing of acid anhydrides using interleukin-8 release assays.

    Science.gov (United States)

    Narita, Kazuto; Vo, Phuc Thi Hong; Yamamoto, Kenta; Kojima, Hajime; Itagaki, Hiroshi

    2017-08-01

    In vitro safety tests may be used as replacements for animal tests owing to their accuracy and high-throughput performance. However, several in vitro skin sensitization tests produce false-negative results such as acid anhydride. Here, we investigated the relationship between false-negative results of acid anhydride and its hydrolysis by aqueous vehicle. Differences in the pattern of hydrolysis for phthalic anhydride (PAH) due to addition of 1 drop of stock solution of PAH in liquid paraffin (LP) dispersion medium and PAH in DMSO were analyzed in a cell-free system. The results showed that use of LP dispersion medium stabilized the concentration of PAH in water over 5min by sustained-release, although almost all PAH converted to phthalic acid in water within 5min using DMSO. Additionally, treatment of THP-1 cells with PAH and phthalic acid using LP dispersion medium for 5min resulted in a 32-fold increase in IL-8 release for PAH as compared with that in the vehicle control. In contrast, for PAH using aqueous vehicle and phthalic acid using LP dispersion medium, there were no significant increases in IL-8 release. Similarly, using LP dispersion medium, trimellitic anhydride significantly increased IL-8 release was observed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Direct monitoring of dopamine and 5-HT release in substantia nigra and ventral tegmental area in vitro

    DEFF Research Database (Denmark)

    Rice, M E; Richards, C D; Nedergaard, S

    1994-01-01

    Fast-scan cyclic voltammetry with carbon fibre microelectrodes was used to detect endogenous dopamine (DA) and 5-hydroxytryptamine (5-HT) release from three distinct regions of guinea-pig mid-brain in vitro: rostral and caudal substantia nigra (SN) and the ventral tegmental area (VTA). Previous...... electrophysiological studies have demonstrated that cells of the caudal SN and the VTA have similar characteristics, whereas cells in the rostral SN have distinctly different properties. In the present study, we confirmed that each region has tyrosine hydroxylase-positive neurons and determined, using high......-HT. Release signals were monitored every 250 ms with a spatial resolution of less than 50 microns.l DA release was calcium-dependent and was not detectable in a catecholamine-poor area such as the cerebellum, or in mid-brain tissue pre-treated with reserpine. Within the normal mid-brain, the amount...

  6. MAOA-VNTR polymorphism modulates context-dependent dopamine release and aggressive behavior in males.

    Science.gov (United States)

    Schlüter, Thorben; Winz, Oliver; Henkel, Karsten; Eggermann, Thomas; Mohammadkhani-Shali, Siamak; Dietrich, Claudia; Heinzel, Alexander; Decker, Michel; Cumming, Paul; Zerres, Klaus; Piel, Markus; Mottaghy, Felix M; Vernaleken, Ingo

    2016-01-15

    A recent [(18)F]FDOPA-PET study reports negative correlations between dopamine synthesis rates and aggressive behavior. Since dopamine is among the substrates for monoamine oxidase A (MAOA), this investigation examines whether functional allelic variants of the MAOA tandem repeat (VNTR) promotor polymorphism, which is known to modulate aggressive behavior, influences dopamine release and aggression in response to violent visual stimuli. We selected from a genetic prescreening sample, strictly case-matched groups of 2×12 healthy male subjects with VNTRs predictive of high (MAOA-High) and low (MAOA-Low) MAOA expression. Subjects underwent pairs of PET sessions (dopamine D2/3 ligand [(18)F]DMFP) while viewing a movie of neutral content, versus violent content. Directly afterwards, aggressive behavior was assessed by the Point Subtraction Aggression Paradigm (PSAP). Finally, PET data of 23 participants and behavioral data of 22 participants were analyzed due to post hoc exclusion criteria. In the genetic prescreening sample MAOA-Low carriers had significantly increased scores on the Buss-Perry Aggression Questionnaire. In the PET-study-group, aggressive behavior under the emotional neutral condition was significantly higher in the MAOA-Low group. Interestingly, the two MAOA-groups showed inverse dopaminergic and behavioral reactions to the violent movie: The MAOA-High group showed higher dopamine release and increased aggression after the violent movie; MAOA-Low subjects showed decreases in aggressive behavior and no consistent dopamine release. These results indicate a possible impact of the MAOA-promotor polymorphism on the neurobiological modulation of aggressive behavior. However, the data do not support approaches stating that MAOA-Low fosters aggression by a simple pro-dopaminergic mechanism. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. The effect of difference in saliva pH against Hg release from amalgam restoration on in vitro research

    Directory of Open Access Journals (Sweden)

    Oksana Megasari

    2007-07-01

    Full Text Available Hg release from amalgam restoration is continuos as long as an amalgam in the mouth. The difference in saliva pH is one factor that influences Hg releasing from amalgam restoration. The purpose of this research was to find data the effect of the difference in saliva pH against Hg release from amalgam restoration. This research was a true experimental in vitro research. This research used 40 samples of premolar teeth of the maxilla, prepared in occlusal Class I, restored with amalgam and then divided into 4 Groups. Teeth belonging to Group 1 were immersed in saliva artificial with a pH content 5, Group 2 with a pH content of 6, Group 3 with a pH content of 7 as a control, and Group 4 with a pH content of 8. All tooth Groups were immersed for one week after condensation. Research data results analyzed using the One-Way Analysis of Variance (ANOVA. Research results measured using the Atomic Absorption Spectrophotometry (AAS indicated that Group 1 with a pH content of 5 had the highest average release, namely, 19,276 ppb, followed by Group 4 with a pH content of 8, with a Hg release of 17,691 ppb, followed by Group 3 with a pH content of 7 as a control, with a Hg release of 13,702 ppb, and Group 2 with a pH content of 6 the lowest Hg release, namely 12,377 ppb. Summary of this research showed that there was no effect of saliva pH difference against Hg release from amalgam restoration.

  8. Characterization and in vitro release studies of tetracycline and rolitetracycline imobilized on anionic collagen membranes

    Directory of Open Access Journals (Sweden)

    Gilberto Goissis

    2009-03-01

    Full Text Available This work reports the covalent immobilization of tetracycline and rolitetracycline over anionic collagen membranes and the drug release studies as an effort to develop a two stage drug release based on diffusion (fast release and on the rate of membrane biodegradation (slow release. Independent from casting conditions antibiotics incorporated by dispersion were released in the range from 80 to 100% within 7 hours in concentrations significantly higher than those described for the prevention of bacterial growth. Antibiotic release within this period was predominantly diffusion controlled. Covalent immobilization by a modified azide procedure occurred with preservation of collagen structure independently from pH of casting and reaction conditions. Its expected that anionic collagen membranes with dispersed and covalently bound rolitetracycline or tetracycline, in association with conventional therapy, may significantly reduce membrane induced infections observed post-implantation, one of the major problem associated with periodontal ligaments reconstruction by the Guided Tissue Regeneration procedure.

  9. Renin release from different parts of rat afferent arterioles in vitro

    DEFF Research Database (Denmark)

    Baumbach, L; Skøtt, O

    1986-01-01

    A technique was designed to study renin release from superfused rat glomeruli with short attached arterioles (SAG), from single glomeruli with long attached arterioles (LAG), and from single afferent arterioles (AA). The preparations obtained by magnetic isolation and microdissection were...... superfused individually, and the renin release was measured by an ultramicroradioimmunoassay with a detection limit of 3 X 10(-9) Goldblatt units. The renin content of one SAG was about one-fifth of that contained in one AA. Isoprenaline (10(-5) M) did not change renin release from SAG, whereas renin release...... from AA and LAG increased threefold (P less than 0.01). A 30-mosmol/kg reduction in medium sodium chloride concentration increased renin release from SAG 50% (P less than 0.01). This challenge caused no change in renin release from AA. It is concluded that the isoprenaline-sensitive juxtaglomerular (JG...

  10. In vitro release of theophylline from starch-based matrices prepared via high hydrostatic pressure treatment and autoclaving.

    Science.gov (United States)

    Błaszczak, Wioletta; Buciński, Adam; Górecki, Adrian R

    2015-03-06

    Recent works have demonstrated that release behavior of bioactive compounds varies with the nature of the matrix regarding its chemical composition, morphology and surface properties. Starch matrices varying in amylose content (maize, sorghum, Hylon VII) or pure amylopectin ones (waxy maize, amaranth starch), containing theophylline (10 mg, 50 mg/0.5 g of starch), were obtained via high hydrostatic pressure treatment (650 MPa/9 min) and autoclaving (120 °C/20 min). Both the treatment used and drug dose affected the theophylline release profiles from the matrices studied. The profiles of amylopectin starch matrices satisfactorily fitted with selected mathematical models, indicating a controlled theophylline release. The principal component analysis confirmed substantial differences in drug release between the amylose and amylopectin matrices. The differences in matrix morphology, internal surface area and porosity (mesopore diameter, cumulative pore volume) between the matrices studied were found to be key factors affecting the theophylline dissolution. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Synthesis and release of luteinizing hormone in vitro: manipulations of Ca2+ environment

    Energy Technology Data Exchange (ETDEWEB)

    Liu, T.C.; Jackson, G.L.

    1985-08-01

    The authors determined if luteinizing hormone (LH) synthesis is Ca2+ dependent and coupled to LH release. They monitored LH synthesis when LH release was stimulated either by specific (gonadotropin-releasing hormone (GnRH)) or nonspecific stimuli (50 mM K+ and 2 or 20 microM Ca2+ ionophore A23187) and inhibited by Ca2+-reduced medium. LH synthesis was estimated by measuring incorporation of (/sup 3/H)glucosamine (glycosylation) and (/sup 14/C)alanine (translation) into total (cell and medium) immunoprecipitable LH by cultured rat anterior pituitary cells. Both GnRH (1 nM) and 50 mM K+ significantly stimulated LH release and glycosylation, but had no effect on LH translation. A23187 also stimulated LH release, but significantly depressed glycosylation of LH and total protein and (/sup 14/C)alanine uptake. Deletion of Ca2+ from the medium depressed both GnRH-induced LH release and glycosylation. Addition of 0.1 mM EGTA to Ca2+-free medium not only inhibited GnRH-induced release and glycosylation of LH but also uptake of precursors and glycosylation and translation of total protein. Thus, glycosylation and release of LH are Ca2+ dependent. Whether parallel changes in LH release and glycosylation reflect a cause and effect relationship remains to be determined.

  12. Formulation of an injectable implant for peptide delivery and mechanistic study of the effect of polymer molecular weight on its release behavior

    Directory of Open Access Journals (Sweden)

    Reyhaneh Astaneh

    2006-05-01

    Full Text Available The effects of polymer molecular weight on drug release from erodible matrices are not well known. It would be more complicated for in-situ forming injectable implants that change gradually from liquid to solid after injection. To investigate this phenomenon, two commerciallyaavailable PLGA polymers (lactic acid-co-glycolic acid with molecular weights of 12000 and 48000 Da were used to prepare injectable implants containing leuprolide acetate as a model peptide. The influence of polymer molecular weight on the morphology and erosion of matrices and also on their in-vitro drug release behavior over a period of 28 days was investigated. Results showed that the amount of drug released (32% over the first 24 hours (burst phase for 12 kDa PLGA system, was significantly (P<0.05 higher than that of the one higher molecular weight (13%. There was no difference between the steady-state release fluxes of drug from the systems. Erosion profiles were also in agreement with those of release behavior in both burst and steady-state phases. Electron microscopy studies showed that the lower molecular weight system is more porous than the higher one, which can explain the difference between burst effects.

  13. Effect of calcium on the kinetics of free fatty acid release during in vitro lipid digestion in model emulsions.

    Science.gov (United States)

    Ye, Aiqian; Cui, Jian; Zhu, Xiangqian; Singh, Harjinder

    2013-08-15

    The effects of different calcium salts on in vitro lipid digestion were examined by determining the free fatty acids released from various oil-in-water emulsions. The kinetics of the total and individual free fatty acids released by lipolysis were monitored by the pH-stat method and gas chromatography, respectively. The rate and the extent of free fatty acid release increased with an increase in the added calcium concentration, but the increase was dependent on the emulsifying agent. The effect of calcium was diminished when the emulsion contained phosphate. Soluble calcium salts, such as calcium gluconate, calcium acetate and CaCl2, had greater effects on the rate and extent of free fatty acid release than did insoluble salts, such as CaO and CaSO4, suggesting that the ionic state of calcium plays a critical role in lipid digestion in emulsions. The addition of calcium did not alter the profiles of the individual free fatty acids released. This study provides useful information for food formulation with respect to lipid digestion. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Effects of milk proteins on release properties and particle morphology of β-carotene emulsions during in vitro digestion.

    Science.gov (United States)

    Liu, Yuwei; Lei, Fei; Yuan, Fang; Gao, Yanxiang

    2014-11-01

    In the present study, β-lactoglobulin, sodium caseinate, lactalbumin and lactoferrin were used to prepare β-carotene emulsions. The milk protein-stabilized emulsions were explored using an in vitro release model to elucidate the effects of different milk proteins on β-carotene release properties in the stomach, duodenum and small intestine, respectively. Notable changes in the droplet size and size distribution were observed among these four oil-in-water (O/W) milk protein emulsions. In the gastric environment, the highest β-carotene release rate (2.9%) was achieved in β-lactoglobulin emulsion with a remarkable change in the particle size. In the simulated intestine, the best β-carotene micellarization potency (92%) was observed in β-lactoglobulin emulsion and its droplet diameter moderately increased from 215 nm to 471 nm. Moreover, substantial release of β-carotene was found in the small intestine for the four types of emulsions. It was concluded that β-carotene release in different digestive stages was characterized by the emulsion interfacial composition.

  15. Ion release from orthodontic brackets in 3 mouthwashes: an in-vitro study.

    Science.gov (United States)

    Danaei, Shahla Momeni; Safavi, Afsaneh; Roeinpeikar, S M Mehdi; Oshagh, Morteza; Iranpour, Shiva; Omidkhoda, Maryam; Omidekhoda, Maryam

    2011-06-01

    Stainless steel orthodontic brackets can release metal ions into the saliva. Fluoridated mouthwashes are often recommended to orthodontic patients to reduce the risk of white-spot lesions around their brackets. However, little information is available regarding the effect of different mouthwashes in ion release of orthodontic brackets. The purpose of this study was to measure the amount of metal ion release from orthodontic brackets when kept in different mouthwashes. One hundred sixty stainless steel brackets (0.022-in, 3M Unitek, Monrovia, Calif) were divided randomly into 4 equal groups and immersed in Oral B (Procter & Gamble, Weybridge, United Kingdom), chlorhexidine (Shahdaru Labratories, Tehran, Iran), and Persica (Poursina Pharmaceutical Laboratories, Tehran, Iran) mouthwashes and distilled deionized water and incubated at 37°C for 45 days. Nickel, chromium, iron, copper, and manganese released from the orthodontic brackets were measured with an inductively coupled plasma spectrometer. For statistical analysis, 1-way analysis of variance (ANOVA) and the Duncan multiple-range tests were used. The results showed that ion release in deionized water was significantly (P 0.05) in nickel, chromium, iron, and copper ion release in the Oral B and Persica mouthwashes. The level of manganese release was significantly different in all 4 groups. If ion release is a concern, Oral B and Persica mouthwashes might be better options than chlorhexidine for orthodontic patients with stainless steel brackets. Copyright © 2011 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  16. Cortico-accumbens fiber stimulation does not induce dopamine release in the nucleus accumbens in vitro.

    Science.gov (United States)

    Benoit-Marand, Marianne; O'Donnell, Patricio

    2008-09-01

    Interactions between dopamine (DA) and glutamate in the nucleus accumbens (NA) are important for a variety of cognitive and limbic functions. Although, there is strong evidence that DA controls glutamate responses, the converse (glutamate affecting DA release) is controversial. To determine whether endogenous glutamate released from corticostriatal terminals can evoke DA release by local interactions in the NA, we measured DA release with amperometry simultaneously with whole cell recordings from NA medium spiny neurons (MSNs) in a slice preparation preserving DA terminals (but not cell bodies) and cortico-accumbens fibers. MSNs responded to cortical stimulation with a postsynaptic potential that was blocked by the AMPA antagonist CNQX, but no DA overflow was detected with the carbon fiber electrode. This absence of DA release cannot be accounted for by a deterioration of the DA terminals in this slice preparation since DA release was evoked with a caudal stimulation in the same slices. The DA signal was modulated as expected by bath application of a DA transporter blocker. The data show that cortico-striatal activation does not induce DA release by local interactions, suggesting that observations of glutamate-evoked DA release previously reported in vivo may be taking place via an extra-NA circuit.

  17. SCN-AVP release of mPer1/mPer2 double-mutant mice in vitro

    Directory of Open Access Journals (Sweden)

    Oster Henrik

    2008-03-01

    Full Text Available Abstract Background Circadian organisation of behavioural and physiological rhythms in mammals is largely driven by the clock in the suprachiasmatic nuclei (SCN of the hypothalamus. In this clock, a molecular transcriptional repression and activation mechanism generates near 24 hour rhythms. One of the outputs of the molecular clock in specific SCN neurons is arginine-vasopressin (AVP, which is responsive to transcriptional activation by clock gene products. As negative regulators, the protein products of the period genes are thought to repress transcriptional activity of the positive limb after heterodimerisation with CRYPTOCHROME. When both the Per1 and Per2 genes are dysfunctional by targeted deletion of the PAS heterodimer binding domain, mice lose circadian organization of behaviour upon release into constant environmental conditions. To which degree the period genes are involved in the control of AVP output is unknown. Methods Using an in vitro slice culture setup, SCN-AVP release of cultures made of 10 wildtype and 9 Per1/2 double-mutant mice was assayed. Mice were sacrificed in either the early light phase of the light-dark cycle, or in the early subjective day on the first day of constant dark. Results Here we report that in arrhythmic homozygous Per1/2 double-mutant mice there is still a diurnal peak in in vitro AVP release from the SCN similar to that of wildtypes but distinctively different from the release pattern from the paraventricular nucleus. Such a modulation of AVP release is unexpected in mice where the circadian clockwork is thought to be disrupted. Conclusion Our results suggest that the circadian clock in these animals, although deficient in (most behavioural and molecular rhythms, may still be (partially functional, possibly as an hourglass mechanism. The level of perturbation of the clock in Per1/2 double mutants may therefore be less than was originally thought.

  18. Investigation of drug loading and in vitro release mechanisms of insulin-lauryl sulfate complex loaded PLGA nanoparticles.

    Science.gov (United States)

    Shi, K; Cui, F; Yamamoto, H; Kawashima, Y

    2008-12-01

    Insulin, a water soluble peptide hormone, was hydrophobically ion-paired with sodium lauryl sulfate (SDS) at the stoichiometric molar ratio of 6:1. The obtained insulin-SDS complex precipitation was subsequently formulated in biodegradable poly (D,L-lactic-co-glycolic acid) (PLGA) nanoparticles by a modified spontaneous emulsion solvent diffusion method. Compared with a conventional method for free insulin encapsulation, direct dissolution of SDS-paired insulin in the non-aqueous organic phase led to an increase in drug recovery from 42.5% to 89.6%. The more hydrophobic complex contributes to the improved affinity of insulin to the polymer matrix, resulting in a higher drug content in the nanoparticles. The drug loading was investigated by determining initial burst release at the first 30 min. The results showed that 64.8% of recovered drug were preferentially surface bound on complex loaded nanoparticles. The in vitro drug release was characterized by an initial burst and subsequent delayed release in dissolution media of deionized water and phosphate buffer saline (PBS). Compared with that in PBS, nanoparticles in deionized water medium presented very low initial burst release (15% vs. 65%) and incomplete cumulative release (25% vs. 90%) of the drug. In addition, dialysis experiments were performed to clarify the form of the released insulin in the dissolution media. The results suggested that the ion-pair complex was sensitive to ionic strength, insulin was released from the particular matrix as complex form and subsequently suffered dissociation from SDS in buffer saline. Moreover, the in vivo bioactivity of the SDS-paired insulin and nanoparticulate formulations were evaluated in mice by estimation of their blood sugar levels. The results showed that the bioactivity of insulin was unaltered after the ion-pairing process.

  19. Nickel release from new conventional stainless steel, recycled, and nickel-free orthodontic brackets: An in vitro study.

    Science.gov (United States)

    Sfondrini, Maria Francesca; Cacciafesta, Vittorio; Maffia, Elena; Scribante, Andrea; Alberti, Giancarla; Biesuz, Raffaela; Klersy, Catherine

    2010-06-01

    The aim of this study was to compare the nickel released from 3 kinds of orthodontic brackets: new conventional stainless steel, recycled stainless steel, and nickel-free brackets. This in-vitro study was performed by using a classic batch procedure. Samples were immersed in artificial saliva at various acidities (pH 4.2, 6.5, 7.6) over an extended time interval (0.25, 1, 24, 48, and 120 hours). The amount of nickel released was determined by using an atomic absorption spectrophotometer and an inductively coupled plasma atomic emission spectrometer. Statistical analysis included a linear regression model for repeated measures, with calculation of Huber White robust standard errors to account for intrabracket correlation of data. For post-hoc comparisons, the Bonferroni correction was applied. The recycled brackets released the most nickel (74.02 +/- 170.29 microg per gram); the new stainless steel brackets released 7.14 +/- 20.83 microg per gram. The nickel-free brackets released the least nickel (0.03 +/- 0.06 microg per gram). All the differences among the groups were statistically significant (P = 0.000). Reconditioned brackets released the most nickel. Moreover, the highest nickel release was recorded in the 2 experiments performed at pH 4.2; it was lower at pH 6.5 and 7.6. Conversely, no relevant differences were observed overall between the maxillary and mandibular arches. 2010 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  20. Strontium-releasing fluorapatite glass-ceramics: Crystallization behavior, microstructure, and solubility.

    Science.gov (United States)

    Denry, Isabelle; Goudouri, Ourania-Menti; Harless, Jeffrey D; Hubbard, E M; Holloway, Julie A

    2017-06-21

    The purpose of this work was to investigate the effect of strontium partial replacement for calcium on the crystallization behavior, microstructure and solubility of fluorapatite glass-ceramics. Four glass compositions were prepared with increasing amounts of strontium partially replacing calcium. The crystallization behavior was analyzed by differential scanning calorimetry and X-ray diffraction (XRD). The microstructure was investigated by scanning electron microscopy. The chemical solubility was quantified according to ISO standard 10993-14. The amount of strontium released in solution after incubation in TRIS-HCl or citric acid buffer was measured by atomic absorption spectroscopy. XRD analyses revealed that partially substituted strontium-fluorapatite and strontium-åkermanite crystallized after strontium additions. The lattice cell volume of both phases increased linearly with the amount of strontium in the composition. Strontium additions led to a reduction in crystal size and an increase in crystal number density. The chemical solubility and amount of strontium released in solution increased linearly with the amount of strontium present in the composition in both TRIS-HCl and citric acid buffers. Total amounts of strontium released reached a maximum of 547 ± 80 ppm in TRIS-HCl and 1252 ± 290 ppm in citric acid buffer for the glass composition with the highest amount of strontium. For all strontium-containing compositions, the amount released in TRIS-HCl continued to increase between 70 and 120 h, indicating sustained release rather than burst release. © 2017 Wiley Periodicals, Inc. J Biomater Res Part B, 2017. © 2017 Wiley Periodicals, Inc.

  1. In vitro release of metformin from iron (III) cross-linked alginate-carboxymethyl cellulose hydrogel beads.

    Science.gov (United States)

    Swamy, Bala Yerri; Yun, Yeoung-Sang

    2015-01-01

    In the present study, sodium alginate (NaAlg)/sodium carboxymethyl cellulose (NaCMC) blend hydrogel beads were prepared in ferric chloride solution. The developed hydrogel beads exhibited pH sensitive for deliver Metformin hydrochloride (MH). Preparation conditions of the beads (ferric chloride solution) were significantly affected the encapsulation efficiency, swelling and in vitro release profiles of the beads. Swelling studies were accomplished in gastric and intestine stimuli atmosphere at 37°C. The swelling studies reveal that the beads at pH 7.4 showed higher swelling properties compare to pH 1.2. Exterior morphology of beads was analyzed by scanning electron microscope. SEM indicates the surface of the beads is spherical with smooth surface and size of beads drastically reduced with increasing crosslinker concentration. The crosslinking reaction between NaAlg and NaCMC with ferric chloride was confirmed by FTIR analysis. XRD analysis indicates that MH drug molecularly dispersed in the polymer matrix. In vitro release studies of MH loaded beads showed higher release profiles at pH 7.4 compared to pH 1.2. The polymeric matrices followed slightly deviation with Fickian diffusion and fit for experimental co-relation (r(2)) values. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. A low molecular weight ES-20 protein released in vivo and in vitro with diagnostic potential in lymph node tuberculosis

    Directory of Open Access Journals (Sweden)

    Shende N

    2008-01-01

    Full Text Available Purpose: To determine role of antigens released in vivo and in vitro in immunodiagnosis of tuberculosis (TB. Methods: In vivo released circulating tuberculosis antigen (CTA was obtained from TB sera by ammonium sulphate precipitation and in vitro released excretory-secretory (ES antigens from Mycobacterium tuberculosis culture filtrate. CTA and ES antigens were fractionated by SDS-PAGE and electro-eluted gel fractions were analysed for antigen by ELISA. Results: Low molecular weight proteins CTA-9 and ES-9 showed high titre of antigen activity. To explore the diagnostic potential of low molecular weight ES antigen, M. tuberculosis ES antigen was further fractionated by gel filtration chromatography followed by purification on anion exchange column using fast protein liquid chromatography and a highly seroreactive ESG-5D (ES-20 antigen was obtained. Competitive inhibition showed that CTA-9 and ES-9 antigens inhibit the binding of ES-20 antigen to its antibody. Seroanalysis showed sensitivity of 83 and 80% for ES-20 antigen and antibody detection, respectively, in pulmonary TB and 90% in lymph node TB. Conclusions: Seroreactivity studies using M. tuberculosis ES-20 antigen showed usefulness in detection of TB; in particular, lymph node TB.

  3. Postprison release HIV-risk behaviors in a randomized trial of methadone treatment for prisoners.

    Science.gov (United States)

    Wilson, Monique E; Kinlock, Timothy W; Gordon, Michael S; O'Grady, Kevin E; Schwartz, Robert P

    2012-01-01

    This secondary analysis examined the impact of methadone initiated in prison on postrelease HIV risk behaviors. The parent study was a three-group randomized clinical trial in which participants received drug abuse counseling in prison and were randomly assigned to: (1) passive referral to substance abuse treatment upon release; (2) guaranteed methadone treatment admission upon release; and (3) methadone in prison and guaranteed continuation of methadone upon release. Participants were 211 adult males with preincarceration histories of opiate dependence. The AIDS Risk Assessment was administered at baseline (in prison) and at 1-, 3-, 6-, and 12-month postrelease. Data were analyzed for the entire sample (N = 211) as well as the subsamples who reported injecting drugs in the 30 days prior to incarceration (n = 131) and who reported having unprotected sex in that time frame (n = 144) using generalized linear mixed model on an intent-to-treat basis. There were no significant changes in sex- or drug-risk by Condition over Time. There were significant Time and Condition main effects for the total sample as well as the injector subsample for drug-risk behaviors. There were no significant Condition main effects for HIV sex-risk behaviors, but there were significant Time main effects. Methadone initiated in prison or immediately postrelease is associated with reduced HIV drug-risk compared to counseling in prison without methadone and passive referral to treatment at release. Participation in several drug- and sex-risk behaviors also showed significant declines during the postrelease time periods. Copyright © American Academy of Addiction Psychiatry.

  4. EFFECT OF COGNITIVE BEHAVIOR THERAPY AS COMPARED TO MYOFASCIAL RELEASE TECHNIQUE IN FIBROMYALGIA SYNDROME

    OpenAIRE

    Kaur kusumpreet; Armugam Narkeesh; Khurana Sonia

    2013-01-01

    Background and introduction:Fibromyalgia or fibromyalgic syndrome is a common form of non-articularrheumatism characterized by variety of non-specific symptoms including diffuse widespread musculoskeletalaching associated with fatigue, morning stiffness and sleep disturbances (Bennett, 1997). The current study willcompare the beneficial effects of Cognitive behavior therapy (CBT) and Myofascial release (MFR) along withconventional treatment. This study tries to find out new effective method f...

  5. Mechanical properties and drug release behavior of PCL/zein coated 45S5 bioactive glass scaffolds for bone tissue engineering application.

    Science.gov (United States)

    Fereshteh, Zeinab; Nooeaid, Patcharakamon; Fathi, Mohammadhossein; Bagri, Akbar; Boccaccini, Aldo R

    2015-09-01

    This article presents data related to the research article entitled "The effect of coating type on mechanical properties and controlled drug release of PCL/zein coated 45S5 bioactive glass scaffolds for bone tissue engineering" [1]. We provide data on mechanical properties, in vitro bioactivity and drug release of bioactive glass (BG) scaffolds coated by poly (ε-caprolactone) (PCL) and zein used as a controlled release device for tetracycline hydrochloride (TCH). By coating the BG scaffolds with PCL or PCL/zein blend the mechanical properties of the scaffolds were substantially improved, i.e., the compressive strength increased from 0.004±0.001 MPa (uncoated BG scaffolds) to 0.15±0.02 MPa (PCL/zein coated BG scaffolds). A dense bone-like apatite layer formed on the surface of PCL/zein coated scaffolds immersed for 14 days in simulated body fluid (SBF). The data describe control of drug release and in vitro degradation behavior of coating by engineering the concentration of zein. Thus, the developed scaffolds exhibit attractive properties for application in bone tissue engineering research.

  6. In vitro degradation behavior and cytocompatibility of Mg–Zn–Zr alloys

    NARCIS (Netherlands)

    Huan, Z.G.; Leeflang, M.A.; Zhou, J.; Fratila-Apachitei, L.E.; Duszczyk, J.

    2010-01-01

    Zinc and zirconium were selected as the alloying elements in biodegradable magnesium alloys, considering their strengthening effect and good biocompatibility. The degradation rate, hydrogen evolution, ion release, surface layer and in vitro cytotoxicity of two Mg–Zn–Zr alloys, i.e. ZK30 and ZK60,

  7. Long-Term Fluoride Release from Dental Resins Affects STRO-1+ Cell Behavior.

    Science.gov (United States)

    Calarco, A; Di Salle, A; Tammaro, L; De Luca, I; Mucerino, S; Petillo, O; Riccitiello, F; Vittoria, V; Peluso, G

    2015-08-01

    Fluoride-releasing restorative dental materials can be beneficial to remineralize dentin and help prevent secondary caries. However, the effects of fluoride release from dental materials on the activity of dental pulp stem cells are not known. Here we investigate whether different fluoride release kinetics from dental resins supplemented with modified hydrotalcite (RK-F10) or fluoride-glass filler (RK-FG10) could influence the behavior of a human dental pulp stem cell subpopulation (STRO-1(+) cells) known for its ability to differentiate toward an odontoblast-like phenotype. The 2 resins, characterized by similar physicochemical properties and fluoride content, exhibited different long-term fluoride release kinetics. Our data demonstrate that long-term exposure of STRO-1(+) cells to a continuous release of a low amount of fluoride by RK-F10 increases their migratory response to transforming growth factor β1 (TGF-β1) and stromal cell-derived factor 1 (SDF-1), both important promoters of pulp stem cell recruitment. Moreover, the expression patterns of dentin sialoprotein (dspp), dentin matrix protein 1 (dmp1), osteocalcin (ocn), and matrix extracellular phosphoglycoprotein (mepe) indicate a complete odontoblast-like cell differentiation only when STRO-1(+) cells were cultured on RK-F10. On the contrary, RK-FG10, characterized by an initial fluoride release burst and reduced lifetime of the delivery, did not elicit any significant effect on both STRO-1(+) cell migration and differentiation. Taken together, our results highlight the importance of taking into account fluoride release kinetics in addition to fluoride concentration when designing new fluoride-restorative materials. © International & American Associations for Dental Research 2015.

  8. Behavior of failed bonded interfaces under in vitro cariogenic challenge

    NARCIS (Netherlands)

    Montagner, A.F.; Opdam, N.J.; Ruben, J.L.; Bronkhorst, E.M.; Cenci, M.S.; Huysmans, M.C.

    2016-01-01

    OBJECTIVE: This in vitro study aimed to compare dentin wall caries development at different composite-dentin interfaces. METHODS: Dentin samples (10.4mm(2)) were restored with composite resin using two adhesive systems (etch-and-rinse and self-etch techniques). Different composite-dentin interfaces

  9. An attempt to establish an in vitro-in vivo correlation: case of paracetamol immediate-release tablets.

    Science.gov (United States)

    Radovanović, J; Durić, Z; Jovanović, M; Ibrić, S; Petrović, M

    1998-01-01

    The purpose of this study was to investigate the possibility of developing different levels of in vitro-in vivo correlation for immediate-release paracetamol tablets using in vitro dissolution data obtained under various experimental conditions. The influence of agitation intensity and pH value of the dissolution media was investigated. The level B approach, using statistical moment analysis led to poor correlation results. The results obtained by numerical deconvolution in order to study level A correlation indicated that good correlation should be sought with moderate levels of agitation (beyond 50 rpm in rotating basket apparatus). Results obtained by numerical convolution showed the highest level of correlation, level A, with one-to-one relationship between observed and predicted in vivo profiles.

  10. Interactions between Surfactants in Solution and Electrospun Protein Fibers: Effects on Release Behavior and Fiber Properties.

    Science.gov (United States)

    Stephansen, Karen; García-Díaz, María; Jessen, Flemming; Chronakis, Ioannis S; Nielsen, Hanne M

    2016-03-07

    Intermolecular interaction phenomena occurring between endogenous compounds, such as proteins and bile salts, and electrospun compounds are so far unreported, despite the exposure of fibers to such biorelevant compounds when applied for biomedical purposes, e.g., tissue engineering, wound healing, and drug delivery. In the present study, we present a systematic investigation of how surfactants and proteins, as physiologically relevant components, interact with insulin-loaded fish sarcoplasmic protein (FSP) electrospun fibers (FSP-Ins fibers) in solution and thereby affect fiber properties such as accessible surface hydrophilicity, physical stability, and release characteristics of an encapsulated drug. Interactions between insulin-loaded protein fibers and five anionic surfactants (sodium taurocholate, sodium taurodeoxycholate, sodium glycocholate, sodium glycodeoxycholate, and sodium dodecyl sulfate), a cationic surfactant (benzalkonium chloride), and a neutral surfactant (Triton X-100) were studied. The anionic surfactants increased the insulin release in a concentration-dependent manner, whereas the neutral surfactant had no significant effect on the release. Interestingly, only minute amounts of insulin were released from the fibers when benzalkonium chloride was present. The FSP-Ins fibers appeared dense after incubation with this cationic surfactant, whereas high fiber porosity was observed after incubation with anionic or neutral surfactants. Contact angle measurements and staining with the hydrophobic dye 8-anilino-1-naphthalenesulfonic acid indicated that the FSP-Ins fibers were hydrophobic, and showed that the fiber surface properties were affected differently by the surfactants. Bovine serum albumin also affected insulin release in vitro, indicating that also proteins may affect the fiber performance in an in vivo setting.

  11. Thermosensitive mPEG-b-PA-g-PNIPAM comb block copolymer micelles: effect of hydrophilic chain length and camptothecin release behavior.

    Science.gov (United States)

    Yang, Xiao-Li; Luo, Yan-Ling; Xu, Feng; Chen, Ya-Shao

    2014-02-01

    Block copolymer micelles are extensively used as drug controlled release carriers, showing promising application prospects. The comb or brush copolymers are especially of great interest, whose densely-grafted side chains may be important for tuning the physicochemical properties and conformation in selective solvents, even in vitro drug release. The purpose of this work was to synthesize novel block copolymer combs via atom transfer radical polymerization, to evaluate its physicochemical features in solution, to improve drug release behavior and to enhance the bioavailablity, and to decrease cytotoxicity. The physicochemical properties of the copolymer micelles were examined by modulating the composition and the molecular weights of the building blocks. A dialysis method was used to load hydrophobic camptothecin (CPT), and the CPT release and stability were detected by UV-vis spectroscopy and high-performance liquid chromatography, and the cytotoxicity was evaluated by MTT assays. The copolymers could self-assemble into well-defined spherical core-shell micelle aggregates in aqueous solution, and showed thermo-induced micellization behavior, and the critical micelle concentration was 2.96-27.64 mg L(-1). The micelles were narrow-size-distribution, with hydrodynamic diameters about 128-193 nm, depending on the chain length of methoxy polyethylene glycol (mPEG) blocks and poly(N-isopropylacrylamide) (PNIPAM) graft chains or/and compositional ratios of mPEG to PNIPAM. The copolymer micelles could stably and effectively load CPT but avoid toxicity and side-effects, and exhibited thermo-dependent controlled and targeted drug release behavior. The copolymer micelles were safe, stable and effective, and could potentially be employed as CPT controlled release carriers.

  12. Injectable PLGA/Hydroxyapatite/Chitosan Microcapsules Produced by Supercritical Emulsion Extraction Technology: An In Vitro Study on Teriparatide/Gentamicin Controlled Release.

    Science.gov (United States)

    Della Porta, Giovanna; Campardelli, Roberta; Cricchio, Vincenzo; Oliva, Francesco; Maffulli, Nicola; Reverchon, Ernesto

    2016-07-01

    Supercritical emulsion extraction (SEE) is proposed as a green and effective strategy for the fabrication of chitosan-covered poly-lactic-co-glycolic acid (chi-PLGA) injectable microcapsules for the controlled release of teriparatide (THA) and teriparatide/gentamicin sulfate (THA/Gen). These formulations can be used for locally bone pathologies treatment or in complex fracture healing of aged patients. Several oil-water (o-w) and water-oil-water (w-o-w) emulsions were processed by SEE to produce multifunctional microcapsules containing hydroxyapatite (HA) within a poly-lactic-co-glycolic acid (PLGA) matrix (up to 24 mg/g) and with both THA (0.45 mg/g) and Gen (up to 9 mg/g). Chitosan coating was also successfully added, as external layer (0.4 μm). SEE-fabricated microcapsules showed good encapsulation efficiency (up to 90%) for all the drugs tested and a mean size ranging between 1.4 (±0.4) μm and 2.2 (±0.5) μm. Different drug amounts loaded and microcapsules compositions assured a controlled drug release over a wide range of times and concentrations, as in vitro monitored in PBS medium at 37°C for 15/20 days. HA embedded into the biopolymer structure delayed the THA release profile; chitosan coating strongly reduced the initial drug "burst" release. In addition, the coencapsulation of both THA and Gen, which have very different water solubility, accelerated the release profile of the less water-soluble drug. No drugs degradation was also monitored after the SEE manufacturing. Apparent drug diffusivities (D) were calculated by fitting of the release profiles. In the case of Gen, D ranged between 2.9 × 10(-8) and 1.6 × 10(-9) cm(2)s(-1) if the drug was entrapped in simple PLGA or in the chitosan-coated microcapsules, respectively. In the case of THA, the calculated values ranged between 8.1 × 10(-9) and 7.4 × 10(-10) cm(2)s(-1) when the drug was entrapped in PLGA/HA microcapsules or in the chitosan-coated ones, respectively. These mass transfer values

  13. In vitro characterization of a controlled-release ocular insert for delivery of brimonidine tartrate.

    Science.gov (United States)

    Mealy, J E; Fedorchak, M V; Little, S R

    2014-01-01

    Glaucoma is the second leading cause of blindness in the US. Brimonidine tartrate (BT) is a modern anti-glaucoma agent that is currently administered as frequently as a thrice-daily topical eye drop medication. Accordingly, compliance with BT regimens is low, limiting overall effectiveness. One attempt that has previously proved effective in addressing non-adherence is the formation of ocular inserts, such as the Ocusert(®), whose diffusion-based control released an older drug (pilocarpine) for a week-long period. Modern controlled drug-release technology provides an avenue for extending the release of practically any drug (including new drugs such as BT) for as long as 1 month from a singular insert. Currently, no controlled-release formulations for BT exist. This work outlines the development and characterization of a BT-releasing ocular insert designed from poly(lactic co-glycolic) acid/polyethylene glycol (PEG). It was found that a formulation containing 15% PEG can be created that produces a linear BT-release profile corresponding to BT eye drop delivery estimates. Additionally, these inserts were shown, through the use of atomic force microscopy and scanning electron microscopy, to have smooth surfaces and physical properties suitable for ophthalmic use. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  14. Spectrophotometric evaluation of calcium ion release from different calcium hydroxide preparations: An in-vitro study.

    Directory of Open Access Journals (Sweden)

    Atul Jain

    2017-03-01

    Full Text Available Pulp tissue conditions such as infections have long been treated with calcium hydroxide (CaOH. In the last decade, use of mineral trioxide aggregate (MTA has gained ground. This study was carried out to comparatively evaluate the Ca release from CaOH powder with different vehicles and different types of MTA. Materials and Methods: 40 single rooted mandibular premolars were selected, decoronated and biomechanically prepared. They were randomly divided into four groups, consisting of 10 samples each. Root canals were packed with different preparations of CaOH and MTA. Calcium ion release was evaluated with an UV-spectrophotometer. Result: Amongst the CaOH preparations, using propylene glycol as a vehicle produced extended release of calcium ions (7.34±0.01 for a period of 14 days. Whereas, amongst MTA based products, MTA angelus produced the maximum release of calcium ions (2.42±0.010. A statistically significant difference was present between the four groups (p<0.05. Conclusion: Propylene glycol mixed with CaOH powder, produces a higher and extended release of calcium ions compared to distilled water. MTA angelus produces consistent calcium ion release.

  15. Two-step method for encapsulation of oregano essential oil in chitosan nanoparticles: preparation, characterization and in vitro release study.

    Science.gov (United States)

    Hosseini, Seyed Fakhreddin; Zandi, Mojgan; Rezaei, Masoud; Farahmandghavi, Farhid

    2013-06-05

    In this study, oregano essential oil (OEO) has been encapsulated in chitosan nanoparticles by a two-step method, i.e., oil-in-water emulsion and ionic gelation of chitosan with sodium tripolyphosphate (TPP). The success of OEO encapsulation was confirmed by Fourier transform infrared (FT-IR) spectroscopy, UV-vis spectrophotometry, thermogravimetric analysis (TGA) and X-ray diffraction (XRD) techniques. The obtained nanoparticles exhibited a regular distribution and spherical shape with size range of 40-80 nm as observed by scanning electron microscopy (SEM) and atomic force microscopy (AFM). As determined by TGA technique, the encapsulation efficiency (EE) and loading capacity (LC) of OEO-loaded chitosan nanoparticles were about 21-47% and 3-8%, respectively, when the initial OEO content was 0.1-0.8 g/g chitosan. In vitro release studies showed an initial burst effect and followed by a slow drug release. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Bacteria-induced release of white cell--and platelet-derived vascular endothelial growth factor in vitro

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Werther, K; Mynster, T

    2001-01-01

    BACKGROUND AND OBJECTIVES: Poor prognosis after resection of primary colorectal cancer may be related to the combination of perioperative blood transfusion and subsequent development of infectious complications. White blood cell--and platelet-derived cancer growth substances, including vascular...... endothelial growth factor (VEGF), may be involved in this process. Therefore, we studied the in vitro release of VEGF from white blood cells and platelets stimulated by bacterial antigens and supernatants from stored red cell components. MATERIALS AND METHODS: Eight units of whole blood (WB) and eight units....... CONCLUSIONS: Extracellular VEGF may accumulate in non-filtered red cell components, but this can be prevented by prestorage leucocyte depletion using filtration. In addition, bacterial antigens appear to induce release of VEGF from white blood cells and platelets. Addition of supernatants from stored, non...

  17. In vitro element release and biological aspects of base?metal alloys for metal-ceramic applications

    OpenAIRE

    Holm, Charlotta; Morisbak, Else; Kalfoss, Torill; Dahl, Jon E.

    2015-01-01

    Abstract Objective: The aims of this study were to investigate the release of element from, and the biological response in vitro to, cobalt?chromium alloys and other base?metal alloys used for the fabrication of metal-ceramic restorations. Material and methods: Eighteen different alloys were investigated. Nine cobalt?chromium alloys, three nickel?chromium alloys, two cobalt?chromium?iron alloys, one palladium?silver alloy, one high-noble gold alloy, titanium grade II and one type III copper?a...

  18. Sustained release donepezil loaded PLGA microspheres for injection: Preparation, in vitro and in vivo study

    DEFF Research Database (Denmark)

    Guo, Wenjia; Quan, Peng; Fang, Liang

    2015-01-01

    was in amorphous state or molecularly dispersed in microspheres. The Tg of PLGA was increased with the addition of DP. The release profile in vitro was characterized with slow but continuous release that lasted for about one week and fitted well with first-order model, which suggested the diffusion governing...

  19. Comparative evaluation of fluoride release from hydroxyapatite incorporated and conventional glass ionomer cement: an in vitro study.

    Science.gov (United States)

    Tiwari, S; Nandlal, B

    2012-01-01

    Glass ionomers are most commonly used esthetic restorative material, but has inferior mechanical properties. The search to improve its mechanical properties led to the use of hydroxyapatite (HA) whiskers as strengthening material for glass ionomer cement but its effect on fluoride release is still not clear. To evaluate and compare the fluoride release from HA incorporated glass ionomer and conventional glass ionomer cement (CGIC). This in vitro study comprised of total forty sample. Twenty Specimens of each HA incorporated glass ionomer and conventional glass ionomer were fabricated. Specimens were suspended individually in 25 mL of distilled water in a 50 mL plastic container and stored at 37°C. Distilled water was renewed every 24 h for 21 days. Fluoride release of sample was measured every 24 h for 7 days and weekly from 7 th day to 21 st day using Sension4 pH/ion selective electrode/mV meter. Descriptive statistics, Repeated Measure analysis of variance, Paired Sample t-test, Independent Sample t-test, scheffe post hoc test. There was a significant decrease in the mean fluoride release from day 1 to day 21 for both the groups hydroxyapatite glass ionomer cement and conventional glass ionomer cement ([HA-GIC] and CGIC). Though, the mean values of HA-GIC were slightly lower than C GIC, there was no statistically significant difference in the mean fluoride release between HA-GIC and CGIC throughout the experimental period. Within the limitations of this experimental design, definitive conclusions cannot be drawn and further investigations at a molecular level are needed to evaluate the trend of fluoride release from this material.

  20. Influence of urea, isopropanol, and propylene glycol on rutin in vitro release from cosmetic semisolid systems estimated by factorial design.

    Science.gov (United States)

    Baby, Andre Rolim; Haroutiounian-Filho, Carlos Alberto; Sarruf, Fernanda Daud; Pinto, Claudineia Aparecida Sales de Oliveira; Kaneko, Telma Mary; Velasco, Maria Valeria Robles

    2009-03-01

    Rutin, one of the major flavonoids found in an assortment of plants, was reported to act as a sun protection factor booster with high anti-UVA defense, antioxidant, antiaging, and anticellulite, by improvement of the cutaneous microcirculation. This research work aimed at evaluating the rutin in vitro release from semisolid systems, in vertical diffusion cells, containing urea, isopropanol and propylene glycol, associated or not, according to the factorial design with two levels with center point. Urea (alone and in association with isopropanol and propylene glycol) and isopropanol (alone and in association with propylene glycol) influenced significant and negatively rutin liberation in diverse parameters: flux (microg/cm(2).h); apparent permeability coefficient (cm/h); rutin amount released (microg/cm(2)); and liberation enhancement factor. In accordance with the results, the presence of propylene glycol 5.0% (wt/wt) presented statistically favorable to promote rutin release from this semisolid system with flux = 105.12 +/- 8.59 microg/cm(2).h; apparent permeability coefficient = 7.01 +/- 0.572 cm/h; rutin amount released = 648.80 +/- 53.01 microg/cm(2); and liberation enhancement factor = 1.21 +/- 0.07.

  1. Preparation and in vitro characterization of solid dispersion floating tablet by effervescent control release technique with improved floating capabilities.

    Science.gov (United States)

    Singhal, Peeush; Kaushik, Rajneesh Dutt; Kumar, Vijay Jyoti; Verma, Anurag; Gupta, Pranav

    2016-09-01

    In this Research, an effort has been done for the development of effervescent controlled release floating tablet (ECRFT) from solid dispersions (SDs) of diclofenac sodium (DS) for upsurge the solubility and dissolution rate. ECRFT of DS was prepared by using SDs of DS and its SDs prepared with PEG as carrier using thermal method (Simple fusion). SDs of DS were formulated in many ratio (1:1, 1:2, 1:3 and 1:4). Prepared SDs was optimized for its solubility, % drug content and % dissolution studies. Tablets were formulated by using optimized SDs products and all formulation was evaluated for various parameters. A clear rise in dissolution rate was detected with entirely SD, amid that the optimized SD (SD4) was considered for ECRFT. Among all the tablet formulations, its F3 formulation was better in all the terms of pre compression and post compression parameters. It had all the qualities of a good ECRFT, based on this F3 formulation was selected as the best formulation. Data of in vitro release was fitted in several kinetics models to explain release mechanism. The F3 formulation shows zero order release. From this study we can concluded that ECRFT containing SDs of DS can be successfully used for achieving better therapeutic objective.

  2. Analysis of in vitro release through reconstructed human epidermis and synthetic membranes of multi-vitamins from cosmetic formulations.

    Science.gov (United States)

    Gabbanini, Simone; Matera, Riccardo; Beltramini, Claudia; Minghetti, Andrea; Valgimigli, Luca

    2010-08-01

    A convenient method for in vitro investigation of the release of lipid- and water-soluble vitamins from cosmetic formulations was developed. The permeation of (d)-alpha-tocopherol (vitamin E), retinyl acetate (pro-vitamin A), ascorbic acid (vitamin C) and pyridoxine (vitamin B6) through SkinEthic reconstructed human epidermis (RHE), and synthetic polyethersulfone and polycarbonate membranes was studied in vitro using a Franz-type diffusion apparatus, coupled either to a spectrophotometer for continuous reading (dynamic setting) or to HPLC-DAD analysis of the receptor medium (static setting). O/W and W/O emulsions were compared with simple aqueous solutions for their kinetic of vitamins release, to evaluate the influence of the cosmetic formulation on the bioavailability of active ingredients. Results indicate that synthetic membranes offer a limited barrier to the diffusion of vitamins, but may provide information on the release ability of the formulation. Penetration was more effective when water was the external phase of the formulation, i.e. W/O emulsions were less effective in the release of vitamins than O/W emulsion or aqueous solutions. RHE (17 days old) offered a significantly higher barrier to penetration of vitamins, as expected for native human epidermis. The relative ranking in coefficient of permeability (Ps (cm/h)) was: ascorbic acid>pyridoxine>retinyl acetate>alpha-tocopherol approximately 0, the absolute values depending on the formulation. The method herein described showed to be a practical and convenient tool for the quality-control and efficacy evaluation of cosmetic formulations. Copyright (c) 2010 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Juçara Ribeiro Franca

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

  4. In vitro reinforcement of hippocampal bursting: a search for Skinner's atoms of behavior.

    OpenAIRE

    Stein, L.; Xue, B G; Belluzzi, J D

    1994-01-01

    A novel "in vitro reinforcement" paradigm was used to investigate Skinner's (1953) hypotheses (a) that operant behavior is made up of infinitesimal "response elements" or "behavioral atoms" and (b) that these very small units, and not whole responses, are the functional units of reinforcement. Our tests are based on the assumption that behavioral atoms may plausibly be represented at the neural level by individual cellular responses. As a first approach, we attempted to reinforce the bursting...

  5. Glucocorticoid regulation of gonadotropin release from gonadotropes of ovine pituitary gland in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Nangalama, A.W.

    1989-01-01

    In order to understand the role of glucocorticoids in the regulation of gonadotropin release by the pituitary gland, the short-term effects of cortisol perifusion (1.5 h to 8 hrs) on GnRH-induced LH secretion were investigated. To determine the biochemical mechanism(s) by which cortisol can act to modulate GnRH-induced LH release, the interactions of cortisol and arachidonic acid in GnRH-stimulated LH release were examined. Cortisol perifusion for 1.5 hr had no effect on GnRH-induced LH release, but longer treatment periods (4 hr-8 hrs) significantly reduced GnRH-stimulated LH release (4.0 hr, p < 0.01; 6.0 hr, p < 0.001; 8.0 hr, p < 0.01). Treatment and animal effects were highly significant (p < 0.001). There were significant interactions (p < 0.001) between treatment and animal as determined by a two-way ANOVA. Cortisol treatment also produced progressive increases in basal LH secretion with time (1.5 hr, p < 0.05; 4.0 hr, p < 0.01; 6.0 hr, p < 0.01; 8.0 hr, p < 0.001). Incubation of pituitary tissue with arachidonic acid (AA) resulted in a linear dose-response of LH (p < 0.001). Cortisol infusion failed to inhibit GnRH-induced LH release in which 10{sup {minus}4}M AA was administered for 20 min before a 10 min, 10{sup {minus}10}M GnRH pulse. Like cortisol, chloroquine also failed to inhibit AA-induced LH release. Perifusion with 10{sup {minus}6}M cortisol for 6.0 hours significantly (p < 0.001) blocked GnRH-stimulated (H{sup 3})AA release 24% below the basal (100%) ({sup 3}H)AA secretion. Reduction of ({sup 3}H)AA release was accompanied by decreased GnRH-stimulated LH secretion.

  6. Optimizing Prednisolone Loading into Distiller's Dried Grain Kafirin Microparticles, and In vitro Release for Oral Delivery.

    Science.gov (United States)

    Lau, Esther T L; Johnson, Stuart K; Williams, Barbara A; Mikkelsen, Deirdre; McCourt, Elizabeth; Stanley, Roger A; Mereddy, Ram; Halley, Peter J; Steadman, Kathryn J

    2017-05-19

    Kafirin microparticles have potential as colon-targeted delivery systems because of their ability to protect encapsulated material from digestive processes of the upper gastrointestinal tract (GIT). The aim was to optimize prednisolone loading into kafirin microparticles, and investigate their potential as an oral delivery system. Response surface methodology (RSM) was used to predict the optimal formulation of prednisolone loaded microparticles. Prednisolone release from the microparticles was measured in simulated conditions of the GIT. The RSM models were inadequate for predicting the relationship between starting quantities of kafirin and prednisolone, and prednisolone loading into microparticles. Compared to prednisolone released in the simulated gastric and small intestinal conditions, no additional drug release was observed in simulated colonic conditions. Hence, more insight into factors affecting drug loading into kafirin microparticles is required to improve the robustness of the RSM model. This present method of formulating prednisolone-loaded kafirin microparticles is unlikely to offer clinical benefits over commercially available dosage forms. Nevertheless, the overall amount of prednisolone released from the kafirin microparticles in conditions simulating the human GIT demonstrates their ability to prevent the release of entrapped core material. Further work developing the formulation methods may result in a delivery system that targets the lower GIT.

  7. A Review of In Vitro Drug Release Test Methods for Nano-Sized Dosage Forms

    Directory of Open Access Journals (Sweden)

    Susan D’Souza

    2014-01-01

    Full Text Available This review summarizes the methods used to study real-time (37°C drug release from nanoparticulate drug delivery systems and establish an IVIVC. Since no compendial standards exist, drug release is currently assessed using a variety of methods including sample and separate (SS, continuous flow (CF, dialysis membrane (DM methods, and a combination thereof, as well as novel techniques like voltametry and turbidimetry. This review describes the principle of each method along with their advantages and disadvantages, including challenges with set-up and sampling. The SS method allows direct measurement of drug release with simple set-up requirements, but sampling is cumbersome. With the CF method, sampling is straightforward but the set-up is time consuming. Set-up as well as sampling is easier with the DM, but it may not be suitable for drugs that bind to the membrane. Novel methods offer the possibility of real-time drug release measurement but may be restricted to certain types of drugs. Of these methods, Level A IVIVCs have been obtained with dialysis, alone or in combination with the sample and separate technique. Future efforts should focus on developing mathematical models that describe drug release mechanisms as well as facilitate formulation development of nano-sized dosage forms.

  8. Serotonin modifies corticotropin-releasing factor-induced behaviors of chicks.

    Science.gov (United States)

    Zhang, Rong; Tachibana, Tetsuya; Takagi, Tomo; Koutoku, Tomoyuki; Denbow, D Michael; Furuse, Mitsuhiro

    2004-05-05

    Glucagon-like peptide-1 (GLP-1) decreased corticotropin-releasing factor (CRF)-induced behaviors in neonatal chicks, and serotonin is one of the possible mechanisms through which GLP-1 affects CRF-induced behaviors. The present experiments were conducted to confirm the effect of serotonin on CRF-induced behaviors. In Experiment 1, chicks were intracerebroventricularly injected with either saline, 0.1 microg of CRF, 5.0 microg of serotonin, or 0.1 microg of CRF plus 5.0 microg of serotonin. Injection of CRF caused excitation as evidenced by increased spontaneous activities and distress vocalizations (DVs) compared to the control group. The effect of CRF was attenuated by serotonin since chicks became quiet after given CRF with serotonin. Sleep-like behaviors were observed in the serotonin group. The number of defecations was increased by CRF and decreased by serotonin. Both CRF and serotonin increased plasma corticosterone, and the effect was synergistic. Serotonin dose-dependently decreased locomotor activities of chicks after central administration of 0.1 microg of CRF, 0.1 microg of CRF plus 2.5, 5.0, or 10.0 microg of serotonin in Experiment 2. CRF-induced DVs were modified by serotonin. Instead of DVs, tender and low-pitched vocalizations were observed in chicks treated with CRF plus serotonin, the voice frequencies of which were less than 10 kHz. In conclusion, serotonin attenuated the CRF-induced behaviors while stimulating corticosterone release. These results indicate that the role of serotonin is dependent on the behaviors being measured. Copyright 2003 Elsevier B.V.

  9. Microspheres prepared with biodegradable PHBV and PLA polymers as prolonged-release system for ibuprofen: in vitro drug release and in vivo evaluation

    Directory of Open Access Journals (Sweden)

    Giovana Carolina Bazzo

    2012-12-01

    Full Text Available In this study, poly(hydroxybutyrate-co-hydroxyvalerate (PHBV and poly(l-lactide (PLA microspheres containing ibuprofen were prepared with the aim of prolonging the drug release. The oil-in-water (O/W emulsion solvent evaporation technique was used, varying the polymer ratio. All formulations provided spherical particles with drug crystals on the surface and a porous and rough polymeric matrix when PHBV was used and smooth external surface when prepared with PLA. The in vitro dissolution profiles show that the formulation containing PHBV/PLA at the proportion of 30/70 presented the best results in terms of prolonging the ibuprofen release. The analysis of the concentration of ibuprofen in the blood of rats showed that maximum levels were achieved at between one and two hours after administration of the immediate-release form (pure drug, while the prolonged microspheres led to a small amount of the drug being released within the first two hours and reached the maximum level after six hours of administration. It was concluded that it is possible to prolong the release of ibuprofen through its incorporation into PHBV/PLA microspheres.No presente estudo foram preparadas microesferas de poli(hidroxibutirato-co-hidroxivalerato (PHBV e poli(ácido láctico (PLA com o objetivo de prolongar a liberação do ibuprofeno, utilizado como fármaco modelo. Empregou-se o método de emulsificação e evaporação do solvente óleo em água (O/A, variando-se a proporção entre os polímeros. Todas as formulações originaram partículas esféricas com cristais de fármaco aderidos à superfície externa. As microesferas apresentaram superfície rugosa e porosa, quando o PHBV foi utilizado, e superfície externa lisa, quando preparadas com o PLA. Os perfis de dissolução in vitro evidenciaram que a formulação que continha PHBV/PLA na proporção de 30/70 apresentou melhores resultados para prolongar a liberação do ibuprofeno. Através da análise da concentra

  10. In vitro release of two anti-muscarinic drugs from soft contact lenses

    Directory of Open Access Journals (Sweden)

    Hui A

    2017-09-01

    Full Text Available Alex Hui,1 Magdalena Bajgrowicz-Cieslak,2 Chau-Minh Phan,3 Lyndon Jones3 1School of Optometry and Vision Science, UNSW Sydney, Sydney, NSW, Australia; 2Department of Mechanics, Material Science and Engineering, Wroclaw University of Technology, Wroclaw, Poland; 3Centre for Contact Lens Research, School of Optometry & Vision Science, University of Waterloo, Waterloo, ON, Canada Abstract: The purpose of this study was to investigate the release of the anti-myopia drugs atropine sulfate and pirenzepine dihydrochloride from commercially available soft contact lenses. Standard ultraviolet (UV absorbance–concentration curves were generated for atropine and pirenzepine. Ten commercially available contact lenses, including four multifocal lenses, were loaded by soaking in atropine or pirenzepine solutions at two different concentrations (10 mg/mL and 1 mg/mL. The release of the drugs into phosphate-buffered saline was determined over the course of 24 hours at 34°C using UV absorbance. Materials with surface charge released the greatest amount of atropine when loaded with either concentration when compared to the other lens types (p<0.05, releasing upward of 1.026±0.035 mg/lens and 0.979±0.024 mg/lens from etafilcon A and ocufilcon A, respectively. There were no significant differences in the amount of atropine or pirenzepine released from the multifocal and non-multifocal lenses made from the same lens materials. Narafilcon A material demonstrated prolonged release of up to 8 hours when loaded with pirenzepine, although the overall dose delivered from the lens into the solution was among the lowest of the materials investigated. The rest of the lenses reached a plateau within 2 hours of release, suggesting that they were unable to sustain drug release into the solution for long periods of time. Given that no single method of myopia control has yet shown itself to be completely effective in preventing myopia progression, a combination of

  11. Formulation and evaluation of controlled-release of telmisartan microspheres: In vitro/in vivo study

    Directory of Open Access Journals (Sweden)

    Praveen Kumar Gaur

    2014-12-01

    Full Text Available The aim of this work was to design a controlled-release drug-delivery system for the angiotensin-II receptor antagonist drug telmisartan. Telmisartan was encapsulated with different EUDRAGIT polymers by an emulsion solvent evaporation technique and the physicochemical properties of the formulations were characterized. Using a solvent evaporation method, white spherical microspheres with particle sizes of 629.9–792.1 μm were produced. The in vitro drug release was studied in three different pH media (pH 1.2 for 2 hours, pH 6.8 for 4 hours, and pH 7.4 for 18 hours. The formulations were then evaluated for their pharmacokinetic parameters. The entrapment efficiency of these microspheres was between 58.6% and 90.56%. The obtained microspheres showed good flow properties, which were evaluated in terms of angle of repose (15.29–26.32, bulk and tapped densities (0.37–0.53 and 0.43–0.64, respectively, Carr indices and Hausner ratio (12.94–19.14% and 1.14–1.23, respectively. No drug release was observed in the simulated gastric medium up to 2 hours; however, a change in pH from 1.2 to 6.8 increased the drug release. At pH 7.4, formulations with EUDRAGIT RS 100 showed a steady drug release. The microsphere formulation TMRS-3 (i.e., microspheres containing 2-mg telmisartan gave the highest Cmax value (6.8641 μg/mL at 6 hours, which was three times higher than Cmax for telmisartan oral suspension (TOS. Correspondingly, the area under the curve for TMRS-3 was 8.5 times higher than TOS. Particle size and drug release depended on the nature and content of polymer used. The drug release mechanism of the TMRS-3 formulation can be explained using the Higuchi model. The controlled release of drug from TMRS-3 also provides for higher plasma drug content and improved bioavailability.

  12. Relationship between Surface Properties and In Vitro Drug Release from Compressed Matrix Containing Polymeric Materials with Different Hydrophobicity Degrees

    Directory of Open Access Journals (Sweden)

    Cristhian J. Yarce

    2017-01-01

    Full Text Available This work is the continuation of a study focused on establishing relations between surface thermodynamic properties and in vitro release mechanisms using a model drug (ampicillin trihydrate, besides analyzing the granulometric properties of new polymeric materials and thus establishing the potential to be used in the pharmaceutical field as modified delivery excipients. To do this, we used copolymeric materials derived from maleic anhydride with decreasing polarity corresponding to poly(isobutylene-alt-maleic acid (hydrophilic, sodium salt of poly(maleic acid-alt-octadecene (amphiphilic, poly(maleic anhydride-alt-octadecene (hydrophobic and the reference polymer hydroxyl-propyl-methyl-cellulose (HPMC. Each material alone and in blends underwent spectroscopic characterization by FTIR, thermal characterization by DSC and granulometric characterization using flow and compaction tests. Each tablet was prepared at different polymer ratios of 0%, 10%, 20%, 30% and 40%, and the surface properties were determined, including the roughness by micro-visualization, contact angle and water absorption rate by the sessile drop method and obtaining Wadh and surface free energy (SFE using the semi-empirical models of Young–Dupré and  Owens-Wendt-Rabel-Käelbe (OWRK, respectively. Dissolution profiles were determined simulating physiological conditions in vitro, where the kinetic models of order-zero, order-one, Higuchi and Korsmeyer–Peppas were evaluated. The results showed a strong relationship between the proportion and nature of the polymer to the surface thermodynamic properties and kinetic release mechanism.

  13. Relationship between Surface Properties and In Vitro Drug Release from Compressed Matrix Containing Polymeric Materials with Different Hydrophobicity Degrees.

    Science.gov (United States)

    Yarce, Cristhian J; Echeverri, Juan D; Palacio, Mario A; Rivera, Carlos A; Salamanca, Constain H

    2017-01-24

    This work is the continuation of a study focused on establishing relations between surface thermodynamic properties and in vitro release mechanisms using a model drug (ampicillin trihydrate), besides analyzing the granulometric properties of new polymeric materials and thus establishing the potential to be used in the pharmaceutical field as modified delivery excipients. To do this, we used copolymeric materials derived from maleic anhydride with decreasing polarity corresponding to poly(isobutylene-alt-maleic acid) (hydrophilic), sodium salt of poly(maleic acid-alt-octadecene) (amphiphilic), poly(maleic anhydride-alt-octadecene) (hydrophobic) and the reference polymer hydroxyl-propyl-methyl-cellulose (HPMC). Each material alone and in blends underwent spectroscopic characterization by FTIR, thermal characterization by DSC and granulometric characterization using flow and compaction tests. Each tablet was prepared at different polymer ratios of 0%, 10%, 20%, 30% and 40%, and the surface properties were determined, including the roughness by micro-visualization, contact angle and water absorption rate by the sessile drop method and obtaining Wadh and surface free energy (SFE) using the semi-empirical models of Young-Dupré and  Owens-Wendt-Rabel-Käelbe (OWRK), respectively. Dissolution profiles were determined simulating physiological conditions in vitro, where the kinetic models of order-zero, order-one, Higuchi and Korsmeyer-Peppas were evaluated. The results showed a strong relationship between the proportion and nature of the polymer to the surface thermodynamic properties and kinetic release mechanism.

  14. Thiazolidinediones inhibit airway smooth muscle release of the chemokine CXCL10: in vitro comparison with current asthma therapies

    Directory of Open Access Journals (Sweden)

    Seidel Petra

    2012-10-01

    Full Text Available Abstract Background Activated mast cells are present within airway smooth muscle (ASM bundles in eosinophilic asthma. ASM production of the chemokine CXCL10 plays a role in their recruitment. Thus the effects of glucocorticoids (fluticasone, budesonide, long-acting β2-agonists (salmeterol, formoterol and thiazolidinediones (ciglitazone, rosiglitazone on CXCL10 production by ASM cells (ASMC from people with and without asthma were investigated in vitro. Methods Confluent serum-deprived cells were treated with the agents before and during cytokine stimulation for 0-24 h. CXCL10 protein/mRNA, IκB-α levels and p65 activity were measured using ELISA, RT PCR, immunoblotting and p65 activity assays respectively. Data were analysed using ANOVA followed by Fisher’s post-hoc test. Results Fluticasone and/or salmeterol at 1 and 100 nM inhibited CXCL10 release induced by IL-1β and TNF-α, but not IFNγ or all three cytokines (cytomix. The latter was also not affected by budesonide and formoterol. In asthmatic ASMC low salmeterol, but not formoterol, concentrations increased cytomix-induced CXCL10 release and at 0.01 nM enhanced NF-κB activity. Salmeterol 0.1nM together with fluticasone 0.1 and 10 nM still increased CXCL10 release. The thiazolidinediones ciglitazone and rosiglitazone (at 25 and 100 μM inhibited cytomix-induced CXCL10 release but these inhibitory effects were not prevented by the PPAR-g antagonist GW9662. Ciglitazone did not affect early NF-κB activity and CXCL10 mRNA production. Conclusions Thus the thiazolidinediones inhibited asthmatic ASMC CXCL10 release under conditions when common asthma therapies were ineffective or enhanced it. They may provide an alternative strategy to reduce mast cell-ASM interactions and restore normal airway physiology in asthma.

  15. Multifunctional halloysite nanotubes for targeted delivery and controlled release of doxorubicin in-vitro and in-vivo studies

    Science.gov (United States)

    Hu, Yuwei; Chen, Jian; Li, Xiufang; Sun, Yanhua; Huang, Shen; Li, Yuqing; Liu, Hui; Xu, Jiangfeng; Zhong, Shian

    2017-09-01

    The current state of cancer therapy encourages researchers to develop novel efficient nanocarriers. Halloysite nanotubes (HNTs) are good nanocarrier candidates due to their unique nanoscale (40-80 nm in diamter and 200-500 nm in length) and hollow lumen, as well as good biocompatibility and low cost. In our study, we prepared a type of folate-mediated targeting and redox-triggered anticancer drug delivery system, so that Doxorubicin (DOX) can be specifically transported to tumor sites due to the over-expressed folate-receptors on the surface of cancer cells. Furthermore, it can then be released by the reductive agent glutathione (GSH) in cancer cells where the content of GSH is nearly 103-fold higher than in the extracellular matrix. A series of methods have demonstrated that per-thiol-β-cyclodextrin (β-CD-(SH)7) was successfully combined with HNTs via a redox-responsive disulfide bond, and folic acid-polyethylene glycol-adamantane (FA-PEG-Ad) was immobilized on the HNTs through the strong complexation between β-CD/Ad. In vitro studies indicated that the release rate of DOX raised sharply in dithiothreitol (DTT) reducing environment and the amount of released DOX reached 70% in 10 mM DTT within the first 10 h, while only 40% of DOX was released in phosphate buffer solution (PBS) even after 79 h. Furthermore, the targeted HNTs could be specifically endocytosed by over-expressed folate-receptor cancer cells and significantly accelerate the apoptosis of cancer cells compared to non-targeted HNTs. In vivo studies further verified that the targeted HNTs had the best therapeutic efficacy and no obvious side effects for tumor-bearing nude mice, while free DOX showed damaging effects on normal tissues. In summary, this novel nanocarrier system shows excellent potential for targeted delivery and controlled release of anticancer drugs and provides a potential platform for tumor therapy.

  16. Thiazolidinediones inhibit airway smooth muscle release of the chemokine CXCL10: in vitro comparison with current asthma therapies.

    Science.gov (United States)

    Seidel, Petra; Alkhouri, Hatem; Lalor, Daniel J; Burgess, Janette K; Armour, Carol L; Hughes, J Margaret

    2012-10-04

    Activated mast cells are present within airway smooth muscle (ASM) bundles in eosinophilic asthma. ASM production of the chemokine CXCL10 plays a role in their recruitment. Thus the effects of glucocorticoids (fluticasone, budesonide), long-acting β2-agonists (salmeterol, formoterol) and thiazolidinediones (ciglitazone, rosiglitazone) on CXCL10 production by ASM cells (ASMC) from people with and without asthma were investigated in vitro. Confluent serum-deprived cells were treated with the agents before and during cytokine stimulation for 0-24 h. CXCL10 protein/mRNA, IκB-α levels and p65 activity were measured using ELISA, RT PCR, immunoblotting and p65 activity assays respectively. Data were analysed using ANOVA followed by Fisher's post-hoc test. Fluticasone and/or salmeterol at 1 and 100 nM inhibited CXCL10 release induced by IL-1β and TNF-α, but not IFNγ or all three cytokines (cytomix). The latter was also not affected by budesonide and formoterol. In asthmatic ASMC low salmeterol, but not formoterol, concentrations increased cytomix-induced CXCL10 release and at 0.01 nM enhanced NF-κB activity. Salmeterol 0.1 nM together with fluticasone 0.1 and 10 nM still increased CXCL10 release. The thiazolidinediones ciglitazone and rosiglitazone (at 25 and 100 μM) inhibited cytomix-induced CXCL10 release but these inhibitory effects were not prevented by the PPAR-g antagonist GW9662. Ciglitazone did not affect early NF-κB activity and CXCL10 mRNA production. Thus the thiazolidinediones inhibited asthmatic ASMC CXCL10 release under conditions when common asthma therapies were ineffective or enhanced it. They may provide an alternative strategy to reduce mast cell-ASM interactions and restore normal airway physiology in asthma.

  17. Studies on in vitro release of CPM from semi-interpenetrating ...

    Indian Academy of Sciences (India)

    WINTEC

    methanol solution and the precipitated beads were crosslinked using glutaraldehyde solution. Swelling and drug release studies were carried out. ... pound used for brain fuel. The brain converts glutamic acid to a ... sodium hydroxide–methanol solution (1 :20 w/w) under stirring. The beads were washed thrice with hot ...

  18. Formulation and In vitro/In vivo Evaluation of Sustained Release ...

    African Journals Online (AJOL)

    Purpose: To develop and optimise sustained release (SR) matrix tablets of diltiazem hydrochloride (DHL). Methods: DHL tablets were prepared by direct compression and consisted of hydroxyprpoylmethyl cellulose, Kollidon SR and Eudragit RSPO. A 32 full factorial design was applied to study the effect of polymers used ...

  19. Formulation and In vitro/In vivo Evaluation of Sustained Release ...

    African Journals Online (AJOL)

    HP

    2013-07-15

    Jul 15, 2013 ... Purpose: To develop and optimise sustained release (SR) matrix tablets of diltiazem hydrochloride (DHL). Methods: DHL tablets were prepared by direct compression and consisted of hydroxyprpoylmethyl cellulose,. Kollidon SR and Eudragit RSPO. A 32 full factorial design was applied to study the effect of ...

  20. Real time in vitro studies of doxorubicin release from PHEMA nanoparticles

    Directory of Open Access Journals (Sweden)

    Bajpai AK

    2009-10-01

    Full Text Available Abstract Background Many anticancer agents have poor water solubility and therefore the development of novel delivery systems for such molecules has received significant attention. Nanocarriers show great potential in delivering therapeutic agents into the targeted organs or cells and have recently emerged as a promising approach to cancer treatments. The aim of this study was to prepare and use poly-2-hydroxyethyl methacrylate (PHEMA nanoparticles for the controlled release of the anticancer drug doxorubicin. Results PHEMA nanoparticles have been synthesized and characterized using FTIR and scanning electron microscopy (SEM, particle size analysis and surface charge measurements. We also studied the effects of various parameters such as percent loading of drugs, chemical architecture of the nanocarriers, pH, temperature and nature of the release media on the release profiles of the drug. The chemical stability of doxorubicin in PBS was assessed at a range of pH. Conclusion Suspension polymerization of 2-hydroxyethyl methacrylate (HEMA results in the formation of swellable nanoparticles of defined composition. PHEMA nanoparticles can potentially be used for the controlled release of the anticancer drug doxorubicin.

  1. In vitro evaluation of fluoride release of Jeltrate® dental alginate

    Directory of Open Access Journals (Sweden)

    Delmo Santiago Vaitsman

    2009-01-01

    Full Text Available Objective: To evaluate of fluoride release from Jeltrate alginate®. Materials and Methods: Four Trademarks of alginate were divided in four groups: conventional Jeltrate®, Plus Jeltrate®, Chromatic Jeltrate® and Chromatic Ortho Jeltrate®. The alginates were handled following the guidelines of the manufacturers. After this was followed by the construction of evidence bodies using silicone molds of the dimensions of 4 mm in diameter and 4mm in height. After take prey, the evidence bodies were removed from the molds and placed in container with 10 ml of ultra purified water, for 2 min. The fluoride release was measured by selective ion electrode connected to an analyzer of ions. Results: The Plus Jeltrate® showed a higher releasing fluoride 247.85 μg/cm2 followed by Chromatic Ortho Jeltrate® (217.83 μg/cm2, Chromatic Jeltrate ® (138.21 μg/cm2 and Jeltrate® (79.61 μg/cm2. Conclusion: Plus Jeltrate® had the best performance in releasing fluoride, followed by Chromatic Ortho Jeltrate®, Chromatic Jeltrate® and conventional Jeltrate®.

  2. CONTROLLED-RELEASE OF THEOPHYLLINE MONOHYDRATE FROM AMYLODEXTRIN TABLETS - IN-VITRO OBSERVATIONS

    NARCIS (Netherlands)

    VANDERVEEN, J; TEWIERIK, GHP; VANDERWAL, L; EISSENS, AC; LERK, CF

    Amylodextrin is a linear dextrin and can be produced by enzymatic hydrolysis of the alpha-1,6 glycosidic bonds of amylopectin. Tablets compacted from pure amylodextrin showed good binding properties and did not disintegrate in aqueous media. Extended and decreasing drug release rates were found for

  3. Aluminium-free glass polyalkenoate cements: ion release and in vitro antibacterial efficacy.

    Science.gov (United States)

    Wren, A W; Hansen, J P; Hayakawa, S; Towler, M R

    2013-05-01

    Glass polyalkenoate cements (GPCs) have exhibited potential as bone cements. This study investigates the effect of substituting TiO₂ for SiO₂ in the glass phase and the subsequent effect on cement rheology, mechanical properties, ion release and antibacterial properties. Glass characterization revealed a reduction in glass transition temperature (T(g)) from 685 to 669 °C with the addition of 6 mol % TiO₂ (AT-2). Magic angle spinning nuclear magnetic resonance (MAS-NMR) revealed a shift from -81 ppm to -76 pmm when comparing a Control glass to AT-2, indicating de-polymerization of the Si network. The incorporation of TiO₂ also increased the working time (T(w)) from 19 to 61 s and setting time (T(s)) from 70 to 427 s. The maximum compressive strength (σ(c)) increased from 64 to 85 MPa. Ion release studies determined that the addition of Ti to the glass reduced the release of zinc, calcium and strontium ions, with low concentrations of titanium being released. Antibacterial testing in E. coli resulted in greater bactericidal effects when tested in aqueous broth for both titanium containing cements.

  4. Growth hormone-releasing factor stimulates proliferation of somatotrophs in vitro

    DEFF Research Database (Denmark)

    Billestrup, Nils; Swanson, L W; Vale, W

    1986-01-01

    The mitogenic effect of the hypothalamic peptides growth hormone-releasing factor (GRF) and somatostatin on cultured growth hormone (GH)-producing cells (somatotrophs) was studied. Using autoradiographic detection of [3H]thymidine uptake and immunocytochemical identification of GH-producing cells...

  5. Endothelial cells are able to synthesize and release catecholamines both in vitro and in vivo.

    Science.gov (United States)

    Sorriento, Daniela; Santulli, Gaetano; Del Giudice, Carmine; Anastasio, Antonio; Trimarco, Bruno; Iaccarino, Guido

    2012-07-01

    Recently it has been demonstrated that catecholamines are produced and used by macrophages and mediate immune response. The aim of this study is to verify whether endothelial cells (ECs), which are of myeloid origin, can produce catecholamines. We demonstrated that genes coding for tyrosine hydroxylase, Dopa decarboxylase, dopamine β hydroxylase (DβH), and phenylethanolamine-N-methyl transferase, enzymes involved in the synthesis of catecholamines, are all expressed in basal conditions in bovine aorta ECs, and their expression is enhanced in response to hypoxia. Moreover, hypoxia enhances catecholamine release. To evaluate the signal transduction pathway that regulates catecholamine synthesis in ECs, we overexpressed in bovine aorta ECs either protein kinase A (PKA) or the transcription factor cAMP response element binding, because PKA/cAMP response element binding activation induces tyrosine hydroxylase transcription and activity in response to stress. Both cAMP response element binding and PKA overexpression enhance DβH and phenylethanolamine-N-methyl transferase gene expression and catecholamine release, whereas H89, inhibitor of PKA, exerts the opposite effect, evidencing the role of PKA/cAMP response element binding transduction pathway in the regulation of catecholamine release in bovine aorta ECs. We then evaluated by immunohistochemistry the expression of tyrosine hydroxylase, Dopa decarboxylase, DβH, and phenylethanolamine-N-methyl transferase in femoral arteries from hindlimbs of C57Bl/6 mice 3 days after removal of the common femoral artery to induce chronic ischemia. Ischemia evokes tyrosine hydroxylase, Dopa decarboxylase, DβH, and phenylethanolamine-N-methyl transferase expression in the endothelium. Finally, the pharmacological inhibition of catecholamine release by fusaric acid, an inhibitor of DβH, reduces the ability of ECs to form network-like structures on Matrigel matrix. In conclusion, our study demonstrates for the first time that ECs

  6. Paracetamol (acetaminophen) attenuates in vitro mast cell and peripheral blood mononucleocyte cell histamine release induced by N-acetylcysteine.

    Science.gov (United States)

    Coulson, James; Thompson, John Paul

    2010-02-01

    The treatment of acute paracetamol (acetaminophen) poisoning with N-acetylcysteine (NAC) is frequently complicated by an anaphylactoid reaction to the antidote. The mechanism that underlies this reaction is unclear. We used the human mast cell line 1 (HMC-1) and human peripheral blood mononucleocytes (PBMCs) to investigate the effects of NAC and paracetamol on histamine secretion in vitro. HMC-1 and human PBMCs were incubated in the presence of increasing concentrations of NAC +/- paracetamol. Cell viability was determined by the Trypan Blue Assay, and histamine secretion was measured by ELISA. NAC was toxic to HMC-1 cells at 100 mg/mL and to PBMCs at 67 mg/mL. NAC increased HMC-1 and PBMC histamine secretion at concentrations of NAC from 20 to 50 mg/mL and 2.5 to 100 mg/mL, respectively. NAC-induced histamine secretion by both cell types was reduced by co-incubation with 2.5 mg/mL of paracetamol. Paracetamol (acetaminophen) is capable of modifying histamine secretion in vitro. This may explain the clinical observation of a lower incidence of adverse reactions to NAC in vivo when higher concentrations of paracetamol are present than when paracetamol concentrations are low. Paracetamol (acetaminophen) attenuates in vitro mast cell and PBMC cell histamine release induced by NAC.

  7. Physicochemical characterization and in vitro dissolution behavior of olanzapine-mannitol solid dispersions

    Directory of Open Access Journals (Sweden)

    Venkateskumar Krishnamoorthy

    2012-06-01

    Full Text Available The objective of the present work is to study the dissolution behavior of olanzapine from its solid dispersions with mannitol. Solid dispersions were prepared by melt dispersion method and characterized by phase solubility studies, drug content and in vitro dissolution studies. The best releasing dispersions were selected from release data, dissolution parameters and their release profiles. Solid state characterization techniques like Fourier transform infrared (FT-IR spectroscopy, X-ray diffractometry, differential scanning calorimetry, near-infrared and Raman spectroscopy were used to characterize the drug in selected dispersions. The dispersions were also evaluated by wettability studies and permeation studies. The results of phase solubility studies and the thermodynamic parameters indicated the spontaneity and solubilization effect of the carrier. The release study results showed greater improvement of drug release from solid dispersions compared to pure drug, and the release was found to increase with an increase in carrier content. The possible mechanism for increased release rate from dispersions may be attributed to solubilization effect of the carrier, change in crystal quality, phase transition from crystalline to amorphous state, prevention of agglomeration or aggregation of drug particles, change in surface hydrophobicity of the drug, and increased wettability and dispersability of the drug in dissolution medium. The suggested reasons for increased release rate from dispersions were found to be well supported by results of solid state characterization, wettability and permeation studies. The absence of any interaction between the drug and the carrier was also proved by FT-IR analysis.O objetivo do presente trabalho é estudar o comportamento de dissolução da olanzapina a partir de suas dispersões sólidas de manitol. As dispersões sólidas foram preparadas por dispersão por fusão e caracterizadas por estudos de solubilidade de

  8. Ascorbyl Tetraisopalmitate Inclusion into Υ-Cyclodextrin and Mesoporous SBA-15: Preparation, Characterization and In Vitro Release Study

    Directory of Open Access Journals (Sweden)

    Maria Bastianini

    2017-07-01

    Full Text Available Ascorbic acid or vitamin C is a strong antioxidant widely used in cosmetic and food fields. This vitamin is very unstable and rapidly undergoes degradation. In order to solve this problem and to obtain a stable ascorbic acid, Nikkol Group has developed ascorbyltetraisopalmitate (VC-IP. This raw material is an oil phase, already well-known and employed in the cosmetic market. The objective of this study is to obtain VC-IP in micro-powder form, in order to produce a new raw material that is easily dispersible in oil and water phases and useful for make-up and color cosmetic applications. Various types of drug carriers were studied and considered in order to support VC-IP and obtain the conversion in powder. Υ-cyclodextrin and mesoporous silica SBA-15 were chosen as the best candidates. A white powder of supported VC-IP was obtained with each carrier (VC-IP@cyclodextrin, VC-IP@SBA-15. The systems underwent physicochemical characterization and in vitro release tests were carried out. Based on the conducted study, it can be concluded that by supporting VC-IP on Υ-cyclodextrin and SBA-15, it is feasible to obtain a new raw material in powder form. The two carriers possess different release profiles, adding the possibility to finely tune the release of the active component in smart formulations.

  9. Effect of different cleansers on the weight and ion release of removable partial denture: an in vitro study

    Directory of Open Access Journals (Sweden)

    Daniela N.B. Felipucci

    2011-10-01

    Full Text Available OBJECTIVE: Removable partial dentures (RPD require different hygiene care, and association of brushing and chemical cleansing is the most recommended to control biofilm formation. However, the effect of cleansers has not been evaluated in RPD metallic components. The aim of this study was to evaluate in vitro the effect of different denture cleansers on the weight and ion release of RPD. MATERIAL AND METHODS: Five specimens (12x3 mm metallic disc positioned in a 38x18x4 mm mould filled with resin, 7 cleanser agents [Periogard (PE, Cepacol (CE, Corega Tabs (CT, Medical Interporous (MI, Polident (PO, 0.05% sodium hypochlorite (NaOCl, and distilled water (DW (control] and 2 cobalt-chromium alloys [DeguDent (DD, and VeraPDI (VPDI] were used for each experimental situation. One hundred and eighty immersions were performed and the weight was analyzed with a high precision analytic balance. Data were recorded before and after the immersions. The ion release was analyzed using mass spectrometry with inductively coupled plasma. Data were analyzed by two-way ANOVA and Tukey HSD post hoc test at 5% significance level. RESULTS: Statistical analysis showed that CT and MI had higher values of weight loss with higher change in VPDI alloy compared to DD. The solutions that caused more ion release were NaOCl and MI. CONCLUSIONS: It may be concluded that 0.05% NaOCl and Medical Interporous tablets are not suitable as auxiliary chemical solutions for RPD care.

  10. Multilayer, degradable coating as a carrier for the sustained release of antibiotics: preparation and antimicrobial efficacy in vitro.

    Science.gov (United States)

    Guillaume, Olivier; Garric, Xavier; Lavigne, Jean-Philippe; Van Den Berghe, Helene; Coudane, Jean

    2012-09-28

    One of the most critical post-surgical complications is mesh-related infection. This paper describes how a commercially available polypropylene (PP) mesh was modified to minimize the risk of post-implantation infection. A dual drug-release coating was created around mesh filaments using an airbrush spray system. This coating was composed of three layers containing ofloxacin and rifampicin dispersed in a degradable polymer reservoir made up of [poly(ε-caprolactone) (PCL) and poly(DL-lactic acid) (PLA)]. Drug release kinetics were managed by varying the structure of the degradable polymer and the multilayer coating. In vitro, this new drug delivery polymer system was seen to be more rapidly invaded by fibroblasts than was the initial PP mesh. Active mesh showed excellent antibacterial properties with regard to microorganism adhesion, biofilm formation and the periprosthetic inhibition of bacterial growth. Sustained release of the two antibiotics from the coated mesh prevented mesh contamination for at least 72 h. This triple-layer coating technology is potentially of great interest for it can be easily extrapolated to other medical devices and drug combinations for the prevention or treatment of other diseases. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Surface properties and ion release from fluoride-containing bioactive glasses promote osteoblast differentiation and mineralization in vitro.

    Science.gov (United States)

    Gentleman, E; Stevens, M M; Hill, R G; Brauer, D S

    2013-03-01

    Bioactive glasses (BG) are suitable for bone regeneration applications as they bond with bone and can be tailored to release therapeutic ions. Fluoride, which is widely recognized to prevent dental caries, is efficacious in promoting bone formation and preventing osteoporosis-related fractures when administered at appropriate doses. To take advantage of these properties, we created BG incorporating increasing levels of fluoride whilst holding their silicate structure constant, and tested their effects on human osteoblasts in vitro. Our results demonstrate that, whilst cell proliferation was highest on low-fluoride-containing BG, markers for differentiation and mineralization were highest on BG with the highest fluoride contents, a likely effect of a combination of surface effects and ion release. Furthermore, osteoblasts exposed to the dissolution products of fluoride-containing BG or early doses of sodium fluoride showed increased alkaline phosphatase activity, a marker for bone mineralization, suggesting that fluoride can direct osteoblast differentiation. Taken together, these results suggest that BG that can release therapeutic levels of fluoride may find use in a range of bone regeneration applications. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  12. In vitro determination of the release of alendronic acid from alendronate tablets of different brands during deglutition.

    Science.gov (United States)

    Lamprecht, Guenther

    2009-10-01

    Alendronic acid, a frequently applied compound for the treatment of different forms of diseases of bone metabolism, is a strong acid with a high solubility in water. In connection with the oral administration this exhibits a potential health risk for the upper gastrointestinal tract. The in vitro release of tablets containing alendronic acid of different brands (Stada, ratiopharm, interpharm, Fosamax) was determined by dissolution tests for the time period required for oral intake. The effect of rotation speed, temperature, and solvent volume on the release rate of alendronic acid was determined for the used dissolution apparatus. Analysis of alendronic acid was performed by a validated HPLC method. The highest rate of release was found for the original brand. The dissolution rate of the generic formulations was significantly lower in the early stage of dissolution. Over the complete range of dissolution, more than 85% of the claimed amount was dissolved within 4 min. Dissolution profiles were compared by calculation of the similarity factor f(2) showing equal products with the exception of one generic product, whose dissolution rate was lower.

  13. Formulation and in-vitro release studies on chitosan-alginate ...

    African Journals Online (AJOL)

    La présente étude examine la libération in vitro de Vibrio bacterin, un vaccin pour les poissons produit à partir de microcapsules chitosan-alginate modifiées de HPMCAS pour l\\'administration par voie orale chez les poissons. Les microcapsules ont été préparées avec la méthode de coacervation counterion en utilisant un ...

  14. Design and in vitro/in vivo evaluation of sustained-release floating tablets of itopride hydrochloride

    Directory of Open Access Journals (Sweden)

    Ahmed SM

    2016-12-01

    Full Text Available Sayed M Ahmed,1 Adel Ahmed Ali,2 Ahmed MA Ali,2,3 Omiya A Hassan2,4 1Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, 2Department of Pharmaceutics, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt; 3Department of Pharmaceutics, Faculty of Pharmacy, Taif University, Taif, Kingdom of Saudi Arabia; 4Department of Pharmaceutics, Faculty of Pharmacy, Deraya University, El-Minia Gadida, Egypt Purpose: The aim of the present study was to improve the bioavailability of itopride (ITO and sustain its action by formulating as a floating dosage form. Materials and methods: Sustained-release floating tablets of ITO hydrochloride (HCl were prepared by direct compression using different hydrocolloid polymers such as hydroxypropyl methylcellulose and ethylcellulose and/or methacrylic acid polymers Eudragit RSPM and Carbopol 934P. The floating property was achieved using an effervescent mixture of sodium bicarbonate and anhydrous citric acid (1:1 mol/mol. Hardness, friability, content uniformity, and dissolution rate of the prepared floating tablets were evaluated. The formulation F10 composed of 28.5% Eudragit RSPM, 3% NaHCO3, and 7% citric acid provided sustained drug release. Results: In vitro results showed sustained release of F10 where the drug release percentage was 96.51%±1.75% after 24 hours (P=0.031.The pharmacokinetic results indicated that the area under the curve (AUC0–∞ of the prepared sustained-release floating tablets at infinity achieved 93.69 µg·h/mL compared to 49.89 µg·h/mL for the reference formulation (Ganaton® and the relative bioavailability of the sustained-release formulation F10 increased to 187.80% (P=0.022. Conclusion: The prepared floating tablets of ITO HCl (F10 could be a promising drug delivery system with sustained-release action and enhanced drug bioavailability. Keywords: itopride HCl, oral drug delivery, stability study, bioavailability

  15. Nanoemulsion-based gel formulation of diclofenac diethylamine: design, optimization, rheological behavior and in vitro diffusion studies.

    Science.gov (United States)

    Hamed, Rania; Basil, Marwa; AlBaraghthi, Tamadur; Sunoqrot, Suhair; Tarawneh, Ola

    2016-12-01

    Chronic oral administration of the non-steroidal anti-inflammatory drug, diclofenac diethylamine (DDEA), is often associated with gastrointestinal ulcers and bleeding. As an alternative to oral administration, a nanoemulsion-based gel (NE gel) formulation of DDEA was developed for topical administration. An optimized formulation for the o/w nanoemulsion of oil, surfactant and cosurfactant was selected based on nanoemulsion mean droplet size, clarity, stability, and flowability, and incorporated into the gelling agent Carbopol® 971P. Rheological studies of the DDEA NE gel were conducted and compared to those of conventional DDEA gel and emulgel. The three gels exhibited an elastic behavior, where G' dominated G″ at all frequencies, indicating the formation of strong gels. NE gel exhibited higher G' values than conventional gel and emulgel, which indicated the formation of a stronger gel network. Strat-M® membrane, a synthetic membrane with diffusion characteristics that are well correlated to human skin, was used for the in vitro diffusion studies. The release of DDEA from conventional gel, emulgel and NE gel showed a controlled release pattern over 12 h, which was consistent with the rheological properties of the gels. DDEA release kinetics from the three gels followed super case II transport as fitted by Korsmeyer-Peppas model.

  16. Release of Moxifloxacin from Contact Lenses Using an In Vitro Eye Model: Impact of Artificial Tear Fluid Composition and Mechanical Rubbing

    Science.gov (United States)

    Phan, Chau-Minh; Bajgrowicz-Cieslak, Magdalena; Subbaraman, Lakshman N.; Jones, Lyndon

    2016-01-01

    Purpose The aim of this study was to evaluate and compare the release of moxifloxacin from a variety of daily disposable (DD) contact lenses (CLs) under various conditions using a novel in vitro eye model. Methods Four commercially available DD conventional hydrogel (CH) CLs (nelfilcon A, omafilcon A, etafilcon A, and ocufilcon B) and three silicone hydrogel (SH) CLs (somofilcon A, narafilcon A, and delefilcon A) were evaluated. These lenses were incubated in moxifloxacin for 24 hours. The release of the drug was measured using a novel in vitro model in three experimental conditions: (1) phosphate buffered saline (PBS); (2) artificial tear solution (ATS) containing a variety of proteins and lipids; and (3) ATS with mechanical rubbing produced by the device. Results Overall, CH CLs had a higher drug release than SH CLs (P < 0.05) under all conditions. Typically, a higher drug release was observed in PBS than ATS (P < 0.05). For CH, drug release was found to be higher in ATS with rubbing than PBS or ATS (P < 0.05). For most lens types, ATS with rubbing produced higher drug release than ATS alone (P < 0.05). Generally, the release kinetics for all conditions were sustained over the 24-hour testing period, and no burst release was observed (P < 0.05). Conclusions Moxifloxacin release from a CL into ATS is lower when compared to release into PBS. When mechanical rubbing is introduced, the amount of drugs released is increased. Translational Relevance Results suggest that sophisticated in vitro models are necessary to adequately model on-eye drug release from CL materials. PMID:27847690

  17. Cytotoxicity studies of AZ31D alloy and the effects of carbon dioxide on its biodegradation behavior in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jiali, E-mail: wangjialicsu@yahoo.cn [Center for Translational Medicine Research and Development, Institute of Biomedical and Health Engineering, Chinese Academy of Sciences, Shenzhen 518055 (China); Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong SAR (China); Qin, Ling [Center for Translational Medicine Research and Development, Institute of Biomedical and Health Engineering, Chinese Academy of Sciences, Shenzhen 518055 (China); Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong SAR (China); Wang, Kai [School of Humanities and Social Sciences, Hunan University of Chinese Medicine, Changsha 410208 (China); Wang, Jue; Yue, Ye [Center for Translational Medicine Research and Development, Institute of Biomedical and Health Engineering, Chinese Academy of Sciences, Shenzhen 518055 (China); Li, Yangde [Guangdong Innovation Team for Biodegradable Magnesium and Medical Implants, E-ande, Dongguan 523660 (China); Tang, Jian [Center for Translational Medicine Research and Development, Institute of Biomedical and Health Engineering, Chinese Academy of Sciences, Shenzhen 518055 (China); Li, Weirong [Guangdong Innovation Team for Biodegradable Magnesium and Medical Implants, E-ande, Dongguan 523660 (China)

    2013-10-01

    Magnesium alloys have been advocated as potential artificial bone materials due to their biocompatibility and biodegradability. The understanding of their corrosive mechanism in physiological environments is therefore essential for making application-orientated designs. Thus, this in vitro study was designed to assess the effects of CO{sub 2} on corrosive behavior of AZ31D to mimic in vivo special ingredient. Electrochemical technologies accompanied with Scanning electron microscope, Fourier transform infrared, X-ray diffraction, Energy dispersive spectroscopy and hydrogen evolution measurement were employed to analyze corrosive rates and mechanisms of AZ31D. Moreover, the biocompatibility of AZ31D was assessed with a direct cell attachment assay and an indirect cytotoxicity test in different diluted extracts. The ion concentrations in extracts were measured using inductively coupled plasma mass spectrometry to offer explanations on the differences of cell viability in the indirect test. The results of the direct cytotoxicity assay showed that the corrosive rate of AZ31D was too rapid to allow for cell adhesion. Extracts diluted less than 20 times would cause adverse effects on cell proliferation, likely due to excessive ions and gas release. Moreover, the presence of CO{sub 2} did not cause significant differences on corrosive behavior of AZ31D according to the results of electrochemical testing and hydrogen evolution measurement. This might be caused by the simultaneous process of precipitation and dissolution of MgCO{sub 3} due to the penetration role of CO{sub 2}. This analysis of corrosive atmospheres on the degradation behavior of magnesium alloys would contribute to the design of more scientific in vitro testing systems in the future. - Highlights: • We evaluate the effects of CO{sub 2} on corrosion behavior of magnesium alloys. • We assess the feasibility of commercial AZ31D alloy as potential implants. • CO{sub 2} is not the key factor to minimize

  18. DESIGN, IN VITRO EVALUATION AND IN VIVO STUDIES OF NOVEL DELAYED RELEASE TABLETS OF PANTOPRAZOLE

    OpenAIRE

    Choudhry, Pooja; patel, kuldeep singh; jain, Prince kumar; Arora, Monika; nagar, Mona; nagar, mayank; sinde, sandeep; TRIVEDI, PIYUSH

    2012-01-01

    In an effort to reduce production costs, a simple, direct compression delayed release formulation consisting of pantoprazole was investigated. Pantoprazole is a proton pump inhibitor belongs to group of benzimidazole. It is very efficient for the treatment of gastric and duodenum ulcers. Even in solid state pantoprazole is sensitive to heat, humidity, light and especially to substances containing an acidic group. For such types of drugs, enteric coating added to the formulation tends to avoid...

  19. HPMA copolymer conjugate with pirarubicin: In vitro and ex vivo stability and drug release study.

    Science.gov (United States)

    Islam, Waliul; Fang, Jun; Etrych, Tomas; Chytil, Petr; Ulbrich, Karel; Sakoguchi, Akihiro; Kusakabe, Katsuki; Maeda, Hiroshi

    2017-11-10

    We have developed a tumor environment-responsive polymeric anticancer prodrug containing pirarubicin (THP) conjugated to N-(2-hydroxypropyl) methacrylamide copolymer (PHPMA), [P-THP], through a spacer containing pH-sensitive hydrazone bond, that showed remarkable therapeutic effect against various tumor models and in a human pilot study. Toward clinical development, here we report THP release profile from its HPMA copolymer conjugate, the conjugate stability, protein and cell-binding and solubility of P-THP. Size exclusion chromatography of P-THP (molecular weight 38 kDa) showed similar hydrodynamic volume as bovine serum albumin (BSA) in aqueous solution, with no apparent interactions with BSA, nor aggregation by itself. pH-responsive release of free THP was reconfirmed at pHs 6.5 and lower. The drug release was significantly affected by a type of used buffer. Phosphate buffer seems to facilitate faster hydrazone bond cleavage at pH 7.4 whereas higher stability was achieved in L-arginine solution which yielded only little cleavage and THP release, approx. 15% within 2 weeks at the same pH at 25 °C. Furthermore, ex vivo study using sera of different animal species showed very high stability of P-THP. Incubation with blood showed high stability of P-THP during circulation, without binding to blood cells. These findings revealed that L-arginine solution provides appropriate media for formulation of P-THP infusion solution as tumor-targeted polymeric anticancer drug based on EPR effect. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. In vitro Expression and Mutagenesis of a Gene for Corticotropin Releasing Factor

    Science.gov (United States)

    1989-10-31

    AS RPT 0 DTIC USERS (U) 22a NAME OF RESPONSIBLE INDIVIDUAL 22b. TELEPHONE (Include Area Code) 22c OFFICE SYMBOL Dr. J.A. Maide (2n?) AQA -4097 nNR DD...the release of ACTH from pituitary cells. We will pursue this goal using a recently described and novel technique of molecular biology to synthesize...of Pharmacology Depts. of Biology & Psychology Univ. of Pennsylvania Georgia State University School of Medicine Atlanta, GA 30303 36th and Hamilton

  1. In vitro release profile of anti-ulcer drug rabeprazole from biocompatible psyllium-PVA hydrogels.

    Science.gov (United States)

    Singh, Baljit; Lal, Harinder; Pal, Lok; Sharma, Vikrant

    2012-04-01

    The present article discusses the synthesis, characterization and haemocompatibility behaviour of the psyllium-PVA hydrogels prepared by chemical method in the presence of N,N'-methylenebisacrylamide. These hydrogels have been characterized by Fourier Transform infrared spectroscopy, thermo gravimetric analysis, swelling and drug release studies. The release of model drug rabeprazole sodium from the drug loaded hydrogels occurred through non-Fickian diffusion mechanism. Psyllium itself acts as anti-ulcer agent and release of rabeprazole from the drug loaded hydrogels may enhance the curing potential of the drug delivery device. The haemocompatibility was evaluated by studying the blood interactions with hydrogels with reference to thrombogenicity and haemolytic potential. Thrombogenicity results indicate that hydrogels are non-thrombogenic as the weight of clot formed and thrombus percentage for hydrogels was less than the positive control. The haemolytic index has been observed <5%. These observations indicate that these hydrogels are haemo-compatible and hence could be used for oral administration of antiulcer drugs.

  2. Anisotropic kinetic energy release and gyroscopic behavior of CO2 super rotors from an optical centrifuge

    Science.gov (United States)

    Murray, Matthew J.; Ogden, Hannah M.; Mullin, Amy S.

    2017-10-01

    An optical centrifuge is used to generate an ensemble of CO2 super rotors with oriented angular momentum. The collision dynamics and energy transfer behavior of the super rotor molecules are investigated using high-resolution transient IR absorption spectroscopy. New multipass IR detection provides improved sensitivity to perform polarization-dependent transient studies for rotational states with 76 ≤ J ≤ 100. Polarization-dependent measurements show that the collision-induced kinetic energy release is spatially anisotropic and results from both near-resonant energy transfer between super rotor molecules and non-resonant energy transfer between super rotors and thermal molecules. J-dependent studies show that the extent and duration of the orientational anisotropy increase with rotational angular momentum. The super rotors exhibit behavior akin to molecular gyroscopes, wherein molecules with larger amounts of angular momentum are less likely to change their angular momentum orientation through collisions.

  3. In vitro element release and biological aspects of base–metal alloys for metal-ceramic applications

    Science.gov (United States)

    Holm, Charlotta; Morisbak, Else; Kalfoss, Torill; Dahl, Jon E.

    2015-01-01

    Abstract Objective: The aims of this study were to investigate the release of element from, and the biological response in vitro to, cobalt–chromium alloys and other base–metal alloys used for the fabrication of metal-ceramic restorations. Material and methods: Eighteen different alloys were investigated. Nine cobalt–chromium alloys, three nickel–chromium alloys, two cobalt–chromium–iron alloys, one palladium–silver alloy, one high-noble gold alloy, titanium grade II and one type III copper–aluminium alloy. Pure copper served as positive control. The specimens were prepared according to the ISO standards for biological and corrosion testing. Passive leaching of elements was measured by using Inductively Coupled Plasma – Mass Spectrometry (ICP-MS) after incubation in cell culture media, MEM, for 3 days. Corrosion testing was carried out in 0.9% sodium chloride (NaCl) and 1% lactic acid for 7 days, and the element release was measured by Inductively Coupled Plasma – Optical Emission Spectroscopy (ICP-OES). The biological response from the extract solutions was measured though MTT cytotoxicity testing and the Hen's egg test-chorio-allantoic membrane (HET-CAM) technique for irritationt. Results: The corrosion test showed similar element release from base-metal alloys compared to noble alloys such as gold. Apart from the high-copper alloy, all alloys expressed low element release in the immersion test, no cytotoxic effect in the MTT test, and were rated non-irritant in the HET-CAM test. Conclusions: Minimal biological response was observed for all the alloys tested, with the exception of the high-copper alloy. PMID:28642904

  4. Controlled release of raloxifene by nanoencapsulation: effect on in vitro antiproliferative activity of human breast cancer cells

    Science.gov (United States)

    Fontana, Márcia Camponogara; Beckenkamp, Aline; Buffon, Andréia; Beck, Ruy Carlos Ruver

    2014-01-01

    Raloxifene hydrochloride (RH) is considered to be an antiproliferative agent of mammary tissue. The aim of this study was to investigate the effect of the encapsulation of RH in polymeric nanocapsules with anionic or cationic surface on its release profile and antiproliferative activity. They were prepared by interfacial deposition of preformed polymer, followed by wide physicochemical characterization. The in vitro RH release was assessed by the dialysis membrane method and the data analyzed by mathematical modeling. The antiproliferative effect on MCF-7 cell viability was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay as well as by counting viable cells. They had high encapsulation efficiency, low polydispersity, and nanometric mean size. Nanocapsules prepared with Eudragit® RS100 and Eudragit® S100 presented positive and negative zeta potentials, respectively. Drug release studies demonstrated controlled release of RH from anionic nanocapsules, which could be explained due to a stronger interaction of the drug to these nanocapsules and the larger amount of entrapped drug. On the other hand, this control was not observed from cationic nanocapsules due to the larger amount of drug adsorbed onto their surface. MCF-7 cell viability studies and cell counting showed that RH-loaded Eudragit® RS100 nanocapsules promote the best antiproliferative activity after 24 hours of treatment, whereas the best activity was observed for RH-loaded Eudragit® S100 nanocapsules after 72 hours. Furthermore, the combined treatment of these formulations improved the antiproliferative effect during the entire treatment. PMID:24971009

  5. Cooperative loading and release behavior of a metal-organic receptor.

    Science.gov (United States)

    Gan, Quan; Ronson, Tanya K; Vosburg, David A; Thoburn, John D; Nitschke, Jonathan R

    2015-02-11

    In order to design artificial chemical systems that are capable of achieving complex functions, it is useful to design synthetic receptors that mimic their biological counterparts. Biological functions are underpinned by properties that include specific binding with high affinity and selectivity, cooperativity, and release triggered by external stimuli. Here we show that a metal-organic receptor constructed through subcomponent self-assembly can selectively and cooperatively load and release oxocarbon anions. The flexible coordination spheres of its cadmium(II) centers allow the receptor to dynamically adjust its structure upon exchanging four triflate or triflimide counterions for two oxocarbon anions, resulting in strong cooperativity and very tight binding, with an apparent association constant for C5O5(2-) of 5 × 10(10) M(-1). Substituting the cadmium(II) ions for copper(I) by switching solvent prompted a structural reorganization and release of the oxocarbon anions. Its cooperative behavior allows the receptor to carry a greater payload than would be possible in a noncooperative analogue.

  6. Dual delivery nanosystem for biomolecules. Formulation, characterization, and in vitro release.

    Science.gov (United States)

    Ortega-Oller, Inmaculada; Del Castillo-Santaella, Teresa; Padial-Molina, Miguel; Galindo-Moreno, Pablo; Jódar-Reyes, Ana Belén; Peula-García, José Manuel

    2017-11-01

    Because of the biocompatible and biodegradable properties of poly (lactic-co-glycolic acid) (PLGA), nanoparticles (NPs) based on this polymer have been widely studied for drug/biomolecule delivery and long-term sustained-release. In this work, two different formulation methods for lysozyme-loaded PLGA NPs have been developed and optimized based on the double-emulsion (water/oil/water, W/O/W) solvent evaporation technique. They differ mainly in the phase in which the surfactant (Pluronic® F68) is added: water (W-F68) and oil (O-F68). The colloidal properties of these systems (morphology by SEM and STEM, hydrodynamic size by DLS and NTA, electrophoretic mobility, temporal stability in different media, protein encapsulation, release, and bioactivity) have been analyzed. The interaction surfactant-protein depending on the formulation procedure has been characterized by surface tension and dilatational rheology. Finally, cellular uptake by human mesenchymal stromal cells and cytotoxicity for both systems have been analyzed. Spherical hard NPs are made by the two methods However, in one case, they are monodisperse with diameters of around 120nm (O-F68), and in the other case, a polydisperse system of NPs with diameters between 100 and 500nm is found (W-F68). Protein encapsulation efficiency, release and bioactivity are maintained better by the W-F68 formulation method. This multimodal system is found to be a promising "dual delivery" system for encapsulating hydrophilic proteins with strong biological activity at the cell-surface and cytoplasmic levels. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. α-Tocopherol loaded thermosensitive polymer nanoparticles: preparation, in vitro release and antioxidant properties

    Directory of Open Access Journals (Sweden)

    Cirley Quintero

    Full Text Available Abstract α-Tocopherol is the most bioavailable and active compound found in vitamin E with potential application in pharmaceutical, alimentary and cosmetic industries. However, its low solubility in aqueous medium and environmental instability limit its dosage. In this paper, we report the preparation of α-tocopherol loaded nanoparticles (TOC-NP based on amphiphilic thermosensitive triblock copolymers PNIPAM-b-PCL-b-PNIPAM. The nanoparticles exhibited a core – shell structure, were positively charged and presented average diameters below 300 nm. TOC-NP presented controlled release of α-tocopherol at room temperature along 140h, and exhibited antioxidant properties in aqueous medium.

  8. Sustained release ophthalmic dexamethasone: In vitro in vivo correlations derived from the PK-Eye.

    Science.gov (United States)

    Awwad, Sahar; Day, Richard M; Khaw, Peng T; Brocchini, Steve; Fadda, Hala M

    2017-04-30

    Corticosteroids have long been used to treat intraocular inflammation by intravitreal injection. We describe dexamethasone loaded poly-DL-lactide-co-glycolide (PLGA) microparticles that were fabricated by thermally induced phase separation (TIPS). The dexamethasone loaded microparticles were evaluated using a two-compartment, in vitro aqueous outflow model of the eye (PK-Eye) that estimates drug clearance time from the back of the eye via aqueous outflow by the anterior route. A dexamethasone dose of 0.20±0.02mg in a 50μL volume of TIPS microparticles resulted in a clearance t1/2 of 9.6±0.3days using simulated vitreous in the PK-Eye. Since corticosteroids can also clear through the retina, it is necessary to account for clearance through the back of the eye. Retinal permeability data, published human ocular pharmacokinetics (PK) and the PK-Eye clearance times were then used to establish in vitro in vivo correlations (IVIVCs) for intraocular clearance times of corticosteroid formulations. A t1/2 of 48h was estimated for the dexamethasone-TIPS microparticles, which is almost 9 times longer than that reported for dexamethasone suspension in humans. The prediction of human clearance times of permeable molecules from the vitreous compartment can be determined by accounting for drug retinal permeation and determining the experimental clearance via the anterior aqueous outflow pathway using the PK-Eye. Copyright © 2017. Published by Elsevier B.V.

  9. Compression-coated tablets of glipizide using hydroxypropylcellulose for zero-order release: in vitro and in vivo evaluation.

    Science.gov (United States)

    Huang, Haiqin; Wu, Zhenghong; Qi, Xiaole; Zhang, Huiting; Chen, Qin; Xing, Jiayu; Chen, Haiyan; Rui, Yao

    2013-03-25

    Compression coating, which presents some advantages like short manufacturing process and non-solvent residue over liquid coating, has been introduced to the oral administration systems for decades. The purpose of this study was to design a zero-order release of compression-coated tablets using hydroxypropylcellulose (HPC) as the coating layer and glipizide which was solubilized by manufacturing the inclusion complex of β-cyclodextrin as a model drug. The effects of the weight ratio of drug and the viscosity of HPC on the release profile were investigated by "f2" factor with Glucotrol XL(®). The uptake and erosion study, the correlation coefficient (R) and the exponent (n) were used as indicators to justify drug release mechanism. Bioavailability in vivo was determined by administering the compression-coated tablets to rabbits in contrast with Glucotrol XL(®). It was found that the formulation presented a well zero-order behavior at the weight ratio of drug 11:14 (core:layer) and the combination of HPC-L (8.0 mPa s) and HPC-M (350 mPa s) (8:9), with the "f2" of 66.90. The mechanism for zero-order release of these compression-coated tablets was solvent penetration into the dosage form and drug dissolution from the erosion of the gelled HPC matrix. The parameter AUC0-∞ of the compression coated tablets and the market tablets were 37,255.93±1474.08 h ng/ml and 43265.40±1015.28 h ng/ml, while the relative bioavailability was 87.66±1.56%. These studies demonstrate that the designed compression-coated tablets may be a promising strategy for peroral controlled release delivery system of water-insoluble drugs. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Release of volatile organic compounds (VOCs from the lung cancer cell line CALU-1 in vitro

    Directory of Open Access Journals (Sweden)

    Schubert Jochen

    2008-11-01

    Full Text Available Abstract Background The aim of this work was to confirm the existence of volatile organic compounds (VOCs specifically released or consumed by lung cancer cells. Methods 50 million cells of the human non-small cell lung cancer (NSCLC cell line CALU-1 were incubated in a sealed fermenter for 4 h or over night (18 hours. Then air samples from the headspace of the culture vessel were collected and preconcentrated by adsorption on solid sorbents with subsequent thermodesorption and analysis by means of gas chromatography mass spectrometry (GC-MS. Identification of altogether 60 compounds in GCMS measurement was done not only by spectral library match, but also by determination of retention times established with calibration mixtures of the respective pure compounds. Results The results showed a significant increase in the concentrations of 2,3,3-trimethylpentane, 2,3,5-trimethylhexane, 2,4-dimethylheptane and 4-methyloctane in the headspace of CALU-1 cell culture as compared to medium controls after 18 h. Decreased concentrations after 18 h of incubation were found for acetaldehyde, 3-methylbutanal, butyl acetate, acetonitrile, acrolein, methacrolein, 2-methylpropanal, 2-butanone, 2-methoxy-2-methylpropane, 2-ethoxy-2-methylpropane, and hexanal. Conclusion Our findings demonstrate that certain volatile compounds can be cancer-cell derived and thus indicative of the presence of a tumor, whereas other compounds are not released but seem to be consumed by CALU-1 cells.

  11. Application of 4,5-diaminofluorescein to reliably measure nitric oxide released from endothelial cells in vitro

    Directory of Open Access Journals (Sweden)

    Räthel Thomas R.

    2003-01-01

    Full Text Available Here we describe in more depth the previously published application of the fluorescent probe 4,5-diaminofluorescein (DAF-2 in order to reliably measure low levels of nitric oxide (NO as released from human endothelial cells in vitro. The used approach is based on the following considerations a use low concentrations of DAF-2 (0.1 µM in order to reduce the contribution of DAF-2 auto-fluorescence to the measured total fluorescence, and b subtract the DAF-2 auto-fluorescence from the measured total fluorescence. The advantage of this method is the reliable quantification of NO in a biological system in the nanomolar range once thoroughly validated. Here we focus in addition to the previous publication (Leikert et al., FEBS Lett 2001, 506:131-134 on aspects of validation procedures as well as limitations and pitfalls of this method.

  12. Mechanical cell-substrate feedback explains pairwise and collective endothelial cell behavior in vitro

    NARCIS (Netherlands)

    R.F.M. van Oers (Rene); R.M.H. Merks (Roeland)

    2013-01-01

    htmlabstractIn vitro cultures of endothelial cells are a widely used model system of the collective behavior of endothelial cells during vasculogenesis and angiogenesis. When seeded in a extracellular matrix, endothelial cells can form blood vessel-like structures, including vascular networks and

  13. Behavioral differences of Heterodera glycines and Meloidogyne incognita infective juveniles exposed to root extracts in vitro

    Science.gov (United States)

    The in vitro behaviors of infective juveniles (J2) of Heterodera glycines and Meloidogyne incognita were compared in the presence and absence of plant root extracts. In an agar plate attraction-retention assay, H. glycines was 15-fold more responsive to a chemical attractant (CaCl2; P < 0.05) than w...

  14. Investigation of In-Vitro Biological Behavior and Pro-Angiogenic ...

    African Journals Online (AJOL)

    Prof. Ogunji

    Investigation of In-Vitro Biological Behavior and Pro-Angiogenic. Potential of Baicalein as ... Current research is tackling the problem of vascularization with four distinct strategies, all of which have demonstrated ... To overcome this problem a lot of research effort has gone into the search for hypoxia mimics. (Xia et al., 2009, ...

  15. Improvement of cellular uptake, in vitro antitumor activity and sustained release profile with increased bioavailability from a nanoemulsion platform.

    Science.gov (United States)

    Choudhury, Hira; Gorain, Bapi; Karmakar, Sanmoy; Biswas, Easha; Dey, Goutam; Barik, Rajib; Mandal, Mahitosh; Pal, Tapan Kumar

    2014-01-02

    Paclitaxel, a potential anticancer agent against solid tumors has been restricted from its oral use due to poor water solubility as well as Pgp efflux property. The present study was aimed to improve the oral bioavailability of paclitaxel through development of (o/w) nanoemulsion consisting of Capryol 90 as internal phase with Tween 20 as emulsifier with water as an external phase. Formulations were selected from the nanoemulsion region of pseudo-ternary phase diagrams, formulated by aqueous titration method. The developed nanoemulsion has been characterized by its thermodynamic stability, morphology, droplet size, zeta potential, viscosity where in vitro release was evaluated through dialysis. Paclitaxel nanoemulsion exhibited thermodynamical stability with low viscosity, nano-sized oil droplets in water with low poly-dispersity index. The shelf life of the paclitaxel nanoemulsion was found to be approximately 2.38 years. Increased permeability through the Caco-2 cell monolayer and decreased efflux is great advantageous for nanoemulsion formulation. The effects of paclitaxel nanoemulsion on breast cancer cell proliferation, morphology and DNA fragmentation were analyzed in vitro which showed significant anti-proliferation and decreased IC50 values in nanoemulsion group which may be due to enhanced uptake of paclitaxel through the oil core. Moreover, the absolute oral bioavailability and sustained release profile of the paclitaxel nanoemulsion evaluated in mouse model was found to improve up to 55.9%. The concentration of paclitaxel in mice plasma was determined by our validated LC-MS/MS method. By reviewing the significant outcome of the present investigation based on stability study, Caco-2 permeability, cell proliferative assay and pharmacokinetic profile it may be concluded that the oral nanoemulsion has got encouraging advantages over the presently available formulations of this injectable chemotherapeutic drug. Copyright © 2013 Elsevier B.V. All rights

  16. The preparation of 3,5-dihydroxy-4-isopropylstilbene nanoemulsion and in vitro release

    Science.gov (United States)

    Zhang, Yue; Gao, Jungang; Zheng, Hetang; Zhang, Ran; Han, Yucui

    2011-01-01

    We have reported a novel procedure to prepare 3,5-dihydroxy-4-isopropylstilbene (DHPS) nanoemulsion, using a low-energy emulsification method. Based on the phase diagram, the optimum prescription of nanoemulsion preparation was screened. With polyoxyethylenated castor oil (EL-40) as the surfactant, ethanol as the co-surfactant, and isopropyl myristate (IPM) as the oil phase, the DHPS nanoemulsion was obtained with a transparent appearance, little viscosity, and spherically uniform distribution verified by transmission electron microscopy and laser scattering analyzer. The nanoemulsion was also determined by FT-Raman spectroscopy. The DHPS nanoemulsion demonstrated good stability and stable physical and chemical properties. The nanoemulsion dramatically improved the transdermal release of DHPS (from 8.02 μg · cm−2 to 273.15 μg · cm−2) and could become a favorable new dosage form for DHPS. PMID:21674020

  17. Formulation of a modified release metformin. HCl matrix tablet: influence of some hydrophilic polymers on release rate and in-vitro evaluation

    Directory of Open Access Journals (Sweden)

    John Rojas

    2011-09-01

    Full Text Available Metformin hydrochloride is an antidiabetic agent which improves glucose tolerance in patients with type 2 diabetes and reduces basal plasma levels of glucose. In this study, a simplex centroid experimental design with 69 runs was used to select the best combination of some hydrophilic polymers that rendered a 24 h in-vitro release profile of metformin.HCl. The Korsmeyer-Peppas model was used to model the dissolution profiles since it presented the best fit to the experimental data. Further, a cubic model predicted the best formulation of metformin.HCl containing polyvinyl pyrrolidone, ethyl cellulose, hydroxypropyl methyl cellulose, carrageenan, sodium alginate, and gum arabic at 6.26, 68.7, 6.26, 6.26, 6.26 and 6.26 % levels, respectively. The validation runs confirmed the accuracy of the cubic model with six components for predicting the best set of components which rendered a once-a-day modified release hydrophilic matrix tablet in compliance with the USP specifications.O cloridrato de metformina é um agente antidiabético que melhora a tolerância à glicose em pacientes com diabetes tipo 2 e reduz os níveis plasmáticos basais de glicose. Neste estudo, um projeto experimental do tipo "centróide simplex" com 69 tomadas foi usado para selecionar a melhor combinação de alguns polímeros hidrofílicos que gerou um perfil de liberação da metformina.HCl de 24 horas. O modelo Korsmeyer-Peppas foi usado para modelar os perfis de dissolução, uma vez que apresentou os melhores ajustes aos dados experimentais. Além disso, um modelo cúbico previu a melhor formulação de metformina.HCl sendo aquela contendo polivinilpirrolidona, etilcelulose, hidroxipropilmetil celulose, carragena, alginato de sódio e goma arábica nos níveis 6.26, 68.7, 6.26, 6.26, 6.26 e 6.26 %, respectivamente. As corridas de validação confirmaram a precisão do modelo cúbico com os seis componentes para prever o melhor conjunto de componentes que originou uma

  18. Release of dibenzoyl peroxide from polymethyl methacrylate denture base resins: an in vitro evaluation.

    Science.gov (United States)

    Boeckler, Arne F; Morton, Dean; Poser, Sven; Dette, Karl-Ernst

    2008-12-01

    Dibenzoyl peroxide (BPO), an initiator in polymethyl methacrylate denture base resins, has been associated with allergic reactions in human patients. This study evaluated the content of BPO in acrylic denture base materials (ADBM) prior and subsequent to recommended and additional post-polymerization, and subsequent to storage in varying solutions. The goal was to determine differences in BPO content in ADBMs, to determine whether differences are seen in BPO release over time and to test different procedures for additional BPO reduction. Three heat-polymerizing, two auto-polymerizing and a microwave polymerizing "hypoallergic" ADBM were investigated. Five samples (Ø414.57mg) were polymerized according to manufacturers' instructions from each of the six acrylic resins for each of the variables to be investigated. For each material the BPO content was measured as delivered by the manufacturer and subsequent to recommended and post-polymerization protocols. The BPO content was also evaluated after storage in distilled water (22 degrees C, 192h), in artificial saliva (35 degrees C, 192h), in ethanol, potassium permanganate and ammonium ferric(II) sulfate solutions (22 degrees C, 48h). High performance liquid chromatography (HPLC) and indirect iodometry were used to detect BPO concentrations. Significant differences were noted in BPO concentrations between the polymers as delivered from the manufacturer (0.13-1.20%), subsequent to polymerization (0.05-0.32%) and to the various treatment and storage procedures (H and U-tests, pBPO. No reduction of BPO content was noted after 8 days of storage in artificial saliva or water. The most notable reduction (63-95%) occurred subsequent to post-polymerization cycles. BPO was detected in all investigated ADBMs. It is unlikely, under oral conditions, that BPO is released from the investigated ADBMs. The BPO concentration can be reduced effectively by additional post-polymerization.

  19. Fast Dissolving Sublingual Films Containing Sumatriptan Alone and Combined with Methoclopramide: Evaluation in Vitro Drug Release and Mucosal Permeation

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    Maryam Maghsoodi, Mahdieh Rahmani, Hamed Ghavimi, Seyed Hassan Montazam, Saieede Soltani, Mitra Alami, Sara Salatin, Mitra Jelvehgari

    2016-10-01

    Full Text Available ackground: Sumatriptan succinate is a 5-HT1 receptor agonist which is used in the treatment of migraine. It shows low bioavailability (15% due to high hepatic first pass metabolism. The present work intended to formulate mucoadhesive sublingual films of sumatriptan combined with metoclopramide and sumatriptan alone with the objective of improving the therapeutic efficacy, patient compliance, and bioavailability. Methods: The sublingual films were formulated by solvent casting technique using mucoadhesive polymer of hydroxypropyl methylcellulose and propylene glycol as plasticizers. This study was also designed to evaluate the physicochemical and mucoadhesive characteristics of the films. The films were evaluated for their mechanical strength, folding endurance, drug content uniformity, swelling, in vitro residence time, in vitro release, in vitro bioadhesion, and in vivo mucoadhesion. Results: They showed good appearance and elasticity. The best drugs of polymer ratio were S3 (1:2 and SM2 (2.7:1:8. The film of S3 and SM2 showed 10.6 and 11.01 mg weight, 2.2 and 22.5 µm thickness, 300 folding endurance, 55.9 and 100% content uniformity, respectively. The Differential Scanning Calorimetry (DSC showed no stable sample of sumatriptan and metoclopramide in the drug loaded films and revealed amorphous form and transition of hydrate to anhydrous form for metoclopramide. The results showed that the films prepared were fast dissolving. The films (sumatriptan combined with metoclopramide and sumatriptan alone exhibited very good mucoadhesive properties and shorter retention time (15-30 s. Conclusion: The formulations were found to be suitable candidates for the development of sublingual films for therapeutic uses.

  20. In vitro Incubation of Platelets with oxLDL Does Not Induce Microvesicle Release When Measured by Sensitive Flow Cytometry.

    Science.gov (United States)

    Nielsen, Tine Bo; Nielsen, Morten Hjuler; Handberg, Aase

    2015-01-01

    Microvesicles (MVs) are submicron vesicles with sizes of 0.1-1.0 μm in diameter, released from various cell types upon activation or apoptosis. Their involvement in a variety of diseases has been intensively investigated. In blood, platelets are potent MV secretors, and oxidized low-density lipoprotein (oxLDL), a platelet ligand, induces platelet activation and thus potentially MV secretion. This interaction occurs through binding of oxLDL with CD36, located on the platelet membrane. In this study, we investigated the effect of in vitro incubation of platelets with oxLDL on MV release. Furthermore, we compared the results obtained when separating MVs larger than 0.5 μm as a measure of results obtained from less sensitive conventional flow cytometers with MVs below the 0.5 μm limit. MV size distribution was analyzed in plasma from 11 healthy volunteers (four females and seven males). MVs were identified as Platelet-rich plasma (PRP) was incubated without and with oxLDL or LDL (as control) to investigate the impact on platelet activation, evident by release of MVs. Size-calibrated fluorescent beads were used to establish the MV gate, and separate small- and large-size vesicles. CD41(+) and CD41(+)CD36(+) MVs increased by six to eightfold in PRP, when left at room temperature, and the presence of cell-specific markers increased. Total MV count was unaffected. Incubations with oxLDL did not increase the MV release or affect the distribution of small- and large-size MVs. We found a large interindividual variation in the fraction of small- and large-size MVs of 73%. In conclusion, we propose that procoagulant activity and activation of platelets induced by interaction of platelet CD36 with oxLDL may not involve release of MVs. Furthermore, our results demonstrate great interindividual variability in size distribution of platelet-derived MVs and thereby stress the importance for generation of standardized protocols for MV quantification by flow cytometry.

  1. Synthesis, characterization and in vitro drug release of cisplatin loaded Cassava starch acetate–PEG/gelatin nanocomposites

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    V. Raj

    2016-10-01

    Full Text Available The aim of the present study is to examine the feasibility of Cassava starch acetate (CSA–polyethylene glycol (PEG–gelatin (G nanocomposites as controlled drug delivery systems. It is one of the novel drug vehicles which can be used for the controlled release of an anticancer drug. Simple nano precipitation method was used to prepare the carriers CSA–PEG–G nanocomposites and they were used for entrapping cisplatin (CDDP. Through FT-IR spectroscopy, the linking among various components of the system was proved and with the help of scanning electron microscope and transmission electron microscopy (TEM, the surface morphology was investigated. The particle sizes of the CSA–CDDP, CSA–CDDP–PEG and CSA–CDDP–PEG–G polymer composites were between 140 and 350 nm, as determined by a Zetasizer. Drug encapsulation efficiency, drug loading capacity and in vitro release of CDDP were evaluated respectively. The findings revealed that the cross linked CSA–PEG–G nanocomposites can be a potential polymeric carrier for controlled delivery of CDDP.

  2. The development, physicochemical characterisation and in vitro drug release studies of pectinate gel beads containing Thai mango seed kernel extract.

    Science.gov (United States)

    Nithitanakool, Saruth; Pithayanukul, Pimolpan; Bourgeois, Sandrine; Fessi, Hatem; Bavovada, Rapepol

    2013-06-03

    Pectinate gel beads containing Thai mango seed kernel extract (MSKE, cultivar 'Fahlun') were developed and characterised for the purpose of colon-targeted delivery. The MSKE-loaded pectinate beads were prepared using ionotropic gelation with varying pectin-to-MSKE ratios, MSKE concentrations, and concentrations of two cross-linkers (calcium chloride and zinc acetate). The formulated beads were spherical in shape and ranged in size between 1.13 mm and 1.88 mm. Zinc-pectinate (ZPG) beads containing high amounts of MSKE showed complete entrapment efficiency (EE) of MSKE (100%), while calcium-pectinate (CPG) beads demonstrated 70% EE. The in vitro release tests indicated that MSKE-loaded CPG beads were unstable in both simulated gastric medium (SGM) and simulated intestinal medium (SIM), while MSKE-loaded ZPG beads were stable in SIM but unable to prevent the release of MSKE in SGM. The protection of ZPG beads with gastro-resistant capsules (Eudragit® L 100-55) resulted in stability in both SGM and SIM; they disintegrated immediately in simulated colonic medium containing pectinolytic enzymes. MSKE-loaded ZPG beads were stable at 4, 25 and 45 °C during the study period of four months. The present study revealed that ZPG beads in enteric-coated capsules might be a promising carrier for delivering MSKE to the colon.

  3. The Development, Physicochemical Characterisation and in Vitro Drug Release Studies of Pectinate Gel Beads Containing Thai Mango Seed Kernel Extract

    Directory of Open Access Journals (Sweden)

    Hatem Fessi

    2013-06-01

    Full Text Available Pectinate gel beads containing Thai mango seed kernel extract (MSKE, cultivar ‘Fahlun’ were developed and characterised for the purpose of colon-targeted delivery. The MSKE-loaded pectinate beads were prepared using ionotropic gelation with varying pectin-to-MSKE ratios, MSKE concentrations, and concentrations of two cross-linkers (calcium chloride and zinc acetate. The formulated beads were spherical in shape and ranged in size between 1.13 mm and 1.88 mm. Zinc-pectinate (ZPG beads containing high amounts of MSKE showed complete entrapment efficiency (EE of MSKE (100%, while calcium-pectinate (CPG beads demonstrated 70% EE. The in vitro release tests indicated that MSKE-loaded CPG beads were unstable in both simulated gastric medium (SGM and simulated intestinal medium (SIM, while MSKE-loaded ZPG beads were stable in SIM but unable to prevent the release of MSKE in SGM. The protection of ZPG beads with gastro-resistant capsules (Eudragit® L 100-55 resulted in stability in both SGM and SIM; they disintegrated immediately in simulated colonic medium containing pectinolytic enzymes. MSKE-loaded ZPG beads were stable at 4, 25 and 45 °C during the study period of four months. The present study revealed that ZPG beads in enteric-coated capsules might be a promising carrier for delivering MSKE to the colon.

  4. [Preliminary study on the release of DNA from Pseudomona aeruginosa induced by piperacillin/tazobactam in vitro].

    Science.gov (United States)

    Peng, Dai-zhi; Guymon, Charles H; McManus, Albert T; Xiao, Guang-xia

    2005-04-01

    To observe the release of DNA from Pseudomonas aeruginosa (P. aeruginosa) induced by different concentrations of piperacillin/tazobactam (Piper) in vitro. The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of Piper against 1244 strain (ATCC 27317) of P. aeruginosa were determined, respectively. This strain of P. aeruginosa was separately cultured with Piper in different concentrations at 37 degrees C for 4 h and 24 h. The samples of cultural supernatant were filtered and electrophoresis was conducted in 1.8% agarose with SYBR Gold stain. Then the images of the gel sheets were photographed. This strain of P. aeruginosa was sensitive to Piper. The bacterial DNA was not detected in 4-h cultured P. aeruginosa either with or without Piper by this method. The bacterial DNA molecules could be detected in 24 h samples in cultures without Piper, and they were displayed in two zones of molecular weight over 2000 base pairs (bp) and lower than 100 bp. Similar results were observed when the MIC of piper (0.002, 0.004 g/L) were under the MIC measured at the 3rd time (0.008 g/L), but there was much more bacterial DNA with molecular weight lower than 100 bp. When Piper concentration was higher than its MIC, only smaller quantities of bacterial DNA in the area with molecular weight lower than 400 bp could be detected in 24-h culture samples. A certain amount of bacterial DNA was released from P. aeruginosa under its natural growth circumstance. Different concentrations of Piper showed different effects on DNA release, in regard to its quantity and molecular weight, from P. aeruginosa cultures.

  5. In vitro RNA release from a human rhinovirus monitored by means of a molecular beacon and chip electrophoresis.

    Science.gov (United States)

    Weiss, Victor U; Bliem, Christina; Gösler, Irene; Fedosyuk, Sofiya; Kratzmeier, Martin; Blaas, Dieter; Allmaier, Günter

    2016-06-01

    Liquid-phase electrophoresis either in the classical capillary format or miniaturized (chip CE) is a valuable tool for quality control of virus preparations and for targeting questions related to conformational changes of viruses during infection. We present an in vitro assay to follow the release of the RNA genome from a human rhinovirus (common cold virus) by using a molecular beacon (MB) and chip CE. The MB, a probe that becomes fluorescent upon hybridization to a complementary sequence, was designed to bind close to the 3' end of the viral genome. Addition of Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), a well-known additive for reduction of bleaching and blinking of fluorophores in fluorescence microscopy, to the background electrolyte increased the sensitivity of our chip CE set-up. Hence, a fast, sensitive and straightforward method for the detection of viral RNA is introduced. Additionally, challenges of our assay will be discussed. In particular, we found that (i) desalting of virus preparations prior to analysis increased the recorded signal and (ii) the MB-RNA complex signal decreased with the time of virus storage at -70 °C. This suggests that 3'-proximal sequences of the viral RNA, if not the whole genome, underwent degradation during storage and/or freezing and thawing. In summary, we demonstrate, for two independent virus batches, that chip electrophoresis can be used to monitor MB hybridization to RNA released upon incubation of the native virus at 56 °C. Graphical Abstract Schematic of the study strategy: RNA released from HRV-A2 is detected by chip electrophoresis through the increase in fluorescence after genom complexation to a cognate molecular beacon.

  6. Investigation of Microbubble Cavitation-Induced Calcein Release from Cells In Vitro.

    Science.gov (United States)

    Maciulevičius, Martynas; Tamošiūnas, Mindaugas; Jakštys, Baltramiejus; Jurkonis, Rytis; Venslauskas, Mindaugas Saulius; Šatkauskas, Saulius

    2016-12-01

    In the present study, microbubble (MB) cavitation signal analysis was performed together with calcein release evaluation in both pressure and exposure duration domains of the acoustic field. A passive cavitation detection system was used to simultaneously measure MB scattering and attenuation signals for subsequent extraction efficiency relative to MB cavitation activity. The results indicate that the decrease in the efficiency of extraction of calcein molecules from Chinese hamster ovary cells, as well as cell viability, is associated with MB cavitation activity and can be accurately predicted using inertial cavitation doses up to 0.18 V × s (R 2  > 0.9, p cavitation in the sono-extraction process. To our knowledge, this study is the first to (i) investigate small molecule extraction from cells via sonoporation and (ii) relate the extraction process to the quantitative characteristics of MB cavitation acoustic spectra. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  7. A new formulation of controlled release amitriptyline pellets and its in vivo/in vitro assessments.

    Science.gov (United States)

    Park, Eun-Seok; Lee, Dong-Soo; Kwon, Seok-Young; Chi, Sang-Cheol

    2003-07-01

    Controlled-release amitriptyline pellets (ATP) were formulated and its oral bioavailability was assessed in human volunteers after oral administration under fasting conditions. Core pellets were prepared using a CF granulator by two different methods (powder layering and solvent spraying) and coated with Eudragit RS or RL 100. Physical characteristics and dissolution rates of core pellets and coated pellets were evaluated to optimize the formulation. Powder layering method resulted in a better surface morphology than solvent spraying method. However, physical properties of the products were poorer when prepared by powder layering method with respect to hardness, friability and density. The dissolution profile of amitriptyline coated with Eudragit RS 100 was comparable to that of commercially available amitriptyline enteric-coated pellets (Saroten retard). After the oral administration of both products at the dose of 50 mg, the mean maximum concentrations (Cmax) were 36.4 and 29.7 ng/mL, and the mean areas under the concentration-time curve (AUC(0-96)) were 1180.2 and 1010.7 ng.h/mL for ATP and Saroten retard, respectively. The time to reach the maximum concentrations (Tmax) was 6 h for both formulations. Statistical evaluation suggested that ATP was bioequivalent to Saroten retard.

  8. The role of gonadotropin-releasing hormone antagonists in in vitro fertilization.

    Science.gov (United States)

    Diedrich, K; Ludwig, M; Felberbaum, R E

    2001-09-01

    Gonadotropin-releasing hormone (GnRH)-antagonists can suppress the pituitary hormone secretion completely within a few hours, allowing the avoidance of premature luteinization within controlled ovarian hyperstimulation (COH) for assisted reproductive technologies (ART) by midcycle administration. Two different protocols were described, which were widely used in COH in several phase II and III studies as well as in clinical practice since the GnRH-antagonists Cetrorelix (Cetrotidesound recording copyright sign; Serono International S.A., Geneva, Switzerland) and Ganirelix (Orgalutansound recording copyright sign, Antagonsound recording copyright sign; Organon, Oss, The Netherlands) are available on the market. Cetrorelix was applied in single- and multiple-dose protocols; Ganirelix was used until now only according to the multiple-dose protocol. Fertilization rates of >60% as well as clinical pregnancy rates of about 30% per transfer sound most promising. Estradiol secretion is not compromised by the GnRH-antagonists using recombinant follicle-stimulating hormone (FSH) for COH. The incidence of a premature leutinizing hormone (LH) surge is far below 2% while the pituitary response remains preserved, allowing the induction of ovulation by GnRH or GnRH-agonists. However, luteal phase support remains mandatory. The incidence of severe ovarian hyperstimulation syndrome (OHSS) seems to be lower under antagonist treatment than in the long agonistic protocol. Treatment time is significantly shortened. Without any doubt GnRH-antagonists have the potential to become the new standard for controlled ovarian hyperstimulation.

  9. Effects of Amanita phalloides toxins on insulin release: in vivo and in vitro studies.

    Science.gov (United States)

    De Carlo, Eugenio; Milanesi, Anna; Martini, Chiara; Maffei, Pietro; Tamagno, Gianluca; Parnigotto, Pier Paolo; Scandellari, Cesare; Sicolo, Nicola

    2003-08-01

    The clinical picture of Amanita phalloides poisoning includes hypoglycaemia, usually related to hepatic damage. In fact, Amanita toxins induce hepatic glycogen depletion in humans and animals. However, in animals morphological changes of pancreatic beta cells are reported, suggesting that an alteration of insulin secretion might be involved in the pathogenesis of hypoglycaemia. Therefore, we determined fasting glucose, insulin and C-peptide levels in ten patients intoxicated by Amanita phalloides and in ten control subjects. Fasting blood samples were drawn on 3 consecutive days, beginning 48-72 h after mushroom ingestion, and glucose, insulin and C-peptide concentrations were determined by routine methods. Serum glucose concentrations did not differ between poisoned subjects and controls, whereas insulin and C-peptide concentrations were significantly higher in poisoned subjects ( PAmanita toxins might play a role in the clinical context of Amanita poisoning. We demonstrate, for the first time, that alpha-amanitin induces insulin release and may exert a cytotoxic effect on beta cells.

  10. Impact of pore characteristics of silica materials on loading capacity and release behavior of ibuprofen

    Energy Technology Data Exchange (ETDEWEB)

    Numpilai, Thanapha [Department of Chemical Engineering, Faculty of Engineering, Kasetsart University, Bangkok 10900 (Thailand); Muenmee, Suthaporn [Department of Chemical Engineering, Faculty of Engineering, Kasetsart University, Bangkok 10900 (Thailand); Center for Advanced Studies in Nanotechnology and Its Applications in Chemical Food and Agricultural Industries, Kasetsart University, Bangkok 10900 (Thailand); Witoon, Thongthai, E-mail: fengttwi@ku.ac.th [Department of Chemical Engineering, Faculty of Engineering, Kasetsart University, Bangkok 10900 (Thailand); Center for Advanced Studies in Nanotechnology and Its Applications in Chemical Food and Agricultural Industries, Kasetsart University, Bangkok 10900 (Thailand); NANOTEC-KU-Center of Excellence on Nanoscale Materials Design for Green Nanotechnology, Kasetsart University, Bangkok 10900 (Thailand)

    2016-02-01

    Impact of pore characteristics of porous silica supports on loading capacity and release behavior of ibuprofen was investigated. The porous silica materials and ibuprofen-loaded porous silica materials were thoroughly characterized by N{sub 2}-sorption, thermal gravimetric and derivative weight analyses (TG-DTW), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), transmission electron microscope (TEM) to determine the physical properties of materials, amount of ibuprofen adsorbed and position of ibuprofen. The detailed characterization reveals that the ibuprofen molecules adsorbed inside the mesopores. Increasing the mesopore size from 5 nm to 10 nm increased the ibuprofen loading from 0.74 to 0.85 mmol/g, respectively. Incorporation of macropore into the structure of porous silica materials enhanced the ibuprofen loading capacity of 11.8–20.3%. The ibuprofen-loaded bimodal meso-macroporous silica materials exhibited the highest dissolution of 92 wt.% within an hour. The ibuprofen particles deposited on the external surface of the porous silica materials showed a lower dissolution rate than the ibuprofen adsorbed inside the mesopores due to the formation of ibuprofen crystalline. - Highlights: • Impacts of pore characteristics of supports on adsorption and release of ibuprofen • Increasing mesopore size increased the ibuprofen loading and dissolution rate. • Macropores reduced the diffusion pathway of ibuprofen and dissolution medium.

  11. Mechanical properties and tritium release behavior of neutron irradiated beryllium pebbles

    Energy Technology Data Exchange (ETDEWEB)

    Ishitsuka, E.; Kawamura, H. [Japan Atomic Energy Research Inst., Oarai, Ibaraki (Japan). Oarai Research Establishment; Terai, T.; Tanaka, S. [Tokyo Univ. (Japan)

    2000-04-01

    Beryllium pebbles are expected as a neutron multiplier of a fusion reactor blanket. Mechanical properties and tritium release behaviors of the neutron irradiated beryllium pebbles were tested as a post irradiation examination (PIE). Two kinds of beryllium specimens (diameter:1 mm, grain size: about 0.5 mm), which were fabricated by the rotating electrode method (REM) and by the Mg reduction method (MRM), were irradiated with a total fast neutron fluence of 1.6 x 10{sup 22} n/cm{sup 2} (E>0.1 MeV) at 673, 773 and 873 K. The estimated helium concentration and dpa value were about 1 x 10{sup 3} appmHe and 10 dpa, respectively. Compression tests were carried out at the room temperature in the Beryllium PIE facility of JMTR (Japan materials testing reactor) hot laboratory. Compression speed was 0.2 mm/min in ten tests for each specimen. From the results of compression test, no significant difference in the compression strength was observed between two kinds of beryllium pebbles. Additionally, it was clear that not only helium concentration but also dpa value was an important factor on the mechanical properties, because the compression strength of the high dpa specimens (10 dpa) was smaller than that of the low dpa specimens (6 dpa) with similar helium concentration (about 1 x 10{sup 3} appmHe). Also, the tritium release experiment will be carried out for these specimens, and results will be presented in this workshop. (orig.)

  12. Particulate matter-mediated release of long pentraxin 3 (PTX3) and vascular endothelial growth factor (VEGF) in vitro: Limited importance of endotoxin and organic content.

    Science.gov (United States)

    Herseth, J I; Volden, V; Bolling, A K

    2017-01-01

    Exposure to particulate matter (PM) is associated with adverse health effects, but it is still relatively unknown which role PM sources and physicochemical properties play in the observed effects. It was postulated that PM in vitro induces release of long pentraxin 3 (PTX3) and vascular endothelial growth factor (VEGF) and that endotoxin and organic compounds present in the PM regulate this release. A contact coculture of THP-1 human leukemia monocytes and A549 human adenocarcinoma alveolar pneumocytes was exposed to PM from Traffic, Wood, Diesel, and Quartz (10-40 µg/cm(2)) for 12-64 h to determine release of PTX3 and VEGF. The role of endotoxin and the organic fraction in the mediator release was assessed using polymyxin B sulfate and organic extracts, respectively. Finally, antagonists were used to investigate whether the early proinflammatory cytokines interleukin (IL)-1 and tumor necrosis factor (TNF)-α affected the PTX3 and VEGF release. All PM samples induced a time-dependent release of both PTX3 and VEGF. Traffic mediated the greatest release of PTX3, whereas Wood and Diesel were more potent inducers of VEGF. The endotoxin content did not markedly affect release of either mediator, while the organic fraction exerted no significant effect on VEGF release and limited influence on PTX3 release. In addition, the IL-1 and TNF-α agonists affected PTX3 release more strongly than VEGF release. In conclusion, the current data show a limited impact of endotoxin and organic compounds on PTX3 and VEGF release. Further, the observed differences in response patterns may point toward differential regulation of PM-mediated release of PTX3 and VEGF.

  13. Cryptotanshinone-Loaded Cerasomes Formulation: In Vitro Drug Release, in Vivo Pharmacokinetics, and in Vivo Efficacy for Topical Therapy of Acne

    Directory of Open Access Journals (Sweden)

    Ting Zuo

    2016-12-01

    Full Text Available Cerasomes (CS, evolved from liposomes, are novel drug-delivery systems that have potential medical application as carriers for drugs or active ingredients. Although many studies have been conducted on the pharmaceutical and physicochemical properties of CS, the role of CS in influencing the in vivo plasma and topical pharmacokinetics and efficacy of topical drug delivery remain unclear. In this context, we chose cryptotanshinone (CTS as a model drug for the preparation of CTS-CS by means of the ethanol injection method to investigate their in vitro/in vivo drug-release behavior and in vivo efficacy. (1 In in vitro studies, CTS-CS gel was proven to be capable of achieving a higher permeation rate and significant accumulation in the dermis of isolated rat skin using Franz diffusion cells. (2 In in vivo studies, microdialysis experiments used to measure the plasma and topical pharmacokinetics demonstrated that the CS had a high drug concentration, short peak time, and slow elimination. Meanwhile, the plasma area under the concentration–time curve of CTS-CS gel was less than half that for the CTS gel in 12 h, which indicates that the drug bioavailability dramatically increased in the experiments. (3 In in vivo efficacy studies, we duplicated a rat acne model and performed antiacne efficacy experiments. The CTS-CS gel improved the antiacne efficacy compared to that of ordinary CTS gel. Moreover, it inhibited the expression of interleukin-1α and androgen receptors effectively. All of these results show that CTS-CS gel has significant potential for the treatment of acne induced by inflammation and excessive secretion of androgen, suggesting that CS formulations were designed as a good therapeutic option for skin disease.

  14. In-vitro trials to ascertain sustained release efficacy of assembly pheromone micro particles for the control of brown dog tick, Rhipicephalus sanguineus.

    Science.gov (United States)

    Bhoopathy, Dhivya; Bhaskaran Ravi, Latha

    2017-12-01

    Sustained release micro particles were prepared incorporating assembly pheromone and deltamethrin. Two natural polymers, namely, chitosan and calcium alginate and a synthetic polymer, poly-ε-caprolactone were used for encapsulating the assembly pheromone-acaricide combination. The micro particles were subjected to in vitro evaluation freshly after preparation and then at monthly intervals to assess their sustained release efficacy. The response of the unfed stages of dog tick, Rhipicephalus sanguineus to fresh and aged micro particles was assessed and results were recorded. The micro particles were found to release assembly pheromone in a sustained manner up to 2 months of study period.

  15. In vitro drug release of natamycin from β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin-functionalized contact lens materials.

    Science.gov (United States)

    Phan, Chau-Minh; Subbaraman, Lakshman N; Jones, Lyndon

    2014-01-01

    The antifungal agent natamycin can effectively form inclusion complexes with beta-cyclodextrin (β-CD) and 2-hydroxypropyl-β-cyclodextrin (HP-βCD) to improve the water solubility of natamycin by 16-fold and 152-fold, respectively (Koontz, J. Agric. Food. Chem. 2003). The purpose of this study was to develop contact lens materials functionalized with methacrylated β-CD (MβCD) and methacrylated HP-βCD (MHP-βCD), and to evaluate their ability to deliver natamycin in vitro. Model conventional hydrogel (CH) materials were synthesized by adding varying amounts of MβCD and MHP-βCD (0, 0.22, 0.44, 0.65, 0.87, 1.08% of total monomer weight) to a monomer solution containing 2-hydroxyethyl methacrylate (HEMA). Model silicone hydrogel (SH) materials were synthesized by adding similar concentrations of MβCD and MHP-βCD to N,N-dimethylacrylamide (DMAA)/10% 3-methacryloxypropyltris(trimethylsiloxy)silane (TRIS). The gels were cured with UV light, washed with ethanol and then, hydrated for 24 h (h). The model materials were then incubated with 2 mL of 100 μg/mL of natamycin in phosphate buffered saline (PBS) pH 7.4 for 48 h at room temperature. The release of natamycin from these materials in 2 mL of PBS, pH 7.4 at 32 ± 2 °C was monitored using UV-vis spectrophotometry at 304 nm over 24 h. For both CH and SH materials, functionalization with MβCD and MHP-βCD improved the total amount of drugs released up to a threshold loading concentration, after which further addition of methacrylated CDs decreased the amount of drugs released (p DMAA/10% TRIS materials released significantly more drug than HEMA materials (p DMAA/10% TRIS gels (p DMAA/10% TRIS materials functionalized with MHP-βCD are more effective than those functionalized with MβCD to deliver natamycin.

  16. Dentate gyrus-CA3 glutamate release/NMDA transmission mediates behavioral despair and antidepressant-like responses to leptin.

    Science.gov (United States)

    Wang, X; Zhang, D; Lu, X-Y

    2015-04-01

    Compelling evidence supports the important role of the glutamatergic system in the pathophysiology of major depression and also as a target for rapid-acting antidepressants. However, the functional role of glutamate release/transmission in behavioral processes related to depression and antidepressant efficacy remains to be elucidated. In this study, glutamate release and behavioral responses to tail suspension, a procedure commonly used for inducing behavioral despair, were simultaneously monitored in real time. The onset of tail suspension stress evoked a rapid increase in glutamate release in hippocampal field CA3, which declined gradually after its offset. Blockade of N-methyl-D-aspartic acid (NMDA) receptors by intra-CA3 infusion of MK-801, a non-competitive NMDA receptor antagonist, reversed behavioral despair. A subpopulation of granule neurons that innervated the CA3 region expressed leptin receptors and these cells were not activated by stress. Leptin treatment dampened tail suspension-evoked glutamate release in CA3. On the other hand, intra-CA3 infusion of NMDA blocked the antidepressant-like effect of leptin in reversing behavioral despair in both the tail suspension and forced swim tests, which involved activation of Akt signaling in DG. Taken together, these results suggest that the DG-CA3 glutamatergic pathway is critical for mediating behavioral despair and antidepressant-like responses to leptin.

  17. Dentate gyrus–CA3 glutamate release/NMDA transmission mediates behavioral despair and antidepressant-like responses to leptin

    Science.gov (United States)

    Wang, Xuezhen; Zhang, Di; Lu, Xin-Yun

    2014-01-01

    Compelling evidence supports the important role of the glutamatergic system in the pathophysiology of major depression and also as a target for rapid-acting antidepressants. However, the functional role of glutamate release/transmission in behavioral processes related to depression and antidepressant efficacy remains to be elucidated. In this study, glutamate release and behavioral responses to tail suspension, a procedure commonly used for inducing behavioral despair, were simultaneously monitored in real time. The onset of tail suspension stress evoked a rapid increase in glutamate release in hippocampal field CA3, which declined gradually after its offset. Blockade of NMDA receptors by intra-CA3 infusion of MK-801, a non-competitive NMDA receptor antagonist, reversed behavioral despair. The CA3 was innervated by granule neurons expressing the leptin receptor (LepRb) in the dentate gyrus (DG), representing a subpopulation of granule neurons that were devoid of stress-induced activation. Leptin treatment dampened tail suspension-evoked glutamate release in CA3. On the other hand, intra-CA3 infusion of NMDA blocked the antidepressant-like effect of leptin in reversing behavioral despair in both the tail suspension and forced swim tests, which involved activation of Akt signaling in DG. Together, these results suggest that the DG-CA3 glutamatergic pathway is critical for mediating behavioral despair and antidepressant-like responses to leptin. PMID:25092243

  18. Improved Mechanical Properties and Sustained Release Behavior of Cationic Cellulose Nanocrystals Reinforeced Cationic Cellulose Injectable Hydrogels.

    Science.gov (United States)

    You, Jun; Cao, Jinfeng; Zhao, Yanteng; Zhang, Lina; Zhou, Jinping; Chen, Yun

    2016-09-12

    Polysaccharide-based injectable hydrogels have several advantages in the context of biomedical use. However, the main obstruction associated with the utilization of these hydrogels in clinical application is their poor mechanical properties. Herein, we describe in situ gelling of nanocomposite hydrogels based on quaternized cellulose (QC) and rigid rod-like cationic cellulose nanocrystals (CCNCs), which can overcome this challenge. In all cases, gelation immediately occurred with an increase of temperature, and the CCNCs were evenly distributed throughout the hydrogels. The nanocomposite hydrogels exhibited increasing orders-of-magnitude in the mechanical strength, high extension in degradation and the sustained release time, because of the strong interaction between CCNCs and QC chains mediated by the cross-linking agent (β-glycerophosphate, β-GP). The results of the in vitro toxicity and in vivo biocompatibility tests revealed that the hydrogels did not show obvious cytotoxicity and inflammatory reaction to cells and tissue. Moreover, DOX-encapsulated hydrogels were injected beside the tumors of mice bearing liver cancer xenografts to assess the potential utility as localized and sustained drug delivery depot systems for anticancer therapy. The results suggested that the QC/CCNC/β-GP nanocomposite hydrogels had great potential for application in subcutaneous and sustained delivery of anticancer drug to increase therapeutic efficacy and improve patient compliance.

  19. Synthesis, characterization, swelling and drug release behavior of semi-interpenetrating network hydrogels of sodium alginate and polyacrylamide.

    Science.gov (United States)

    Samanta, Himadri Sekhar; Ray, Samit Kumar

    2014-01-01

    Several semi interpenetrating network (SIPN) type hydrogels were synthesized by in-situ free radical crosslink copolymerization of acrylamide and crosslinker N,N'-methylene bisacrylamide (MBA) in aqueous solution of sodium alginate (SA).These SIPN hydrogels were characterized by FTIR, NMR SEM, DTA-TGA, XRD, PZC and also by swelling characteristics and network parameters. Adsorption (loading) and release of acetaminophen drug were studied with these hydrogels. Solution pH, crosslinker concentration and monomer to SA weight ratio of the hydrogels were found to have a strong effect on adsorption and in vitro release profile of the drug from the gel matrix. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. A Novel Active Targeting Preparation, Vinorelbine Tartrate (VLBT Encapsulated by Folate-Conjugated Bovine Serum Albumin (BSA Nanoparticles: Preparation, Characterization and in Vitro Release Study

    Directory of Open Access Journals (Sweden)

    Xinyang Yu

    2012-11-01

    Full Text Available Vinorelbine tartrate (VLBT, as a kind of high hydrophilic and temperature-induced degradation drug, was prepared into nanoparticles by a desolvation procedure. Bovine serum albumin (BSA, as a drug carrier, was stabilized by chemical cross-linking with glutaraldehyde. Firstly, the optimization process of preparing VLBT-loaded BSA nanoparticles (VLBT-BSANPs was accomplished using response surface methodology (RSM by desolvation. Then VLBT-BSANPs were conjugated with folate, namely Fa-BSANPs-VLBT. Hence targeting drug carrier delivery system loading VLBT was produced. In this study, the characteristics of the nanoparticles, such as the amount of folate conjugation, surface morphology, surface chemistry, physical status of VLBT in Fa-BSANPs-VLBT, stability of Fa-BSANPs-VLBT with mannitol and in vitro drug release behavior were all investigated. The VLBT-BSANPs were obtained under optimum conditions, with a mean particle size (MPS of 155.4 nm and a zeta potential (ZP of −32.97 mV at a pH value of 5.4. Drug loading efficiency (DLE and drug entrapment efficiency (DEE of this obtained drug were approximately 45.6% and 90.6%, respectively.

  1. Self-soothing behaviors with particular reference to oxytocin release induced by non-noxious sensory stimulation

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    Kerstin eUvnäs-Moberg

    2015-01-01

    Full Text Available Oxytocin, a hypothalamic nonapeptide, is linked to increased levels of social interaction, well-being and anti-stress effects. The effects of oxytocin that is released by sensory stimulation during different kinds of interactive behaviors are often underestimated or even forgotten. In fact, many of the positive effects caused during interaction, such a wellbeing, stress reduction and even health promotion, are indeed linked to oxytocin released in response to activation of various types of sensory nerves. Oxytocin is released in response to activation of sensory nerves during labor, breastfeeding and sexual activity. In addition oxytocin is released in response to low intensity stimulation of the skin, e.g. in response to touch, stroking, warm temperature etc . Consequently oxytocin is not only released during interaction between mothers and infants, but also during positive interaction between adult or between humans and animals. Finally oxytocin is also released in response to suckling and food intake. Oxytocin released in the brain in response to sensory stimulation as a consequence of these types of interactive behaviors, contributes to every day wellbeing and ability to handle stress. Food intake or sex may be used or even abused to achieve oxytocin-linked wellbeing and stress relief to compensate for lack of good relationships or when the levels of anxiety are high. The present review article will summarize the role played by oxytocin released by sensory (in particular somatosensory stimulation, during various kinds of interactive behaviors. Also the fact that the anti-stress effects of oxytocin are particularly strong when oxytocin is released in response to low intensity stimulation of the skin will be highlighted.

  2. Entrapment of proteins and peptides in chitosan-polyphosphoric acid hydrogel beads: A new approach to achieve both high entrapment efficiency and controlled in vitro release.

    Science.gov (United States)

    Yuan, Dongdong; Jacquier, Jean Christophe; O'Riordan, E Dolores

    2018-01-15

    Bovine serum albumin (BSA), whey protein isolate (WPI), insulin and a casein hydrolysate were entrapped in chitosan-polyphosphoric acid (PPA) beads. The in vitro release of protein from the beads in simulated gastric fluid (SGF, pH 3) and simulated intestinal fluid (SIF, pH 7) was evaluated. High entrapment efficiencies were achieved for intact proteins (>95% in all cases) but entrapment was lower for the casein hydrolysate (circa 50%), possibly indicating a physical or steric entrapment of the proteins in these chitosan-PPA beads. Inhibited release of BSA, in both SGF and SIF, was achieved with low PPA concentration. Insulin and WPI were effectively retained in SGF and gradually released in SIF. Peptides from casein hydrolysate were partially (circa 35%) but quickly released in SGF with no further release in SIF. Overall, these results indicate that chitosan-PPA beads show potential for lower gastrointestinal delivery of bioactive protein material. Copyright © 2017. Published by Elsevier Ltd.

  3. In vitro regulation of LH biosynthesis and release by GnRH and estradiol

    Energy Technology Data Exchange (ETDEWEB)

    Ramey, J.W.

    1986-01-01

    Anterior pituitaries were taken from female rats at random stages of the estrous cycle, enzymatically dispersed, and cultured for 48h in steroid-free ..cap alpha..-modified Eagles medium followed by 24h in fresh medium +/- estradiol (E/sub 2/). The pituitary cells were then incubated in fresh medium containing radiolabeled precursors +/- gonadotropin releasing hormone (GnRH). Radioactive precursor incorporation into LH was determined by immuno-precipitation. The dose-dependent effects of E/sub 2/(10/sup -11/ to 10/sup -8/M) on /sup 3/H-glucosamine (/sup 3/H-Gln) and /sup 35/S-methionine (/sup 35/S-Met) incorporation into LH +/- 1 nM GnRH (4h) were investigated. GnRH (10/sup -9/M) and E/sub 2/ (all doses) significantly increased total /sup 3/H-Gln LH. Moreover, E/sub 2/ at 10/sup -9/M and 10/sup -8/M significantly enhanced GnRH stimulated LH glycosylation. In contrast, addition of GnRH and/or E/sub 2/ did not significantly increase /sup 35/S-Met incorporation into LH over a 4h period. The effects of various GnRH concentrations (10/sup -11/ to 10/sup -9/M; 8h) +/- E/sub 2/ (0.05 nM) on /sup 3/H-Gln LH and /sup 35/S-Met LH production were also investigated. In the absence of E/sub 2/, only 10/sup -9/M GnRH was effective in increasing total /sup 3/H-Gln LH and /sup 35/S-Met LH synthesis. However, in the presence of E/sub 2/, all concentrations of GnRH stimulated LH synthesis with /sup 3/H-Gln LH production responding in a dose related manner whereas /sup 35/S-Met LH production was maximally stimulated at all doses of GnRH. In the final series of experiments, pituitary cells previously exposed to estradiol were incubated for 4 h in normal calcium or low calcium medium containing /sup 3/H-Gln or /sup 35/S-Met +/- GnRH. Removal of extracellular calcium completely inhibited GnRH stimulated /sup 3/H-Gln LH and /sup 35/S-Met LH production.

  4. Evaluation of an in vitro sulphidoleukotriene release test for diagnosis of insect bite hypersensitivity in horses.

    Science.gov (United States)

    Baselgia, S; Doherr, M G; Mellor, P; Torsteinsdottir, S; Jermann, T; Zurbriggen, A; Jungi, T; Marti, E

    2006-01-01

    Insect bite hypersensitivity (IBH) is an IgE-mediated allergic dermatitis caused by bites of Culicoides and Simulium species, and improved means of diagnosis are required. The cellular antigen simulation test (CAST) with C. nubeculosus and S. vittatum extracts was assessed in a population of IBH-affected and healthy horses. Variations in test results over a one year period and possible cross-reactivity between different insect extracts was studied. A total of 314 mature horses were studied using the CAST. Influence of severity of clinical signs, gender and age were evaluated, and 32 horses were tested repeatedly over one year. The kappa reliability test was used to assess agreement of the test results with different insect extracts. Horses with IBH had significantly higher sLT release than controls with C. nubeculosus and S. vittatum. The highest diagnostic sensitivity and specificity levels were attained when using adult C. nubeculosus extracts with the CAST (78% and 97%, respectively), suggesting that most horses with IBH are sensitised against Culicoides allergens. A proportion of IBH-affected horses was found to be sensitised to allergens of Simulium spp. in addition to those of C. nubeculosus. The CAST with C. nubeculosus had positive and negative predictive values > or = 80% for a true prevalence of IBH of 12-52%. In the follow-up study, the proportion of IBH-affected horses with a positive test result ranged from 90% in November to 68% in March. Severity of clinical signs or age did not influence test results significantly. However, IBH-affected males achieved significantly more positive test results than IBH-affected females. The CAST with adult C. nubeculosus has high specificity and good sensitivity for diagnosis of IBH. Horses with IBH are mainly sensitised to Culicoides allergens, and some horses are additionally also sensitised to allergens in Simulium spp. The CAST is likely to be a useful test for diagnosis of IBH, even allowing the identification of

  5. Hydrogen sulfide-releasing aspirin modulates xenobiotic metabolizing enzymes in vitro and in vivo.

    Science.gov (United States)

    Chattopadhyay, Mitali; Kodela, Ravinder; Nath, Niharika; Street, Cherease R; Velázquez-Martínez, Carlos A; Boring, Daniel; Kashfi, Khosrow

    2012-03-15

    The balance between phase-I carcinogen-activating and phase-II detoxifying xenobiotic metabolizing enzymes is critical to determining an individual's risk for cancer. We evaluated the effect of Hydrogen sulfide-releasing aspirin (HS-ASA) on xenobiotic metabolizing enzymes in HT-29 human colon and Hepa 1c1c7 mouse liver adenocarcinoma cells and in Wistar rats. HS-ASA inhibited the growth of HT-29 and Hepa 1c1c7 cells, with an IC(50) of 3.2 ± 0.3 μM and 4.2 ± 0.4 μM, respectively. The IC(50) for ASA in both cell lines was greater than 5000 μM at 24h. In these cell lines, HS-ASA caused a dose-dependent increase in activity and expression of the phase-II enzymes glutathione S-transferase (GST) and NAD(P)H:quinoneoxireductase (NQO1). It also caused an increase in UDP-glucuronosyltransferase (UGT) expression. The levels of CYP 1A1 a phase-I enzyme was increased by HS-ASA in both cell lines. Pretreatment of cells with NaF, an esterase inhibitor, abrogated the HS-ASA-mediated increases in NQO1 enzyme activity. HS-ASA increased the protein levels of the transcription factor Nrf2, which is a regulator of the phase-II enzymes. In vivo, HS-ASA at 100mg/kg/day had no effect on rat's weights; it induced a 3.4-fold and 1.4-fold increase in hepatic GST and NQO1 enzyme activities, respectively. GST and NQO1 protein levels were also increased. In contrast to that in cultured cells, CYP 1A1 protein levels were not altered in vivo. Therefore, HS-ASA induces phase-II enzymes, at least in part, through the action of H(2)S and by modulating Nrf2; these effects may be part of its mechanism of action against carcinogenesis. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Heparin-mimetic polyurethane hydrogels with anticoagulant, tunable mechanical property and controllable drug releasing behavior.

    Science.gov (United States)

    Chen, Yuan; Wang, Rui; Wang, Yonghui; Zhao, Weifeng; Sun, Shudong; Zhao, Changsheng

    2017-05-01

    In the present study, novel heparin-mimetic polyurethane hydrogels were prepared by introducing chemical crosslinked sulfated konjac glucomannan (SKGM). Scanning electron microscopy (SEM) results indicated that the introduction of SKGM and the increase of the molecular weight of diol segments could enlarge the pore sizes of the hydrogels. The swelling behavior corresponded with the SEM results, and the hydrogels could absorb more water after the modification. The modification also led to an improvement in the mechanical property. Meanwhile, the SKGM and the modified polyurethane hydrogels showed excellent hemocompatibility. The thromboplastin time of SKGM could reach up to 182.9s. Gentamycin sulfate (GS) was used as a model drug to be loaded into the hydrogels, and the loading amount was increased ca. 50% after the introduction of SKGM, thus resulting in high bactericidal efficiency. The results indicated that the introduction of SKGM and the alternation in the diol's molecular weight bestowed polyurethane hydrogels with promising properties of integrated blood-compatibility, mechanical properties and drug loading-releasing behavior. Therefore, the heparin-mimetic multifunctional polyurethane hydrogels have great potential to be used in biomedical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Brain Genomics Superstruct Project initial data release with structural, functional, and behavioral measures.

    Science.gov (United States)

    Holmes, Avram J; Hollinshead, Marisa O; O'Keefe, Timothy M; Petrov, Victor I; Fariello, Gabriele R; Wald, Lawrence L; Fischl, Bruce; Rosen, Bruce R; Mair, Ross W; Roffman, Joshua L; Smoller, Jordan W; Buckner, Randy L

    2015-01-01

    The goal of the Brain Genomics Superstruct Project (GSP) is to enable large-scale exploration of the links between brain function, behavior, and ultimately genetic variation. To provide the broader scientific community data to probe these associations, a repository of structural and functional magnetic resonance imaging (MRI) scans linked to genetic information was constructed from a sample of healthy individuals. The initial release, detailed in the present manuscript, encompasses quality screened cross-sectional data from 1,570 participants ages 18 to 35 years who were scanned with MRI and completed demographic and health questionnaires. Personality and cognitive measures were obtained on a subset of participants. Each dataset contains a T1-weighted structural MRI scan and either one (n=1,570) or two (n=1,139) resting state functional MRI scans. Test-retest reliability datasets are included from 69 participants scanned within six months of their initial visit. For the majority of participants self-report behavioral and cognitive measures are included (n=926 and n=892 respectively). Analyses of data quality, structure, function, personality, and cognition are presented to demonstrate the dataset's utility.

  8. In Vitro Release Kinetics and Transferrin Saturation Study of Intravenous Iron Sucrose Entrapped in Poly(ethylene glycol)-Assisted Silica Xerogel.

    Science.gov (United States)

    Jha, Jahnavi; Chakraborty, Suparna; Chaudhuri, Mahua Ghosh; Dey, Rajib

    2016-04-01

    The presence of labile iron fractions in intravenous iron supplements compromises their safety. Poly(ethylene glycol) (PEG)-assisted silica xerogel was evaluated as a potential drug carrier for iron sucrose with the purpose of limiting labile iron available for in vitro uptake by transferrin. The drug entrapped xerogels were synthesized by the sol-gel process with varying amounts of PEG. In vitro release studies were conducted in simulated body fluid (SBF) at 37 ± 0.02 °C (pH 7.4). The results indicated that the cumulative release percentage increased with the increase in the amount of PEG in the matrix. The biphasic release profile followed first-order kinetics for the first 6 h and Higuchi model for the remaining time (up to 168 h). The sample showing highest percentage of cumulative release (the xerogel with 16 % PEG) was used for in vitro transferrin saturation studies in contrast with the plain drug. The xerogel formulation exhibited 7.25 ± 0.4 % transferrin saturation in 180 min as compared to 12.89 ± 0.2 % for the raw drug. These results indicate that encapsulation of iron sucrose in PEG-assisted silica xerogel and subsequent sustained release from the matrix can improve the safety of the drug when presence of labile iron is a major concern.

  9. Influence of dissolution media composition on drug release and in-vitro/in-vivo correlation for paracetamol matrix tablets prepared with novel carbomer polymers.

    Science.gov (United States)

    Parojcić, J; Ethurić, Z; Jovanović, M; Ibrić, S; Jovanović, D

    2004-06-01

    The influence of dissolution media composition on drug release kinetics and in-vitro/in-vivo correlation (IVIVC) for hydrophilic matrix tablets based on Carbopol 971P and Carbopol 71G was investigated. A number of buffered and unbuffered media differing with respect to their pH value, ionic strength and ionic species was evaluated. The observed in-vitro drug release profiles were compared with the hypothetical drug release profiles in-vivo calculated by numerical deconvolution from the results of an in-vivo study. The obtained IVIVC plots were examined using linear and non-linear (proportional odds, proportional hazards and proportional reversed hazards) mathematical models. Although the studied sustained release agents were chemically identical, they exhibited pronounced differences in drug product behaviour both in-vitro and in-vivo. The use of non-linear modelling resulted in an improved level of correlation, especially in the case of Carbopol 71G matrices. The obtained results indicated the susceptibility of drug release kinetics and hence IVIVC in the case of anionic polymer matrices to media composition, and emphasized the need for thorough evaluation of applied media during the development of biorelevant dissolution methodology. Although the use of non-linear modelling could be advantageous, the need for a simple and meaningful non-linear relationship is pointed out. Copyright 2004 The Authors

  10. Controlled release of optimized electroporation enhances the transdermal efficiency of sinomenine hydrochloride for treating arthritis in vitro and in clinic

    Directory of Open Access Journals (Sweden)

    Feng S

    2017-06-01

    Full Text Available Shun Feng,1,* Lijun Zhu,1,* Zhisheng Huang,2 Haojia Wang,1 Hong Li,1 Hua Zhou,3 Linlin Lu,1 Ying Wang,1 Zhongqiu Liu,1,3 Liang Liu1,3 1International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 2Department of Acupuncture and Rehabilitation, Guangzhou Hospital of Integrated Traditional Chinese and Western Medicine, Guangzhou, Guangdong, 3State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, People’s Republic of China *These authors contributed equally to this work Abstract: Sinomenine hydrochloride (SH is an ideal drug for the treatment of rheumatoid arthritis and osteoarthritis. However, high plasma concentration of systemically administered SH can release histamine, which can cause rash and gastrointestinal side effects. Topical delivery can increase SH concentration in the synovial fluid without high plasma level, thus minimizing systemic side effects. However, passive diffusion of SH was found to be inefficient because of the presence of the stratum corneum layer. Therefore, an effective method is required to compensate for the low efficiency of SH passive diffusion. In this study, transdermal experiments in vitro and clinical tests were utilized to explore the optimized parameters for electroporation of topical delivery for SH. Fluorescence experiment and hematoxylin and eosin staining analysis were performed to reveal the mechanism by which electroporation promoted permeation. In vitro, optimized electroporation parameters were 3 KHz, exponential waveform, and intensity 10. Using these parameters, transdermal permeation of SH was increased by 1.9–10.1 fold in mice skin and by 1.6–47.1 fold in miniature pig skin compared with passive diffusion. After the electroporation stimulation, the intercellular intervals and epidermal cracks in the skin increased. In clinical tests, SH concentration in synovial fluid was 20

  11. Generating favorable growth factor and protease release profiles to enable extracellular matrix accumulation within an in vitro tissue engineering environment.

    Science.gov (United States)

    Zhang, Xiaoqing; Battiston, Kyle G; Labow, Rosalind S; Simmons, Craig A; Santerre, J Paul

    2017-05-01

    Tissue engineering (particularly for the case of load-bearing cardiovascular and connective tissues) requires the ability to promote the production and accumulation of extracellular matrix (ECM) components (e.g., collagen, glycosaminoglycan and elastin). Although different approaches have been attempted in order to enhance ECM accumulation in tissue engineered constructs, studies of underlying signalling mechanisms that influence ECM deposition and degradation during tissue remodelling and regeneration in multi-cellular culture systems have been limited. The current study investigated vascular smooth muscle cell (VSMC)-monocyte co-culture systems using different VSMC:monocyte ratios, within a degradable polyurethane scaffold, to assess their influence on ECM generation and degradation processes, and to elucidate relevant signalling molecules involved in this in vitro vascular tissue engineering system. It was found that a desired release profile of growth factors (e.g. insulin growth factor-1 (IGF-1)) and hydrolytic proteases (e.g. matrix-metalloproteinases 2, 9, 13 and 14 (MMP2, MMP9, MMP13 and MMP14)), could be achieved in co-culture systems, yielding an accumulation of ECM (specifically for 2:1 and 4:1 VSMC:monocyte culture systems). This study has significant implications for the tissue engineering field (including vascular tissue engineering), not only because it identified important cytokines and proteases that control ECM accumulation/degradation within synthetic tissue engineering scaffolds, but also because the established culture systems could be applied to improve the development of different types of tissue constructs. Sufficient extracellular matrix accumulation within cardiovascular and connective tissue engineered constructs is a prerequisite for their appropriate function in vivo. This study established co-culture systems with tissue specific cells (vascular smooth muscle cells (VSMCs)) and defined ratios of immune cells (monocytes) to investigate

  12. Influence of exogenous gonadotropin-releasing hormone on seasonal reproductive behavior of the coyote (Canis latrans).

    Science.gov (United States)

    Carlson, D A; Gese, E M

    2009-10-01

    Wild Canis species such as the coyote (C. latrans) express a suite of reproductive traits unusual among mammals, including perennial pair-bonds and paternal care of the young. Coyotes also are monestrous, and both sexes are fertile only in winter; thus, they depend upon social and physiologic synchrony for successful reproduction. To investigate the mutability of seasonal reproduction in coyotes, we attempted to evoke an out-of-season estrus in October using one of two short-acting gonadotropin-releasing hormone (GnRH) agents: (1) a GnRH analogue, deslorelin (6-D-tryptophan-9-(N-ethyl-L-prolinamide)-10-deglycinamide), 2.1mg pellet sc; or (2) gonadorelin, a GnRH (5-oxoPro-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-GlyNH(2)) porcine hypothalamic extract, 2.0 microg/kg im once daily for 3 consecutive days. A transient increase in serum concentrations of estradiol and progesterone (1 and 2 wk, respectively) was detected after treatment with deslorelin but not gonadorelin. Also, socio-sexual behaviors reminiscent of winter mating (including courtship, mate-guarding, precoital mounts, and copulatory ties) were observed among the deslorelin group. During the subsequent breeding season (January and February), however, preovulatory courtship behavior and olfactory sampling appeared suppressed; emergence of mounts and copulations were delayed in both deslorelin and gonadorelin treatment groups. Furthermore, whereas 8 of 12 females treated in October ovulated and produced healthy litters in the spring, 4 naïve coyotes failed to copulate or become pregnant. Thus, perturbation of hormones prior to ovulation in species with complex mating behaviors may disrupt critical intrapair relationships, even if fertility is not impaired physiologically.

  13. In vitro effect of low intensity laser on the cytotoxicity produced by substances released by bleaching gel

    Directory of Open Access Journals (Sweden)

    Caroline Maria Gomes Dantas

    2010-12-01

    Full Text Available This in vitro study aimed to analyze the effect of different parameters of phototherapy with low intensity laser on the viability of human dental pulp fibroblasts under the effect of substances released by bleaching gel. Cells were seeded into 96 wells plates (1 x 10³ cells/well and placed in contact with culture medium conditioned by a 35 % hydrogen peroxide bleaching gel for 40 minutes, simulating the clinical condition of the in-office bleaching treatment. Cells cultured in ideal growth conditions served as positive control group (PC, and the cells grown in conditioned medium and non-irradiated served as negative control group (NC. Cells grown in conditioned medium were submitted to a single irradiation with a diode laser (40 mW, 0.04 cm² emitting at visible red (660 nm; RL or near infrared (780 nm; NIR using punctual technique, in contact mode and energy densities of 4, 6 or 10 J/cm². The cell viability was analyzed through the MTT reduction assay immediately and 24 hours after the irradiation. The data was compared by ANOVA followed by the Tukey's test (p < 0.05. The cell viability increased significantly in 24 hours within each group. The PC presented cell viability significantly higher than NC in both experimental times. Only the NIR/10 J/cm² group presented cell viability similar to that of PC in 24 hours. The phototherapy with low intensity laser in defined parameters is able to compensate the cytotoxic effects of substances released by 35 % hydrogen peroxide bleaching gel.

  14. Leptin amplifies the action of thyrotropin-releasing hormone in the solitary nucleus: an in vitro calcium imaging study.

    Science.gov (United States)

    Rogers, Richard C; McDougal, David H; Hermann, Gerlinda E

    2011-04-18

    Leptin exerts a powerful permissive influence on neurogenic thermogenesis. During starvation and an absence of leptin, animals cannot produce thermogenic reactions to cold stress. However, thermogenesis is rescued by restoring leptin. We have previously observed a highly cooperative interaction between leptin and thyrotropin-releasing hormone [TRH] to activate hindbrain-generated thermogenic responses (Hermann et al., 2006). In vivo physiological studies (Rogers et al., 2009) suggested that the thermogenic impact of TRH in the hindbrain is amplified by the action of leptin through a leptin receptor-mediated production of phosphoinositol-trisphosphate [PIP3]. In turn, PIP3 can activate a tyrosine kinase whose target is the Src-SH2 regulatory site on the phospholipase C [PLC] complex. The TRH receptor signals through the PLC complex. Our immunohistochemical studies (Barnes et al., 2010) suggest that this transduction interaction between leptin and TRH occurs within neurons of the solitary nucleus [NST], though this interaction had not been verified. The present in vitro live cell calcium imaging study shows that while medial NST neurons are rarely activated by leptin alone, leptin pre-treatment significantly augments NST neurons' responsiveness to TRH. This leptin-mediated priming of NST neurons was uncoupled by pre-treatment with the phosphoinositide 3-kinase [PI3K] inhibitor [wortmannin], the phospholipase C inhibitor [U73122] and the Src-SH2 antagonist [PP2]. TTX did not eliminate the synergistic response of the agonists, thus the sensitization cannot be attributed to pre-synaptic mechanisms. It seems likely that NST neurons are involved in the leptin-mediated increase in BAT temperature by sensitizing the TRH-PLC-IP3-calcium release mechanism. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Rosiglitazone Suppresses In Vitro Seizures in Hippocampal Slice by Inhibiting Presynaptic Glutamate Release in a Model of Temporal Lobe Epilepsy.

    Directory of Open Access Journals (Sweden)

    Shi-Bing Wong

    Full Text Available Peroxisomal proliferator-activated receptor gamma (PPARγ is a nuclear hormone receptor whose agonist, rosiglitazone has a neuroprotective effect to hippocampal neurons in pilocarpine-induced seizures. Hippocampal slice preparations treated in Mg2+ free medium can induce ictal and interictal-like epileptiform discharges, which is regarded as an in vitro model of N-methyl-D-aspartate (NMDA receptor-mediated temporal lobe epilepsy (TLE. We applied rosiglitazone in hippocampal slices treated in Mg2+ free medium. The effects of rosiglitazone on hippocampal CA1-Schaffer collateral synaptic transmission were tested. We also examined the neuroprotective effect of rosiglitazone toward NMDA excitotoxicity on cultured hippocampal slices. Application of 10 μM rosiglitazone significantly suppressed amplitude and frequency of epileptiform discharges in CA1 neurons. Pretreatment with the PPARγ antagonist GW9662 did not block the effect of rosiglitazone on suppressing discharge frequency, but reverse the effect on suppressing discharge amplitude. Application of rosiglitazone suppressed synaptic transmission in the CA1-Schaffer collateral pathway. By miniature excitatory-potential synaptic current (mEPSC analysis, rosiglitazone significantly suppressed presynaptic neurotransmitter release. This phenomenon can be reversed by pretreating PPARγ antagonist GW9662. Also, rosiglitazone protected cultured hippocampal slices from NMDA-induced excitotoxicity. The protective effect of 10 μM rosiglitazone was partially antagonized by concomitant high dose GW9662 treatment, indicating that this effect is partially mediated by PPARγ receptors. In conclusion, rosiglitazone suppressed NMDA receptor-mediated epileptiform discharges by inhibition of presynaptic neurotransmitter release. Rosiglitazone protected hippocampal slice from NMDA excitotoxicity partially by PPARγ activation. We suggest that rosiglitazone could be a potential agent to treat patients with TLE.

  16. Withania somnifera aqueous extract facilitates the expression and release of GnRH: In vitro and in vivo study.

    Science.gov (United States)

    Kataria, Hardeep; Gupta, Muskan; Lakhman, Sukhwinder; Kaur, Gurcharan

    2015-10-01

    Ashwagandha (Withania somnifera) has a long history in traditional medicines as an aphrodisiac. It has been known to influence sexual behaviour in animal models but mechanism of action is still unknown. The present study was aimed to investigate the mechanisms by which Ashwagandha extract exert its gonadotropic activities. Due to the complexity of neuroendocrine pathways, there are limited in vitro models available despite the strong demand for such systems to study and predict neuroendocrine effects of chemicals or natural products. Immortalized rat hypothalamic GnV-3 cell line was investigated as a model to screen for neuroendocrine effects of Ashwagandha extract. GnV-3 cells were cultured under different media conditions and evaluated after treatment with Ashwagandha water extract, for GnRH expression and release by immunostaining and ELISA respectively. These cells acquired differentiated morphology, characteristic shape displayed by preoptic GnRH neurons in vivo. In addition, GnV-3 cells exhibited upregulation of plasticity related polysialylated neural cell adhesion molecule (PSA-NCAM) and mature dendrite marker microtubule associated protein (MAP2) as well as GnRH expression and release. Chloroform fraction of the extract proved to exhibit all the bioactive properties as it induced differentiation and upregulated GnRH and MAP2 expression in GnV-3 cells, similar to Ashwagandha extract. Withanone and Withaferin A were found to be present in ASH-WEX and chloroform fraction while Withanone came out to be the major constituent of chloroform fraction. The preliminary in vivo studies in adult male animals showed that ASH-WEX was able to upregulate the GnRH levels although non-significantly. Taken together, this data demonstrate significant morphological and physiological changes in GnV-3 cells after treatment with Ashwagandha extract and may suggest the potential beneficial effects of Ashwagandha on reproductive functions in vivo. Copyright © 2015 Elsevier Ltd

  17. Improvement of penile erection, sperm count and seminal fructose levels in vivo and nitric oxide release in vitro by ayurvedic herbs.

    Science.gov (United States)

    Thakur, M; Thompson, D; Connellan, P; Deseo, M A; Morris, C; Dixit, V K

    2011-08-01

    In the present study, the effect of four Vajikaran Rasayana herbs on penile erection, sperm count, seminal fructose content in vivo and nitric oxide (NO) release in vitro was assessed. Lyophilised aqueous extracts of Asparagus racemosus Willd. (AR), Chlorophytum borivilianum Sant. F. (CB), Curculigo orchioides Gaertn. (CO), and Dactylorhiza hatagirea (D. Don) Soo (DH) were orally administered at 100 mg/kg body weight to Wistar strain male albino rats. Penile erection index and sperm count were determined by visual observation; the seminal fructose concentration was measured spectrophotometrically using resorcinol reagent; and NO release was assessed in a mouse macrophage cell line (RAW264) spectrophotometrically using a commercial Griess reagent kit. Penile erection index, sperm count, seminal fructose concentration and in vitro NO release were the parameters measured. A significant effect on the sperm count, seminal fructose content and penile erection index was observed upon treatment with the extracts. The effect of extracts on inducible NO release in vitro directly correlated with the enhanced erectile function in vivo. The aphrodisiac claims attributed to the four Vajikaran Rasayana herbs were tested and a distinctive effect of all extracts tested was observed, with C. borivilianum showing a highly significant response for all parameters measured in vivo and in vitro. The present study also provides a good correlation between the in vivo improvement of penile erection and in vitro NO releasing activity of the extracts. Increase in seminal fructose levels and sperm count further validates the role of these herbs in improving reproductive function. © 2011 Blackwell Verlag GmbH.

  18. Effect of processing on polyamine content and bioactive peptides released after in vitro gastrointestinal digestion of infant formulas.

    Science.gov (United States)

    Gómez-Gallego, C; Recio, I; Gómez-Gómez, V; Ortuño, I; Bernal, M J; Ros, G; Periago, M J

    2016-02-01

    This study examined the influence of processing on polyamines and peptide release after the digestion of a commercial infant formula designed for children during the first months of life. Polyamine oxidase activity was not suppressed during the manufacturing process, which implicates that polyamine concentrations were reduced over time and during infant formula self-life. In gel electrophoresis, in vitro gastrointestinal digestion of samples with reduced amount of enzymes and time of digestion shows an increase in protein digestibility, reflected in the increase in nonprotein nitrogen after digestion and the disappearance of β-lactoglobulin and α-lactalbumin bands in gel electrophoresis. Depending on the sample, between 22 and 87 peptides were identified after gastrointestinal digestion. A peptide from β-casein f(98-105) with the sequence VKEAMAPK and antioxidant activity appeared in all of the samples. Other peptides with antioxidant, immunomodulatory, and antimicrobial activities were frequently found, which could have an effect on infant health. The present study confirms that the infant formula manufacturing process determines the polyamine content and peptidic profile after digestion of the infant formula. Because compositional dissimilarity between human milk and infant formula in polyamines and proteins could be responsible for some of the differences in health reported between breast-fed and formula-fed children, these changes must be taken into consideration because they may have a great effect on infant nutrition and development. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  19. Schwann cells are activated by ATP released from neurons in an in vitro cellular model of Miller Fisher syndrome.

    Science.gov (United States)

    Rodella, Umberto; Negro, Samuele; Scorzeto, Michele; Bergamin, Elisanna; Jalink, Kees; Montecucco, Cesare; Yuki, Nobuhiro; Rigoni, Michela

    2017-05-01

    The neuromuscular junction is exposed to different types of insult, including mechanical trauma, toxins and autoimmune antibodies and, accordingly, has retained through evolution a remarkable ability to regenerate. Regeneration is driven by multiple signals that are exchanged among the cellular components of the junction. These signals are largely unknown. Miller Fisher syndrome is a variant of Guillain-Barré syndrome caused by autoimmune antibodies specific for epitopes of peripheral axon terminals. Using an animal model of Miller Fisher syndrome, we recently reported that a monoclonal anti-polysialoganglioside GQ1b antibody plus complement damages nerve terminals with production of mitochondrial hydrogen peroxide, which activates Schwann cells. Several additional signaling molecules are likely to be involved in the activation of the regeneration program in these cells. Using an in vitro cellular model consisting of co-cultured primary neurons and Schwann cells, we found that ATP is released by neurons injured by the anti-GQ1b antibody plus complement. Neuron-derived ATP acts as an alarm messenger for Schwann cells, where it induces the activation of intracellular pathways, including calcium signaling, cAMP and CREB, which, in turn, produce signals that promote nerve regeneration. These results contribute to defining the cross-talk taking place at the neuromuscular junction when it is attacked by anti-gangliosides autoantibodies plus complement, which is crucial for nerve regeneration and is also likely to be important in other peripheral neuropathies. © 2017. Published by The Company of Biologists Ltd.

  20. Schwann cells are activated by ATP released from neurons in an in vitro cellular model of Miller Fisher syndrome

    Directory of Open Access Journals (Sweden)

    Umberto Rodella

    2017-05-01

    Full Text Available The neuromuscular junction is exposed to different types of insult, including mechanical trauma, toxins and autoimmune antibodies and, accordingly, has retained through evolution a remarkable ability to regenerate. Regeneration is driven by multiple signals that are exchanged among the cellular components of the junction. These signals are largely unknown. Miller Fisher syndrome is a variant of Guillain–Barré syndrome caused by autoimmune antibodies specific for epitopes of peripheral axon terminals. Using an animal model of Miller Fisher syndrome, we recently reported that a monoclonal anti-polysialoganglioside GQ1b antibody plus complement damages nerve terminals with production of mitochondrial hydrogen peroxide, which activates Schwann cells. Several additional signaling molecules are likely to be involved in the activation of the regeneration program in these cells. Using an in vitro cellular model consisting of co-cultured primary neurons and Schwann cells, we found that ATP is released by neurons injured by the anti-GQ1b antibody plus complement. Neuron-derived ATP acts as an alarm messenger for Schwann cells, where it induces the activation of intracellular pathways, including calcium signaling, cAMP and CREB, which, in turn, produce signals that promote nerve regeneration. These results contribute to defining the cross-talk taking place at the neuromuscular junction when it is attacked by anti-gangliosides autoantibodies plus complement, which is crucial for nerve regeneration and is also likely to be important in other peripheral neuropathies.

  1. Premature luteinization during gonadotropin-releasing hormone antagonist cycles and its relationship with in vitro fertilization outcome.

    Science.gov (United States)

    Bosch, Ernesto; Valencia, Iván; Escudero, Ernesto; Crespo, Juana; Simón, Carlos; Remohí, José; Pellicer, Antonio

    2003-12-01

    To determine the prevalence and the effect of premature luteinization in GnRH antagonist IVF-ET cycles. Prospective observational study. In vitro fertilization-embryo transfer (IVF-ET) program at the Instituto Valenciano de Infertilidad. Eighty-one infertile patients undergoing controlled ovarian hyperstimulation with gonadotropins and GnRH antagonist for IVF-ET. Gonadotropin-releasing hormone (GnRH) antagonist was administered from stimulation day 6. Serum P, E(2), and LH were determined on the day of hCG administration. Cycles were grouped according to serum P level on the day of hCG administration ( or =1.2 ng/mL). Clinical pregnancy and implantation rates were determined. The incidence of premature luteinization was 38.3%. Total recombinant FSH dose and stimulation days differed significantly between the groups. Pregnancy rate (25.8% vs. 54.0%) and implantation rate (13.8% vs. 32.0%) were significantly lower in the premature luteinization group. Premature luteinization during GnRH antagonist IVF-ET cycles is a frequent event that is associated with lower pregnancy and implantation rates. Progesterone elevations are not related to serum LH levels and may reflect the mature granulosa cell response to high FSH exposure.

  2. In vitro uptake and release studies of ocular pharmaceutical agents by silicon-containing and p-HEMA hydrogel contact lens materials.

    Science.gov (United States)

    Karlgard, C C S; Wong, N S; Jones, L W; Moresoli, C

    2003-05-12

    The in vitro uptake and release behaviour of cromolyn sodium, ketotifen fumarate, ketorolac tromethamine and dexamethasone sodium phosphate with silicon-containing (lotrafilcon and balafilcon) and p-HEMA-containing (etafilcon, alphafilcon, polymacon, vifilcon and omafilcon) hydrogel contact lenses indicated that both drug and material affected the uptake and release behaviour. Rapid uptake and release (within 50 min) was observed for all drugs except ketotifen fumarate which was more gradual taking approximately 5h. Furthermore, the maximum uptake differed significantly between drugs and materials. The highest average uptake (7879+/-684 microg/lens) was cromolyn sodium and the lowest average uptake (67+/-13 microg/lens) was dexamethasone sodium phosphate. Partial release of the drug taken up was observed for all drugs except dexamethasone sodium phosphate where no release was detected. Sustained release was demonstrated only by ketotifen fumarate. Drug uptake/release appeared to be a function of lens material ionicity, water and silicon content. The silicon-containing materials released less drug than the p-HEMA-containing materials. The lotrafilcon material demonstrated less interactions with the drugs than the balafilcon material which can be explained by their different bulk composition and surface treatment.

  3. Sustained-release effervescent floating matrix tablets of baclofen: development, optimization and in vitro-in vivo evaluation in healthy human volunteers.

    Science.gov (United States)

    Gande, S; Rao, Ym

    2011-01-01

    Baclofen, a centrally acting skeletal muscle relaxant, is indicated in the long-term treatment of spasticity. It is difficult to formulate baclofen sustained release dosage forms because its absorption on arrival to colon (or even before) is low or nonexistent. In the present investigation efforts were made to improve the bioavailability of baclofen by increasing the residence time of the drug through sustained-release matrix tablet formulation via gastroretentive mechanism. Tablets were prepared by wet granulation technique. The influence of gas generating and gel forming agents, amount of baclofen and total weight of tablet on physical properties, in vitro buoyancy, floating lag time, drug release, DSC, X-ray studies were investigated. The release mechanisms were explored and explained by applying zero order, first order, Higuchi and Korsmeyer equations. The selected formulations were subjected to stability study for the period of three months. For all formulations, kinetics of drug release from tablet followed Higuchi's square root of time kinetic treatment heralding diffusion as predominant mechanism of drug release. Formulations containing 20 mg and 40 mg (F-1 and F-7) showed similar release profiles. There was no significant change in the selected formulations, when subjected to accelerated stability conditions over a period of three months. X-ray imaging in six healthy human volunteers revealed a mean gastric retention period of 5.50±0.7 hrs for the selected formulation. Stable, sustained release effervescent floating matrix tablets of baclofen could be prepared by wet granulation technique.

  4. Results of a Pilot Study of Pre-release STD Testing and Inmates’ Risk Behaviors in an Ohio Prison

    National Research Council Canada - National Science Library

    Sieck, Cynthia J; Dembe, Allard E

    2011-01-01

    ...) and a behavioral risk survey for male inmates at an Ohio prison. Approximately 4–6 weeks prior to scheduled release, inmates took part in a mandatory blood test and optional genital swab and physical examination to test for STDs...

  5. Antibacterial Behavior of Additively Manufactured Porous Titanium with Nanotubular Surfaces Releasing Silver Ions.

    Science.gov (United States)

    Amin Yavari, S; Loozen, L; Paganelli, F L; Bakhshandeh, S; Lietaert, K; Groot, J A; Fluit, A C; Boel, C H E; Alblas, J; Vogely, H C; Weinans, H; Zadpoor, A A

    2016-07-13

    Additive manufacturing (3D printing) has enabled fabrication of geometrically complex and fully interconnected porous biomaterials with huge surface areas that could be used for biofunctionalization to achieve multifunctional biomaterials. Covering the huge surface area of such porous titanium with nanotubes has been already shown to result in improved bone regeneration performance and implant fixation. In this study, we loaded TiO2 nanotubes with silver antimicrobial agents to equip them with an additional biofunctionality, i.e., antimicrobial behavior. An optimized anodizing protocol was used to create nanotubes on the entire surface area of direct metal printed porous titanium scaffolds. The nanotubes were then loaded by soaking them in three different concentrations (i.e., 0.02, 0.1, and 0.5 M) of AgNO3 solution. The antimicrobial behavior and cell viability of the developed biomaterials were assessed. As far as the early time points (i.e., up to 1 day) are concerned, the biomaterials were found to be extremely effective in preventing biofilm formation and decreasing the number of planktonic bacteria particularly for the middle and high concentrations of silver ions. Interestingly, nanotubes not loaded with antimicrobial agents also showed significantly smaller numbers of adherent bacteria at day 1, which may be attributed to the bactericidal effect of high aspect ratio nanotopographies. The specimens with the highest concentrations of antimicrobial agents adversely affected cell viability at day 1, but this effect is expected to decrease or disappear in the following days as the rate of release of silver ions was observed to markedly decrease within the next few days. The antimicrobial effects of the biomaterials, particularly the ones with the middle and high concentrations of antimicrobial agents, continued until 2 weeks. The potency of the developed biomaterials in decreasing the number of planktonic bacteria and hindering the formation of biofilms make

  6. Effects of Polymeric Additives on the Crystallization and Release Behavior of Amorphous Ibuprofen

    Directory of Open Access Journals (Sweden)

    Su Yang Lee

    2013-01-01

    Full Text Available Some polymeric additives were studied to understand their effects on the amorphous phase of ibuprofen (IBU, used as a poorly water soluble pharmaceutical model compound. The amorphous IBU in bulk, as well as in nanopores (diameter ~24 nm of anodic aluminum oxide, was examined with the addition of poly(acrylic acid, poly(N-vinyl pyrrolidone, or poly(4-vinylphenol. Results of bulk crystallization showed that they were effective in limiting the crystal growth, while the nucleation of the crystalline phase in contact with water was nearly instantaneous in all cases. Poly(N-vinyl pyrrolidone, the most effective additive, was in specific interaction with IBU, as revealed by IR spectroscopy. The addition of the polymers was combined with the nanoscopic confinement to further stabilize the amorphous phase. Still, the IBU with addition of polymeric additives showed sustained release behavior. The current study suggested that the inhibition of the crystal nucleation was probably the most important factor to stabilize the amorphous phase and fully harness its high solubility.

  7. Sol-Gel Behavior of Hydroxypropyl Methylcellulose (HPMC) in Ionic Media Including Drug Release.

    Science.gov (United States)

    Joshi, Sunil C

    2011-10-24

    Sol-gel transformations in HPMC (hydroxypropyl methylcellulose) are being increasingly studied because of their role in bio-related applications. The thermo-reversible behavior of HPMC is particularly affected by its properties and concentration in solvent media, nature of additives, and the thermal environment it is exposed to. This article contains investigations on the effects of salt additives in Hofmeister series on the HPMC gelation. Various findings regarding gelation with salt ions as well as with the ionic and non-ionic surfactants are presented. The gel formation in physiological salt fluids such as simulated gastric and intestine fluids is also examined with the interest in oral drug delivery systems. The processes of swelling, dissolution and dispersion of HPMC tablets in simulated bio-fluids are explored and the release of a drug from the tablet affected by such processes is studied. Explanations are provided based on the chemical structure and the molecular binding/association of HPMC in a media. The test results at the body or near-body temperature conditions helped in understanding the progress of the gelation process within the human body environment. The detailed interpretation of various molecule level interactions unfolded the sol-gel mechanisms and the influence of a few other factors. The obtained test data and the established mathematical models are expected to serve as a guide in customizing applications of HPMC hydrogels.

  8. Sol-Gel Behavior of Hydroxypropyl Methylcellulose (HPMC in Ionic Media Including Drug Release

    Directory of Open Access Journals (Sweden)

    Sunil C. Joshi

    2011-10-01

    Full Text Available Sol-gel transformations in HPMC (hydroxypropyl methylcellulose are being increasingly studied because of their role in bio-related applications. The thermo-reversible behavior of HPMC is particularly affected by its properties and concentration in solvent media, nature of additives, and the thermal environment it is exposed to. This article contains investigations on the effects of salt additives in Hofmeister series on the HPMC gelation. Various findings regarding gelation with salt ions as well as with the ionic and non-ionic surfactants are presented. The gel formation in physiological salt fluids such as simulated gastric and intestine fluids is also examined with the interest in oral drug delivery systems. The processes of swelling, dissolution and dispersion of HPMC tablets in simulated bio-fluids are explored and the release of a drug from the tablet affected by such processes is studied. Explanations are provided based on the chemical structure and the molecular binding/association of HPMC in a media. The test results at the body or near-body temperature conditions helped in understanding the progress of the gelation process within the human body environment. The detailed interpretation of various molecule level interactions unfolded the sol-gel mechanisms and the influence of a few other factors. The obtained test data and the established mathematical models are expected to serve as a guide in customizing applications of HPMC hydrogels.

  9. Chronotherapeutic drug delivery of Tamarind gum, Chitosan and Okra gum controlled release colon targeted directly compressed Propranolol HCl matrix tablets and in-vitro evaluation.

    Science.gov (United States)

    Newton, A M J; Indana, V L; Kumar, Jatinder

    2015-08-01

    The main objective of this investigation is to develop a chronotherapeutic drug delivery of various natural polymers based colon targeted drug delivery systems to treat early morning sign in BP. The polymers such as Tamarind gum, Okra gum and Chitosan were used in the formulation design. A model drug Propranolol HCl was incorporated in the formulation in order to assess the controlled release and time dependent release potential of various natural polymers. A novel polymer Tamarind gum was extracted and used as a prime polymer in this study to prove the superiority of this polymer over other leading natural polymer. Propranolol HCl was used as a model drug which undergoes hepatic metabolism and witnesses the poor bioavailability. The matrix tablets of Propranolol HCl were prepared by direct compression. The tablets were evaluated for various quality control parameters and found to be within the limits. Carbopol 940 was used as an auxiliary polymer to modify the drug release and physicochemical characteristics of the tablets. The in vitro release studies were performed in 0.1N HCl for 1.5h, followed by pH 6.8 phosphate buffer for 2h and pH 7.4 phosphate buffer till maximum amount of drug release. The in vitro release profile of the formulations were fitted with various pharmacokinetic mathematical models and analyzed for release profile. The formulations prepared with Tamarind gum prolonged the release for an extended period of time compared to other polymer based formulation and showed an excellent compression characteristic. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. INFLUENCE OF ETHYLENE-OXIDE GAS TREATMENT ON THE IN-VITRO DEGRADATION BEHAVIOR OF DERMAL SHEEP COLLAGEN

    NARCIS (Netherlands)

    DAMINK, LHHO; DIJKSTRA, PJ; VANLUYN, MJA; VANWACHEM, PB; NIEUWENHUIS, P; FEIJEN, J

    The influence of ethylene oxide gas treatment on the in vitro degradation behavior of noncrosslinked, glutaraldehyde crosslinked or hexamethylene diisocyanate crosslinked dermal sheep collagen (DSC) using bacterial collagenase is described. The results obtained were compared with the degradation

  11. Effect of bone graft density on in vitro cell behavior with enamel matrix derivative.

    Science.gov (United States)

    Miron, Richard J; Caluseru, Oana M; Guillemette, Vincent; Zhang, Yufeng; Buser, Daniel; Chandad, Fatiha; Sculean, Anton

    2015-09-01

    Bone replacement grafting materials play an important role in regenerative dentistry. Despite a large array of tested bone-grafting materials, little information is available comparing the effects of bone graft density on in vitro cell behavior. Therefore, the aim of the present study is to compare the effects of cells seeded on bone grafts at low and high density in vitro for osteoblast adhesion, proliferation, and differentiation. The response of osteoblasts to the presence of a growth factor (enamel matrix derivative, (EMD)) in combination with low (8 mg per well) or high (100 mg per well) bone grafts (BG; natural bone mineral, Bio-Oss®) density, was studied and compared for osteoblast cell adhesion, proliferation, and differentiation as assessed by real-time PCR. Standard tissue culture plastic was used as a control with and without EMD. The present study demonstrates that in vitro testing of bone-grafting materials is largely influenced by bone graft seeding density. Osteoblast adhesion was up to 50 % lower when cells were seeded on high-density BG when compared to low-density BG and control tissue culture plastic. Furthermore, proliferation was affected in a similar manner whereby cell proliferation on high-density BG (100 mg/well) was significantly increased when compared to that on low-density BG (8 mg/well). In contrast, cell differentiation was significantly increased on high-density BG as assessed by real-time PCR for markers collagen 1 (Col 1), alkaline phosphatase (ALP), and osteocalcin (OC) as well as alizarin red staining. The effects of EMD on osteoblast adhesion, proliferation, and differentiation further demonstrated that the bone graft seeding density largely controls in vitro results. EMD significantly increased cell attachment only on high-density BG, whereas EMD was able to further stimulate cell proliferation and differentiation of osteoblasts on control culture plastic and low-density BG when compared to high-density BG. The results

  12. Effect of inclusion complexation of meloxicam with β-cyclodextrin- and β-cyclodextrin-based nanosponges on solubility, in vitro release and stability studies.

    Science.gov (United States)

    Shende, Pravin K; Gaud, R S; Bakal, Ravindra; Patil, Dipmala

    2015-12-01

    The objective of the present work was to develop inclusion complexes of meloxicam with β-cyclodextrin- and β-cyclodextrin-based nanosponges to enhance their solubility and stability and to prolong release using different methods that included physical mixing, kneading and sonication. Particle size, zeta potential, encapsulation efficiency, stability study results, in vitro and in vivo drug release study results, FTIR, DSC and XRPD were used as characterization parameters. SEM (Scanning Electron Microscope) studies revealed that the particle sizes of the inclusion complexes of meloxicam were within the range of 350 ± 5.69-765 ± 13.29 nm. The zeta potentials were sufficiently high to obtain stable formulations. In vitro and in vivo release studies revealed the controlled release of meloxicam from the nanosponges for 24h. The interaction of the meloxicam with the nanosponges was confirmed by FTIR and DSC. A XRPD study revealed that the crystalline nature of meloxicam was changed to an amorphous form due to the complexation with the nanosponges. A stability study revealed that the meloxicam nanosponges were stable. Therefore, β-cyclodextrin-based nanosponges represent a novel approach for the controlled release of meloxicam for anti-inflammatory and analgesic effects. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Montmorillonite-alginate nanocomposites as a drug delivery system: intercalation and in vitro release of vitamin B1 and vitamin B6.

    Science.gov (United States)

    Kevadiya, Bhavesh D; Joshi, Ghanshyam V; Patel, Hasmukh A; Ingole, Pravin G; Mody, Haresh M; Bajaj, Hari C

    2010-08-01

    Sustained intestinal delivery of thiamine hydrochloride (Vitamin B(1); VB(1)) and pyridoxine hydrochloride (Vitamin B(6); VB(6)) seems to be a feasible alternative to existing therapy. The vitamins (VB(1)/VB(6)) intercalated in montmorillonite (MMT) and intercalated VB(1)/VB(6)-MMT hybrid is further used for synthesis of VB(1)/VB(6)-MMT-alginate nanocomposite beads by gelation method and in vitro release in the intestinal environment. The structure and surface morphology of the synthesized VB(1)/VB(6)-MMT hybrid, VB(1)/VB(6)-alginate and VB(1)/VB(6)-MMT-alginate nanocomposite beads were characterized by XRD, FT-IR, TGA and SEM. In vitro release experiments revealed that the VB(1)/VB(6) releases suddenly from VB(1)/VB(6)-MMT hybrid and is pH dependent. The controlled release of VB(1)/VB(6) from VB(1)/VB(6)-MMT-alginate nanocomposite beads was observed to be controlled as compared to their release from VB(1)/VB(6)-MMT hybrid and VB(1)/VB(6)-alginate beads.

  14. Bovine oviductal monolayers cultured under three-dimension conditions secrete factors able to release spermatozoa adhering to the tubal reservoir in vitro.

    Science.gov (United States)

    Gualtieri, R; Mollo, V; Braun, S; Barbato, V; Fiorentino, I; Talevi, R

    2013-02-01

    Different in vitro models have been developed to understand the interaction of gametes and embryos with the maternal reproductive tract. We recently showed that bovine oviductal monolayers three-dimensionally cultured in Gray's medium on collagen-coated microporous polycarbonate inserts under liquid-air interface conditions are well polarized, develop cilia, remain viable for at least 3 weeks postconfluence, and mantain the viability of bound spermatozoa significantly better than bidimensionally cultured monolayers. Herein, we used these culture conditions to understand whether: (1) spermatozoa adhering to three-dimensionally cultured oviductal monolayers can be released by heparin or penicillamine as previously shown with bidimensionally cultured oviductal monolayers and explants; and (2) media conditioned by three-dimensionally cultured oviductal monolayers were able to release spermatozoa adhering to oviductal explants. Findings demonstrated that (1) spermatozoa adhering to three-dimensionally cultured oviductal monolayers are readily released by heparin and penicillamine, (2) media conditioned by three-dimensionally cultured oviductal monolayers are able to release spermatozoa bound to oviductal explants, (3) do not depress sperm motility and viability, (4) they improve sperm kinetics, and (5) promote binding to the zona pellucida. In conclusion, in vitro data suggest that the release of spermatozoa adhering to the oviductal reservoir in vivo can be triggered by factors secreted by the oviduct itself that induce sperm capacitation. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. The development of a link model consisting of in vitro drug release and tablets gastric emptying time: application to diclofenac enteric coated tablets

    OpenAIRE

    Mrhar, Aleš; Grabnar, Iztok; Bogataj, Marija; Locatelli, Igor

    2015-01-01

    Objectives: The bioavailability of well permeable drugs administered as single-unit modified release tablet is markedly dependent on the gastric emptying time of such tablet, especially when taken in fasted stomach state. The influence of pH on drug release can be evaluated in vitro. On the other hand, the vector of tablets gastric emptying times is a random variable and can be generated from Weibull distribution function [1,2]. The purpose was to develop a link model consisting of the kineti...

  16. Influence of drug property and product design on in vitro-in vivo correlation of complex modified-release dosage forms.

    Science.gov (United States)

    Qiu, Yihong; Li, Xia; Duan, John Z

    2014-02-01

    The present study examines how drug's inherent properties and product design influence the evaluation and applications of in vitro-in vivo correlation (IVIVC) for modified-release (MR) dosage forms consisting of extended-release (ER) and immediate-release (IR) components with bimodal drug release. Three analgesic drugs were used as model compounds, and simulations of in vivo pharmacokinetic profiles were conducted using different release rates of the ER component and various IR percentages. Plasma concentration-time profiles exhibiting a wide range of tmax and maximum observed plasma concentration (Cmax) were obtained from superposition of the simulated IR and ER profiles based on a linear IVIVC. It was found that depending on the drug and dosage form design, direct use of the superposed IR and ER data for IVIVC modeling and prediction may (1) be acceptable within errors, (2) become unreliable and less meaningful because of the confounding effect from the non-negligible IR contribution to Cmax, or (3) be meaningless because of the insensitivity of Cmax to release rate change of the ER component. Therefore, understanding the drug, design and drug release characteristics of the product is essential for assessing the validity, accuracy, and reliability of IVIVC of complex MR products obtained via directly modeling of in vivo data. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

  17. Release of arachidonic and linoleic acid metabolites in skin organ cultures as characteristics of in vitro skin irritancy

    NARCIS (Netherlands)

    Sandt, J.J.M. van de; Maas, W.J.M.; Doornink, P.C.; Rutten, A.A.J.J.L.

    1995-01-01

    In vitro techniques make a major contribution to the development of alternatives to the in vivo 'Draize' skin irritation test, and the development of sensitive and generally applicable in vitro endpoints of cutaneous toxicity is an area of intensive research. To investigate in vitro characteristics

  18. Zeolite-based hemostat QuikClot releases calcium into blood and promotes blood coagulation in vitro.

    Science.gov (United States)

    Li, Jing; Cao, Wei; Lv, Xiao-xing; Jiang, Li; Li, Yue-jun; Li, Wang-zhou; Chen, Shao-zong; Li, Xue-yong

    2013-03-01

    To examine the changes in electrolyte concentrations after addition of zeolite-based hemostat QuikClot in blood and the effects of zeolite on blood coagulation in vitro. Fresh blood was taken from healthy adult volunteers and sheep, and the electrolyte concentrations in blood were measured using a blood electrolyte analyzer. Zeolite Saline Solution (ZSS) was prepared by addition of 2 g zeolite to 0.9% NaCl solution (4, 8, or 16 mL). The electrolytes in ZSS were measured using inductively coupled plasma atomic emission spectroscopy. The prothrombin time (PT) and activated partial thromboplastin time (APTT) of blood were measured using the test tube method. The activated clotting time (ACT) and clotting rate (CR) of blood were measured with Sonoclot Coagulation and Platelet Function Analyzer. Addition of zeolite (50 and 100 mg) in 2 mL human blood significantly increased Ca(2+) concentration, while Na(+) and K(+) concentrations were significantly decreased. Addition of zeolite (50 and 100 mg) in 0.9% NaCl solution (2 mL) caused similar changes in Ca(2+) and Na(+) concentrations. Si(4+) (0.2434 g/L) and Al(3+) (0.2575 g/L) were detected in ZSS (2 g/8 mL). Addition of ZSS in sheep blood shortened APTT in a concentration dependent manner, without changing PT. ZSS or aqueous solution of CaCl2 that contained Ca(2+) concentration identical to that of ZSS significantly shortened ACT in human blood without significantly changing CR, and the effect of ZSS on ACT was not significantly different from that of CaCl2. Zeolite releases Ca(2+) into blood, thus accelerating the intrinsic pathway of blood coagulation and shortening the clot formation time.

  19. Surfacing behavior and gas release of the physostome sprat (Sprattus sprattus) in ice-free and ice-covered waters

    KAUST Repository

    Solberg, Ingrid

    2013-10-04

    Upward-facing echosounders that provided continuous, long-term measurements were applied to address the surfacing behavior and gas release of the physostome sprat (Sprattus sprattus) throughout an entire winter in a 150-m-deep Norwegian fjord. During ice-free conditions, the sprat surfaced and released gas bubbles at night with an estimated surfacing rate of 3.5 times per fish day-1. The vertical swimming speeds during surfacing were considerably higher (~10 times) than during diel vertical migrations, especially when returning from the surface, and particularly when the fjord was not ice covered. The sprat released gas a few hours after surfacing, suggesting that the sprat gulped atmospheric air during its excursions to the surface. While the surface activity increased after the fjord became ice covered, the records of gas release decreased sharply. The under-ice fish then displayed a behavior interpreted as "searching for the surface" by repeatedly ascending toward the ice, apparently with limited success of filling the swim bladder. This interpretation was supported by lower acoustic target strength in ice-covered waters. The frequent surfacing behavior demonstrated in this study indicates that gulping of atmospheric air is an important element in the life of sprat. While at least part of the population endured overwintering in the ice-covered habitat, ice covering may constrain those physostome fishes that lack a gas-generating gland in ways that remain to be established. 2013 The Author(s).

  20. In vitro solubility, dissolution and permeability studies combined with semi-mechanistic modeling to investigate the intestinal absorption of desvenlafaxine from an immediate- and extended release formulation

    DEFF Research Database (Denmark)

    Franek, F; Jarlfors, A; Larsen, F.

    2015-01-01

    (ERF). Semi-mechanistic models of desvenlafaxine were built (using SimCyp®) by combining in vitro data on dissolution and permeation (mechanistic part of model) with clinical data (obtained from literature) on distribution and clearance (non-mechanistic part of model). The model predictions...... for desvenlafaxine absorption (i.e. intestinal dissolution or permeation) is not fully clarified. The aim of this study was to investigate whether dissolution and/or intestinal permeability rate-limit desvenlafaxine absorption from an immediate-release formulation (IRF) and Pristiq®, an extended release formulation...... of desvenlafaxine pharmacokinetics after IRF and ERF administration were compared with published clinical data from 14 trials. Desvenlafaxine in vivo dissolution from the IRF and ERF was predicted from in vitro solubility studies and biorelevant dissolution studies (using the USP3 dissolution apparatus...

  1. Evaporation release behavior of volatile fission products from liquid sodium pool to the inert cover gas

    Energy Technology Data Exchange (ETDEWEB)

    Nakagiri, T.; Miyahara, S. [Oarai Engineering Center, Power Reactor and Nuclear Fuel Development Corp., Oaraimachi, Ibaraki (Japan)

    1996-12-01

    In fuel failure of sodium cooled fast breeder reactors, released volatile fission products (VFPs) such as iodine and cesium from the fuel will be dissolved into the liquid sodium coolant and transferred to the cover vaporization. In the cover gas system of the reactor, natural convection occurs due to temperature differences between the sodium pool and the gas phase. The release rates of VFPs together with sodium vaporization are considered to be controlled by the convection. In this study, three analytical models are developed and examined to calculate the transient release rates using the equilibrium partition coefficients of VFPs. The calculated release rates are compared with experimental results for sodium and sodium iodide. The release rate of sodium is closest to the calculation by the heterogeneous nucleation theory. The release rate of sodium iodide obtained from the experiment is between the release rates calculated by the model based on heat-and-mass transfer analogy and the Hill`s theory. From this study, it is confirmed that the realistic release rate of sodium is able to be calculated by the model based on the heterogeneous nucleation theory. The conservative release rate of sodium iodide is able to be calculated by the model based on the Hill`s theory using the equilibrium partition coefficient of sodium iodide. (author) 7 figs., 1 tab., 3 refs.

  2. Effects of coating layer and release medium on release profile from coated capsules with Eudragit FS 30D: an in vitro and in vivo study.

    Science.gov (United States)

    Moghimipour, Eskandar; Rezaei, Mohsen; Kouchak, Maryam; Fatahiasl, Jafar; Angali, Kambiz Ahmadi; Ramezani, Zahra; Amini, Mohsen; Dorkoosh, Farid Abedin; Handali, Somayeh

    2018-05-01

    The aim of the present research was to evaluate the impact of coating layers on release profile from enteric coated dosage forms. Capsules were coated with Eudragit FS 30D using dipping method. The drug profile was evaluated in both phosphate buffer and Hank's solutions. Utilization X-ray imaging, gastrointestinal transmission of enteric coated capsules was traced in rats. According to the results, no release of the drug was found at pH 1.2, and the extent of release drug in pH 6.8 medium was decreased by adding the coating layers. The results indicated single-layer coated capsules in phosphate buffer were significantly higher than that in Hank's solution. However, no significant difference was observed from capsules with three coating layers in two different dissolution media. X-ray imaging showed that enteric coated capsules were intact in the stomach and in the small intestine, while disintegrated in the colon.

  3. Mechanical cell-matrix feedback explains pairwise and collective endothelial cell behavior in vitro.

    Directory of Open Access Journals (Sweden)

    René F M van Oers

    2014-08-01

    Full Text Available In vitro cultures of endothelial cells are a widely used model system of the collective behavior of endothelial cells during vasculogenesis and angiogenesis. When seeded in an extracellular matrix, endothelial cells can form blood vessel-like structures, including vascular networks and sprouts. Endothelial morphogenesis depends on a large number of chemical and mechanical factors, including the compliancy of the extracellular matrix, the available growth factors, the adhesion of cells to the extracellular matrix, cell-cell signaling, etc. Although various computational models have been proposed to explain the role of each of these biochemical and biomechanical effects, the understanding of the mechanisms underlying in vitro angiogenesis is still incomplete. Most explanations focus on predicting the whole vascular network or sprout from the underlying cell behavior, and do not check if the same model also correctly captures the intermediate scale: the pairwise cell-cell interactions or single cell responses to ECM mechanics. Here we show, using a hybrid cellular Potts and finite element computational model, that a single set of biologically plausible rules describing (a the contractile forces that endothelial cells exert on the ECM, (b the resulting strains in the extracellular matrix, and (c the cellular response to the strains, suffices for reproducing the behavior of individual endothelial cells and the interactions of endothelial cell pairs in compliant matrices. With the same set of rules, the model also reproduces network formation from scattered cells, and sprouting from endothelial spheroids. Combining the present mechanical model with aspects of previously proposed mechanical and chemical models may lead to a more complete understanding of in vitro angiogenesis.

  4. Continuous production of controlled release dosage forms based on hot-melt extruded gum arabic: Formulation development, in vitro characterization and evaluation of potential application fields.

    Science.gov (United States)

    Kipping, Thomas; Rein, Hubert

    2016-01-30

    Controlled release matrices based on gum arabic are prepared by applying a continuous hot-melt extrusion technology: the pre-mixture consisting of gum arabic and the incorporated API is plasticized by a co-rotating twin-screw extruder, an intermediate strand is formed by a round nozzle. Single dosed matrices are prepared by cutting the semi elastic strand with a rotary fly cutter. Paracetamol and phenazone are used as model drug substances. High drug loadings up to 70% can be realized. Matrices are characterized concerning their crystalline structure, in vitro dissolution, disintegration time and various physical parameters including glass transition temperature (Tg). Release characteristic behavior is mainly influenced by erosion of the matrices. At higher drug loadings also diffusion based transport gain importance. The solubility of the API shows an influence on the erosion rate of the matrix and should therefore be considered during formulation development. Tg is mainly influenced by the solubility of the API in the surrounding matrix. High soluble phenazone shows a decrease, whereas paracetamol addition has nearly no influence on the Tg of the polymeric system. Activation energy (EA) of the glass transition is determined via dynamic mechanical analysis. The addition of APIs leads to a reduction of EA indicating an increased molecular movement at Tg region compared to placebo extrudates. X-ray diffraction is used to determine the crystalline state of the extruded matrices and interaction between matrix and incorporated APIs. The production of thin layer matrices is an interesting option to provide a fast drug delivery to the oral cavity. High mechanical strength combined with fast disintegration times can be a great advantage for the development of oro-dispersible tablets. A great benefit of the evaluated processing technology is the simple adaption of the final dose by varying either the cutting length or the diameter of the nozzle resulting in a cost

  5. Assessing the risk of alcohol-induced dose dumping from sustained-release oral dosage forms: in vitro-in silico approach.

    Science.gov (United States)

    Cvijić, Sandra; Aleksić, Ivana; Ibrić, Svetlana; Parojčić, Jelena

    2017-10-29

    Consumption of alcoholic beverages with sustained-release oral dosage forms may pose a risk to patients due to potential alcohol-induced dose dumping (ADD). Regulatory guidances recommend in vitro dissolution testing to identify the risk of ADD, but the question remains whether currently proposed test conditions can be considered biopredictive. The purpose of this study was to evaluate different dissolution setups to assess ADD, and the potential of combined in vitro-in silico approach to predict drug absorption after concomitant alcohol intake for hydrophilic and lipophilic sustained-release tablets containing ibuprofen or diclofenac sodium. According to the obtained results, the impact of ethanol was predominantly governed by the influence on matrix integrity, with the increase in drug solubility being less significant. Hydrophilic matrix tablets were less susceptible to ADD than lipophilic matrices, although the conclusion on formulation ethanol-vulnerability depended on the employed experimental conditions. In silico predictions indicated that the observed changes in drug dissolution would not result in plasma concentrations beyond therapeutic window, but sustained-release characteristics of the formulations might be lost. Overall, the study demonstrated that in vitro-in silico approach may provide insight into the effect of ADD on drug clinical performance, and serve as a tool for ADD risk assessment.

  6. The differences in Hg content released from high copper amalgam and silverfil argentum restoration into artificial saliva after one week of soaking (in vitro

    Directory of Open Access Journals (Sweden)

    Deriz Rieskanoerbachra Wisuardy

    2008-07-01

    Full Text Available Dental restoration is a treatment in dentistry that very often implemented. One of the restoration materials used is an amalgam. Amalgam has some deficiencies, among others, the presence of free Hg. The purpose of this study was to find out the difference in Hg content released from two different kinds of amalgam, namely, high copper amalgam and silverfil argentum carried out in vitro. This study was carried out on thirty premolar teeth of the maxilla which underwent class one occlusal restoration. The Hg content released was measured using the Atomic Absorption Spectrophotometry (AAS. This was a quasi-experimental study. The study results analyzed using the independent t paired statistical test method indicated that after one week of immersion, the average Hg content released from high copper amalgam restoration was 10,695 ng/mL and from silverfil argentum restoration was 5,602 ng/mL. The conclusion of the study was that there was a difference in Hg content released from high copper amalgam restoration and silverfil argentum restoration. The Hg content released from high copper amalgam restoration was higher than the Hg content released from silverfil argentum restoration.

  7. In vitro release studies on drugs suspended in non-polar media I. Release of sodium chloride from suspensions in liquid paraffin

    NARCIS (Netherlands)

    Crommelin, D.J.A.; Blaey, C.J. de

    The release of a readily water-soluble substance (sodium chloride) from a liquid paraffin phase to an underlying water phase was investigated as a function of particle size (10–50 μm) and concentration (up to 10% m/m). Transport of the suspended particles to the interface by sedimentation was the

  8. In vitro release studies on drugs suspended in non-polar media II. The release of paracetamol and chloramphenicol from suspensions in liquid paraffin

    NARCIS (Netherlands)

    Crommelin, D.J.A.; Blaey, C.J. de

    The release of paracetamol and chloramphenicol (water solubility 13 and 3.6 mg · g−1, respectively), suspended in liquid paraffin, to an underlying aqueous layer was investigated as a function of particle size (10–60 μm), concentration (0.5–6% m/m) and the presence of additives (DOSS-Na:

  9. Characterization and in vitro release of cyclosporine-A from poly(D,L-lactide-co-glycolide implants obtained by solvent/extraction evaporation

    Directory of Open Access Journals (Sweden)

    Juliana Barbosa Saliba

    2012-01-01

    Full Text Available Cyclosporine-A-loaded PLGA implants were developed intended for ocular route. Implants were prepared using solvent extraction/evaporation technique followed by casting of the cake into rods in a heated surface. XRD patterns showed that cyclosporine-A was completely incorporated into PLGA. FTIR and DSC results indicated alterations on drug molecular conformation aiming to reach the most stable thermodynamic conformation at polymer/drug interface. Implants provided controlled/sustained in vitro release of the drug. During the first 7 weeks, the drug release was controlled by the diffusion of the cyclosporine-A; and between 7-23 week period, the drug diffusion and degradation of PLGA controlled the drug release.

  10. Microfluidic synthesis of dye-loaded polycaprolactone-block-poly(ethylene oxide) nanoparticles: Insights into flow-directed loading and in vitro release for drug delivery.

    Science.gov (United States)

    Bains, Aman; Wulff, Jeremy E; Moffitt, Matthew G

    2016-08-01

    Using the fluorescent probe dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) as a surrogate for hydrophobic drugs, we investigate the effects of water content and on-chip flow rate on the multiscale structure, loading and release properties of DiI-loaded poly(ε-caprolactone)-block-poly(ethylene oxide) (PCL-b-PEO) nanoparticles produced in a gas-liquid segmented microfluidic device. We find a linear increase in PCL crystallinity within the nanoparticle cores with increasing flow rate, while mean nanoparticle sizes first decrease and then increase with flow rate coincident with the disappearance and reappearance of long filament nanoparticles. Loading efficiencies at the lower water content (cwc+10wt%) are generally higher (up to 94%) compared to loading efficiencies (up to 53%) at the higher water content (cwc+75wt%). In vitro release times range between ∼2 and 4days for nanoparticles produced at cwc+10wt% and >15days for nanoparticles produced at cwc+75wt%. At the lower water content, slower release of DiI is found for nanoparticles produced at higher flow rate, while at high water content, release times first decrease and then increase with flow rate. Finally, we investigate the effects of the chemical and physical characteristics of the release medium on the kinetics of in vitro DiI release and nanoparticle degradation. This work demonstrates the general utility of dye-loaded nanoparticles as model systems for screening chemical and flow conditions for producing drug delivery formulations within microfluidic devices. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Self-carried curcumin nanoparticles for in vitro and in vivo cancer therapy with real-time monitoring of drug release

    Science.gov (United States)

    Zhang, Jinfeng; Li, Shengliang; An, Fei-Fei; Liu, Juan; Jin, Shubin; Zhang, Jin-Chao; Wang, Paul C.; Zhang, Xiaohong; Lee, Chun-Sing; Liang, Xing-Jie

    2015-08-01

    The use of different nanocarriers for delivering hydrophobic pharmaceutical agents to tumor sites has garnered major attention. Despite the merits of these nanocarriers, further studies are needed to improve their drug loading capacities (which are typically self-carried nanodrug delivery strategies without using inert carriers is highly desirable. In this study, we developed a self-carried curcumin (Cur) nanodrug for highly effective cancer therapy in vitro and in vivo with real-time monitoring of drug release. With a biocompatible C18PMH-PEG functionalization, the Cur nanoparticles (NPs) showed excellent dispersibility and outstanding stability in physiological environments with drug loading capacities >78 wt%. Both confocal microscopy and flow cytometry confirmed the cellular fluorescence ``OFF-ON'' activation and real-time monitoring of the Cur molecule release. In vitro and in vivo experiments clearly show that the therapeutic efficacy of the PEGylated Cur NPs is considerably better than that of free Cur. This self-carried strategy with real-time monitoring of drug release may open a new way for simultaneous cancer therapy and monitoring.The use of different nanocarriers for delivering hydrophobic pharmaceutical agents to tumor sites has garnered major attention. Despite the merits of these nanocarriers, further studies are needed to improve their drug loading capacities (which are typically self-carried nanodrug delivery strategies without using inert carriers is highly desirable. In this study, we developed a self-carried curcumin (Cur) nanodrug for highly effective cancer therapy in vitro and in vivo with real-time monitoring of drug release. With a biocompatible C18PMH-PEG functionalization, the Cur nanoparticles (NPs) showed excellent dispersibility and outstanding stability in physiological environments with drug loading capacities >78 wt%. Both confocal microscopy and flow cytometry confirmed the cellular fluorescence ``OFF-ON'' activation and real

  12. Release behavior of uranium in uranium mill tailings under environmental conditions.

    Science.gov (United States)

    Liu, Bo; Peng, Tongjiang; Sun, Hongjuan; Yue, Huanjuan

    2017-05-01

    Uranium contamination is observed in sedimentary geochemical environments, but the geochemical and mineralogical processes that control uranium release from sediment are not fully appreciated. Identification of how sediments and water influence the release and migration of uranium is critical to improve the prevention of uranium contamination in soil and groundwater. To understand the process of uranium release and migration from uranium mill tailings under water chemistry conditions, uranium mill tailing samples from northwest China were investigated with batch leaching experiments. Results showed that water played an important role in uranium release from the tailing minerals. The uranium release was clearly influenced by contact time, liquid-solid ratio, particle size, and pH under water chemistry conditions. Longer contact time, higher liquid content, and extreme pH were all not conducive to the stabilization of uranium and accelerated the uranium release from the tailing mineral to the solution. The values of pH were found to significantly influence the extent and mechanisms of uranium release from minerals to water. Uranium release was monitored by a number of interactive processes, including dissolution of uranium-bearing minerals, uranium desorption from mineral surfaces, and formation of aqueous uranium complexes. Considering the impact of contact time, liquid-solid ratio, particle size, and pH on uranium release from uranium mill tailings, reducing the water content, decreasing the porosity of tailing dumps and controlling the pH of tailings were the key factors for prevention and management of environmental pollution in areas near uranium mines. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Sustained-release effervescent floating matrix tablets of baclofen: development, optimization and in vitro-in vivo evaluation in healthy human volunteers

    Directory of Open Access Journals (Sweden)

    YM Rao

    2011-07-01

    Full Text Available "n  Background and the purpose of the study: Baclofen, a centrally acting skeletal muscle relaxant, is indicated in the long-term treatment of spasticity. It is difficult to formulate baclofen sustained release dosage forms because its absorption on arrival to colon (or even before is low or nonexistent. In the present investigation efforts were made to improve the bioavailability of baclofen by increasing the residence time of the drug through sustained-release matrix tablet formulation via gastroretentive mechanism. "n  Methods: Tablets were prepared by wet granulation technique. The influence of gas generating and gel forming agents, amount of baclofen and total weight of tablet on physical properties, in vitro buoyancy, floating lag time, drug release, DSC, X-ray studies were investigated. The release mechanisms were explored and explained by applying zero order, first order, Higuchi and Korsmeyer equations. The selected formulations were subjected to stability study for the period of three months. "n  Results: For all formulations, kinetics of drug release from tablet followed Higuchi's square root of time kinetic treatment heralding diffusion as predominant mechanism of drug release. Formulations containing 20 mg and 40 mg (F-1 and F-7 showed similar release profiles. There was no significant change in the selected formulations, when subjected to accelerated stability conditions over a period of three months. X-ray imaging in six healthy human volunteers revealed a mean gastric retention period of 5.50±0.7 hrs for the selected formulation. "n  Conclusion:Stable, sustained release effervescent floating matrix tablets of baclofen could be prepared by wet granulation technique.

  14. Potential Use of Polyvinyl Acetate-Polyvinylpyrrolidone Mixture for the Development of Atenolol Sustained Release Matrix Tablets: Optimization of Formulation through in Vitro-in Vivo Assessment Study.

    Science.gov (United States)

    Owayez, Ali Saeed; Abd El-Ghany, Galal Mahmoud; Abu Hashim, Irhan Ibrahim

    2017-01-01

    The objective of this study was to develop sustained release matrix tablets of atenolol (AT) using different concentrations of polyvinyl acetate-polyvinylpyrrolidone mixture (KSR) (20, 30, or 40%) with various types of fillers such as spray dried lactose (SP.D.L), avicel pH 101 (AV), and emcompress (EMS). The physical characteristics of the prepared tablets were evaluated. Characterization of the optimized formulation was performed using Fourier transform (FT)-IR spectroscopy and differential scanning calorimetry (DSC). Moreover, the in vitro release profiles of AT formulations were investigated in different pH dissolution media. Drug release kinetics and mechanisms were also determined. The results revealed that there was no potential incompatibility of the drug with the polymer. The release profiles of AT were affected by the concentration of KSR, fillers used, and pH of the dissolution media. The drug release kinetic from most of the formulations obeyed Higuchi diffusion model. The selected formulae were investigated for their stability by storage at 30 and 40°C with atmospheric humidity and 75% relative humidity (RH), respectively. The results demonstrated that no change in the physicochemical properties of the tablets stored at 30°C/atmospheric RH in comparison with some changes at 40°C/75% RH. Finally, the in vivo study provided an evidence that the optimized AT tablet containing 40% KSR and SP.D.L exhibited prominent higher oral bioavailability and more efficient sustained-release effect than the drug alone or the commercial tablet product. It is noteworthy that KSR could be considered as a promising useful release retardant for the production of AT sustained release matrix tablets.

  15. A comparative in vitro study on fluoride release and water sorption of different flowable esthetic restorative materials

    OpenAIRE

    Harhash, Asmaa Youssif; ElSayad, Iman Ibrahim; Zaghloul, Ahmad G. S.

    2017-01-01

    Objectives: The objective of the study was to evaluate fluoride release and water sorption of three flowable esthetic restorative materials: a giomer, a fluoride-releasing resin composite, and a nonfluoridated resin composite. Materials and Methods: Ten samples from a giomer, a fluoride releasing nano-hybrid, and a nonfluoridated nano-hybrid composite were prepared and immersed in deionized water. Fluoride measurements were done using an ion-specific electrode attached to a microprocessor-bas...

  16. Effects of modified surfaces produced at plasma-facing surface on hydrogen release behavior in the LHD

    Directory of Open Access Journals (Sweden)

    Y. Nobuta

    2017-08-01

    Full Text Available In the present study, an additional deuterium (D ion irradiation was performed against long-term samples mounted on the helical coil can and in the outer private region in the LHD during the 17th experimental campaign. Based on the release behavior of the D and hydrogen (H retained during the experimental campaign, the difference of release behavior at the top surface and in bulk of modified surfaces is discussed. Almost all samples on the helical coil can were erosion-dominant and some samples were covered with boron or carbon, while a very thick carbon films were formed in the outer private region. In the erosion-dominant area, the D desorbed at much lower temperatures compared to that of H retained during the LHD plasma operation. For the samples covered with boron, the D tended to desorb at lower temperatures compared to H. For the carbon deposition samples, the D desorbed at much higher temperatures compared to no deposition and boron-covered samples, which was very similar to that of H. The D retention capabilities at the top surface of carbon and boron films were 2–3 times higher than no deposition area. The results indicate that the retention and release behavior at the top surface of the modified layer can be different from that of bulk substrate material.

  17. An in vitro evaluation of fenugreek mucilage as a potential excipient for oral controlled-release matrix tablet.

    Science.gov (United States)

    Nokhodchi, Ali; Nazemiyeh, Hossein; Khodaparast, Afagh; Sorkh-Shahan, Tarifeh; Valizadeh, Hadi; Ford, J L

    2008-03-01

    A polysaccharide mucilage derived from the seeds of fenugreek, Trigonella foenum-graceum L (family Fabaceae) was investigated for use in matrix formulations containing propranolol hydrochloride. Methocel hypomellose K4M was used as a standard controlled release polymer for comparison purposes. In this study the effect of lactose on the release behaviour of propranolol hydrochloride from matrices formulated to contain the fenugreek mucilage also was investigated. An increase in concentration of the mucilage in matrices resulted in a reduction in the release rate of propranolol hydrochloride comparable to that observed with hypomellose matrices. The rate of release of propranolol hydrochloride from fenugreek mucilage matrices was mainly controlled by the drug:mucilage ratio. However, the mechanism of release from matrices containing drug:mucilage ratios of 1:1, 1:1.25, 1:1.5, and 1:2 remained the same. The kinetics of release, utilising the release exponent n, showed that the values of n were between 0.46-0.57 indicating that the release from fenugreek mucilage matrices was predominantly by diffusion. The presence of lactose in matrices containing mucilage increased the release rate of propranolol hydrochloride. This is due to a reduction in tortuoisity and increased pore size of channels caused by lactose through which propranolol diffuses and therefore diffusion of water into the tablet is facilitated.

  18. Quantitative assessment of fluoride release and recharge ability of different restorative materials in different media: an in vitro study.

    Science.gov (United States)

    Jingarwar, Mahesh M; Pathak, Anuradha; Bajwa, Navroop Kaur; Sidhu, Haridarshan Singh

    2014-12-01

    To measure fluoride release and recharge ability of restorative materials in deionised water, artificial saliva and lactic acid. Pellets were prepared from GC2, Ketac N100 and Beautifil II. Each pellets were individually immersed in 10 ml deionised water, artificial saliva or lactic acid as per respective subgroup for 24 h and then elutes were collected. Specimens were reimmersed in respective container. Fluoride released was analysed after 24 h, 7(th) and 15(th) day. On 15(th) day all specimens were exposed to 1.23% APF gel and fluoride release in respective solution was measured on 16(th), 22(nd), 30(th) day. Fluoride release was more after 24 h for all materials in all media then decrease gradually. GC2 shows more fluoride release than Ketac N100 at 24 hours and on 7(th) day but onwards Ketac N100 released significantly more fluoride. Beautifil II showed least fluoride release at all measured intervals in all media. Order of fluoride release in media was lactic acid > deionised water > artificial saliva for all materials. GICs are smart material which release more fluoride when environment become more acidic and also show tendency to recharge which helps clinically in caries risk children.

  19. Effect of silica sources in nanoporous silica synthesis on releasing behavior of indigo carmine

    Directory of Open Access Journals (Sweden)

    Chanatip Samart

    2009-11-01

    Full Text Available Nanoporous silica was applied in controlled releasing experiments. Different physical properties of the nanoporous silica, related to variations of the silica sources, affected the releasing behaviour. Two different silica precursors in nanoporous silica synthesis were investigated, tetraethoxysilane and sodium silicate. The nanoporous silica, which was obtained by tetraethoxysilane, gave the highest surface area (800 m2/g and pore volume (1.2 cc/g. On the other hand, the nanoporous silica obtaining from sodium silicate showed the largest pore size (9 nm. The nanoporous silica with larger pore volume can load a higher amount of indigo carmine, which resulted in a fast release due to the large driving force between the silicaparticle and media solution. However, the releasing rate was not only affected by the pore volume, but also by the interactionbetween the silanol groups on the silica surface and molecules of indigo carmine.

  20. Effect of Plasticizer Type on Tensile Property and In Vitro Indomethacin Release of Thin Films Based on Low-Methoxyl Pectin

    Directory of Open Access Journals (Sweden)

    Pensak Jantrawut

    2017-07-01

    Full Text Available This study developed the interests of low-methoxyl pectin (LMP together with plasticizers for the preparation of elastic thin films. The effect of different plasticizer types (glycerol: Gly; sorbitol: Sor; propylene glycol: PG; and polyethylene glycol 300: PEG 300 and concentrations (20–40% w/w on mechanical and thermal properties of LMP films as well as on in vitro release of indomethacin were evaluated. Without any plasticizer, a brittle LMP film with low tensile strength and % elongation at break was obtained. Addition of plasticizers from 20% to 40% caused reduction in the tensile strength and Young’s modulus values, whereas percent elongation was increased. Forty percent Gly-plasticized and PG-plasticized films were selected to deliver indomethacin in comparison with non-plasticized film. No significant difference in indomethacin release profiles was displayed between the films. The analysis of indomethacin release model indicated that more than one drug release mechanism from the film formulation was involved and possibly the combination of both diffusion and erosion. Even though indomethacin incorporated in non-plasticized film showed similar release profile, Gly or PG should be added to enhanced film flexibility and decrease film brittleness.

  1. Effects of surface friction treatment on the in vitro release of constituent metals from the biomedical Co–29Cr–6Mo–0.16N alloy

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xiaoyu [Graduate School of Engineering, Tohoku University, Sendai 980-8577 (Japan); Li, Yunping, E-mail: lyping@csu.edu.cn [State Key Lab for Powder Metallurgy, Central South University, Changsha 410083 (China); School of Materials Science and Engineering, Central South University, Changsha (China); Hou, Yuhang [Graduate School of Engineering, Tohoku University, Sendai 980-8577 (Japan); Bian, Huakang; Koizumi, Yuichiro; Chiba, Akihiko [Institute for Materials Research, Tohoku University, Sendai 980-8577 (Japan)

    2016-07-01

    Due to the ignorance by many researchers on the influence of starting microstructure on the metal release of biomedical materials in human body after implant, in this study, the effect of surface friction treatment on the in vitro release of the constituent elements of the biomedical Co–29Cr–6Mo–0.16N (CCM) alloy is investigated for the first time by immersion test in lactic acid solution combined with electron backscatter diffraction, transmission electron microscope, X-ray diffraction, X-ray photoelectron spectroscopy, and inductively coupled plasma atomic emission spectroscopy (ICP-EOS). The results indicate that friction treatment on the as-annealed CCM alloy sample surface leads to a planar strain-induced martensitic transformation (SIMT) on sample surface; this greatly accelerates the release of all the constituent elements and, in particular, that of Co as indicated by the ICP-EOS analysis. This increase can be ascribed to a localized deformation that occurred over the entire sample surface, with the dislocation density being high within the SIMTed phase and low in the alloy matrix. - Highlights: • Immersion test of biomedical CCM alloy in lactic acid solution was conducted. • Surface friction on CCM alloy leads to martensitic transformation. • The friction treatment accelerated the release of all the elements especially Co. • Localized deformation accounts for the accelerated release of elements.

  2. Recreational anglers' attitudes, beliefs, and behaviors related to catch-and-release practices of Pacific salmon in British Columbia.

    Science.gov (United States)

    Nguyen, Vivian M; Rudd, Murray A; Hinch, Scott G; Cooke, Steven J

    2013-10-15

    The fate of captured and released fish in recreational fisheries depends in large part on fisher handling and behavior. As such, there is a need for promoting adoption of responsible fishing practices. We interviewed recreational sockeye salmon anglers in the lower Fraser River, British Columbia, to assess their awareness of responsible fishing practices and identify gaps where improved education could promote conservation-oriented behaviors. Based on our interview data, we developed three latent class models of salmon angler typologies based on: 1) anglers' fishing behaviors and preferences, 2) anglers' perceived risks to salmon survival due to post-capture live release, and 3) anglers' level of support for education programs. In the first model, we identified salmon-only anglers (33% of sample), lake-species specialists (46%), and all-around anglers (21%). These classes were differentiated primarily by non-salmon fishing activities (e.g., other target species). In the second model, we found four classes of anglers who differed with regards to key factors they thought affected post-release survival: air exposure (39% of sample); water temperature (24%); hook location (22%); and revival effort (15%). In the third model, we found anglers were either supporters (73%) or non-supporters (27%) of angler education programs. Heterogeneity existed among anglers but we found no correlations in angler classes across models, nor any significant demographic or experiential predictors of class membership. Respondents generally had high awareness and application of catch-and-release best practices, with lake-species specialists rating a higher awareness and usage of recommended catch-and-release technique, and were significantly more likely to cut the line on deeply hooked fish than other groups. Our findings provide resource managers with important insight into the attitudes and behaviors of sockeye salmon anglers in the important lower Fraser River recreational fishery. Our

  3. Activity-Dependent Adenosine Release May Be Linked to Activation of Na+-K+ ATPase: An In Vitro Rat Study

    Science.gov (United States)

    Sims, Robert Edward; Dale, Nicholas

    2014-01-01

    In the brain, extracellular adenosine increases as a result of neuronal activity. The mechanisms by which this occurs are only incompletely understood. Here we investigate the hypothesis that the Na+ influxes associated with neuronal signalling activate the Na+-K+ ATPase which, by consuming ATP, generates intracellular adenosine that is then released via transporters. By measuring adenosine release directly with microelectrode biosensors, we have demonstrated that AMPA-receptor evoked adenosine release in basal forebrain and cortex depends on extracellular Na+. We have simultaneously imaged intracellular Na+ and measured adenosine release. The accumulation of intracellular Na+ during AMPA receptor activation preceded adenosine release by some 90 s. By removing extracellular Ca2+, and thus preventing indiscriminate neuronal activation, we used ouabain to test the role of the Na+-K+ ATPase in the release of adenosine. Under conditions which caused a Na+ influx, brief applications of ouabain increased the accumulation of intracellular Na+ but conversely rapidly reduced extracellular adenosine levels. In addition, ouabain greatly reduced the amount of adenosine released during application of AMPA. Our data therefore suggest that activity of the Na+-K+ ATPase is directly linked to the efflux of adenosine and could provide a universal mechanism that couples adenosine release to neuronal activity. The Na+-K+ ATPase-dependent adenosine efflux is likely to provide adenosine-mediated activity-dependent negative feedback that will be important in many diverse functional contexts including the regulation of sleep. PMID:24489921

  4. Effect of micro-environment modification and polymer type on the in-vitro dissolution behavior and in-vivo performance of amorphous solid dispersions.

    Science.gov (United States)

    Sun, Weiwei; Pan, Baoliang

    2017-06-15

    This study investigates the effects of micro-environment modification and polymer type on the in-vitro dissolution behavior and in-vivo performance of micro-environment pH modifying solid dispersions (pHM-SD) for the poorly water-soluble model drug Toltrazuril (TOL). Various pHM-SDs were prepared using Ca(OH)2 as a pH-modifier in hydrophilic polymers, including polyethylene glycol 6000 (PEG6000), polyvinylpyrrolidone k30 (PVPk30) and hydroxypropyl methylcellulose (HPMC). Based on the results of physicochemical characterizations and in-vitro dissolution testing, the representative ternary (Ca(OH)2:TOL:PEG6000/HPMC/PVPk30=1:8:24, w/w/w) and binary (TOL:PVPk30=1:3, w/w) solid dispersions were selected and optimized to perform in-vivo pharmacokinetic study. The micro-environment pH modification improved the in-vitro water-solubility and in-vivo bioavailability of parent drug TOL. Furthermore, the addition of alkalizers not only enhanced the release and absorption of prototype drug, but also promoted the generation of active metabolites, including toltrazuril sulfoxide (TOLSO) and toltrazuril sulfone (TOLSO2). The in-vitro dissolution profiles and in-vivo absorption, distribution and metabolism behaviors of the pHM-SDs varied with polymer type. Moreover, in-vivo bioavailability of three active pharmaceutical ingredients increased with an increase in in-vitro dissolution rates of the drug from the pHM-SDs prepared with various polymers. Therefore, a non-sink in-vitro dissolution method can be used to predict the in-vivo performance of pHM-SDs formulated with various polymers with trend consistency. In-vitro and in-vivo screening procedures revealed that the pHM-SD composed of Ca(OH)2, TOL and PVPk30 at a weight ratio of 1:8:24, of which the safety was adequately proved via histopathological examination, may be a promising candidate for providing better clinical outcomes. Copyright © 2017. Published by Elsevier B.V.

  5. In vitro fluoride release from a different kind of conventional and resin modified glass-ionomer cements.

    Science.gov (United States)

    Selimović-Dragaš, Mediha; Hasić-Branković, Lajla; Korać, Fehim; Đapo, Nermin; Huseinbegović, Amina; Kobašlija, Sedin; Lekić, Meliha; Hatibović-Kofman, Šahza

    2013-08-01

    Fluoride release is important characteristic of glass-ionomer cements. Quantity of fluoride ions released from the glass-ionomer cements has major importance in definition of their biological activity. The objectives of this study were to define the quantity of fluoride ions released from the experimental glass-ionomer cements and to define the effect of fluoride ions released from the experimental glass-ionomer cements on their cytotoxicity. Concentrations of the fluoride ions released in the evaluated glass-ionomer cements were measured indirectly, by the fluoride-selective WTW, F500 electrode potential, combined with reference R503/D electrode. Statistical analyses of F-ion concentrations released by all glass-ionomers evaluated at two time points, after 8 and after 24 hours, show statistically higher fluoride releases from RMGICs: Vitrebond, Fuji II LC and Fuji Plus, when compared to conventional glass-ionomer cements: Fuji Triage, Fuji IX GP Fast and Ketac Silver, both after 8 and after 24 hours. Correlation coefficient between concentrations of fluoride ion released by evaluated glass-ionomer cements and cytotoxic response of UMR-106 osteoblast cell-line are relatively high, but do not reach levels of biological significance. Correlation between concentrations of fluoride ion released and cytotoxic response of NIH3T3 mouse fibroblast cell line after 8 hours is high, positive and statistically significant for conventional GICs, Fuji Triage and Fuji IX GP Fast, and RMGIC, Fuji II LC. Statistically significant Correlation coefficient between concentrations of fluoride ion released and cytotoxic response of NIH3T3 cell line after 24 hours is defined for RMGIC Fuji II LC only.

  6. Detection of Fractal Behavior in Temporal Series of Synaptic Quantal Release Events: A Feasibility Study

    Directory of Open Access Journals (Sweden)

    Jacopo Lamanna

    2012-01-01

    Full Text Available Since the pioneering work of Fatt and Katz at the neuromuscular junction (NMJ, spontaneous synaptic release (minis, that is, the quantal discharge of neurotransmitter molecules which occurs in the absence of action potentials, has been unanimously considered a memoryless random Poisson process where each quantum is discharged with a very low release probability independently from other quanta. When this model was thoroughly tested, for both population and single-synapse recordings, some clear evidence in favor of a more complex scenario emerged. This included short- and long-range correlation in mini occurrences and divergence from mono-exponential inter-mini-interval distributions, both unexpected for a homogeneous Poisson process, that is, with a rate parameter that does not change over time. Since we are interested in accurately quantifying the fractal exponent α of the spontaneous neurotransmitter release process at central synaptic sites, this work was aimed at evaluating the sensitivity of the most established methods available, such as the periodogram, the Allan, factor and the detrended fluctuation analysis. For this analysis we matched spontaneous release series recorded at individual hippocampal synapses (single-synapse recordings to generate large collections of simulated quantal events by means of a custom algorithm combining Monte Carlo sampling methods with spectral methods for the generation of 1/f series. These tests were performed by varying separately: (i the fractal exponent α of the rate driving the release process; (ii the distribution of intervals between successive releases, mimicking those encountered in single-synapse experimental series; (iii the number of samples. The aims were to provide a methodological framework for approaching the fractal analysis of single-unit spontaneous release series recorded at central synapses.

  7. Controllable biodegradability, drug release behavior and hemocompatibility of PTX-eluting magnesium stents.

    Science.gov (United States)

    Lu, Ping; Fan, Hainan; Liu, Yin; Cao, Lu; Wu, Xiangfeng; Xu, Xinhua

    2011-03-01

    Cardiovascular magnesium-based stents have been already applied in patients. However, their high corrosion rate hinders their clinical application. In this study, we adopt a new approach in the design of a Mg-based stent to improve the biodegradation rate and the drug release rate. By fabricating a micro-arc oxidation/poly-l-lactic acid (MAO/PLLA) composite coating on the magnesium alloy AZ81 substrate, the corrosion resistance decreased and the biodegradation rate became controllable. The drug release coating was composed of one Poly(dl-lactide-co-glycolide)/paclitaxel (PLGA/PTX) layer and one pure PLGA blank layer without paclitaxel, and this coating also functions to provide controlled biodegradation rate of the stent. The drug release rate was controlled by controlling the ratio of the LA:GA of the PLGA without PTX. The scanning electron microscopy (SEM) images were used to demonstrate the morphology of the samples before and after this modification. The blood compatibility of the samples was demonstrated by the platelet adhesion test. The drug release was determined by ultraviolet-visible (UV-visible) spectrophotometer. The result showed that the PLLA effectively sealed the micro-cracks and micro-holes on the surface of the MAO coating to give controllable biodegradation of the AZ81. The drug release rate of PTX exhibited a nearly linear sustained-release profile with no significant burst releases that would come from the uncontrolled oxidation/corrosion of AZ81. The samples modified had better hemocompatibility than 316L stainless steel. 2010 Elsevier B.V. All rights reserved.

  8. Dynamics of rapid dopamine release in the nucleus accumbens during goal-directed behaviors for cocaine versus natural rewards.

    Science.gov (United States)

    Cameron, Courtney M; Wightman, R Mark; Carelli, Regina M

    2014-11-01

    Electrophysiological studies show that distinct subsets of nucleus accumbens (NAc) neurons differentially encode information about goal-directed behaviors for intravenous cocaine versus natural (food/water) rewards. Further, NAc rapid dopamine signaling occurs on a timescale similar to phasic cell firing during cocaine and natural reward-seeking behaviors. However, it is not known whether dopamine signaling is reinforcer specific (i.e., is released during responding for only one type of reinforcer) within discrete NAc locations, similar to neural firing dynamics. Here, fast-scan cyclic voltammetry (FSCV) was used to measure rapid dopamine release during multiple schedules involving sucrose reward and cocaine self-administration (n = 8 rats) and, in a separate group of rats (n = 6), during a sucrose/food multiple schedule. During the sucrose/cocaine multiple schedule, dopamine increased within seconds of operant responding for both reinforcers. Although dopamine release was not reinforcer specific, more subtle differences were observed in peak dopamine concentration [DA] across reinforcer conditions. Specifically, peak [DA] was higher during the first phase of the multiple schedule, regardless of reinforcer type. Further, the time to reach peak [DA] was delayed during cocaine-responding compared to sucrose. During the sucrose/food multiple schedule, increases in dopamine release were also observed relative to operant responding for both natural rewards. However, peak [DA] was higher relative to responding for sucrose than food, regardless of reinforcer order. Overall, the results reveal the dynamics of rapid dopamine signaling in discrete locations in the NAc across reward conditions, and provide novel insight into the functional role of this system in reward-seeking behaviors. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Design and in vitro and in vivo characterization of mucoadhesive matrix pellets of metformin hydrochloride for oral controlled release: a technical note.

    Science.gov (United States)

    Ige, Pradum Pundlikrao; Gattani, Surendra Ganeshlal

    2012-03-01

    The aim of the current work was to design and develop matrix pellets of hydroxy propyl methyl cellulose K200M and microcrystalline cellulose in an admixture for a mucoadhesive gastroretentive drug delivery system. Pellets containing metformin hydrochloride (500 mg) were prepared by the pelletization technique using an extruder-spheronizer. Pellets were characterized by differential scanning calorimetry (DSC), x-ray diffraction (XRD), scanning electron microscopy (SEM), circularity, roundness, percent drug content, percent production yield, in vitro swelling, ex vivo mucoadhesion, in vitro drug release and in vivo x-ray imaging studies. Optimized pellets were sufficiently porous spheroids, free flowing, had smooth surfaces, had yields up to 75.45 ± 0.52% and had drug content up to 96.45 ± 0.19%. The average particle size of formulations MF2 and MF6 were 1.13 ± 0.41 mm and 1.22 ± 0.18 mm, respectively. Formulation MF6 exhibited strong adhesion, about 94.67%, to goat mucosal tissue, and the desired in vitro swelling, with a sustained drug release profile for 12 h and with retention in the upper small intestine of rabbits for 10 h. We conclude that hydroxy propyl methyl cellulose K200M and microcrystalline cellulose at a 2.80:1.00 w/w ratio could be an effective carrier for multiple unit controlled delivery of metformin hydrochloride.

  10. A controlled release of antibiotics from calcium phosphate-coated poly(lactic-co-glycolic acid) particles and their in vitro efficacy against Staphylococcus aureus biofilm.

    Science.gov (United States)

    Bastari, Kelsen; Arshath, Mohamed; Ng, Zhi Hui Melissa; Chia, Jia Hua; Yow, Zhi Xian Daniel; Sana, Barindra; Tan, Meng Fong Cherine; Lim, Sierin; Loo, Say Chye Joachim

    2014-03-01

    Ceramic-polymer hybrid particles, intended for osteomyelitis treatment, were fabricated by preparing poly(lactic-co-glycolic acid) particles through an emulsion solvent evaporation technique, followed by calcium phosphate (CaP) coating via a surface adsorption-nucleation method. The presence of CaP coating on the surface of the particles was confirmed by scanning electron microscopy, energy-dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy. Subsequently, two antibiotics for treating bone infection, nafcillin (hydrophilic) and levofloxacin (amphiphilic), were loaded into these hybrid particles and their in vitro drug release studies were investigated. The CaP coating was shown to reduce burst release, while providing sustained release of the antibiotics for up to 4 weeks. In vitro bacterial study against Staphylococcus aureus demonstrated the capability of these antibiotic-loaded hybrid particles to inhibit biofilm formation as well as deteriorate established biofilm, making this hybrid system a potential candidate for further investigation for osteomyelitis treatment.

  11. Prereproductive stress to female rats alters corticotropin releasing factor type 1 expression in ova and behavior and brain corticotropin releasing factor type 1 expression in offspring.

    Science.gov (United States)

    Zaidan, Hiba; Leshem, Micah; Gaisler-Salomon, Inna

    2013-11-01

    Human and animal studies indicate that vulnerability to stress may be heritable and that changes in germline may mediate some transgenerational effects. Corticotropin releasing factor type 1 (CRF1) is a key component in the stress response. We investigated changes in CRF1 expression in brain and ova of stressed female rats and in the brain of their neonate and adult offspring. Behavioral changes in adulthood were also assessed. Adult female rats underwent chronic unpredictable stress. We extracted mature oocytes and brain regions from a subset of rats and mated the rest 2 weeks following the stress procedure. CRF1 expression was assessed using quantitative reverse-transcription polymerase chain reaction. Tests of anxiety and aversive learning were used to examine behavior of offspring in adulthood. We show that chronic unpredictable stress leads to an increase in CRF1 messenger RNA expression in frontal cortex and mature oocytes. Neonatal offspring of stressed female rats show an increase in brain CRF1 expression. In adulthood, offspring of stressed female rats show sex differences in both CRF1 messenger RNA expression and behavior. Moreover, CRF1 expression patterns in frontal cortex of female offspring depend upon both maternal and individual adverse experience. Our findings demonstrate that stress affects CRF1 expression in brain but also in ova, pointing to a possible mechanism of transgenerational transmission. In offspring, stress-induced changes are evident at birth and are thus unlikely to result from altered maternal nurturance. Finally, brain CRF1 expression in offspring depends upon gender and upon maternal and individual exposure to adverse environment. © 2013 Society of Biological Psychiatry.

  12. Influence of formulation and process variables on in vitro release of theophylline from directly-compressed Eudragit matrix tablets.

    Science.gov (United States)

    Ceballos, A; Cirri, M; Maestrelli, F; Corti, G; Mura, P

    2005-01-01

    Extended-release theophylline (TP) matrix tablets were prepared by direct compression of drug and different pH-dependent (Eudragit L100, S100 and L100-55) and pH-independent (Eudragit RLPO and RSPO) polymer combinations. The influence of varying the polymer/polymer (w/w) ratio and the drug incorporation method (simple blend or solid dispersion) was also evaluated. Drug release, monitored using the Through Flow Cell system, markedly depended on both the kind of Eudragit polymer combinations used and their relative content in the matrix. Maintaining a constant 1:1 (w/w) drug/polymers ratio, the selection of appropriate mixtures of pH-dependent and pH-independent polymers enabled achievement of a suitable control of TP release. In particular, matrices with a 0.7:0.3 w/w mixture of Eudragit L100-Eudragit RLPO showed highly reproducible drug release profiles, with an almost zero-order kinetic, and allowed 100% released drug after 360 min. As for the effect of the drug incorporation method, simple blending was better than the solid dispersion technique, which not only did not improve the release data reproducibility, but also caused, unexpectedly, a marked slowing down in drug release rate.

  13. In vitro modulation of the behavior of adhering macrophages by medications is biomaterial-dependent.

    Science.gov (United States)

    Utomo, Lizette; Boersema, Geesien S A; Bayon, Yves; Lange, Johan F; van Osch, Gerjo J V M; Bastiaansen-Jenniskens, Yvonne M

    2017-03-07

    After implantation of a biomaterial, an inflammatory response involving macrophages is induced. The behavior of macrophages depends on their phenotype, and by directing macrophage polarization unwanted effects may be avoided. In this study, the possibility to modulate the behavior of macrophages activated by biomaterials was assessed in an in vitro model. Primary human monocytes were seeded on polyethylene terephthalate, polypropylene and polylactic acid yarns, and treated with medications frequently used by patients: rapamycin, dexamethasone, celecoxib or pravastatin. Modulation of the adhering macrophages with rapamycin resulted in a generally pro-inflammatory effect. Dexamethasone caused an overall anti-inflammatory effect on the macrophages cultured on either material, while celecoxib only affected macrophages adhering to polyethylene terephthalate and polylactic acid. Pravastatin increased the pro-inflammatory genes of macrophages cultured on polypropylene and polylactic acid. Pairwise comparison revealed that macrophages adhering to polylactic acid seemed to be more susceptible to phenotype modulation than when adhering to polypropylene or polyethylene terephthalate. The data show that macrophages activated by the biomaterials can be modulated, yet the degree of the modulatory capacity depends on the type of material. Combined, this model provides insights into the possibility of using a medication in combination with a biomaterial to direct macrophage behavior and thereby possibly avoid unwanted effects after implantation.

  14. N-Methyl-d-aspartate Modulation of Nucleus Accumbens Dopamine Release by Metabotropic Glutamate Receptors: Fast Cyclic Voltammetry Studies in Rat Brain Slices in Vitro.

    Science.gov (United States)

    Yavas, Ersin; Young, Andrew M J

    2017-02-15

    The N-methyl-d-aspartate (NMDA) receptor antagonist, phencyclidine, induces behavioral changes in rodents mimicking symptoms of schizophrenia, possibly mediated through dysregulation of glutamatergic control of mesolimbic dopamine release. We tested the hypothesis that NMDA receptor activation modulates accumbens dopamine release, and that phencyclidine pretreatment altered this modulation. NMDA caused a receptor-specific, dose-dependent decrease in electrically stimulated dopamine release in nucleus accumbens brain slices. This decrease was unaffected by picrotoxin, making it unlikely to be mediated through GABAergic neurones, but was decreased by the metabotropic glutamate receptor antagonist, (RS)-α-methyl-4-sulfonophenylglycine, indicating that NMDA activates mechanisms controlled by these receptors to decrease stimulated dopamine release. The effect of NMDA was unchanged by in vivo pretreatment with phencyclidine (twice daily for 5 days), with a washout period of at least 7 days before experimentation, which supports the hypothesis that there is no enduring direct effect of PCP at NMDA receptors after this pretreatment procedure. We propose that NMDA depression of accumbal dopamine release is mediated by metabotropic glutamate receptors located pre- or perisynaptically, and suggest that NMDA evoked increased extrasynaptic spillover of glutamate is sufficient to activate these receptors that, in turn, inhibit dopamine release. Furthermore, we suggest that enduring functional changes brought about by subchronic phencyclidine pretreatment, modeling deficits in schizophrenia, are downstream effects consequent on chronic blockade of NMDA receptors, rather than direct effects on NMDA receptors themselves.

  15. Effect of drug physicochemical properties on drug release and their relationship with drug skin permeation behaviors in hydroxyl pressure sensitive adhesive.

    Science.gov (United States)

    Liu, Chao; Quan, Peng; Fang, Liang

    2016-10-10

    The aim of this study was to investigate the influence of drug physicochemical properties on drug release behaviors and their relationship with skin permeation behaviors, which provided transdermal enhancement strategies for the design of transdermal drug delivery system. Six model drugs with different physicochemical properties were selected and hydroxyl pressure sensitive adhesive (PSA) was synthesized. Horizontal diffusion cell was used to evaluate drug release and skin permeation behaviors. The relationship between physicochemical properties and release behaviors was conducted with regression analysis. Release behavior of 0.25% drug loading was linear related with polar surface area, which represented the hydrogen bond. Release behavior of 2.0% drug loading was dependent on the polarizability and log P, which represented dipole-dipole interaction and lipophilicity, respectively. According to the results of Fourier transform infrared spectroscopy, it was inferred that hydrogen bond was limited in controlling release of drug due to the limited quantity of bonding site, thus dipole-dipole interaction and log P became dominate control factors. Combining the drug release study and drug skin permeation study, it was concluded that drugs with different physicochemical properties should be applied with different transdermal enhancement strategies, which was useful for the design of transdermal drug delivery system. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Mesenchymal stem cells modulate release of matrix proteins from tendon surfaces in vitro: a potential beneficial therapeutic effect.

    Science.gov (United States)

    Garvican, Elaine R; Dudhia, Jayesh; Alves, Ana-Liz; Clements, Lucy E; Plessis, Francois Du; Smith, Roger K W

    2014-05-01

    Injury of tendons contained within a synovial environment, such as joint, bursa or tendon sheath, frequently fails to heal and releases matrix proteins into the synovial fluid, driving inflammation. This study investigated the effectiveness of cells to seal tendon surfaces and provoke matrix synthesis as a possible effective injectable therapy. Equine flexor tendon explants were cultured overnight in suspensions of bone marrow and synovium-derived mesenchymal stems cells and, as controls, two sources of fibroblasts, derived from tendon and skin, which adhered to the explants. Release of the most abundant tendon extracellular matrix proteins into the media was assayed, along with specific matrix proteins synthesis by real-time PCR. Release of extracellular matrix proteins was influenced by the coating cell type. Fibroblasts from skin and tendon appeared less capable of preventing the release of matrix proteins than mesenchymal stems cells. The source of cell is an important consideration for cell therapy.

  17. Fluoride uptake in human teeth from fluoride-releasing restorative material in vivo and in vitro: two-dimensional mapping by EPMA-WDX.

    Science.gov (United States)

    Yamamoto, H; Iwami, Y; Unezaki, T; Tomii, Y; Ebisu, S

    2001-01-01

    Class V cavities were prepared in the upper and lower left second premolars from an individual under infiltration anesthesia. The cavities were filled with fluoride- releasing resin (TF). One month later, the teeth were extracted. As a control (in vitro), the upper and lower right second premolars were extracted at the time of the cavity preparation in vivo. Immediately after extraction, class V cavities were prepared and filled with TF, and immersed in normal saline solution for 1 month at 37 degrees C. All four premolars were bisected longitudinally and the fluoride uptake around the cavity wall on the cut surface was measured using an electron probe microanalyzer-wavelength dispersive X-ray method. The fluoride uptake was given in the form of a two-dimensional map. Comparison of the observed values of each corresponding part of the tooth in vivo and in vitro revealed no characteristic differences. The maps were quite analogous as a whole.

  18. In vitro immunomodulation of a whole blood IFN-γ release assay enhances T cell responses in subjects with latent tuberculosis infection.

    Directory of Open Access Journals (Sweden)

    Rajiv L Gaur

    Full Text Available Activation of innate immunity via pathogen recognition receptors (PRR modulates adaptive immune responses. PRR ligands are being exploited as vaccine adjuvants and as therapeutics, but their utility in diagnostics has not been explored. Interferon-gamma (IFN-γ release assays (IGRAs are functional T cell assays used to diagnose latent tuberculosis infection (LTBI; however, novel approaches are needed to improve their sensitivity.In vitro immunomodulation of a whole blood IGRA (QuantiFERON®-TB GOLD In-Tube with Toll-like receptor agonists poly(I:C, LPS, and imiquimod was performed on blood from subjects with LTBI and negative controls.In vitro immunomodulation significantly enhanced the response of T cells stimulated with M. tuberculosis antigens from subjects with LTBI but not from uninfected controls. Immunomodulation of IGRA revealed T cell responses in subjects with LTBI whose T cells otherwise do not respond to in vitro stimulation with antigens alone. Similar to their in vivo functions, addition of poly(I:C and LPS to whole blood induced secretion of inflammatory cytokines and IFN-α and enhanced the surface expression of antigen presenting and costimulatory molecules on antigen presenting cells.In vitro immunomodulation of whole blood IGRA may be an effective strategy for enhancing the sensitivity of T cells for diagnosis of LTBI.

  19. Effect of pullulan nanoparticle surface charges on HSA complexation and drug release behavior of HSA-bound nanoparticles.

    Directory of Open Access Journals (Sweden)

    Xiaojun Tao

    Full Text Available Nanoparticle (NP compositions such as hydrophobicity and surface charge are vital to determine the presence and amount of human serum albumin (HSA binding. The HSA binding influences drug release, biocompatibility, biodistribution, and intercellular trafficking of nanoparticles (NPs. Here, we prepared 2 kinds of nanomaterials to investigate HSA binding and evaluated drug release of HSA-bound NPs. Polysaccharides (pullulan carboxyethylated to provide ionic derivatives were then conjugated to cholesterol groups to obtain cholesterol-modified carboxyethyl pullulan (CHCP. Cholesterol-modified pullulan (CHP conjugate was synthesized with a similar degree of substitution of cholesterol moiety to CHCP. CHCP formed self-aggregated NPs in aqueous solution with a spherical structure and zeta potential of -19.9 ± 0.23 mV, in contrast to -1.21 ± 0.12 mV of CHP NPs. NPs could quench albumin fluorescence intensity with maximum emission intensity gradually decreasing up to a plateau at 9 to 12 h. Binding constants were 1.12 × 10(5 M(-1 and 0.70 × 10(5 M(-1 to CHP and CHCP, respectively, as determined by Stern-Volmer analysis. The complexation between HSA and NPs was a gradual process driven by hydrophobic force and inhibited by NP surface charge and shell-core structure. HSA conformation was altered by NPs with reduction of α-helical content, depending on interaction time and particle surface charges. These NPs could represent a sustained release carrier for mitoxantrone in vitro, and the bound HSA assisted in enhancing sustained drug release.

  20. Preparation and in vitro-in vivo evaluation of none gastric resident dipyridamole (DIP) sustained-release pellets with enhanced bioavailability.

    Science.gov (United States)

    Xu, Lishuang; Luo, Yanfei; Feng, Jia; Xu, Ming; Tao, Xiaoguang; He, Haibing; Tang, Xing

    2012-01-17

    The objective of this study was to develop none gastric resident sustained-release pellets loaded with dipyridamole with a high bioavailability. Two different kinds of core pellets, one containing citric acid as a pH-modifier (CAP) and, the other without pH-modifier (NCAP) were prepared by extrusion-spheronization and then coated with mixtures of enteric soluble and insoluble polymers (referred to as CAP(1) and NCAP(1)) or insoluble polymer alone (referred to as CAP(2) and NCAP(2)). The relative bioavailability of the sustained-release pellets was studied in fasted beagle dogs after oral administration using a commercially available immediate release tablet (IRT) as a reference. The in vitro release, in vivo absorption and in vitro-in vivo correlation were also evaluated. Results revealed that the plasma drug concentrations after administration of CAP(2), NCAP(1) and NCAP(2) were undetectable, indicating that the drug release was almost zero from the preparations throughout the gastro-intestinal tract. The C(max), T(max) and AUC((0→24)) of CAP(1) were 0.78 ± 0.23 (μg/ml), 3.80 ± 0.30 (h), and 6.74 ± 0.47 (μg/mlh), respectively. While the corresponding values were 2.23 ± 0.32 (μg/ml), 3.00 ± 0.44 (h) and 9.42 ± 0.69 (μg/mlh) for IRT. The relative bioavailability of CAP(1) was 71.55% compared with IRT. By combined incorporation of a pH-modifier into the core of pellets to modify the inner micro-environment and employing mixtures of enteric soluble and insoluble polymers as a retarding layer, drugs with high solubility in stomach and limited solubility in small intestine, such as DIP, could be successfully formulated as sustained release preparations with no pH-dependence in drug release and enhanced bioavailability. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Preparation and In Vitro Behavior of a Poly(lactic acid-Fiber/Hydroxyapatite Composite Sheet

    Directory of Open Access Journals (Sweden)

    Yasuhiro Tanimoto

    2009-01-01

    Full Text Available This paper describes the processing and in vitro behavior of a poly(lactic acid (PLA-fiber/hydroxyapatite (HA composite sheet consisting of a knitted PLA-fiber sheet and HA powder for bone tissue engineering. Type I collagen was used as a binding agent to combine the PLA fibers and the HA powder. Precipitate formation in Hanks' balanced salt (HBS solution was monitored to evaluate the in vitro apatite formation ability of the PLA-fiber/HA composite sheet. Precipitate formation was observed on the surface of the PLA-fiber/HA composite sheet after immersion in HBS solution for only 1 day, while no precipitate formation was observed on the PLA-fiber sheet without HA as a control. In conclusion, a PLA-fiber/HA composite sheet for use as a scaffold was successfully prepared. Within the limitations of this investigation, we confirmed that the PLA-fiber/HA composite sheet has a high apatite formation activity compared with the PLA-fiber sheet and represents a promising material for use as a scaffold.

  2. Nanoformulations for dimethyl fumarate: Physicochemical characterization and in vitro/in vivo behavior.

    Science.gov (United States)

    Esposito, Elisabetta; Cortesi, Rita; Drechsler, Markus; Fan, Jie; Fu, Bingmei M; Calderan, Laura; Mannucci, Silvia; Boschi, Federico; Nastruzzi, Claudio

    2017-06-01

    Dimethyl fumarate has been demonstrated useful in relapsing remitting multiple sclerosis treatment (Tecfidera®). Nevertheless, since Tecfidera® capsules induce flushing, gastro-intestinal events and other more serious drawbacks, in this investigation a nanoparticle based system to be administered by an alternative way is proposed. In particular this study describes the preparation and characterization of dimethyl fumarate-containing solid lipid nanoparticles (SLN). Namely SLN based on tristearin, tristearin SLN treated with polysorbate 80 and cationic SLN constituted of tristearin in mixture with dimethyldioctadecylammonium chloride were investigated. The effect of the presence of dimethyl fumarate, functionalization by polysorbate 80 and dimethyldioctadecylammonium chloride was studied on morphology and dimensional distribution of SLN, by photon correlation spectroscopy and cryogenic transmission electron microscopy. Dimethyl fumarate release from SLN, studied by Franz cell, evidenced a Fickian dissolutive type kinetic in the case of SLN treated by polysorbate 80. Moreover fluorescent SLN were produced and characterized in order to investigate their in vitro permeability and in vivo biodistribution in mice. An in vitro study of fluorescent SLN permeability performed through a model of mouse brain microvascular endothelial cells, indicated that cationic SLN displayed higher permeability values with respect to neutral SLN and SLN treated by polysorbate 80. Biodistribution of polysorbate 80 treated SLN was studied by fluorescent imaging after intraperitoneal or intranasal administration in mice. The in vivo images indicate that polysorbate 80 treated SLN were able to reach the brain, even if they prevalently accumulated in liver and spleen, especially by intraperitoneal route. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Effect of mechanical and electrical behavior of gelatin hydrogels on drug release and cell proliferation.

    Science.gov (United States)

    Biswal, Dibyajyoti; Anupriya, B; Uvanesh, K; Anis, Arfat; Banerjee, Indranil; Pal, Kunal

    2016-01-01

    The present study was aimed to explore the effect of the mechanical and the electrical properties of the gelatin hydrogels on the mammalian cell proliferation and drug release properties. FTIR analysis of the hydrogels suggested that gelatin retained its secondary protein structure. A decrease in the diffusion constant of the water molecules was observed with the increase in the gelatin concentration in the hydrogels. The mechanical and the electrical stabilities of the hydrogels were enhanced with the increase in the gelatin content. Stress relaxation and creep studies were modeled using Weichert and Burger׳s models, respectively. The relaxation time (stress relaxation study) did not follow a concentration-dependent relationship and was found to affect the MG-63 cell (human osteoblast) proliferation. The impedance profile of the hydrogels was modeled using a (RQ)Q model. Release of ciprofloxacin from the hydrogels was inversely dependent on the rate of swelling. The release of the drug was not only dependent on the Fickian diffusion but also on the relaxation process of the gelatin chains. The inhomogeneous constant of the constant phase element representing the hydrogel-electrode interface indicated improved cell proliferation rate with a decrease in the inhomogeneous constant. In gist, the rate of cell proliferation could be related to the relaxation time (stress relaxation) and the inhomogeneous constant of the sample-electrode constant phase element (electrical study) properties, whereas, the drug release properties can be related to the bulk resistance of the formulations. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Assessment of Ions released from Three Types of Orthodontic Brackets immersed in Different Mouthwashes: An in vitro Study.

    Science.gov (United States)

    Nahidh, Mohammed; Garma, Noor Mh; Jasim, Esraa S

    2018-01-01

    Herbs are used widely in medicine. The purpose of the present study was to assess the ion release from gold-plated orthodontic bracket compared with other stainless steel brackets, and based on the findings of the study, the orthodontists can choose the most biocompatible brackets and mouthwashes useful in the clinical practice. A total of 150 orthodontic brackets from Orthotechnology™ Company, USA (50 stainless steel one-piece brackets, 50 stainless steel two-piece brackets, and 50 gold brackets) were immersed in four mouthwashes in addition to distilled water. Ten of each type of brackets in every media were immersed under 37°C for 45 days. Ions released in these mouthwashes were measured, and comparisons among different bracket types and among various mouthwashes were done by one-way analysis of variance (ANOVA) and then with Games-Howell tests. Increased amounts of ions released in herbal mouth-washes were recorded in gold and two-piece brackets in comparison with one-piece stainless steel brackets. Herbal mouthwashes must be used with caution as they showed an increased amount of ions released in comparison with chlorhexidine. One-piece stainless steel bracket system is the most compatible bracket type, as they released the least amount of ions. One-piece stainless steel brackets are better than two-piece brackets in terms of ions released.

  5. Incorporation of zinc oxide to dispersions of biopolymers and release of the metallic ion in vitro; Incorporacao de oxido de zinco a dispersoes de biopolimeros e liberacao do ion metalico in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Barreto, Marina S.R.; Ferreira, Willian H.; Andrade, Cristina T., E-mail: marinarodriguesbarreto@gmail.com [Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil)

    2015-07-01

    Zinc oxide (ZnO) nanoparticles, obtained from a commercial product, were dispersed in different biopolymers, to be added to piglet feeds. The resulting products, prepared with sodium alginate (SA), chitosan (CH) and low methoxyl pectin (LMP) were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The release of Zn{sup 2+} was investigated under simulated conditions of the gastrointestinal tract of piglets, and analyzed by atomic absorption spectroscopy (AA). The results showed that the structural factors, which have influence on the biopolymer/ZnO interactions, govern the behavior of Zn{sup 2+} release. (author)

  6. Solid lipid particles for oral delivery of peptide and protein drugs III - the effect of fed state conditions on the in vitro release and degradation of desmopressin

    DEFF Research Database (Denmark)

    Christophersen, Philip C; Vaghela, Dimple; Müllertz, Anette

    2014-01-01

    The effect of food intake on the release and degradation of peptide drugs from solid lipid particles is unknown and was therefore investigated in vitro using different fed state media in a lipolysis model. Desmopressin was used as a model peptide and incorporated into solid lipid particles...... and the protease or desmopressin. Addition of a medium chain triglyceride, trilaurin, in combination with drug-loaded lipid particles diminished the food effect on the TG18 particles, and trilaurin is therefore proposed to be a suitable excipient for reduction of the food effect. Overall, the present study shows...... that strategies to reduce food effect, such as adding trilaurin, for lipid particle formulations should be considered as drug release from such formulations might be influenced by the presence of food in the gastrointestinal tract....

  7. The Effect in Vitro of Ionizing Irradiation and Small Rises in Temperature on the Uptake and Release of Labelled Lipids by the Human Erythrocyte Membrane

    DEFF Research Database (Denmark)

    Hansen, Heinz Johs. Max; Karle, H.; Stender, S.

    1978-01-01

    1. The effect of X-irradiation (50 000 rad) and an increase in temperature from 37 to 42° C on the synthesis, uptake and release of labelled lipids by erythrocytes was studied in plasma incubations in vitro. 2. Both irradiation and a rise in temperature resulted in an enhanced synthesis of [32P......]phosphatidic acid in the erythrocytes. 3. The uptake by the erythrocytes of 14C- and 3H-labelled cholesterol, [14C, 32P]phosphatidylethanolamine and [14C, 32P]phosphatidylcholine from plasma lipoproteins was increased by a rise in temperature but not by irradiation. These labelled lipids were apparently taken up...... in the ratio in which they were found in plasma. They were not released from the erythrocytes in the same manner....

  8. Phosphorus release behaviors of poultry litter biochar as a soil amendment

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yue [Department of Civil and Environmental Engineering, University of Delaware, Newark, DE 19716 (United States); Lin, Yingxin [Department of Agriculture and Natural Resources, Delaware State University, Dover, DE 19901 (United States); Chiu, Pei C.; Imhoff, Paul T. [Department of Civil and Environmental Engineering, University of Delaware, Newark, DE 19716 (United States); Guo, Mingxin, E-mail: mguo@desu.edu [Department of Agriculture and Natural Resources, Delaware State University, Dover, DE 19901 (United States)

    2015-04-15

    Phosphorus (P) may be immobilized and consequently the runoff loss risks be reduced if poultry litter (PL) is converted into biochar prior to land application. Laboratory studies were conducted to examine the water extractability of P in PL biochar and its release kinetics in amended soils. Raw PL and its biochar produced through 400 °C pyrolysis were extracted with deionized water under various programs and measured for water extractable P species and contents. The materials were further incubated with a sandy loam at 20 g kg{sup −1} soil and intermittently leached with water for 30 days. The P release kinetics were determined from the P recovery patterns in the water phase. Pyrolysis elevated the total P content from 13.7 g kg{sup −1} in raw PL to 27.1 g kg{sup −1} in PL biochar while reduced the water-soluble P level from 2.95 g kg{sup −1} in the former to 0.17 g kg{sup −1} in the latter. The thermal treatment transformed labile P in raw PL to putatively Mg/Ca phosphate minerals in biochar that were water-unextractable yet proton-releasable. Orthophosphate was the predominant form of water-soluble P in PL biochar, with condensed phosphate (e.g., pyrophosphate) as a minor form and organic phosphate in null. Release of P from PL biochar in both water and neutral soils was at a slower and steadier rate over a longer time period than from raw PL. Nevertheless, release of P from biochar was acid-driven and could be greatly promoted by the media acidity. Land application of PL biochar at soil pH-incorporated rates and frequency will potentially reduce P losses to runoffs and minimize the adverse impact of waste application on aquatic environments. - Highlights: • The predominant portion of P in poultry litter biochar is water insoluble. • Poultry litter P was immobilized by forming Ca/Mg (pyro)phosphates in biochar. • Release of P from biochar was slower and steadier than from raw poultry litter. • Soil pH greatly influenced the P release patterns

  9. Negative online word-of-mouth: Behavioral indicator or emotional release?

    NARCIS (Netherlands)

    Verhagen, T.; Nauta, A.; Feldberg, J.F.M.

    2013-01-01

    The influence of negative online word-of-mouth on the behavior of those receiving it has been addressed extensively in the academic literature. Remarkably, the question whether negative online word-of-mouth should also be seen as a behavioral indicator of its sender remains unaddressed. Answering

  10. Effect of no synthesis inhibition on striatal dopamine release and stereotyped behavior induced by a single administration of methamphetamine.

    Science.gov (United States)

    Abekawa, T; Ohmori, T; Koyama, T

    1997-07-01

    1. The authors performed both microdialysis and behavioral measurement in each of rats, in order to examine effects of nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (LNAME;30 mg/kg,i.p.) on striatal dopamine (DA) release and stereotypy induced by a single administration of methamphetamine (MA)(4 mg/kg,s.c.), simultaneously. 2. LNAME administered prior to MA significantly decreased level of locomotion-stereotypy rating scores induced by MA. 3. In the same animals, LNAME had no effect on MA-induced striatal DA release. 4. The results suggest that NO synthesis inhibition attenuated MA-induced stereotypy by modulating neuronal process subsequent to activation of postsynaptic DA receptors.

  11. Behaviors of controlled drug release of magnetic-gelatin hydrogel coated stainless steel for drug-eluting-stents application

    Science.gov (United States)

    Huang, Li-Ying; Yang, Ming-Chien

    2007-03-01

    The behavior of drug release controlled by magnetic fields (MF) for stainless steel coated with magnetic-gelatin (MAG-GE) hydrogel was investigated in this paper. X-ray photoelectron spectroscope (XPS) and vibrating sample magnetometer were used to evaluate the characterizations of MAG-GE hydrogel and the interaction with the surface of SUS316L. A model drug (sirolimus) was loaded to the MAG-GE hydrogel. When applying MF to the MAG-GE hydrogel, the sirolimus release rate of the magnetic hydrogel decreased by {1}/{3}, comparing to that without the field. This suggests a "close" configuration of the MAG-GE hydrogel due to the aggregation of magnetic nanoparticles which reduced the pore size of MAG-GE hydrogel.

  12. Behaviors of controlled drug release of magnetic-gelatin hydrogel coated stainless steel for drug-eluting-stents application

    Energy Technology Data Exchange (ETDEWEB)

    Huang, L.-Y. [Department of Polymer Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan 106 (China)]. E-mail: hliying@ebtnet.net; Yang, M.-C. [Department of Polymer Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan 106 (China)]. E-mail: myang@mail.ntust.edu.tw

    2007-03-15

    The behavior of drug release controlled by magnetic fields (MF) for stainless steel coated with magnetic-gelatin (MAG-GE) hydrogel was investigated in this paper. X-ray photoelectron spectroscope (XPS) and vibrating sample magnetometer were used to evaluate the characterizations of MAG-GE hydrogel and the interaction with the surface of SUS316L. A model drug (sirolimus) was loaded to the MAG-GE hydrogel. When applying MF to the MAG-GE hydrogel, the sirolimus release rate of the magnetic hydrogel decreased by 13, comparing to that without the field. This suggests a ''close'' configuration of the MAG-GE hydrogel due to the aggregation of magnetic nanoparticles which reduced the pore size of MAG-GE hydrogel.

  13. Biscuits with No Added Sugar Containing Stevia, Coffee Fibre and Fructooligosaccharides Modifies α-Glucosidase Activity and the Release of GLP-1 from HuTu-80 Cells and Serotonin from Caco-2 Cells after In Vitro Digestion.

    Science.gov (United States)

    Martinez-Saez, Nuria; Hochkogler, Christina Maria; Somoza, Veronika; Del Castillo, Maria Dolores

    2017-07-04

    This study assessed the in vitro effects of the bioaccessible food components released during the simulated human digestion of a coffee fibre-containing biscuit (CFB) on α-glucosidase activity, antioxidant capacity and satiety hormones. Digest of CFB presented a significantly (p diabetes-related digestive enzyme, and to improve the release of satiety hormones.

  14. Plantago ovata F. Mucilage-Alginate Mucoadhesive Beads for Controlled Release of Glibenclamide: Development, Optimization, and In Vitro-In Vivo Evaluation

    Directory of Open Access Journals (Sweden)

    Amit Kumar Nayak

    2013-01-01

    Full Text Available The current study deals with the development and optimization of ispaghula (Plantago ovata F. husk mucilage- (IHM- alginate mucoadhesive beads containing glibenclamide by ionotropic gelation technique. The effects of sodium alginate (SA to IHM and cross-linker (CaCl2 concentration on the drug encapsulation efficiency (DEE, %, as well as cumulative drug release after 10 hours (R10 h, %, were optimized using 32 factorial design based on response surface methodology. The observed responses were coincided well with the predicted values by the experimental design. The optimized mucoadhesive beads exhibited 94.43±4.80% w/w of DEE and good mucoadhesivity with the biological membrane in wash-off test and sustained drug release profile over 10 hours. The beads were also characterized by SEM and FTIR analyses. The in vitro drug release from these beads was followed by controlled release (zero-order pattern with super case-II transport mechanism. The optimized glibenclamide-loaded IHM-alginate mucoadhesive beads showed significant antidiabetic effect in alloxan-induced diabetic rats over prolonged period after oral administration.

  15. Development of in vitro-in vivo correlation for extended-release niacin after administration of hypromellose-based matrix formulations to healthy volunteers.

    Science.gov (United States)

    Kesisoglou, Filippos; Rossenu, Stefaan; Farrell, Colm; Van Den Heuvel, Michiel; Prohn, Marita; Fitzpatrick, Shaun; De Kam, Pieter-Jan; Vargo, Ryan

    2014-11-01

    Development of in vitro-in vivo correlations (IVIVCs) for extended-release (ER) products is commonly pursued during pharmaceutical development to increase product understanding, set release specifications, and support biowaivers. This manuscript details the development of Level C and Level A IVIVCs for ER formulations of niacin, a highly variable and extensively metabolized compound. Three ER formulations were screened in a cross-over study against immediate-release niacin. A Multiple Level C IVIVC was established for both niacin and its primary metabolite nicotinuric acid (NUA) as well as total niacin metabolites urinary excretion. For NUA, but not for niacin, Level A IVIVC models with acceptable prediction errors were achievable via a modified IVIVC rather than a traditional deconvolution/convolution approach. Hence, this is in contradiction with current regulatory guidelines that suggest that when a Multiple Level C IVIVC is established, Level A models should also be readily achievable. We demonstrate that for a highly variable, highly metabolized compound such as niacin, development of a Level A IVIVC model fully validated according to agency guidelines may be challenging. However, Multiple Level C models are achievable and could be used to guide release specifications and formulation/manufacturing changes. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  16. Exploring polyvinylpyrrolidone in the engineering of large porous PLGA microparticles via single emulsion method with tunable sustained release in the lung: In vitro and in vivo characterization.

    Science.gov (United States)

    Ni, Rui; Muenster, Uwe; Zhao, Jing; Zhang, Lan; Becker-Pelster, Eva-Maria; Rosenbruch, Martin; Mao, Shirui

    2017-03-10

    Sustained pulmonary drug delivery is regarded as an effective strategy for local treatment of chronic lung diseases. Despite of the progress made so far, there remains a need for respirable drug loaded porous microparticles, where porosity of the microparticles can be readily engineered during the preparation process, with tunable sustained drug release upon lung deposition. In this work, polyvinyl pyrrolidone (PVP) was used as a novel porogen to engineer PLGA-based large porous particles (LPPs) using single emulsion method, with fine tuning of the porosity, sustained drug release both in vitro and in vivo. Using cinaciguat as the model drug, influence of PVP content and PLGA type on the properties of the LPPs was characterized, including geometric particle size, drug encapsulation efficiency, tap density, theoretical and experimental aerodynamic particle size, specific surface area, morphology, and in vitro drug release. Solid state of cinaciguat in the LPPs was studied based on DSC and X-ray analysis. LPPs retention in the rat lung was carried out using bronchoalveolar lavage fluid method. Raw 264.7 macrophage cells were used for LPPs uptake study. Pharmacodynamic study was performed in mini-pigs in a well-established model of pulmonary arterial hypertension (thromboxane challenge). It was demonstrated that porosity of the LPPs is tunable via porogen content variation. Cinaciguat can be released from the LPP in a controlled manner for over 168h. Significant reduction of macrophage phagocytosis was presented for LPPs. Furthermore, LPPs was found to have extended retention time (~36h) in the rat lung and accordingly, sustained pharmacodynamics effect was achieved in mini-pig model. Taken together, our results demonstrated that this simple PLGA based LPPs engineering using single emulsion method with PVP as porogen may find extensive application for the pulmonary delivery of hydrophobic drugs to realize tunable sustained effect with good safety profile. Copyright

  17. Analytical and electrochemical evaluation of the in vitro corrosion behavior of nickel-chrome and cobalt-chrome casting alloys for metal-ceramic restorations.

    Science.gov (United States)

    Yfantis, Constaninos; Yfantis, Dimitrios; Anastassopoulou, Jane; Theophanides, Theophilos

    2007-03-01

    In this study we examined the hypothesis based on relevant literature survey that the in vitro corrosion behavior of a Cobalt-chrome dental casting alloy for metal-ceramic restorations is better than that of a Nickel-chrome dental casting alloy. The corrosion released metal ions were analysed by Inductively Coupled Plasma-Atomic Emission Spectroscopy. Moreover, the specimens were electrochemically tested by linear polarization. The statistical analysis of the results showed statistically significant differences in corrosion rates of Nickel-chrome alloy and Cobalt-chrome alloy calculated by analytical and electrochemical measurements. The hypothesis was confirmed and the results showed that the corrosion rates of the Cobalt-chrome alloy were lower than that of the Nickel-chrome alloy.

  18. Effect of ethylene glycol dimethacrylate on swelling and on metformin hydrochloride release behavior of chemically crosslinked pH-sensitive acrylic acid-polyvinyl alcohol hydrogel

    National Research Council Canada - National Science Library

    Akhtar, Muhammad Faheem; Ranjha, Nazar Muhammad; Hanif, Muhammad

    2015-01-01

    The present work objective was to prepare and to observe the effect of ethylene glycol dimethacrylate on swelling and on drug release behavior of pH-sensitive acrylic acid-polyvinyl alcohol hydrogel...

  19. Alpha-melanocyte-stimulating hormone attenuates behavioral effects of corticotropin-releasing factor in isolated guinea pig pups.

    Science.gov (United States)

    Schiml-Webb, Patricia A; Miller, Emily; Deak, Terrence; Hennessy, Michael B

    2009-07-01

    During a 3-hr period of social isolation in a novel environment, guinea pig pups exhibit an initial active phase of behavioral responsiveness, characterized primarily by vocalizing, which is then followed by a stage of passive responsiveness in which pups display a distinctive crouch, eye-closing, and extensive piloerection. Prior treatment of pups with alpha-melanocyte-stimulating hormone (alpha-MSH) reduces each of the passive behaviors. The onset of passive responding during separation can be accelerated with peripheral injection of corticotropin-releasing factor (CRF). To examine whether CRF produces its effects through a mechanism similar to that of prolonged separation, we examined the effect of administering alpha-MSH to pups injected with CRF. As expected, CRF markedly enhanced passive responding during a 60-min period of separation. alpha-MSH delivered by either intracerebroventricular infusion or intraperitoneal injection significantly reduced each of the passive behavioral responses without significantly affecting active behavior. These findings, together with previous results indicating that it is the anti-inflammatory property of alpha-MSH that is responsible for its behavioral effects during prolonged separation, suggest that peripheral CRF speeds the induction of passive responding through a mechanism involving enhanced proinflammatory activity.

  20. Investigation on the ion pair amphiphiles and their in vitro release of amantadine drug based on PLGA–PEG–PLGA gel

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Xiaoxia, E-mail: yxx-678@163.com; Ji, Xiaoqing; Shi, Chunhuan; Liu, Jing [Shandong University, School of Pharmaceutical Science and Center for Pharmaceutical Research & Drug Delivery Systems (China); Wang, Haiyang [Institute of Materia Medica Shandong Academy of Medical Sciences, Shandong Taitian Newdrug Discovery Co.Ltd (China); Luan, Yuxia, E-mail: yuxialuan@sdu.edu.cn [Shandong University, School of Pharmaceutical Science and Center for Pharmaceutical Research & Drug Delivery Systems (China)

    2014-12-15

    The amantadine drug and oleic acid surfactant are used to form amantadine-based ion pair amphiphiles based on proton transfer reaction between the drug and the surfactant molecules. The ion pair amphiphiles are characterized by {sup 1}H-nuclear magnetic resonance, Fourier transform infrared spectroscopy, and X-ray diffraction. Self-assembly properties of amantadine-based ion pair amphiphiles are studied by surface tension determination, transmission electron microscopy, zeta potential, and dynamic light scattering. The aggregation behavior studies indicate that the as-prepared ion pair amphiphiles can self-assemble into vesicles with the size of 200–300 nm in aqueous solution. The drug release results show that the amantadine release rate could be well controlled by incorporating the amantadine-based ion pair vesicles in poly (lactic-co-glycolic acid)-poly (ethylene glycol)-poly (lactic-co-glycolic acid) (PLGA–PEG–PLGA) copolymer hydrogel. The drug release from the AT–OA vesicle-loaded PLGA–PEG–PLGA hydrogel is significantly inhibited in comparison with the AT-loaded PLGA–PEG–PLGA hydrogel. The present work thus demonstrates that the vesicle-loaded hydrogel is a good candidate for the drug delivery system with long-term controlled drug release behavior.

  1. Investigation on the ion pair amphiphiles and their in vitro release of amantadine drug based on PLGA-PEG-PLGA gel

    Science.gov (United States)

    Yang, Xiaoxia; Ji, Xiaoqing; Shi, Chunhuan; Liu, Jing; Wang, Haiyang; Luan, Yuxia

    2014-12-01

    The amantadine drug and oleic acid surfactant are used to form amantadine-based ion pair amphiphiles based on proton transfer reaction between the drug and the surfactant molecules. The ion pair amphiphiles are characterized by 1H-nuclear magnetic resonance, Fourier transform infrared spectroscopy, and X-ray diffraction. Self-assembly properties of amantadine-based ion pair amphiphiles are studied by surface tension determination, transmission electron microscopy, zeta potential, and dynamic light scattering. The aggregation behavior studies indicate that the as-prepared ion pair amphiphiles can self-assemble into vesicles with the size of 200-300 nm in aqueous solution. The drug release results show that the amantadine release rate could be well controlled by incorporating the amantadine-based ion pair vesicles in poly (lactic-co-glycolic acid)-poly (ethylene glycol)-poly (lactic-co-glycolic acid) (PLGA-PEG-PLGA) copolymer hydrogel. The drug release from the AT-OA vesicle-loaded PLGA-PEG-PLGA hydrogel is significantly inhibited in comparison with the AT-loaded PLGA-PEG-PLGA hydrogel. The present work thus demonstrates that the vesicle-loaded hydrogel is a good candidate for the drug delivery system with long-term controlled drug release behavior.

  2. Evaluation and comparison of quantity and pattern of fluoride release from orthodontic adhesives: an in vitro study.

    Science.gov (United States)

    Regalla, Ravindra Reddy; Jadav, Chandulal; Babu, Devatha Ashok; Sriram, Roopa Rani S; Sriram, Sanjay Krishna; Kattimani, Vivekanand S

    2014-01-01

    Orthodontic treatment has gained popularity since beginning of era of dentistry. Now a day, everyone is conscious about their appearance, smile and function. During orthodontic treatment use of brackets and adhesives are common. The bonding of brackets will cause demineralization which requires the fluoridation. So the study has been under- taken to analyze the pattern of fluoride release by commercially available adhesive bonding material for the prevention of demineralization. To evaluate and compare the clinical significance of quantity and pattern of fluoride release from three commercially available adhesives. To assess the pattern of fluoride release and quantity, to reduce the decalcification of enamel around orthodontic brackets and bands during treatment and to prevent further use of topical fluoride both office and self-use agents for prevention of demineralization/for remineralization. The comparison of quantity and pattern of fluoride release study involved commercially available bonding adhesives. They are: Group I--resin reinforced glass Ionomer light cure material (OrthoLC), Group II--fluoride releasing composite resin material (Excel) and Group III--conventional composite (Relay-a-bond) evaluated on 78 freshly extracted premolar teeth divided into three groups consisting 26 specimens in each group. The prepared specimens were stored in artificial saliva at 37°C in an incubator for subsequent fluoride analysis using ORION ion selective electrode coupled with ionalyzer 901. Fluoride analysis made at 24 hours intervals for first 3 consecutive days and thereafter at the end of 10th, 17th, 24th and 31st day of bonding. The data obtained were tabulated and interpreted by statistical analysis using 't' test and one-way analysis of variance (ANOVA). The quantity of fluoride release in groups I and II was significant even at the end of 31st day. The one-way AVOVA showed intra and inter group significance in the quantity of fluoride release. But group III

  3. Measuring the dynamic compression and release behavior of rocks and grouts associated with HYDROPLUS

    Energy Technology Data Exchange (ETDEWEB)

    Furnish, M.D.

    1993-10-01

    Gas-gun impact tests were performed on twelve rocks and rock simulants pertinent to the HYDROPLUS nuclear yield measurement program: A variety of tuffs, rhyolites, carbonates, grouts, an epoxy-alumina mixture and quartzite permafrost samples recovered in an apparently preserved frozen state from northern Canada. The present report presents results for all of these materials except for the carbonates. Two classes of impact techniques were employed for measuring equation-of-state properties for these materials. Both use velocity interferometry diagnostics. One, employing a sample-in-projectile geometry, provides high-precision Hugoniot data and continuous release trajectories for dry or water-saturated materials. The majority of the experiments were performed with this geometry. The other, employing a sample-in-target geometry, provides loading path and Hugoniot data as well as limited release data. Uncertainties in the results have been estimated by analyzing the effects of errors in observables and ancillary material properties.

  4. Patrón de liberación de flúor in vitro en sellantes fluorados de resina In vitro fluoride-release profile of fluoridated resin-based sealants

    Directory of Open Access Journals (Sweden)

    S Gómez

    2011-12-01

    Full Text Available Objetivo: Comparar in vitro la cantidad de fluoruros liberados por los principales sellantes de puntos y fisuras basados en resina comercialmente disponibles en Latinoamérica. Material y Métodos: Se evaluó la liberación de fluoruros in vitro en tres sellantes fluorados de puntos y fisuras: Helioseal F (HF, Fissurit F (FF, Clinpro (CF y Delton (D, sin flúor como control. Se utilizaron 28 discos de 12 mm de diámetro y 2 mm de espesor (n=7 por grupo. Las muestras fueron almacenadas en 5 ml de agua ultra de-ionizada con pH neutro a 37º C por 93 días. La liberación de fluoruros fue medida mediante un electrodo iónico selectivo a los 1, 2, 3, 8, 15, 28 y 93 días. Los datos fueron analizados con el test ANOVA y Tukey (pAim: To compare in vitro the amount of fluoride released from the main pit and fissure sealant resin-based on commercially available in Latin America. Materials and Methods: Twenty-eight samples of 12 x 2 mm were made from three commercial fluoridated resin-based sealants: Helioseal F (HF, Fissurit F (FF, Clinpro (CF and without fluoride Delton (D, as a control. Samples were stored in 5 ml of deionized water at 37° C and neutral pH. Fluoride releases were measured at 1, 2, 3, 8, 15, 28 and 93 days with an ion-selective electrode. Data were analyzed using ANOVA and one-way and Tukey (p0.05. Conclusion: The fluoride-release profile is similar for the fluoridated resin-based sealants under study: a high release during the first two days and afterwards, a very slow release. These results can explain the lack of differences in caries rate between fluoridated and non-fluoridated resin-based sealants observed in clinical trials.

  5. Structural modifications of polymethacrylates: impact on thermal behavior and release characteristics of glassy solid solutions.

    Science.gov (United States)

    Claeys, Bart; De Coen, Ruben; De Geest, Bruno G; de la Rosa, Victor R; Hoogenboom, Richard; Carleer, Robert; Adriaensens, Peter; Remon, Jean Paul; Vervaet, Chris

    2013-11-01

    Polymethacrylates such as Eudragit® polymers are well established as drug delivery matrix. Here, we synthesize several Eudragit E PO (n-butyl-, dimethylaminoethyl-, methyl-methacrylate-terpolymer) analogues via free radical polymerization. These polymers are processed via hot melt extrusion, followed by injection molding and evaluated as carriers to produce immediate release solid solution tablets. Three chemical modifications increased the glass transition temperature of the polymer: (a) substitution of n-butyl by t-butyl groups, (b) reduction of the dimethylaminoethyl methacrylate (DMAEMA) content, and (c) incorporation of a bulky isobornyl repeating unit. These structural modifications revealed the possibility to increase the mechanical stability of the tablets via altering the polymer Tg without influencing the drug release characteristics and glassy solid solution forming properties. The presence of DMAEMA units proved to be crucial with respect to API/polymer interaction (essential in creating glassy solid solutions) and drug release characteristics. Moreover, these chemical modifications accentuate the need for a more rational design of (methacrylate) polymer matrix excipients for drug formulation via hot melt extrusion and injection molding. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. A novel drug carrier based on functional modified nanofiber cellulose and the control release behavior

    Science.gov (United States)

    Shi, Xiangning; Zheng, Yudong; Zhang, Wei; Zhang, Zeyu; Peng, Yunling

    2013-08-01

    This study developed a novel drug carrier based on functional modified bacterial cellulose(BC) which was conjugated with Ibuprofen(IBU) by esterification. BC-Ibuprofen as the macro- molecular prodrugs and drug carrier used to improve the short half-life of the drug, and was able to control release through the hydrolysis of ester bond between the hydroxyl groups of BC with Ibuprofen under different condition. Fourier transform infrared analysis revealed that Ibuprofen had been successfully grafted onto the bacterial cellulose (BC). Thermal and morphological characterization indicated the formation of the BC-Ibuprofen system incompletely reacted maintained the bulk structure of the pristine material such as crystallinity, 3-dimentional network and so on. The drug release behaviours were affected by the ester bond hydrolysis as well as the microstructure characteristics of the modified nanofiber. The release of BC-IBU showed an apparent pH-dependent, fast in alkaline and acid solution but slow relatively in neutral. Such pH-responsiveness, in addition to its morphological characteristics, in this paper suggested a great potential of BC-IBU as a more effective, safe, and stable prodrug candidate.

  7. Investigation into drug release from colon-specific azoreductase-activated steroid prodrugs using in-vitro models.

    Science.gov (United States)

    Ruiz, Juan F Marquez; Kedziora, Kinga; Windle, Henry; Kelleher, Dermot P; Gilmer, John F

    2011-06-01

    The aim of this study was to investigate drug release from a double steroid prodrug, OPN501, which incorporates a phenylpropionate linker, and its phenylacetate analogue. The prodrugs, which were designed to deliver prednisolone to the colon for the treatment of inflammatory bowel disease, are based on a novel design that requires sequential azoreductase activity and cyclization of an amino ester to trigger drug release. We sought to explain the divergent effects of the two compounds in anti-inflammatory models and to justify the selection of OPN-501 for clinical development. The compounds were incubated in mouse colonic contents (10%) fermented in brain heart infusion under anaerobic conditions. The disappearance of the prodrugs and release of prednisolone was monitored by HPLC. We then developed a method for assessment of prodrug activation using suspensions of Clostridium perfringens, an anaerobe from the human colon. The cyclization of the compounds was studied in various media, assessing the influence of pH and bulk solvent polarity on cyclization rate using HPLC and NMR. The prodrugs were activated via multiple pathways releasing prednisolone in mouse colonic ferment. The compounds released prednisolone by reduction-cyclization in C perfringens suspension. The active OPN-501 generated a stoichiometric amount of prednisolone following azoreductase activation, whereas its analogue did not. The pH rate profile for the cyclization of the amino intermediates of the two compounds revealed significant differences in rate at pH values relevant to the inflamed colon, which explain in part the different amounts of drug produced. The steroid prodrug OPN-501 has optimal drug release characteristics for colon targeting because of a kinetic advantage of a six-membered ring formation in the aminolysis reactions of anilides. The results are relevant to the development of OPN-501 but also to cyclization strategies in prodrug design especially for colon targeting. © 2011 The

  8. A poly(glycerol sebacate)-coated mesoporous bioactive glass scaffold with adjustable mechanical strength, degradation rate, controlled-release and cell behavior for bone tissue engineering.

    Science.gov (United States)

    Lin, Dan; Yang, Kai; Tang, Wei; Liu, Yutong; Yuan, Yuan; Liu, Changsheng

    2015-07-01

    Various requirements in the field of tissue engineering have motivated the development of three-dimensional scaffold with adjustable physicochemical properties and biological functions. A series of multiparameter-adjustable mesoporous bioactive glass (MBG) scaffolds with uncrosslinked poly(glycerol sebacate) (PGS) coating was prepared in this article. MBG scaffold was prepared by a modified F127/PU co-templating process and then PGS was coated by a simple adsorption and lyophilization process. Through controlling macropore parameters and PGS coating amount, the mechanical strength, degradation rate, controlled-release and cell behavior of the composite scaffold could be modulated in a wide range. PGS coating successfully endowed MBG scaffold with improved toughness and adjustable mechanical strength covering the bearing range of trabecular bone (2-12MPa). Multilevel degradation rate of the scaffold and controlled-release rate of protein from mesopore could be achieved, with little impact on the protein activity owing to an "ultralow-solvent" coating and "nano-cavity entrapment" immobilization method. In vitro studies indicated that PGS coating promoted cell attachment and proliferation in a dose-dependent manner, without affecting the osteogenic induction capacity of MBG substrate. These results first provide strong evidence that uncrosslinked PGS might also yield extraordinary achievements in traditional MBG scaffold. With the multiparameter adjustability, the composite MBG/PGS scaffolds would have a hopeful prospect in bone tissue engineering. The design considerations and coating method of this study can also be extended to other ceramic-based artificial scaffolds and are expected to provide new thoughts on development of future tissue engineering materials. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Lecithin-based microemulsions for targeted delivery of ceramide AP into the stratum corneum: formulation, characterizations, and in vitro release and penetration studies.

    Science.gov (United States)

    Sahle, Fitsum F; Metz, Hendrik; Wohlrab, Johannes; Neubert, Reinhard H H

    2013-02-01

    To improve the solubility and penetration of Ceramide AP (CER [AP]) into the stratum corneum that potentially restores the barrier function of aged and affected skin. CER [AP] microemulsions (MEs) were formulated using lecithin, Miglyol® 812 (miglyol) and water-1,2 pentandiol (PeG) mixture as amphiphilic, oily and hydrophilic components, respectively. The nanostructure of the MEs was revealed using electrical conductivity, differential scanning calorimeter (DSC) and electron paramagnetic resonance (EPR) techniques. Photon correlation spectroscopy (PCS) was used to measure the sizes and shape of ME droplets. The release and penetration of the CER into the stratum corneum was investigated in vitro using a multi-layer membrane model. The MEs exhibited excellent thermodynamic stability (>2 years) and loading capacity (0.5% CER [AP]). The pseudo-ternary phase diagrams of the MEs were obtained and PCS results showed that the droplets are spherical in shape and bigger in size. In vitro investigations showed that the MEs exhibited excellent rate and extent of release and penetration. Stable lecithin-based CER [AP] MEs that significantly enhance the solubility and penetration of CER [AP] into the stratum corneum were developed. The MEs also have better properties than the previously reported polyglycerol fatty acid surfactant-based CER [AP] MEs.

  10. In vitro fracture behavior of maxillary premolars with metal crowns and several post-and-core systems.

    NARCIS (Netherlands)

    Fokkinga, W.A.; Kreulen, C.M.; Bell-Ronnlof, A.M. Le; Lassila, L.V.; Vallittu, P.K.; Creugers, N.H.J.

    2006-01-01

    The in vitro fracture behavior of severely damaged premolars, restored with metal crowns with limited ferrule and several post-and-core systems, was investigated. Crowns of maxillary premolars were removed and canals were prepared with Gates Glidden drills and with Parapost drills. Groups of 11

  11. In-vitro release pharmacokinetics of amikacin, teicoplanin and polyhexanide in a platelet rich fibrin-layer (PRF-a laboratory evaluation of a modern, autologous wound treatment.

    Directory of Open Access Journals (Sweden)

    Daniela Knafl

    Full Text Available Platelet rich fibrin (PRF is an autologous fibrin glue, produced from patients' blood, which, besides intraoperative use, has applications in the treatment of infected wounds. The combination with antimicrobial agents results in a prolonged antibacterial effect allowing for wound dressing change intervals of seven days even in infected wounds. The aim of this study was to evaluate release kinetics of amikacin, teicoplanin or polyhexanide from a PRF-layer.PRF mixed with teicoplanin, amikacin or polyhexanide was sprayed on a silicon gauze patch and put on a colombia agar with bacteria with known minimal inhibitory concentration (MIC and incubated for 24 hours and afterwards transferred to another agar with the same bacterial strain. Inhibition zones were measured every 24 hours. This was repeated on 7 consecutive days. Antibiotic concentrations were calculated by interpolation.More than 1000 mg/L teicoplanin were released within the first 24 hours and 28.22 mg/L after 168 hours. Amikacin release was above 10,000 mg/L within the first 24 hours and still 120.8 mg/L after 120 hours. A release of polyhexanide could be verified for the first 24 hours only. Consequently teicoplanin and amikacin released from PRF showed antimicrobial in-vitro effects for almost a week, whereas an antimicrobial effect of polyhexanide could only be verified for the first 24 hours.Our Results show that a weekly dressing regimen may be justified in wounds treated with PRF plus amikacin or teicoplanin, since bacteria will be eradicated over a considerable period of time after a single application of PRF.

  12. In-vitro release pharmacokinetics of amikacin, teicoplanin and polyhexanide in a platelet rich fibrin-layer (PRF)-a laboratory evaluation of a modern, autologous wound treatment.

    Science.gov (United States)

    Knafl, Daniela; Thalhammer, Florian; Vossen, Matthias G

    2017-01-01

    Platelet rich fibrin (PRF) is an autologous fibrin glue, produced from patients' blood, which, besides intraoperative use, has applications in the treatment of infected wounds. The combination with antimicrobial agents results in a prolonged antibacterial effect allowing for wound dressing change intervals of seven days even in infected wounds. The aim of this study was to evaluate release kinetics of amikacin, teicoplanin or polyhexanide from a PRF-layer. PRF mixed with teicoplanin, amikacin or polyhexanide was sprayed on a silicon gauze patch and put on a colombia agar with bacteria with known minimal inhibitory concentration (MIC) and incubated for 24 hours and afterwards transferred to another agar with the same bacterial strain. Inhibition zones were measured every 24 hours. This was repeated on 7 consecutive days. Antibiotic concentrations were calculated by interpolation. More than 1000 mg/L teicoplanin were released within the first 24 hours and 28.22 mg/L after 168 hours. Amikacin release was above 10,000 mg/L within the first 24 hours and still 120.8 mg/L after 120 hours. A release of polyhexanide could be verified for the first 24 hours only. Consequently teicoplanin and amikacin released from PRF showed antimicrobial in-vitro effects for almost a week, whereas an antimicrobial effect of polyhexanide could only be verified for the first 24 hours. Our Results show that a weekly dressing regimen may be justified in wounds treated with PRF plus amikacin or teicoplanin, since bacteria will be eradicated over a considerable period of time after a single application of PRF.

  13. Vibrio vulnificus MO6-24/O Lipopolysaccharide Stimulates Superoxide Anion, Thromboxane B2, Matrix Metalloproteinase-9, Cytokine and Chemokine Release by Rat Brain Microglia in Vitro

    Directory of Open Access Journals (Sweden)

    Alejandro M. S. Mayer

    2014-03-01

    Full Text Available Although human exposure to Gram-negative Vibrio vulnificus (V. vulnificus lipopolysaccharide (LPS has been reported to result in septic shock, its impact on the central nervous system’s innate immunity remains undetermined. The purpose of this study was to determine whether V. vulnificus MO6-24/O LPS might activate rat microglia in vitro and stimulate the release of superoxide anion (O2−, a reactive oxygen species known to cause oxidative stress and neuronal injury in vivo. Brain microglia were isolated from neonatal rats, and then treated with either V. vulnificus MO6-24/O LPS or Escherichia coli O26:B6 LPS for 17 hours in vitro. O2− was determined by cytochrome C reduction, and matrix metalloproteinase-2 (MMP-2 and MMP-9 by gelatinase zymography. Generation of cytokines tumor necrosis factor alpha (TNF-α, interleukin-1 alpha (IL-1α, IL-6, and transforming growth factor-beta 1 (TGF-β1, chemokines macrophage inflammatory protein (MIP-1α/chemokine (C-C motif ligand 3 (CCL3, MIP-2/chemokine (C-X-C motif ligand 2 (CXCL2, monocyte chemotactic protein-1 (MCP-1/CCL2, and cytokine-induced neutrophil chemoattractant-2alpha/beta (CINC-2α/β/CXCL3, and brain-derived neurotrophic factor (BDNF, were determined by specific immunoassays. Priming of rat microglia by V. vulnificus MO6-24/O LPS in vitro yielded a bell-shaped dose-response curve for PMA (phorbol 12-myristate 13-acetate-stimulated O2− generation: (1 0.1–1 ng/mL V. vulnificus LPS enhanced O2− generation significantly but with limited inflammatory mediator generation; (2 10–100 ng/mL V. vulnificus LPS maximized O2− generation with concomitant release of thromboxane B2 (TXB2, matrix metalloproteinase-9 (MMP-9, and several cytokines and chemokines; (3 1000–100,000 ng/mL V. vulnificus LPS, with the exception of TXB2, yielded both attenuated O2− production, and a progressive decrease in MMP-9, cytokines and chemokines investigated. Thus concentration-dependent treatment of

  14. INSECTICIDAL TOXIN FROM BACILLUS THURINGIENSIS IS RELEASED FROM ROOTS OF TRANSGENIC BT CORN IN VITRO AND IN SITU. (R826107)

    Science.gov (United States)

    AbstractThe insecticidal toxin encoded by the cry1Ab gene from Bacillus thuringiensis was released in root exudates from transgenic Bt corn during 40 days of growth in soil amended to 0, 3, 6, 9, or 12% (v/v) with montmorillonite or kaolinite in a...

  15. Adenosine triphosphate levels during anaphylactic histamine release in rat mast cells in vitro. Effects of glycolytic and respiratory inhibitors

    DEFF Research Database (Denmark)

    Johansen, Torben

    1979-01-01

    The adenosine triphosphate (ATP) content of rat mast cells was studied during and after anaphylactic histamine release. The almost identical time course of ATP decrease from mast cells treated with either glycolytic or respiratory inhibitors supports the view that the ATP depletion was largely re...

  16. Development of a Physiologically Relevant Population Pharmacokinetic in Vitro-in Vivo Correlation Approach for Designing Extended-Release Oral Dosage Formulation.

    Science.gov (United States)

    Kim, Tae Hwan; Shin, Soyoung; Bulitta, Jürgen B; Youn, Yu Seok; Yoo, Sun Dong; Shin, Beom Soo

    2017-01-03

    Establishing a level A in vitro-in vivo correlation (IVIVC) for a drug with complex absorption kinetics is challenging. The objective of the present study was to develop an IVIVC approach based on population pharmacokinetic (POP-PK) modeling that incorporated physiologically relevant absorption kinetics. To prepare three extended release (ER) tablets of loxoprofen, three types of hydroxypropyl methylcellulose (HPMC 100, 4000, and 15000 cps) were used as drug release modifiers, while lactose and magnesium stearate were used as the diluent and lubricant, respectively. An in vitro dissolution test in various pH conditions showed that loxoprofen dissolution was faster at higher pH. The in vivo pharmacokinetics of loxoprofen was assessed following oral administration of the different loxoprofen formulations to Beagle dogs (n = 22 in total). Secondary peaks or shoulders were observed in many of the individual plasma concentration vs time profiles after ER tablet administration, which may result from secondary absorption in the intestine due to a dissolution rate increase under intestinal pH compared to that observed at stomach pH. In addition, in vivo oral bioavailability was found to decrease with prolonged drug dissolution, indicating site-specific absorption. Based on the in vitro dissolution and in vivo absorption data, a POP-PK IVIVC model was developed using S-ADAPT software. pH-dependent biphasic dissolution kinetics, described using modified Michaelis-Menten kinetics with varying Vmax, and site-specific absorption, modeled using a changeable absorbed fraction parameter, were applied to the POP-PK IVIVC model. To experimentally determine the biphasic dissolution profiles of the ER tablets, another in vitro dissolution test was conducted by switching dissolution medium pH based on an in vivo estimate of gastric emptying time. The model estimated, using linear regression, that in vivo initial maximum dissolution rate (Vmax(0)in vivo) was highly correlated (r2 > 0

  17. Effect of alginate and chitosan on viability and release behavior of Bifidobacterium pseudocatenulatum G4 in simulated gastrointestinal fluid.

    Science.gov (United States)

    Kamalian, Nikoo; Mirhosseini, Hamed; Mustafa, Shuhaimi; Manap, Mohd Yazid Abd

    2014-10-13

    The main aim of this study was to investigate the effect of different coating materials (i.e. Na-alginate and chitosan) on the viability and release behavior of Bifidobacterium pseudocatenulatum G4 in the simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). This study reports the viability of encapsulated B. pseudocatenulatum G4 coated using different alginate (2-4 g/100mL) and chitosan (0.2-0.8 g/100mL) concentrations. The results indicated that the highest concentration of alginate (4.4142 g/100mL) along with 0.5578 g/100mL chitosan resulted in the highest viability of B. pseudocatenulatum G4. The release behavior of the encapsulated probiotics in SGF (pH 1.5) in 2h followed by 4h in SIF (pH 7.4) was also assessed. The resistance rate of alginate-chitosan capsule in SGF was higher than SIF. The alginate-chitosan encapsulated cells had also more resistance than alginate capsules. The current study revealed that alginate encapsulated B. Pseudocatenulatum G4 exhibited longer survival than its free cells (control). Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Analysis of transient migration behavior of natural killer cells imaged in situ and in vitro.

    Science.gov (United States)

    Khorshidi, Mohammad Ali; Vanherberghen, Bruno; Kowalewski, Jacob M; Garrod, Kym R; Lindström, Sara; Andersson-Svahn, Helene; Brismar, Hjalmar; Cahalan, Michael D; Önfelt, Björn

    2011-07-01

    We present a simple method for rapid and automatic characterization of lymphocyte migration from time-lapse fluorescence microscopy data. Time-lapse imaging of natural killer (NK) cells in vitro and in situ, both showed that individual cells transiently alter their migration behavior. Typically, NK cells showed periods of high motility, interrupted by transient periods of slow migration or almost complete arrests. Analysis of in vitro data showed that these periods frequently coincided with contacts with target cells, sometimes leading to target cell lysis. However, NK cells were also commonly observed to stop independently of contact with other cells. In order to objectively characterize the migration of NK cells, we implemented a simple method to discriminate when NK cells stop or have low motilities, have periods of directed migration or undergo random movement. This was achieved using a sliding window approach and evaluating the mean squared displacement (MSD) to assess the migration coefficient and MSD curvature along trajectories from individual NK cells over time. The method presented here can be used to quickly and quantitatively assess the dynamics of individual cells as well as heterogeneity within ensembles. Furthermore, it may also be used as a tool to automatically detect transient stops due to the formation of immune synapses, cell division or cell death. We show that this could be particularly useful for analysis of in situ time-lapse fluorescence imaging data where most cells, as well as the extracellular matrix, are usually unlabelled and thus invisible. This journal is © The Royal Society of Chemistry 2011

  19. Angiogenic properties of sustained release platelet-rich plasma: characterization in-vitro and in the ischemic hind limb of the mouse.

    Science.gov (United States)

    Bir, Shyamal Chandra; Esaki, Jiro; Marui, Akira; Yamahara, Kenichi; Tsubota, Hideki; Ikeda, Tadashi; Sakata, Ryuzo

    2009-10-01

    While single growth factor has limitation to induce optimal neovascularization, platelet-rich plasma (PRP) is an autologous reserver of various growth factors. However, little is known about the mechanism of PRP-related neovascularization.The objective of this investigation was to characterize the angiogenic and growth factor content of PRP and to determine, in vitro, its effect on endothelial cell proliferation. Additionally, this experiment sought to determine the effectiveness of different compositions of PRP (solution versus sustained release) on perfusion and neovascularization in a murine model of hind limb ischemia. Different growth factors were measured by enzyme-linked immunosorbent assay (ELISA). In vivo study, we used gelatin hydrogel as a sustained release carrier for growth factors in PRP. We induced hind limb ischemia by excising right femoral artery in wild type C57BL6 mice. After surgery, mice were randomly assigned to four experimental groups; control (C), 100 muL of sustained release form of platelet-poor plasma (PPP), 100 muL of solution form of PRP (PRP-sol), 100 muL of sustained release form of PRP (PRP-sr); each formulation was administered via an intramuscular injection to the ischemic hind limb. Endpoint evaluations were blood perfusion by laser Doppler perfusion image, vascular density by anti Von Willebrand factor (vWF), and mature vessel density by anti smooth muscle actin (SMA) antibody. Green fluorescent protein (GFP+) transgenic mice were generated by transplantation of bone marrow derived mononuclear cells to wild type C57BL6 mice, and finally CD34+ cell in the ischemic site of transgenic mice was detected by staining with anti-CD34 antibody. In vitro study showed that PRP containing different growth factors induces endothelial cell proliferation and capillary tube formation. In vivo study demonstrated that sustained release of PRP increased perfusion of ischemic tissue as measured by laser Doppler perfusion imaging (LDPI) (57 +/- 12

  20. Release Behavior and Antibacterial Activity of Chitosan/Alginate Blends with Aloe vera and Silver Nanoparticles

    Directory of Open Access Journals (Sweden)

    Luisa Fernanda Gómez Chabala

    2017-10-01

    Full Text Available Aloe vera is a perennial plant employed for medical, pharmaceutical and cosmetic purposes that is rich in amino acids, enzymes, vitamins and polysaccharides, which are responsible for its therapeutic properties. Incorporating these properties into a biopolymer film obtained from alginate and chitosan allowed the development of a novel wound dressing with antibacterial capacity and healing effects to integrate the antibacterial capacity of silver nanoparticles with the healing and emollient properties of Aloe vera gel. Three alginate-chitosan matrices were obtained through blending methods using different proportions of alginate, chitosan, the Aloe vera (AV gel and silver nanoparticles (AgNps, which were incorporated into the polymeric system through immersion methods. Physical, chemical and antibacterial characteristics were evaluated in each matrix. Interaction between alginate and chitosan was identified using the Fourier transform infrared spectroscopy technique (FTIR, porosity was studied using scanning electron microscopy (SEM, swelling degree was calculated by difference in weight, Aloe vera gel release capacity was estimated by applying a drug model (Peppas and finally antibacterial capacity was evaluated against S. Aureus and P. aeruginosa. Results show that alginate-chitosan (A (1:3 Chit 1/Alg 1; B (1:3 Chit 1.5/Alg 1 and C (3:1 Chit 1/Alg 1/B12 matrices with Aloe vera (AV gel and silver nanoparticles (AgNps described here displayed antibacterial properties and absorption and Aloe vera release capacity making it a potential wound dressing for minor injuries.

  1. Release Behavior and Antibacterial Activity of Chitosan/Alginate Blends with Aloe vera and Silver Nanoparticles.

    Science.gov (United States)

    Gómez Chabala, Luisa Fernanda; Cuartas, Claudia Elena Echeverri; López, Martha Elena Londoño

    2017-10-24

    Aloe vera is a perennial plant employed for medical, pharmaceutical and cosmetic purposes that is rich in amino acids, enzymes, vitamins and polysaccharides, which are responsible for its therapeutic properties. Incorporating these properties into a biopolymer film obtained from alginate and chitosan allowed the development of a novel wound dressing with antibacterial capacity and healing effects to integrate the antibacterial capacity of silver nanoparticles with the healing and emollient properties of Aloe vera gel. Three alginate-chitosan matrices were obtained through blending methods using different proportions of alginate, chitosan, the Aloe vera (AV) gel and silver nanoparticles (AgNps), which were incorporated into the polymeric system through immersion methods. Physical, chemical and antibacterial characteristics were evaluated in each matrix. Interaction between alginate and chitosan was identified using the Fourier transform infrared spectroscopy technique (FTIR), porosity was studied using scanning electron microscopy (SEM), swelling degree was calculated by difference in weight, Aloe vera gel release capacity was estimated by applying a drug model (Peppas) and finally antibacterial capacity was evaluated against S. Aureus and P. aeruginosa. Results show that alginate-chitosan (A (1:3 Chit 1/Alg 1); B (1:3 Chit 1.5/Alg 1) and C (3:1 Chit 1/Alg 1/B12)) matrices with Aloe vera (AV) gel and silver nanoparticles (AgNps) described here displayed antibacterial properties and absorption and Aloe vera release capacity making it a potential wound dressing for minor injuries.

  2. Beta amyloid differently modulate nicotinic and muscarinic receptor subtypes which regulate in vitro and in vivo the release of glycine in the rat hippocampus

    Directory of Open Access Journals (Sweden)

    Stefania eZappettini

    2012-07-01

    Full Text Available Using both in vitro (hippocampal synaptosomes in superfusion and in vivo (microdialysis approaches we investigated whether and to what extent β amyloid peptide 1-40 (Aβ 1-40 interferes with the cholinergic modulation of the release of glycine (GLY in the rat hippocampus. The nicotine-evoked overflow of endogenous GLY in hippocampal synaptosomes in superfusion was significantly inhibited by Aβ 1-40 (10 nM while increasing the concentration to 100 nM the inhibitory effect did not further increase. Both the Choline (Ch (α7 agonist; 1 mM and the 5-Iodo-A-85380 dihydrochloride (5IA85380, α4β2 agonist; 10 nM-evoked GLY overflow were inhibited by Aβ1-40 at 100 nM but not at 10nM concentrations. The KCl evoked [3H]GLY and [3H]Acetylcholine (ACh overflow were strongly inhibited in presence of oxotremorine; however this inhibitory muscarinic effect was not affected by Aβ1-40. The effects of Aβ1-40 on the administration of nicotine, veratridine, 5IA85380 and PHA 543613 hydrochloride (PHA543613 (a selective agonist of α7 subtypes on hippocampal endogenous GLY release in vivo were also studied. Aβ 1-40 significantly reduced (at 10 μM but not at 1 μM the nicotine evoked in vivo release of GLY. Aβ 1-40 (at 10 μM but not at 1 μM significantly inhibited the PHA543613 (1 mM-elicited GLY overflow while was ineffective on the GLY overflow evoked by 5IA85380 (1 mM. Aβ 40-1 (10 μM did not produce any inhibitory effect on nicotine evoked GLY overflow both in the in vitro and in vivo experiments. Our results indicate that a the cholinergic modulation of the release of GLY occurs by the activation of both α7 and α4β2 nicotinic ACh receptors (nAChRs as well as by the activation of inhibitory muscarinic ACh receptors (mAChRs and b Aβ 1-40 can modulate cholinergic evoked GLY release exclusively through the interaction with α7 and the α4β2 nAChR nicotinic receptors but not through mAChR subtypes.

  3. Trehalose maintains bioactivity and promotes sustained release of BMP-2 from lyophilized CDHA scaffolds for enhanced osteogenesis in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Jun Zhao

    Full Text Available Calcium phosphate (Ca-P scaffolds have been widely employed as a supportive matrix and delivery system for bone tissue engineering. Previous studies using osteoinductive growth factors loaded Ca-P scaffolds via passive adsorption often experience issues associated with easy inactivation and uncontrolled release. In present study, a new delivery system was fabricated using bone morphogenetic protein-2 (BMP-2 loaded calcium-deficient hydroxyapatite (CDHA scaffold by lyophilization with addition of trehalose. The in vitro osteogenesis effects of this formulation were compared with lyophilized BMP-2/CDHA construct without trehalose and absorbed BMP-2/CDHA constructs with or without trehalose. The release characteristics and alkaline phosphatase (ALP activity analyses showed that addition of trehalose could sufficiently protect BMP-2 bioactivity during lyophilization and achieve sustained BMP-2 release from lyophilized CDHA construct in vitro and in vivo. However, absorbed BMP-2/CDHA constructs with or without trehalose showed similar BMP-2 bioactivity and presented a burst release. Quantitative real-time PCR (RT-qPCR and enzyme-linked immunosorbent assay (ELISA demonstrated that lyophilized BMP-2/CDHA construct with trehalose (lyo-tre-BMP-2 promoted osteogenic differentiation of bone marrow stromal cells (bMSCs significantly and this formulation could preserve over 70% protein bioactivity after 5 weeks storage at 25°C. Micro-computed tomography, histological and fluorescent labeling analyses further demonstrated that lyo-tre-BMP-2 formulation combined with bMSCs led to the most percentage of new bone volume (38.79% ± 5.32% and area (40.71% ± 7.14% as well as the most percentage of fluorochrome stained bone area (alizarin red S: 2.64% ± 0.44%, calcein: 6.08% ± 1.37% and mineral apposition rate (4.13 ± 0.62 µm/day in critical-sized rat cranial defects healing. Biomechanical tests also indicated the maximum stiffness (118.17 ± 15.02 Mpa and

  4. Numerical investigation on three-dimensional dispersion and conversion behaviors of silicon tetrachloride release in the atmosphere.

    Science.gov (United States)

    Jianwen, Zhang; Xinxin, Yin; Yanan, Xin; Jian, Zhang; Xiaoping, Zheng; Chunming, Jiang

    2015-05-15

    The world has experienced heavy thirst of energy as it has to face a dwindling supply of fossil fuel and polycrystalline silicon photovoltaic solar energy technology has been assigned great importance. Silicon tetrachloride is the main byproducts of polysilicon industry, and it's volatile and highly toxic. Once silicon tetrachloride releases, it rapidly forms a dense gas cloud and reacts violently with water vapor in the atmosphere to form a gas cloud consisting of the mixture of silicon tetrachloride, hydrochloric acid and silicic acid, which endangers environment and people. In this article, numerical investigation is endeavored to explore the three dimensional dispersion and conversion behaviors of silicon tetrachloride release in the atmosphere. The k-ϵ model with buoyancy correction on k is applied for turbulence closure and modified EBU model is applied to describe the hydrolysis reaction of silicon tetrachloride. It is illustrated that the release of silicon tetrachloride forms a dense cloud, which sinks onto the ground driven by the gravity and wind and spreads both upwind and downwind. Complicated interaction occurs between the silicon tetrachloride cloud and the air mass. The main body of the dense cloud moves downwind and reacts with the water vapor on the interface between the dense cloud and the air mass to generate a toxic mixture of silicon tetrachloride, hydrogen chloride and silicic acid. A large coverage in space is formed by the toxic mixture and imposes chemical hazards to the environment. The exothermic hydrolysis reaction consumes water and releases reaction heat resulting in dehydration and temperature rise, which imposes further hazards to the ecosystem over the affected space. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Anti-inflammatory homoeopathic drug dilutions restrain lipopolysaccharide-induced release of pro-inflammatory cytokines: In vitro and in vivo evidence

    Directory of Open Access Journals (Sweden)

    Umesh B Mahajan

    2017-01-01

    Full Text Available Context: The lipopolysaccharide (LPS-induced cytokine release and oxidative stress are validated experimental parameters used to test anti-inflammatory activity. We investigated the effects of homoeopathic mother tinctures, 6 CH, 30 CH and 200 CH dilutions of Arnica montana, Thuja occidentalis and Bryonia alba against LPS (1 μg/ml-induced cytokine release from RAW-264.7 cells and human whole-blood culture. Materials and Methods: For in vivo evaluations, mice were orally treated with 0.1 ml drug dilutions twice a day for 5 days followed by an intraperitoneal injection of 0.5 mg/kg LPS. After 24 h, the mice were sacrificed and serum levels of pro-inflammatory cytokines and nitric oxide were determined. The extent of oxidative stress was determined in the liver homogenates as contents of reduced glutathione, malondialdehyde, superoxide dismutase and catalase. Results: The tested drug dilutions significantly reduced in vitro LPS-induced release of tumour necrosis factor-α, interleukin-1 (IL-1 and IL-6 from the RAW-264.7 cells and human whole blood culture. Similar suppression of cytokines was evident in mice serum samples. These drugs also protected mice from the LPS-induced oxidative stress in liver tissue. Conclusions: Our findings substantiate the protective effects of Arnica, Thuja and Bryonia homoeopathic dilutions against LPS-induced cytokine elevations and oxidative stress. This study authenticates the claims of anti-inflammatory efficacy of these homoeopathic drugs.

  6. Prediction of in-vivo pharmacokinetic profile for immediate and modified release oral dosage forms of furosemide using an in-vitro-in-silico-in-vivo approach.

    Science.gov (United States)

    Otsuka, Keiichi; Wagner, Christian; Selen, Arzu; Dressman, Jennifer

    2015-05-01

    To develop a physiologically based pharmacokinetic (PBPK) model for furosemide immediate release (IR) tablets and modified release (MR) capsules by coupling biorelevant dissolution testing results with pharmacokinetic (PK) and physiologic parameters, and to investigate the key factors influencing furosemide absorption using simulation approaches and the PBPK model. Using solubility, dissolution kinetics, gastrointestinal (GI) parameters and disposition parameters, a PBPK model for furosemide was developed with STELLA software. Solubility and dissolution profiles for both formulations were evaluated in biorelevant and compendial media. The simulated plasma profiles were compared with in-vivo profiles using point estimates of area under plasma concentration-time curve, maximal concentration after the dose and time to maximal concentration after the dose. Simulated plasma profiles of both furosemide IR tablets and MR capsules were similar to the observed in-vivo profile in terms of PK parameters. Sensitivity analysis of the IR tablet model indicated that both the gastric emptying and absorption rate have an influence on the plasma profile. For the MR capsules, the sensitivity analysis suggested that the release rate in the small intestine, gastric emptying and the absorption rate all have an influence on the plasma profile. A predictive model to describe both IR and MR dosage forms containing furosemide was attained. Because sensitivity analysis of the model is able to identify key factors influencing the plasma profile, this in-vitro-in-silico-in-vivo approach could be a useful tool for facilitating formulation development of drug products. © 2015 Royal Pharmaceutical Society.

  7. A comprehensive approach to qualify and validate the essential parameters of an in vitro release test (IVRT) method for acyclovir cream, 5.

    Science.gov (United States)

    Tiffner, Katrin I; Kanfer, Isadore; Augustin, Thomas; Raml, Reingard; Raney, Sam G; Sinner, Frank

    2017-09-19

    The rate of release of an active pharmaceutical ingredient (API) from a topical semisolid dosage form can be influenced by its physical and structural properties. An In Vitro Release Test (IVRT) is an established method to characterize this rate of API release and compare the underlying sameness in product quality characteristics. The purpose of this work was to validate an IVRT method to compare acyclovir cream, 5% products. However, despite widespread use of the IVRT since 1997, there has been no established approach to validate an IVRT method. Our approach included: 1) qualification of the diffusion cell apparatus, 2) qualification of the laboratory, 3) validation of the HPLC analytical method, and 4) validation of numerous critical parameters of the IVRT method, itself, and resulted in a comprehensive and successful IVRT method validation. Subsequent to the IVRT validation work described here, the U.S. Food and Drug Administration (FDA) drafted a guidance on the development and validation of an IVRT method for acyclovir cream, 5%. Although there are notable differences between our approach and the approach in that guidance, this report illustrates how many of the same essential qualification parameters and validation concepts were considered and systematically addressed in our approach to IVRT validation. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  8. In Vitro Investigation of Self-Assembled Nanoparticles Based on Hyaluronic Acid-Deoxycholic Acid Conjugates for Controlled Release Doxorubicin: Effect of Degree of Substitution of Deoxycholic Acid

    Directory of Open Access Journals (Sweden)

    Wen-Hao Wei

    2015-03-01

    Full Text Available Self-assembled nanoparticles based on a hyaluronic acid-deoxycholic acid (HD chemical conjugate with different degree of substitution (DS of deoxycholic acid (DOCA were prepared. The degree of substitution (DS was determined by titration method. The nanoparticles were loaded with doxorubicin (DOX as the model drug. The human cervical cancer (HeLa cell line was utilized for in vitro studies and cell cytotoxicity of DOX incorporated in the HD nanoparticles was accessed by the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay. In addition, cellular uptake of fluorescently labeled nanoparticles was also investigated. An increase in the degree of deoxycholic acid substitution reduced the size of the nanoparticles and also enhanced their drug encapsulation efficiency (EE, which increased with the increase of DS. A higher degree of deoxycholic acid substitution also lead to a lower release rate and an initial burst release of doxorubicin from the nanoparticles. In summary, the degree of substitution allows the modulation of the particle size, drug encapsulation efficiency, drug release rate, and cell uptake efficiency of the nanoparticles. The herein developed hyaluronic acid-deoxycholic acid conjugates are a good candidate for drug delivery and could potentiate therapeutic formulations for doxorubicin–mediated cancer therapy.

  9. Pharmacokinetics of Abamectin/Levamisole Combination in a Medium Chain Mono and Diglyceride-Based Vehicle and an In Vitro Release and In Vitro In Vivo Correlation Study for Levamisole.

    Science.gov (United States)

    Sari, Peyami; Sun, Jianguo; Razzak, Majid; Tucker, Ian G

    2017-05-01

    A combination of lipophilic and hydrophilic drugs in a single solution is a challenge due to their different physicochemical properties. In vitro and in vivo release studies are useful to optimize this solution. The in vitro (Franz diffusion cell) release rate of levamisole phosphate from an isotropic vehicle of medium chain mono and diglycerides (MCMDG) was significantly slower than the release from water. The injectable solution of the isotropic MCMDG-based system was prepared with 13.65% of levamisole phosphate and 0.5% of abamectin. Two milliliters/50 kg (0.04 ml/kg) was injected subcutaneously into five healthy adult sheep. None of the animals showed the signs of inflammation at injection site. Both drugs were assayed using validated HPLC methods. The absorption rates for levamisole (0.71 ± 0.32 h -1 ) and abamectin (0.24 ± 0.08 day -1 ) from the MCMDG-based formulation were considerably slower than those of other studies conducted on the commercial products. The t max was delayed for levamisole (2.20 ± 0.45 h) and abamectin (4.20 ± 1.64 days) compared with those in published studies. Longer MRT values for levamisole (6.14 ± 1.14 h) and abamectin (8.80 ± 1.39 days) were found in this study compared to those reported. A correlation was observed between in vivo fraction absorbed and in vitro fraction released for levamisole phosphate in the MCMDG-based formulation. The injection vehicle of isotropic MCMDG-based system delayed the subcutaneous absorption of levamisole phosphate and abamectin compared to the commercial subcutaneous injection products for levamisole and abamectin. Notably, this isotropic MCMDG-based vehicle system is prepared with a combination of two drugs with different physicochemical properties.

  10. Tuning the Surface Composition, Spatial Arrangement, and Thermal Release Behavior of DNA-Gold Nanomaterials

    Science.gov (United States)

    Diaz, Julian

    Combining multiple functions and controlling their relative organization on the surface, as well as controlling the release of payloads will be essential properties of nanomaterials for future medical applications. In this thesis we studied these properties using as a model DNA-gold nanoparticles, one of the most promising nanomaterials for medical purposes. First, we studied strategies to control the density and the ratio of combinations of labeled DNA on gold nanoparticles. Using two approaches, thiol self-assembly and DNA-directed assembly (hybridization) we found that thiol self-assembly leads to a higher density of labeled DNA per particle, but poor ratio control, while DNA-directed assembly is better at controlling the proportions of labeled DNA on the particle but the number of strands is lower than the thiol self-assembly approach. Second, to control the relative position of the labels on the particle we used DNA-doublers and Y-shaped DNA complexes to tune the distance between tags. Off particle experiments indicated that the spacing between labels can be controlled in the Angstrom-nanometer scale. On particle experiments showed the apparent formation of these constructs; however more experiments are needed to attain quantitative results. The aim of the last investigation was to achieve thermal stepwise release of DNA from DNA-gold nanoparticles. To do so, it is necessary to obtain sharp thermal dissociation, or melting, transitions as well as control over the melting temperature. Taking advantage of the cooperative properties of DNA, we found that sharpened melting can be achieved using branched DNA-doublers hybridized with complementary DNA bound to the nanoparticle. Tuning the melting temperature can be achieved by modifying the branches of the hybridized doublers with abasic groups. Using these two findings, we sequentially released two DNA-doublers from the same nanoparticle, in a very narrow temperature window, and with minimal overlapping. Current

  11. Insulin and IGF-I inhibit GH synthesis and release in vitro and in vivo by separate mechanisms.

    Science.gov (United States)

    Gahete, Manuel D; Córdoba-Chacón, José; Lin, Qing; Brüning, Jens C; Kahn, C Ronald; Castaño, Justo P; Christian, Helen; Luque, Raúl M; Kineman, Rhonda D

    2013-07-01

    IGF-I is considered a primary inhibitor of GH secretion. Insulin may also play an important role in regulating GH levels because insulin, like IGF-I, can suppress GH synthesis and release in primary pituitary cell cultures and insulin is negatively correlated with GH levels in vivo. However, understanding the relative contribution insulin and IGF-I exert on controlling GH secretion has been hampered by the fact that circulating insulin and IGF-I are regulated in parallel and insulin (INSR) and IGF-I (IGFIR) receptors are structurally/functionally related and ubiquitously expressed. To evaluate the separate roles of insulin and IGF-I in directly regulating GH secretion, we used the Cre/loxP system to knock down the INSR and IGFIR in primary mouse pituitary cell cultures and found insulin-mediated suppression of GH is independent of the IGFIR. In addition, pharmacological blockade of intracellular signals in both mouse and baboon cultures revealed insulin requires different pathways from IGF-I to exert a maximal inhibitory effect on GH expression/release. In vivo, somatotrope-specific knockout of INSR (SIRKO) or IGFIR (SIGFRKO) increased GH levels. However, comparison of the pattern of GH release, GH expression, somatotrope morphometry, and pituitary explant sensitivity to acute GHRH challenge in lean SIRKO and SIGFRKO mice strongly suggests the primary role of insulin in vivo is to suppress GH release, whereas IGF-I serves to regulate GH synthesis. Finally, SIRKO and/or SIGFRKO could not prevent high-fat, diet-induced suppression of pituitary GH expression, indicating other factors/tissues are involved in the decline of GH observed with weight gain.

  12. Focal release of neurotrophic factors by biodegradable microspheres enhance motor and sensory axonal regeneration in vitro and in vivo

    OpenAIRE

    Santos, Daniel

    2016-01-01

    Neurotrophic factors (NTFs) promote nerve regeneration and neuronal survival after peripheral nerve injury. However, drawbacks related with administration and bioactivity during long periods limit their therapeutic application. In this study, PLGA microspheres (MPs) were used to locally release different NTFs and evaluate whether they accelerate axonal regeneration in comparison with free NTFs or controls. ELISA, SEM, UV/visible light microscopy, organotypic cultures of DRG explants and spina...

  13. About the effect of eye blinking on drug release from pHEMA-based hydrogels: an in vitro study.

    Science.gov (United States)

    Galante, R; Paradiso, P; Moutinho, M G; Fernandes, A I; Mata, J L G; Matos, A P A; Colaço, R; Saramago, B; Serro, A P

    2015-01-01

    The development of new ophthalmic drug delivery systems capable of increasing the residence time of drugs in the eye and improve its bioavailability relatively to eyedrops has been object of intense research in recent years. Several studies have shown that drug-loaded therapeutic soft contact lenses (SCLs) constitute a promising approach, with several potential advantages as compared with collyria. The main objective of this work is to study the effect of repetitive load and friction cycles caused by the eye blinking, on the drug release from hydrogels used in SCLs which, as far as we know, was never investigated before. Two poly-2-hydroxyethylmethacrylate-based hydrogels, pHEMA-T and pHEMA-UV, were used as model materials. Levofloxaxin was chosen as model drug. The hydrogels were fully characterized in what concerns structural and physicochemical properties. pHEMA-UV revealed some superficial porosity and a lower short-range order than pHEMA-T. We observe that the load and friction cycles enhanced the drug release from pHEMA-UV hydrogels. The application of a simple mathematical model, which takes into account the drug dilution caused by the tear flow, showed that the enhancement of the drug release caused by blinking on this hydrogel may be relevant in in vivo conditions. Conversely, the more sustained drug release from pHEMA-T is not affected by load and friction cycles. The conclusion is that, depending on the physicochemical and microstructural characteristics of the hydrogels, blinking is a factor that may affect the amount of drug delivered to the eye by SCLs and should thus be considered.

  14. Formulation and In-vitro Characterization of Sustained Release Matrix Type Ocular Timolol Maleate Mini-Tablet

    OpenAIRE

    Mortazavi, Seyed Alireza; Jafariazar, Zahra; Ghadjahani, Yasaman; Mahmoodi, Hoda; Mehtarpour, Farzaneh

    2014-01-01

    The purpose of this study was preparation and evaluation of sustained release matrix type ocular mini-tablets of timolol maleate, as a potential formulation for the treatment of glaucoma. Following the initial studies on timolol maleate powder, it was formulated into ocular mini-tablets. The polymers investigated in this study included cellulose derivatives (HEC, CMC, EC) and Carbopol 971P. Mannitol was used as the solubilizing agent and magnesium stearate as the lubricant. Mini-tablets were ...

  15. Increased in vitro release of soluble interleukin 2 receptor by colonic lamina propria mononuclear cells in inflammatory bowel disease.

    OpenAIRE

    Schreiber, S; Raedler, A; Conn, A R; Rombeau, J. L.; MacDermott, R P

    1992-01-01

    Increased concentrations of the soluble form of the interleukin 2 receptor have been observed in the sera of Crohn's disease and ulcerative colitis patients. In this study we have observed the spontaneous release of soluble interleukin 2 receptor by unstimulated, isolated normal and inflammatory bowel disease colonic lamina propria mononuclear cells. Lamina propria mononuclear cells from Crohn's disease patients (median = 204 U/ml (interquartile range 126-396, n 17) secreted significantly (p ...

  16. In Vitro Evaluation of Nasogastric Tube Delivery Performance of Esomeprazole Magnesium Delayed-Release Capsules.

    Science.gov (United States)

    Hoover, Alicia; Sun, Dajun; Wen, Hong; Jiang, Wenlei; Cui, Minglei; Jiang, Xiaojian; Keire, David; Guo, Changning

    2017-07-01

    Enteral feeding tubes are used to deliver food or drugs to patients who cannot swallow. To deliver delayed-release drugs that are formulated as enteric coated granules to these patients via feeding tubes requires that they be suspended in water before administration. Importantly, the suspension of enteric granules in water of varying pH can cause damage to the enteric coating and affect the bioavailability of the drug. Here, analytical methods for testing acid resistance stability and particle size distribution (PSD) of esomeprazole granules were used to monitor the integrity of the granule enteric coating after water pretreatment and delivery through an oral syringe and nasogastric (NG) tube. Granules from esomeprazole magnesium delayed-release capsules were transferred to an oral syringe, suspended in water, and delivered on the bench through an NG tube. Subsequently, acid resistance stability (i.e., the amount of drug released after 2-h acid dissolution) was determined via high-performance liquid chromatography, and the PSD were measured with a laser diffraction system. All the granules demonstrated acid resistance stability when the granules were delivered immediately (0 min incubation) through the oral syringe and NG tube. In contrast, some granules demonstrated significant drug release during acid exposure after a 15-min incubation period which mimics a possible delay in delivery of the drug from the syringe by the caregiver. A bimodal PSD was observed with these granules, which was attributed to debris from damaged enteric coating and particle agglomeration. The methods developed in this study could be used to distinguish batches with suboptimal product quality for delivery using NG tubes and to confirm the substitutability of generic drug products for this alternative route of administration. Published by Elsevier Inc.

  17. Critical quality attributes, in vitro release and correlated in vitro skin permeation-in vivo tape stripping collective data for demonstrating therapeutic (non)equivalence of topical semisolids: A case study of "ready-to-use" vehicles.

    Science.gov (United States)

    Ilić, Tanja; Pantelić, Ivana; Lunter, Dominique; Đorđević, Sanela; Marković, Bojan; Ranković, Dragana; Daniels, Rolf; Savić, Snežana

    2017-08-07

    This work aimed to prove the ability of "ready-to-use" topical vehicles based on alkyl polyglucoside-mixed emulsifier (with/without co-solvent modifications) to replace the conventionally used pharmacopoeial bases (e.g., non-ionic hydrophilic cream) in compounding practice. For this purpose, considering the regulatory efforts to establish alternative, scientifically valid methods for evaluating therapeutic equivalence of topical semisolids, we performed a comparative assessment of microstructure, selected critical quality attributes (CQAs) and in vitro/in vivo product performances, by utilizing aceclofenac as a model drug. The differences in composition between investigated samples have imposed remarkable variances in monitored CQAs (particularly in the amount of aceclofenac dissolved, rheological properties and water distribution mode), reflecting the distinct differences in microstructure formed, as partially observed by polarization microscopy and confocal Raman spectral imaging. Although not fully indicative of the in vivo performances, in vitro release data (vertical diffusion vs. immersion cells) proved the microstructure peculiarities, asserting the rheological properties as decisive factor for obtained liberation profiles. Contrary, in vitro permeation results obtained using pig ear epidermis correlated well with in vivo dermatopharmacokinetic data and distinguished unequivocally between tested formulations, emphasizing the importance of skin/vehicle interactions. In summary, suggested multi-faceted approach can provide adequate proof on topical semisolids therapeutic equivalence or lack thereof. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Modification of ChPL (chitosan protein–lipid nanoparticles for in vitro release of rifampicin (RIF

    Directory of Open Access Journals (Sweden)

    Poopak Farnia

    2015-01-01

    Results and conclusions: The average size of RIF ChPL-NPs was about 50–250nm. The release of RIF from the dialysis bag started after 30 min which was 2400ng/ml; after 16 h the release of RIF was 15,000ng/ml; and at 40 h the concentration reached to 19,600ng/ml. Therefore, these results showed a slow release of RIF from ChPL-NPs. Basically, the intensity of the surface charges in nanoparticle is important as it determines their interaction with bioactive compound. In RIF ChPL-NPs, lipid had negative charges, whereas chitosan and gelatin had positive charges. The electrostatic interaction between oppositely charged ions would ultimately cause an effective system drug delivery. RIF ChPL-NPs is not only suitable for intravenous administration, but it can be used as an inhalation aerosol, because this nanoparticle has a capacity to adhere to mucosal surfaces and transiently open the tight junction.

  19. In vitro dissolution study of acetylsalicylic acid solid dispersions. Tunable drug release allowed by the choice of polymer matrix.

    Science.gov (United States)

    Policianova, Olivia; Brus, Jiri; Hruby, Martin; Urbanova, Martina

    2014-07-22

    Abstract Due to their high versatility and diverse excipient options, solid dispersions (SDs) are an elegant choice for the formulation of active pharmaceutical ingredients with inconvenient solubility. Four distinct types of polymers with different physicochemical properties [polyvinylpyrrolidone, poly[N-(2-hydroxypropyl)-metacrylamide], poly(2-ethyl-2-oxazoline), and polyethylene glycol] and variable molecular weights were compared to investigate the influence of the polymer matrix on drug release. To probe the extent of intercomponent interactions, acetylsalicylic acid (ASA) was used as a model active substance. Controlled drug release was demonstrated for all four types of polymer-ASA SDs created by the freeze-drying method. While the polyethylene glycol-ASA SD exhibited an increased dissolution rate, the other polymer-ASA systems exhibited significantly reduced drug dissolution kinetics compared to free ASA. Furthermore, in contrast to physical mixtures, the prepared SDs all exhibited zero-order dissolution kinetics for ASA. The dissolution rate was strongly dependent on the molecular weight of the polymer. These results demonstrate that the type of SD may be controlled by the chemical constitutions of the polymers and that appropriate selection of the molecular weight of the polymer matrix enables finely tuned drug release over a wide range of dissolution rates.

  20. In vitro uptake and release of natamycin Dex-b-PLA nanoparticles from model contact lens materials.

    Science.gov (United States)

    Phan, Chau-Minh; Subbaraman, Lakshman; Liu, Shengyan; Gu, Frank; Jones, Lyndon

    2014-01-01

    To evaluate the uptake and release of the antifungal agent natamycin encapsulated within poly(D,L-lactide)-dextran nanoparticles (Dex-b-PLA NPs) from model contact lens (CL) materials. Six model CL materials (gel 1:poly(hydroxyethyl methacrylate, pHEMA); gel 2:85% pHEMA: 15% [Tris(trimethylsiloxy)silyl]-propyl methacrylate (TRIS); gel 3: 75% pHEMA: 25% TRIS; gel 4: 85% N,N dimethylacrylamide (DMAA): 15% TRIS; gel 5:75% DMAA: 25% TRIS; and gel 6: DMAA) were prepared using a photoinitiation procedure. The gels were incubated in: (1) natamycin dissolved in deionized (DI) water and (2) natamycin encapsulated within Dex-b-PLA NPs in dimethylsulfoxide/DI water. Natamycin release from these materials was monitored using UV-visible spectrophotometry at 304 nm over 7 d. Natamycin uptake by all model CL materials increased between 1 and 7 d (p DMAA than pHEMA (p DMAA-TRIS materials may be more suitable for drug delivery of natamycin due to the higher drug release observed with these materials.

  1. Sustained release of antibiotic complexed by multivalent ion: in vitro and in vivo study for the treatment of peritonitis.

    Science.gov (United States)

    Na, Seung Yeon; Oh, Se Heang; Kim, Tae Ho; Yoon, Jin A; Lee, In Soo; Lee, Jin Ho

    2014-12-10

    The main aims of this study are (i) the development of an antibiotic complexed with multivalent ion, which can allow sustained release of the antibiotic without any additional matrix or difficult process and (ii) the feasibility study of the ion-complexed antibiotic as a therapeutic technique for peritonitis treatment. An ion-complexed antibiotic is prepared by simple mixing of two aqueous solutions containing an ionized (water-soluble) drug (tetracycline) and a multivalent counter ionic compound. The ion-complexed antibiotic shows a continuous release of the antibiotic up to 21 days, and thus prolonged anti-bacterial effect by gradual ionic exchange between the multivalent ions in the complex and same-charged monovalent ions in surrounding medium. From the in vivo animal study using a cecum perforated peritonitis mouse model, the ion-complexed antibiotic group shows sufficient anti-bacterial effect and thus effectively treat the peritonitis because of the extermination of the contaminated enteric bacteria in the peritoneum during wound healing of injury cecum (by the sustained release of antibiotic from the ion complex). These results suggest that the ion-complexed antibiotic system may be promising for the effective treatment of the peritonitis caused by frequent gastrointestinal defect in clinical fields. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Preparation of a magnetic-field-sensitive hydrogel and preliminary study of its drug release behavior.

    Science.gov (United States)

    Namdeo, Mini; Bajpai, S K; Kakkar, S

    2009-01-01

    The study describes the in situ formation of magnetite nanoparticles within a swollen polyacrylamide hydrogel. The average diameter of nanoparticles, as determined by TEM analysis, was found to be nearly 12.5 nm. In XRD analysis the characteristic peaks, observed at d = 3.07, 2.78, 2.64, 2.53, 2.32 and 2.03, also confirmed the formation of magnetite within the polymer network. The percent swelling of magnetite-loaded gel in physiological fluid was observed to decrease with increasing amount of magnetite in the gel. Moreover, the percent swelling increased from 140 to 254% as the strength of the applied magnetic field increased from 500 to 2500 Oe. Finally, the model drug, vitamin B(2), loaded magnetic gels showed relatively slower release in the presence of an applied magnetic field.

  3. Effects of pH on the Shape of Alginate Particles and Its Release Behavior

    Directory of Open Access Journals (Sweden)

    Jui-Jung Chuang

    2017-01-01

    Full Text Available A vast majority of alginate particles exist as spheres in most practical uses, and both the particle shape and size are the key factors dominating the applications and performance of alginate gels. Therefore, it becomes an issue of great interest to investigate the aspheric alginate particles. As the first step, various shaped alginate particles were formed due to various pH values in gelation solutions. It was experimentally demonstrated that a low pH brought about an oblate shape, and particularly lower concentrations of both alginate and divalent cations resulted in a flattened oblate shape. Ba2+ acting as a cross-linker had a less impact on the particle shape than Ca2+ due to a higher affinity in alginate intermolecular cross-linking. With a larger surface area, an oblate particle offered a higher release rate than a spheric one.

  4. Oxygenated gasoline release in the unsaturated zone - Part 1: Source zone behavior.

    Science.gov (United States)

    Freitas, Juliana G; Barker, James F

    2011-11-01

    Oxygenates present in gasoline, such as ethanol and MTBE, are a concern in subsurface contamination related to accidental spills. While gasoline hydrocarbon compounds have low solubility, MTBE and ethanol are more soluble, ethanol being completely miscible with water. Consequently, their fate in the subsurface is likely to differ from that of gasoline. To evaluate the fate of gasoline containing oxygenates following a release in the unsaturated zone shielded from rainfall/recharge, a controlled field test was performed at Canadian Forces Base Borden, in Ontario. 200L of a mixture composed of gasoline with 10% ethanol and 4.5% MTBE was released in the unsaturated zone, into a trench 20cm deep, about 32cm above the water table. Based on soil cores, most of the ethanol was retained in the source, above the capillary fringe, and remained there for more than 100 days. Ethanol partitioned from the gasoline to the unsaturated pore-water and was retained, despite the thin unsaturated zone at the site (~35cm from the top of the capillary fringe to ground surface). Due to its lower solubility, most of the MTBE remained within the NAPL as it infiltrated deeper into the unsaturated zone and accumulated with the gasoline on top of the depressed capillary fringe. Only minor changes in the distribution of ethanol were noted following oscillations in the water table. Two methods to estimate the capacity of the unsaturated zone to retain ethanol are explored. It is clear that conceptual models for sites impacted by ethanol-fuels must consider the unsaturated zone. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. An integrated in vitro imaging platform for characterizing filarial parasite behavior within a multicellular microenvironment.

    Science.gov (United States)

    Kassis, Timothy; Skelton, Henry M; Lu, Iris M; Moorhead, Andrew R; Dixon, J Brandon

    2014-11-01

    Lymphatic Filariasis, a Neglected Tropical Disease, is caused by thread-like parasitic worms, including B. malayi, which migrate to the human lymphatic system following transmission. The parasites reside in collecting lymphatic vessels and lymph nodes for years, often resulting in lymphedema, elephantiasis or hydrocele. The mechanisms driving worm migration and retention within the lymphatics are currently unknown. We have developed an integrated in vitro imaging platform capable of quantifying B. malayi migration and behavior in a multicellular microenvironment relevant to the initial site of worm injection by incorporating the worm in a Polydimethylsiloxane (PDMS) microchannel in the presence of human dermal lymphatic endothelial cells (LECs) and human dermal fibroblasts (HDFs). The platform utilizes a motorized controllable microscope with CO2 and temperature regulation to allow for worm tracking experiments with high resolution over large length and time scales. Using post-acquisition algorithms, we quantified four parameters: 1) speed, 2) thrashing intensity, 3) percentage of time spent in a given cell region and 4) persistence ratio. We demonstrated the utility of our system by quantifying these parameters for L3 B. malayi in the presence of LECs and HDFs. Speed and thrashing increased in the presence of both cell types and were altered within minutes upon exposure to the anthelmintic drug, tetramisole. The worms displayed no targeted migration towards either cell type for the time course of this study (3 hours). When cells were not present in the chamber, worm thrashing correlated directly with worm speed. However, this correlation was lost in the presence of cells. The described platform provides the ability to further study B. malayi migration and behavior.

  6. An integrated in vitro imaging platform for characterizing filarial parasite behavior within a multicellular microenvironment.

    Directory of Open Access Journals (Sweden)

    Timothy Kassis

    2014-11-01

    Full Text Available Lymphatic Filariasis, a Neglected Tropical Disease, is caused by thread-like parasitic worms, including B. malayi, which migrate to the human lymphatic system following transmission. The parasites reside in collecting lymphatic vessels and lymph nodes for years, often resulting in lymphedema, elephantiasis or hydrocele. The mechanisms driving worm migration and retention within the lymphatics are currently unknown. We have developed an integrated in vitro imaging platform capable of quantifying B. malayi migration and behavior in a multicellular microenvironment relevant to the initial site of worm injection by incorporating the worm in a Polydimethylsiloxane (PDMS microchannel in the presence of human dermal lymphatic endothelial cells (LECs and human dermal fibroblasts (HDFs. The platform utilizes a motorized controllable microscope with CO2 and temperature regulation to allow for worm tracking experiments with high resolution over large length and time scales. Using post-acquisition algorithms, we quantified four parameters: 1 speed, 2 thrashing intensity, 3 percentage of time spent in a given cell region and 4 persistence ratio. We demonstrated the utility of our system by quantifying these parameters for L3 B. malayi in the presence of LECs and HDFs. Speed and thrashing increased in the presence of both cell types and were altered within minutes upon exposure to the anthelmintic drug, tetramisole. The worms displayed no targeted migration towards either cell type for the time course of this study (3 hours. When cells were not present in the chamber, worm thrashing correlated directly with worm speed. However, this correlation was lost in the presence of cells. The described platform provides the ability to further study B. malayi migration and behavior.

  7. Nanofiber Orientation and Surface Functionalization Modulate Human Mesenchymal Stem Cell Behavior In Vitro

    Science.gov (United States)

    Kolambkar, Yash M.; Bajin, Mehmet; Wojtowicz, Abigail; Hutmacher, Dietmar W.; García, Andrés J.

    2014-01-01

    Electrospun nanofiber meshes have emerged as a new generation of scaffold membranes possessing a number of features suitable for tissue regeneration. One of these features is the flexibility to modify their structure and composition to orchestrate specific cellular responses. In this study, we investigated the effects of nanofiber orientation and surface functionalization on human mesenchymal stem cell (hMSC) migration and osteogenic differentiation. We used an in vitro model to examine hMSC migration into a cell-free zone on nanofiber meshes and mitomycin C treatment to assess the contribution of proliferation to the observed migration. Poly (ɛ-caprolactone) meshes with oriented topography were created by electrospinning aligned nanofibers on a rotating mandrel, while randomly oriented controls were collected on a stationary collector. Both aligned and random meshes were coated with a triple-helical, type I collagen-mimetic peptide, containing the glycine-phenylalanine-hydroxyproline-glycine-glutamate-arginine (GFOGER) motif. Our results indicate that nanofiber GFOGER peptide functionalization and orientation modulate cellular behavior, individually, and in combination. GFOGER significantly enhanced the migration, proliferation, and osteogenic differentiation of hMSCs on nanofiber meshes. Aligned nanofiber meshes displayed increased cell migration along the direction of fiber orientation compared to random meshes; however, fiber alignment did not influence osteogenic differentiation. Compared to each other, GFOGER coating resulted in a higher proliferation-driven cell migration, whereas fiber orientation appeared to generate a larger direct migratory effect. This study demonstrates that peptide surface modification and topographical cues associated with fiber alignment can be used to direct cellular behavior on nanofiber mesh scaffolds, which may be exploited for tissue regeneration. PMID:24020454

  8. Bioaccessibility of polyphenols associated with dietary fiber and in vitro kinetics release of polyphenols in Mexican 'Ataulfo' mango (Mangifera indica L.) by-products.

    Science.gov (United States)

    Blancas-Benitez, Francisco J; Mercado-Mercado, Gilberto; Quirós-Sauceda, Ana E; Montalvo-González, Efigenia; González-Aguilar, Gustavo A; Sáyago-Ayerdi, Sonia G

    2015-03-01

    The biological properties of polyphenol (PP) depend on its bioaccessibility and bioavailability. Therefore, part of PP released from the food matrix in the gastrointestinal tract through enzymatic hydrolysis is at least partially absorbed. The aim of this study is to determine the bioaccessibility of PP associated with dietary fiber (DF) and the kinetics release of PP in mango (Mangifera indica L.) 'Ataulfo' by-products by an in vitro model. Soluble and insoluble DF values were 7.99 and 18.56% in the mango paste and 6.98 and 22.78% in the mango peel, respectively. PP associated with soluble and insoluble DF was 6.0 and 3.73 g GAE per 100 g in the paste and 4.72 and 4.50 g GAE per 100 g in the peel. The bioaccessibility of PP was 38.67% in the pulp paste and 40.53% in the peel. A kinetics study shows a release rate of 2.66 and 3.27 g PP min(-1) in the paste and peel, respectively. The antioxidant capacity of the paste increased as digestion reached a value of 2.87 mmol TE min(-1) at 180 min. The antioxidant capacity of the peel had its maximum (28.94 mmol TE min(-1)) between 90 and 120 min of digestion; it started with a value of 2.58 mmol TE min(-1), and thereafter increased to 4.20 mmol TE min(-1) at 180 min. The major PPs released during the digestion of paste were gallic and hydroxybenzoic acids, while in the peel, they were hydroxycinnamic and vanillic acids. It was concluded that these phenolic compounds are readily available for absorption in the small intestine and exert different potential health benefits.

  9. A stent for co-delivering paclitaxel and nitric oxide from abluminal and luminal surfaces: Preparation, surface characterization, and in vitro drug release studies

    Energy Technology Data Exchange (ETDEWEB)

    Gallo, Annemarie; Mani, Gopinath, E-mail: Gopinath.Mani@usd.edu

    2013-08-15

    Most drug-eluting stents currently available are coated with anti-proliferative drugs on both abluminal (toward blood vessel wall) and luminal (toward lumen) surfaces to prevent neointimal hyperplasia. While the abluminal delivery of anti-proliferative drugs is useful for controlling neointimal hyperplasia, the luminal delivery of such drugs impairs or prevents endothelialization which causes late stent thrombosis. This research is focused on developing a bidirectional dual drug-eluting stent to co-deliver an anti-proliferative agent (paclitaxel – PAT) and an endothelial cell promoting agent (nitric oxide – NO) from abluminal and luminal surfaces of the stent, respectively. Phosphonoacetic acid, a polymer-free drug delivery platform, was initially coated on the stents. Then, the PAT and NO donor drugs were co-coated on the abluminal and luminal stent surfaces, respectively. The co-coating of drugs was collectively confirmed by the surface characterization techniques such as Fourier transform infrared spectroscopy, scanning electron microscopy (SEM), 3D optical surface profilometry, and contact angle goniometry. SEM showed that the integrity of the co-coating of drugs was maintained without delamination or cracks formation occurring during the stent expansion experiments. In vitro drug release studies showed that the PAT was released from the abluminal stent surfaces in a biphasic manner, which is an initial burst followed by a slow and sustained release. The NO was burst released from the luminal stent surfaces. Thus, this study demonstrated the co-delivery of PAT and NO from abluminal and luminal stent surfaces, respectively. The stent developed in this study has potential applications in inhibiting neointimal hyperplasia as well as encouraging luminal endothelialization to prevent late stent thrombosis.

  10. Prolactin released in vitro from the pituitary of lactating, pregnant, and steroid-treated female or male rats stimulates prolactin secretion from pituitary lactotropes of male rats.

    Science.gov (United States)

    Mena, Flavio; Navarro, Nilda; Castilla, Alejandra; Morales, Teresa; Fiordelisio, Tatiana; Cárabez, Alfonso; Aguilar, Manuel B; Huerta-Ocampo, Icnelia

    2010-01-01

    We have previously shown that soluble factor(s) in conditioned media (CM) from the central and peripheral regions of the anterior pituitary (AP) gland of lactating rats promoted the in vitro dose-related release of prolactin (PRL) from pituitary glands of male rats. In the present experiments we sought to determine whether CM from rats in different physiological states provoked similar effects (like those of lactating rats), and the nature of the factors, whether 23K PRL or other variants of the hormone, were responsible for these effects. Stimulatory effects were induced by CM from pregnant females and steroid-treated castrated males or females, but not from untreated castrated rats, intact males, or by a PRL standard. More potent effects occurred with CM from APs of early- than from mid- or late-lactating rats, and from rats unsuckled for 8 or 16 h than from those unsuckled for 32 h. With respect to the nature of factor(s) responsible for these effects, immunoprecipitation of PRL from the CM of lactating females and of steroid-treated, castrated males eliminated, whereas dephosphorylation or deglycosylation of CM of lactating rats greatly increased its effects upon PRL release. Also, electrophoretic analysis and Western blotting of the CM proteins under native and denaturing conditions revealed a variety of PRL variants, ranging from 14 to <90 kDa, in CM from lactating rats, and the main effects on PRL release were provoked by the 23- to 46-kDa PRL variants. These results indicate that specific effects upon male rat lactotropes may be exerted by PRL variants released from APs of lactating and non-lactating rats. Copyright 2009 S. Karger AG, Basel.

  11. Comparative evaluation of fluoride release and recharge of pre-reacted glass ionomer composite and nano-ionomeric glass ionomer with daily fluoride exposure: an in vitro study.

    Science.gov (United States)

    Mungara, Jayanthi; Philip, John; Joseph, Elizabeth; Rajendran, Sakthivel; Elangovan, Arun; Selvaraju, Girija

    2013-01-01

    This in vitro study was designed to investigate the effects of daily fluoride exposures on fluoride release and recharge by prereacted glass ionomer (PRG) composite and nano-ionomeric glass ionomer. Seventy-two specimens (36 of each material) were prepared and by placing the restorative materials into Teflon mold. Each specimen was subjected to one of three daily treatments (n = 12): (1) No fluoride treatment (control); (2) application of a fluoride dentifrice (1,000 ppm) once daily; and (3) the same regimen as (2), plus immersion in a 0.05% sodium fluoride (NaF) mouth rinse (225 ppm) immediately following the dentifrice application. Specimens were suspended in a storage vial containing 10 ml demineralizing solution for 6 h and transferred to a new test tube containing 10 ml remineralizing solution for 18 h. Fluoride treatments of the specimens were c