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Sample records for vitro release behavior

  1. [In vitro drug release behavior of carrier made of porous glass ceramics].

    Science.gov (United States)

    Wang, De-ping; Huang, Wen-hai; Zhou, Nai

    2002-09-01

    To conduct the in vitro test on drug release of rifampin encapsulated in a carrier made of porous phosphate glass ceramics and to analyze main factors which affect the drug release rate. A certain quantitative of rifampin was sealed in a hollow cylindrical capsule which consisted of chopped calcium phosphate crystal fiber obtained from glass crystallization. The rifampin concentration was measured in the simulated physiological solution in which the capsule soaked. Rifampin could be released in a constant rate from the porous glass ceramic carrier in a long time. The release rate was dependent on the size of crystal fiber and the wall thickness of the capsule. This kind of calcium phosphate glass ceramics can be a candidate of the carrier materials used as long term drug therapy after osteotomy surgery.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

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

    International Nuclear Information System (INIS)

    Meng, Z.X.; Zheng, W.; Li, L.; Zheng, Y.F.

    2011-01-01

    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: → The average diameter increased with the increase of chitosan content and then decreased. → The release rate of fenbufen increased with the increase of chitosan. → The aligned nanofibrous scaffold exhibits lower drug release rate. → 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 would be beneficial

  4. In-Vitro Release of Ketoprofen Behavior Loaded in Polyvinyl Alcohol / Acrylamide Hydrogels Prepared by Gamma Irradiation

    International Nuclear Information System (INIS)

    Mahmoud, Gh.A.; Hegazy, D.E.; Kamal, H.

    2014-01-01

    Hydrogels based on various ratios of polyvinyl alcohol (PVA) and acrylamide (AAm) were prepared by gamma radiation. The formed hydrogels were characterized by spectroscopic analysis (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and swelling studied. It was found that the thermal stability of the hydrogel decreases as the AAm content increases in the hydrogel. The higher the AAm content in the hydrogel, the lower the values of Tm and ΔH m . Ketoprofen was adopted as a model drug to study the adsorption and release behavior of (PVA/AAm) hydrogel. The drug adsorption was decreased by increasing AAm ratio in the hydrogel. From the in vitro drug release study in ph progressive media, the basic medium was showed comparatively the highest release and the (PVA/AAm) hydrogel of composition (70/30) was found to be the highest release one. The mechanism of Ketoprofen release from the (PVA/AAm) matrix was found to be non-Fickian mechanism for all investigated hydrogels at ph 7.

  5. Evaluation of the release behavior of the dexamethasone embedded in polycarbonate polyurethane membranes: an in vitro study

    International Nuclear Information System (INIS)

    Kim, Dong Hyun; Kang, Sung Gwon; Lee, Chul Gab; Park, Sang Soo; Lee, Don Haeng; Lee, Gyu Baek; Song, Ho Young

    2003-01-01

    To evaluate the release behavior of dexamethasone embedded in a polycarbonate polyurethane membrane. Both water-soluble and water-insoluble dexamethasone were tested, and the release behavior of five water-insoluble dexamethasone films of different thickness (78 to 211 μm) was also evaluated. The amount of dexamethasone used was 10% of the total weight of the polyurethan film mass. Each film was placed in a centrifuge tube containing 25 ml of 0.1-M neutral phosphate buffer, and the tubes were placed in a shaking incubator to quantify the amount of drug released into the buffer, absorption spectroscopy (λ max=242 nm) was employed. In the test involving water-soluble dexamethasone, 60%, of the drug was released during the first two hours of the study. Films containing water-insoluble dexamethasone, on the other hand, released 40%, 60% and 75% of the dexamethasone in one, three and seven days, respectively. Both types of film maintained low-dose drug release for 28 days. When release behavior was compared between water-insoluble films of different thickness, thicker film showed less initial burst and more sustained release. Dexamethasone release behavior varies according to drug solubility and membrane thickness, and may thus be conrolled

  6. Functionality Effect of Pressure Sensitive Adhesives on In Vitro Drug Release Behavior of Fentanyl Drug in an Adhesive Patch

    Directory of Open Access Journals (Sweden)

    S.M. Taghizadeh

    2009-12-01

    Full Text Available Some formulations of drug in adhesive transdermal drug delivery systems (TDDSs( with different functional and non-functional acrylic pressure sensitive adhesives PSAs( were prepared. For this purpose fentanyl was used as a drug component. The effects of PSAs type on skin permeation and in vitro drug release from devices were evaluated using hydrodynamically well-characterized Chien permeation system fitted with excised rat abdominal skin. The adhesion properties of devices (peel strength and tack values( were obtained. It was found that TDDS with –COOH functional PSA had the lowest steady state flux. Drug release was followed by Higuchi's kinetic model. Adhesion properties of the samples were improved by addition of functional PSA in the formulations.

  7. Biodegradable polyesters for veterinary drug delivery systems: Characterization, in vitro degradation and release behavior of Oligolactides and Polytartrate

    OpenAIRE

    Schliecker, Gesine

    2004-01-01

    This thesis deals with the degradation and release behavior of aliphatic polyesters with special respect to the influence of oligomers on the degradation rate and the potential use of these biomaterials for the development of veterinary drug delivery systems. In Chapter 1 the animal health care market is introduced with regard to opportunities and challenges of veterinary drug delivery systems. . In the second part of this chapter...

  8. 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.

  9. Three-dimensional Printed Scaffolds with Gelatin and Platelets Enhance In vitro Preosteoblast Growth Behavior and the Sustained-release Effect of Growth Factors

    Directory of Open Access Journals (Sweden)

    Wei Zhu

    2016-01-01

    Conclusions: Our experiments confirmed that the 3D printed scaffolds we had designed could provide a sustained-release effect for growth factors and improve the proliferation of preosteoblasts with little cytotoxicity in vitro. They may hold promise as bone graft substitute materials in the future.

  10. 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.

  11. 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

    Directory of Open Access Journals (Sweden)

    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

  12. Effect of HPMC and mannitol on drug release and bioadhesion behavior of buccal discs of buspirone hydrochloride: In-vitro and in-vivo pharmacokinetic studies.

    Science.gov (United States)

    Jaipal, A; Pandey, M M; Charde, S Y; Raut, P P; Prasanth, K V; Prasad, R G

    2015-07-01

    Delivery of orally compromised therapeutic drug molecules to the systemic circulation via buccal route has gained a significant interest in recent past. Bioadhesive polymers play a major role in designing such buccal dosage forms, as they help in adhesion of designed delivery system to mucosal membrane and also prolong release of drug from delivery system. In the present study, HPMC (release retarding polymer) and mannitol (diluent and pore former) were used to prepare bioadhesive and controlled release buccal discs of buspirone hydrochloride (BS) by direct compression method. Compatibility of BS with various excipients used during the study was assessed using DSC and FTIR techniques. Effect of mannitol and HPMC on drug release and bioadhesive strength was studied using a 3(2) factorial design. The drug release rate from delivery system decreased with increasing levels of HPMC in formulations. However, bioadhesive strength of formulations increased with increasing proportion of HPMC in buccal discs. Increased levels of mannitol resulted in faster rate of drug release and rapid in vitro uptake of water due to the formation of channels in the matrix. Pharmacokinetic studies of designed bioadhesive buccal discs in rabbits demonstrated a 10-fold increase in bioavailability in comparison with oral bioavailability of buspirone reported.

  13. The sustained-release behavior and in vitro and in vivo transfection of pEGFP-loaded core-shell-structured chitosan-based composite particles

    Science.gov (United States)

    Wang, Yun; Lin, Fu-xing; Zhao, Yu; Wang, Mo-zhen; Ge, Xue-wu; Gong, Zheng-xing; Bao, Dan-dan; Gu, Yu-fang

    2014-01-01

    Novel submicron core-shell-structured chitosan-based composite particles encapsulated with enhanced green fluorescent protein plasmids (pEGFP) were prepared by complex coacervation method. The core was pEGFP-loaded thiolated N-alkylated chitosan (TACS) and the shell was pH- and temperature-responsive hydroxybutyl chitosan (HBC). pEGFP-loaded TACS-HBC composite particles were spherical, and had a mean diameter of approximately 120 nm, as measured by transmission electron microscopy and particle size analyzer. pEGFP showed sustained release in vitro for >15 days. Furthermore, in vitro transfection in human embryonic kidney 293T and human cervix epithelial cells, and in vivo transfection in mice skeletal muscle of loaded pEGFP, were investigated. Results showed that the expression of loaded pEGFP, both in vitro and in vivo, was slow but could be sustained over a long period. pEGFP expression in mice skeletal muscle was sustained for >60 days. This work indicates that these submicron core-shell-structured chitosan-based composite particles could potentially be used as a gene vector for in vivo controlled gene transfection. PMID:25364253

  14. [Studies on preparation and dissolution test in vitro of sustained-release dropping pills of curcumin].

    Science.gov (United States)

    Fang, Yu; Xiang, Bai; Pan, Zhen-Hua; Cao, De-Ying

    2010-01-01

    To study the prescription and technique of sustained-release dropping pills of curcumin and inspect their release property in vitro. The orthogonal test was used to screen the prescription and technique which were definited with the colligation evaluation of release and formation of dropping pills. The optimization of prescription and technique were as follows: stearic acid 70 mg, glycery monostearate 25 mg, solutol 6 mg, viscosity of cooling liquid was 100 mm2/s; the temperature of material liquid was 80 degrees C; the cooling temperature was 30 - 0 degrees C; the dropping speed was (21 +/- 2) dripping/min. The release behavior of sustained-release dropping pills of curcumin coincidented with Higuchi equation well and the character of sustained-release was transparent. The sustained-release dropping pills of curcumin have good property of sustained-release in vitro and their release behavior in vivo need to be inspected.

  15. The sustained-release behavior and in vitro and in vivo transfection of pEGFP-loaded core-shell-structured chitosan-based composite particles

    Directory of Open Access Journals (Sweden)

    Wang Y

    2014-10-01

    Full Text Available Yun Wang,1 Fu-xing Lin,2 Yu Zhao,1 Mo-zhen Wang,2 Xue-wu Ge,2 Zheng-xing Gong,1 Dan-dan Bao,1 Yu-fang Gu1 1Department of Plastic Surgery, First Affiliated Hospital of Anhui Medical University, 2CAS Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China Abstract: Novel submicron core-shell-structured chitosan-based composite particles ­encapsulated with enhanced green fluorescent protein plasmids (pEGFP were prepared by complex coacervation method. The core was pEGFP-loaded thiolated N-alkylated chitosan (TACS and the shell was pH- and temperature-responsive hydroxybutyl chitosan (HBC. pEGFP-loaded TACS-HBC composite particles were spherical, and had a mean diameter of approximately 120 nm, as measured by transmission electron microscopy and particle size analyzer. pEGFP showed sustained release in vitro for >15 days. Furthermore, in vitro transfection in human embryonic kidney 293T and human cervix epithelial cells, and in vivo transfection in mice skeletal muscle of loaded pEGFP, were investigated. Results showed that the expression of loaded pEGFP, both in vitro and in vivo, was slow but could be sustained over a long period. pEGFP expression in mice skeletal muscle was sustained for >60 days. This work indicates that these submicron core-shell-structured chitosan-based composite particles could potentially be used as a gene vector for in vivo controlled gene transfection. Keywords: gene therapy, gene transfection, hydroxybutyl chitosan, thiolated N-alkylated chitosan, pEGFP, complex coacervation

  16. Accelerated in-vitro release testing methods for extended-release parenteral dosage forms.

    Science.gov (United States)

    Shen, Jie; Burgess, Diane J

    2012-07-01

    This review highlights current methods and strategies for accelerated in-vitro drug release testing of extended-release parenteral dosage forms such as polymeric microparticulate systems, lipid microparticulate systems, in-situ depot-forming systems and implants. Extended-release parenteral dosage forms are typically designed to maintain the effective drug concentration over periods of weeks, months or even years. Consequently, 'real-time' in-vitro release tests for these dosage forms are often run over a long time period. Accelerated in-vitro release methods can provide rapid evaluation and therefore are desirable for quality control purposes. To this end, different accelerated in-vitro release methods using United States Pharmacopeia (USP) apparatus have been developed. Different mechanisms of accelerating drug release from extended-release parenteral dosage forms, along with the accelerated in-vitro release testing methods currently employed are discussed. Accelerated in-vitro release testing methods with good discriminatory ability are critical for quality control of extended-release parenteral products. Methods that can be used in the development of in-vitro-in-vivo correlation (IVIVC) are desirable; however, for complex parenteral products this may not always be achievable. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

  17. Accelerated in vitro release testing methods for extended release parenteral dosage forms

    Science.gov (United States)

    Shen, Jie; Burgess, Diane J.

    2012-01-01

    Objectives This review highlights current methods and strategies for accelerated in vitro drug release testing of extended release parenteral dosage forms such as polymeric microparticulate systems, lipid microparticulate systems, in situ depot-forming systems, and implants. Key findings Extended release parenteral dosage forms are typically designed to maintain the effective drug concentration over periods of weeks, months or even years. Consequently, “real-time” in vitro release tests for these dosage forms are often run over a long time period. Accelerated in vitro release methods can provide rapid evaluation and therefore are desirable for quality control purposes. To this end, different accelerated in vitro release methods using United States Pharmacopoeia (USP) apparatus have been developed. Different mechanisms of accelerating drug release from extended release parenteral dosage forms, along with the accelerated in vitro release testing methods currently employed are discussed. Conclusions Accelerated in vitro release testing methods with good discriminatory ability are critical for quality control of extended release parenteral products. Methods that can be used in the development of in vitro-in vivo correlation (IVIVC) are desirable, however for complex parenteral products this may not always be achievable. PMID:22686344

  18. Effect of HPMC and mannitol on drug release and bioadhesion behavior of buccal discs of buspirone hydrochloride: In-vitro and in-vivo pharmacokinetic studies

    OpenAIRE

    Jaipal, A.; Pandey, M.M.; Charde, S.Y.; Raut, P.P.; Prasanth, K.V.; Prasad, R.G.

    2015-01-01

    Delivery of orally compromised therapeutic drug molecules to the systemic circulation via buccal route has gained a significant interest in recent past. Bioadhesive polymers play a major role in designing such buccal dosage forms, as they help in adhesion of designed delivery system to mucosal membrane and also prolong release of drug from delivery system. In the present study, HPMC (release retarding polymer) and mannitol (diluent and pore former) were used to prepare bioadhesive and control...

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

    Directory of Open Access Journals (Sweden)

    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.

  20. 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...

  1. Tritium behavior intentionally released in the room

    International Nuclear Information System (INIS)

    Kobayashi, K.; Hayashi, T.; Iwai, Y.; Yamanishi, T.; Willms, R. S.; Carlson, R. V.

    2008-01-01

    To construct a fusion reactor with high safety and acceptability, it is necessary to establish and to ensure tritium safe handling technology. Tritium should be well-controlled not to be released to the environment excessively and to prevent workers from excess exposure. It is especially important to grasp tritium behavior in the final confinement area, such as the room and/or building. In order to obtain data for actual tritium behavior in a room and/or building, a series of intentional Tritium Release Experiments (TREs) were planned and carried out within a radiologically controlled area (main cell) at Tritium System Test Assembly (TSTA) in Los Alamos National Laboratory (LANL) under US-JAPAN collaboration program. These experiments were carried out three times. In these experiments, influence of a difference in the tritium release point and the amount of hydrogen isotope for the initial tritium behavior in the room were suggested. Tritium was released into the main cell at TSTA/LANL. The released tritium reached a uniform concentration about 30 - 40 minutes in all the experiments. The influence of the release point and the amount of hydrogen isotope were not found to be important in these experiments. The experimental results for the initial tritium behavior in the room were also simulated well by the modified three-dimensional eddy flow analysis code FLOW-3D. (authors)

  2. [Preparation of hydrophilic matrix sustained release tablets of total lactones from Andrographis paniculata and study on its in vitro release mechanism].

    Science.gov (United States)

    Xu, Fang-Fang; Shi, Wei; Zhang, Hui; Guo, Qing-Ming; Wang Zhen-Zhong; Bi, Yu-An; Wang, Zhi-Min; Xiao, Wei

    2015-01-01

    In this study, hydrophilic matrix sustained release tablets of total lactones from Andrographis paniculata were prepared and the in vitro release behavior were also evaluated. The optimal prescription was achieved by studying the main factor of the type and amount of hydroxypropyl methylcellulose (HPMC) using single factor test and evaluating through cumulative release of three lactones. No burst drug release from the obtained matrix tablets was observed. Drug release sustained to 14 h. The release mechanism of three lactones from A. paniculata was accessed by zero-order, first-order, Higuchi and Peppas equation. The release behavior of total lactones from A. paniculata was better agreed with Higuchi model and the drug release from the tablets was controlled by degradation of the matrix. The preparation of hydrophilic matrix sustained release tablets of total lactones from A. paniculata with good performance of drug release was simple.

  3. ENDOGENOUS PYROGEN RELEASE FROM RABBIT BLOOD CELLS INCUBATED IN VITRO WITH PARAINFLUENZA VIRUS.

    Science.gov (United States)

    ATKINS, E; CRONIN, M; ISACSON, P

    1964-12-11

    Rabbit blood cells incubated in vitro with purified parainfluenza-5 virus (DA strain) released a rapidly acting pyrogen. Spleen and lymph node cells were inactive. The pyrogen resembled in behavior a pyrogen extracted from granulocytic exudates. Similar cells in the blood are believed to be activated by virus in vivo to produce the circulating endogenous pyrogen that mediates virus-induced fever.

  4. 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

    -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...... 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...

  5. A Comparative Study on Micellar and Solubilizing Behavior of Three EO-PO Based Star Block Copolymers Varying in Hydrophobicity and Their Application for the In Vitro Release of Anticancer Drugs

    Directory of Open Access Journals (Sweden)

    Bijal Vyas

    2018-01-01

    Full Text Available The temperature and pH dependent self-assembly of three star shaped ethylene oxide-propylene oxide (EO-PO block copolymers (Tetronics® 304, 904 and 908 with widely different hydrophobicity was examined in aqueous solutions. Physico-chemical methods viz. viscosity, cloud point, solubilization along with thermal, scattering and spectral techniques shows strongly temperature and salt dependent solution behavior. T304 possessing low molecular weight did not form micelles; moderately hydrophilic T904 remained as micelles at ambient temperature and showed micellar growth while very hydrophilic T908 formed micelles at elevated temperatures. The surface activity/micellization/solubilization power was favored in the presence of salt. The copolymers turn more hydrophilic in acidic pH due to protonation of central ethylene diamine moiety that hinders micelle formation. The solubilization of a model insoluble azo dye 1-(o-Tolylazo-2-naphthol (Orange OT and hydrophobic drugs (quercetin and curcumin for copolymer solutions in aqueous and salt solutions are also reported. Among the three copolymers, T904 showed maximum solubility of dye and drugs, hence the in vitro release of drugs from T904 micelles was estimated and the effect on cytotoxicity of loading the drugs in T904 micelles was compared with the cytotoxicity of free drugs on the CHO-K1 cells. The results from the present work provide a better insight in selection of Tetronics® for their application in different therapeutic applications.

  6. In-vitro release of anti-proliferative paclitaxel from novel balloon-expandable polycaprolactone stents

    International Nuclear Information System (INIS)

    Liu, Shih-Jung; Hsiao, Chao-Ying; Chen, Jan-Kan; Liu, Kuo-Sheng; Lee, Cheng-Hung

    2011-01-01

    This report investigated the in-vitro release characteristics of paclitaxel from novel balloon-expandable polycaprolactone stents. Polycaprolactone stents were first manufactured by a lab-made micro-injection molding machine. Paclitaxel and polylactide-polyglycolide (PLGA) copolymer were dissolved in acetonitrile and were coated onto the surface of the stents by a spray coating device, which was designed and built especially for this study. An elution method was utilized to characterize the in-vitro release characteristics of paclitaxel. The high performance liquid chromatography (HPLC) analysis showed that biodegradable stents could provide sustained release of paclitaxel for more than 70 days. Various process parameters that controlled the release rate of paclitaxel were studied. The experimental results suggested that the total period of drug release could be prolonged by adopting 75:25 PLGA copolymers, employing multi-layer coatings, and increasing the drug loading. In addition, the effectiveness of eluted paclitaxel on cell behavior was examined. The results showed that the eluted drug could effectively inhibit the proliferation of smooth muscle cells. - Research Highlights: → We investigate the in-vitro release characteristics of paclitaxel from polycaprolactone stents. → Biodegradable stents provide sustained release of paclitaxel for more than 70 days. → The eluted drug effectively inhibits the proliferation of smooth muscle cells.

  7. Comparison of metal release from various metallic biomaterials in vitro.

    Science.gov (United States)

    Okazaki, Yoshimitsu; Gotoh, Emiko

    2005-01-01

    To investigate the metal release of each base and alloying elements in vitro, SUS316L stainless steel, Co-Cr-Mo casting alloy, commercially pure Ti grade 2, and Ti-6Al-4V, V-free Ti-6Al-7Nb and Ti-15Zr-4Nb-4Ta alloys were immersed in various solutions, namely, alpha-medium, PBS(-), calf serum, 0.9% NaCl, artificial saliva, 1.2 mass% L-cysteine, 1 mass% lactic acid and 0.01 mass% HCl for 7d. The difference in the quantity of Co released from the Co-Cr-Mo casting alloy was relatively small in all the solutions. The quantities of Ti released into alpha-medium, PBS(-), calf serum, 0.9% NaCl and artificial saliva were much lower than those released into 1.2% L-cysteine, 1% lactic acid and 0.01% HCl. The quantity of Fe released from SUS316L stainless steel decreased linearly with increasing pH. On the other hand, the quantity of Ti released from Ti materials increased with decreasing pH, and it markedly attenuated at pHs of approximately 4 and higher. The quantity of Ni released from stainless steel gradually decreased with increasing pH. The quantities of Al released from the Ti-6Al-4V and Ti-6Al-7Nb alloys gradually decreased with increasing pH. A small V release was observed in calf serum, PBS(-), artificial saliva, 1% lactic acid, 1.2% l-cysteine and 0.01% HCl. The quantity of Ti released from the Ti-15Zr-4Nb-4Ta alloy was smaller than those released from the Ti-6Al-4V and Ti-6Al-7Nb alloys in all the solutions. In particular, it was approximately 30% or smaller in 1% lactic acid, 1.2% L-cysteine and 0.01% HCl. The quantity of (Zr + Nb + Ta) released was also considerably lower than that of (Al + Nb) or (Al + V) released. Therefore, the Ti-15Zr-4Nb-4Ta alloy with its low metal release in vitro is considered advantageous for long-term implants. Copyright 2004 Elsevier Ltd.

  8. Stimulatory effects of neuronally released norepinephrine on renin release in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Matsumura, Yasuo; Kawazoe, Shinka; Ichihara, Toshio; Shinyama, Hiroshi; Kageyama, Masaaki; Morimoto, Shiro (Osaka Univ. of Pharmaceutical Sciences (Japan))

    1988-10-01

    Extracellular high potassium inhibits renin release in vitro by increasing calcium concentrations in the juxtaglomerular cells. The authors found that the decreased response of renin release from rat kidney cortical slices in high potassium solution changed to a strikingly increased one in the presence of nifedipine at doses over 10{sup {minus}6} M. They then examined the stimulatory effect of extracellular high potassium in the presence of nifedipine on renin release. The enhancement of release was significantly suppressed either by propranolol or by metoprolol but not by prazosin. High potassium plus nifedipine-induced increase in renin release was markedly attenuated by renal denervation. The enhancing effect was not observed when the slices were incubated in calcium-free medium. Divalent cations such as Cd{sup 2+}, Co{sup 2+}, and Mn{sup 2+} blocked this enhancement in a concentration-dependent manner. High potassium elicited an increase in {sup 3}H efflux from the slices preloaded with ({sup 3}H)-norepinephrine. The increasing effect was not influenced by nifedipine but was abolished by the removal of extracellular calcium or by the addition of divalent cations. These observations suggest to us that the high potassium plus nifedipine-induced increase in renin release from the slices is mediated by norepinephrine derived from renal sympathetic nerves and that this neuronally released norepinephrine stimulates renin release via activation of {beta}-adrenoceptors.

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

    Science.gov (United States)

    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.

  10. 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

    Introduction 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. Methodology 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. Results and Discussion 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

  11. 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

  12. POLYCAPROLACTONE-POLY (ETHYLENE GLYCOL) BLOCK COPOLYMER Ⅲ DRUG RELEASE BEHAVIOR

    Institute of Scientific and Technical Information of China (English)

    BEI Jianzhong; WANG Zhifeng; WANG Shenguo

    1995-01-01

    The drug release behavior of degradable polymer - polycaprolactone-poly (ethylene glycol)block copolymer(PCE) in vitro was investigated by using 5-Fluoro-uracil (5-Fu) as a model drug under a condition of pH 7.4 at 37℃. It is found that the release rate of 5-Fu from PCE increased with increasing polyether content of the copolymer. The results show that the increasing polyether content of the copolymer caused increasing hydrophilicity and decreasing crystallinity of the PCE copolymer. Thus, the drug release behavior and the degradable property of the PCE can be controlled by adjusting the composition of the copolymer.

  13. In vitro release kinetics of Tolmetin from tabletted Eudragit microparticles.

    Science.gov (United States)

    Pignatello, R; Consoli, P; Puglisi, G

    2000-01-01

    In a previous paper the preparation has been described, by three different techniques, of microparticles made of Eudragit RS 100 and RL 100 containing a NSAI agent, Tolmetin. Freely flowing microparticles failed to affect significantly the in vitro drug release, which displayed a similar dissolution profile after micro-encapsulation to the free drug powder. Microparticles were then converted into tablets and the effect of compression on drug delivery, as well as that of the presence of co-additives, was studied in the present work. Furthermore, microparticles were also prepared by adding MgO to the polymer matrix, to reduce the sensitivity of the drug to pH changes during its dissolution. Similarly, magnesium stearate was also used for microparticle formation as a droplet stabilizer, in order to reduce particle size and hinder rapid drug release. A mathematical evaluation, by using two semi-empirical equations, was applied to evaluate the influence of dissolution and diffusion phenomena upon drug release from microparticle tablets.

  14. 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

  15. 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.

  16. Release of /sup 3/H-. cap alpha. -methyl-m-tyramine from rat striatum in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Dorris, R L [Baylor College of Dentistry, Dallas, Tex. (USA). Dept. of Pharmacology

    1976-01-01

    Release of /sup 3/H-d-..cap alpha..-methyl-m-tyramine (/sup 3/H-MMTA), a false dopaminergic transmitter from rat striatum was studied in vitro. After its initial uptake, /sup 3/H-MMTA was released by high K/sup +/ and by amphetamine. The release requirements were essentially the same as those known to exist for release of dopamine in vitro. These studies indicate that /sup 3/H-MMTA might serve as a useful tool with which to study dopamine release mechanisms in vitro.

  17. Controlled release effervescent buccal discs of buspirone hydrochloride: in vitro and in vivo evaluation studies.

    Science.gov (United States)

    Jaipal, A; Pandey, M M; Charde, S Y; Sadhu, N; Srinivas, A; Prasad, R G

    2016-01-01

    In the present study controlled release effervescent buccal discs of buspirone hydrochloride (BS) were designed using HPMC as rate controlling and bioadhesive polymer by direct compression method. Sodium bicarbonate and citric acid were used in varying amounts as effervescence forming agents. Carbon dioxide evolved due to reaction of sodium bicarbonate and citric acid was explored for its potential as buccal permeation enhancer. The designed buccal discs were evaluated for physical characteristics and in vitro drug release studies. Bioadhesive behavior of designed buccal discs was assessed using texture analyzer. In vivo animal studies were performed in rabbits to study bioavailability of BS in the designed buccal discs and to establish permeation enhancement ability of carbon dioxide. It was observed that effervescent buccal discs have faster drug release compared to non-effervescent buccal discs in vitro and effervescent buccal discs demonstrated significant increase in bioavailability of drug when compared to non-effervescent formulation. Hence, effervescent buccal discs can be used as an alternative to improve the drug permeation resulting in better bioavailability. However, the amount of acid and base used for generation of carbon dioxide should be selected with care as this may damage the integrity of bioadhesive dosage form.

  18. 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 ...

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

    African Journals Online (AJOL)

    decreased while Starch 1500 and lactose monohydrate increased drug release. Drug release mechanism ... case of antihypertensive agents to maintain constant blood levels ... systems because of their low toxicity, pH- independent swelling ...

  20. Physicochemical properties and drug release behavior of biguanidino and O-carboxymethyl chitosan microcapsules.

    Science.gov (United States)

    Huo, Weiqiang; Zhang, Weixin; Wang, Wei; Zhou, Xiaohua

    2014-09-01

    Two types of microcapsules (MCs) were prepared by the emulsion cross-linking method, where biguanidino chitosan (BGCS)and O-carboxymethyl chitosan (O-CMCS) served as the wall materials, and the antibacterial agent 2,4-diamino-6-(2-pyridyl)-1,3,5-triazine (PyTNH) served as a model water-soluble drug. The physicochemical performance of the MCs and their drug release behavior were investigated by Fourier transform infrared spectroscopy, thermogravimetric analysis/derivative thermogravimetric analysis, scanning electron microscopy, and swelling and in vitro drug release studies of the two MCs with unmodified chitosan-MCs (CS-MCs) used as the control. The results indicated that the degree of cross-linking, encapsulation efficiency, and thermal stability of the shell wall of the BGCS-microcapsules (BGCS-MCs) were much higher than those of the control and the O-CMCS-microcapsules (CMCS-MCs), owing to the reduction of steric hindrance and development of the conjugation effect in the cross-linking process. Studies on the swelling and in vitro drug-release behavior revealed a sustained release effect of the BGCS-MCs. Moreover, the CMCS-MCs were found to exhibit a pH-dependent drug release behavior, which can be attributed to the successive formation of H-bonds and repulsive forces with the change in the pH of the medium. Based on these results, the swelling-release models and the drug release kinetics of BGCS-MCs and CMCS-MCs are proposed. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Correlation between the viscoelastic properties of the gel layer of swollen HPMC matrix tablets and their in vitro drug release.

    Science.gov (United States)

    Hamed, Rania; Al Baraghthi, Tamadur; Sunoqrot, Suhair

    2016-11-21

    Drug release from hydroxypropyl methylcellulose (HPMC) hydrophilic matrix tablets is controlled by drug diffusion through the gel layer of the matrix-forming polymer upon hydration, matrix erosion or combination of diffusion and erosion mechanisms. In this study, the relationship between viscoelastic properties of the gel layer of swollen intact matrix tablets and drug release was investigated. Two sets of quetiapine fumarate (QF) matrix tablets were prepared using the high viscosity grade HPMC K4M at low (70 mg/tablet) and high (170 mg/tablet) polymer concentrations. Viscoelastic studies using a controlled stress rheometer were performed on swollen matrices following hydration in the dissolution medium for predetermined time intervals. The gel layer of swollen tablets exhibited predominantly elastic behavior. Results from the in vitro release study showed that drug release was strongly influenced by the viscoelastic properties of the gel layer of K4M tablets, which was further corroborated by results from water uptake studies conducted on intact tablets. The results provide evidence that the viscoelastic properties of the gel layer can be exploited to guide the selection of an appropriate matrix-forming polymer, to better understand the rate of drug release from matrix tablets in vitro and to develop hydrophilic controlled-release formulations.

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

    African Journals Online (AJOL)

    Conclusion: A fair correlation between in vitro dissolution and in vivo data was found. The results obtained indicate successful development of a sustained release formulation of diltiazem. Keywords: Diltiazem, Matrix tablet, Hydroxypropyl methylcellulose Eudragit, In vitro/in vivo correlation, Optimization ...

  3. Role of In Vitro Release Methods in Liposomal Formulation Development: Challenges and Regulatory Perspective.

    Science.gov (United States)

    Solomon, Deepak; Gupta, Nilesh; Mulla, Nihal S; Shukla, Snehal; Guerrero, Yadir A; Gupta, Vivek

    2017-11-01

    In the past few years, measurement of drug release from pharmaceutical dosage forms has been a focus of extensive research because the release profile obtained in vitro can give an indication of the drug's performance in vivo. Currently, there are no compendial in vitro release methods designed for liposomes owing to a range of experimental challenges, which has created a major hurdle for both development and regulatory acceptance of liposome-based drug products. In this paper, we review the current techniques that are most often used to assess in vitro drug release from liposomal products; these include the membrane diffusion techniques (dialysis, reverse dialysis, fractional dialysis, and microdialysis), the sample-and-separate approach, the in situ method, the continuous flow, and the modified United States Pharmacopeia methods (USP I and USP IV). We discuss the principles behind each of the methods and the criteria that assist in choosing the most appropriate method for studying drug release from a liposomal formulation. Also, we have included information concerning the current regulatory requirements for liposomal drug products in the United States and in Europe. In light of increasing costs of preclinical and clinical trials, applying a reliable in vitro release method could serve as a proxy to expensive in vivo bioavailability studies. Graphical Abstract Appropriate in-vitro drug release test from liposomal products is important to predict the in-vivo performance.

  4. Release behavior of drugs from various natural gums and polymers.

    Science.gov (United States)

    Singh, Anupama; Sharma, Pramod Kumar; Malviya, Rishabha

    2011-01-01

    Polymers are the high molecular weight compounds of natural or synthetic origin, widely used in drug delivery of formulations. These polymers are further classified as hydrophilic or hydrophobic in nature. Depending upon this characteristic, polymers exhibit different release behavior in different media. This property plays an important role in the selection of polymers for controlled, sustained or immediate release formulations. The review highlights the literatures related to the research made on several polymers regarding the release kinetics which made them a novel approach for modifying the action of the particular formulation.

  5. Influence of PCL on the material properties of collagen based biocomposites and in vitro evaluation of drug release

    International Nuclear Information System (INIS)

    Kanungo, Ivy; Fathima, Nishter Nishad; Rao, Jonnalagadda Raghava; Nair, Balachandran Unni

    2013-01-01

    Formulation of biodegradable collagen–poly-ε-caprolactone (PCL) based biomaterials for the sustained release of insulin is the main objective of the present work. PCL has been employed to modulate the physico-chemical behavior of collagen to control the drug release. Designed formulations were employed to statistically optimize insulin release parameter profile at different collagen to PCL molar ratios. Circular dichroism, thermoporometry, FTIR, impedance and scanning electron microscopy techniques have been employed to investigate the effect of PCL on hydration dynamics of the collagen molecule, which in turn changes the dissolution parameters of the drug from the systems. Drug entrapment efficiency has been found to be maximum for collagen to PCL molar ratio of 1:2 (> 90%). In vitro dissolution test reveals that 99% of the drug was released from composite at collagen to PCL molar ratio of 1:3 and 1:4 within 2 h, which indicates that hydrophobicity of the matrix results in weak interaction between lipophilic drug and carrier materials. The least burst release was observed for collagen to PCL molar ratio at 1:2 as synergistic interactions between collagen and PCL was maximum at that particular polymer–polymer ratios. The drug release data indicates super case-II transport of drug (n > 1.0). - Graphical abstract: Collagen–poly-ε-caprolactone based biomaterials for the sustained release of insulin were formulated. Circular dichroism, thermoporometry, FTIR, impedance and scanning electron microscopy techniques have been employed to elucidate the effect of PCL on the structure of the collagen and in vitro drug release. The drug release data fitted to the kinetic model indicates super case-II transport due to the combination of diffusion and polymer relaxation/dissolution (n > 1.0). - Highlights: • Poly-ε-caprolactone influences physico-chemical behavior of collagen. • Poly-ε-caprolactone influences in vitro drug release mechanism from biocomposites.

  6. Investigating the in vitro drug release kinetics from controlled release diclofenac potassium-ethocel matrix tablets and the influence of co-excipients on drug release patterns.

    Science.gov (United States)

    Shah, Shefaat Ullah; Shah, Kifayat Ullah; Rehman, Asimur; Khan, Gul Majid

    2011-04-01

    The objective of the study was to formulate and evaluate controlled release polymeric tablets of Diclofenac Potassium for the release rate, release patterns and the mechanism involved in the release process of the drug. Formulations with different types and grades of Ethyl Cellulose Ether derivatives in several drug-to-polymer ratios (D:P) were compressed into tablets using the direct compression method. In vitro drug release studies were performed in phosphate buffer (pH 7.4) as dissolution medium by using USP Method-1 (Rotating Basket Method). Similarity factor f2 and dissimilarity factor f1 were applied for checking the similarities and dissimilarities of the release profiles of different formulations. For the determination of the release mechanism and drug release kinetics various mathematical/kinetic models were employed. It was found that all of the Ethocel polymers could significantly slow down the drug release rate with Ethocel FP polymers being the most efficient, especially at D:P ratios of 10:03 which lead towards the achievement of zero or near zero order release kinetics.

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

    African Journals Online (AJOL)

    Development of release retardant matrix tablets of diclofenac sodium for 24 h by wet granulation technique using different combinations and ratios of hydroxypropylmethylcellulose (HPMC), sodium carboxymethylcellulose (sodium CMC), sodium alginate and cetostearyl alcohol was carried out. The tablets were evaluated ...

  8. 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®..

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

    African Journals Online (AJOL)

    Microcrystalline cellulose (Avicel PH 101), starch (Sta-Rx 1500) and lactose monohydrate were used as diluents in the formulations while the effect of sodium lauryl sulphate (wetting agent) was studied for some of the formulations. The tablets were characterized for carvedilol phosphate release in both simulated gastric and ...

  10. 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.

  11. 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.

  12. Effect of in vitro inorganic lead on dopamine release from superfused rat striatal synaptosomes

    International Nuclear Information System (INIS)

    Minnema, D.J.; Greenland, R.D.; Michaelson, I.A.

    1986-01-01

    The effect of inorganic lead in vitro in several aspects of [ 3 H]dopamine release from superfused rat striatal synaptosomes was examined. Under conditions of spontaneous release, lead (1-30 microM) induced dopamine release in a concentration-dependent manner. The onset of the lead-induced release was delayed by approximately 15-30 sec. The magnitude of dopamine release induced by lead was increased when calcium was removed from the superfusing buffer. Lead-induced release was unaffected in the presence of putative calcium, sodium, and/or potassium channel blockers (nickel, tetrodotoxin, tetraethylammonium, respectively). Depolarization-evoked dopamine release, produced by a 1-sec exposure to 61 mM potassium, was diminished at calcium concentrations below 0.254 mM. The onset of depolarization-evoked release was essentially immediate following exposure of the synaptosomes to high potassium. The combination of lead (3 or 10 microM) with high potassium reduced the magnitude of depolarization-evoked dopamine release. This depression of depolarization-evoked release by lead was greater in the presence of 0.25 mM than 2.54 mM calcium in the superfusing buffer. These findings demonstrate multiple actions of lead on synaptosomal dopamine release. Lead can induce dopamine release by yet unidentified neuronal mechanisms independent of external calcium. Lead can also reduce depolarization-evoked dopamine release by apparent competition with calcium influx at the neuronal membrane calcium channel

  13. Hexa-histidin tag position influences disulfide structure but not binding behavior of in vitro folded N-terminal domain of rat corticotropin-releasing factor receptor type 2a

    OpenAIRE

    Klose, Jana; Wendt, Norbert; Kubald, Sybille; Krause, Eberhard; Fechner, Klaus; Beyermann, Michael; Bienert, Michael; Rudolph, Rainer; Rothemund, Sven

    2004-01-01

    The oxidative folding, particularly the arrangement of disulfide bonds of recombinant extracellular N-terminal domains of the corticotropin-releasing factor receptor type 2a bearing five cysteines (C2 to C6), was investigated. Depending on the position of a His-tag, two types of disulfide patterns were found. In the case of an N-terminal His-tag, the disulfide bonds C2–C3 and C4–C6 were found, leaving C5 free, whereas the C-terminal position of the His-tag led to the disulfide pattern C2–C5 a...

  14. 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.

  15. Controlled release hydrophilic matrix tablet formulations of isoniazid: design and in vitro studies.

    Science.gov (United States)

    Hiremath, Praveen S; Saha, Ranendra N

    2008-01-01

    The aim of the present investigation was to develop oral controlled release matrix tablet formulations of isoniazid using hydroxypropyl methylcellulose (HPMC) as a hydrophilic release retardant polymer and to study the influence of various formulation factors like proportion of the polymer, polymer viscosity grade, compression force, and release media on the in vitro release characteristics of the drug. The formulations were developed using wet granulation technology. The in vitro release studies were performed using US Pharmacopoeia type 1 apparatus (basket method) in 900 ml of pH 7.4 phosphate buffer at 100 rpm. The release kinetics was analyzed using Korsmeyer-Peppas model. The release profiles were also analyzed using statistical method (one-way analysis of variance) and f (2) metric values. The release profiles found to follow Higuchi's square root kinetics model irrespective of the polymer ratio and the viscosity grade used. The results in the present investigation confirm that the release rate of the drug from the HPMC matrices is highly influenced by the drug/HPMC ratio and viscosity grade of the HPMC. Also, the effect of compression force and release media was found to be significant on the release profiles of isoniazid from HPMC matrix tablets. The release mechanism was found to be anomalous non-Fickian diffusion in all the cases. In the present investigation, a series of controlled release formulations of isoniazid were developed with different release rates and duration so that these formulations could further be assessed from the in vivo bioavailability studies. The formulations were found to be stable and reproducible.

  16. Prostaglandin release from in vitro guinea-pig gallbladder.

    Science.gov (United States)

    Booker, M L; LaMorte, W W

    1983-02-01

    In order to study prostaglandin release from guinea pig gallbladder, full thickness tissue sections were incubated for one hour in Krebs solution. Extraction and two dimensional chromatography of incubation media obtained in the presence of radio-labelled arachidonic acid demonstrated the presence of PGE2, PGF2 alpha, 6-keto-PGF1 alpha and thromboxane B2. These results were supported by radioimmunoassay of incubations conducted in the absence of exogenous arachidonate and in the presence of varying concentrations of unlabelled exogenous arachidonate. The previously reported predominance of PGE2 was only seen at high concentrations of exogenous arachidonate.

  17. Comparative assessment of in vitro release kinetics of calcitonin polypeptide from biodegradable microspheres.

    Science.gov (United States)

    Prabhu, Sunil; Sullivan, Jennifer L; Betageri, Guru V

    2002-01-01

    The objective of our study was to compare the in vitro release kinetics of a sustained-release injectable microsphere formulation of the polypeptide drug, calcitonin (CT), to optimize the characteristics of drug release from poly-(lactide-co-glycolide) (PLGA) copolymer biodegradable microspheres. A modified solvent evaporation and double emulsion technique was used to prepare the microspheres. Release kinetic studies were carried out in silanized tubes and dialysis bags, whereby microspheres were suspended and incubated in phosphate buffered saline, sampled at fixed intervals, and analyzed for drug content using a modified Lowry protein assay procedure. An initial burst was observed whereby about 50% of the total dose of the drug was released from the microspheres within 24 hr and 75% within 3 days. This was followed by a period of slow release over a period of 3 weeks in which another 10-15% of drug was released. Drug release from the dialysis bags was more gradual, and 50% CT was released only after 4 days and 75% after 12 days of release. Scanning electron micrographs revealed spherical particles with channel-like structures and a porous surface after being suspended in an aqueous solution for 5 days. Differential scanning calorimetric studies revealed that CT was present as a mix of amorphous and crystalline forms within the microspheres. Overall, these studies demonstrated that sustained release of CT from PLGA microspheres over a 3-week period is feasible and that release of drug from dialysis bags was more predictable than from tubes.

  18. 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.

  19. STUDIES ON TUBERCULIN FEVER. 3. MECHANISMS INVOLVED IN THE RELEASE OF ENDOGENOUS PYROGEN IN VITRO.

    Science.gov (United States)

    ATKINS, E; HEIJN, C

    1965-08-01

    In a search for the source of the circulating endogenous pyrogen (EP) that mediates tuberculin-induced fever, tuberculin was incubated in vitro with various tissues of rabbits sensitized by intravenous infection with BCG. Evidence was obtained that tuberculin specifically stimulates cells in the blood of sensitized rabbits to generate pyrogen in vitro, whereas both lymph node and spleen cells from the same donors were inactive. Since normal blood cells, incubated in plasma of sensitized donors, were similarly activated, it is postulated that circulating antibodies play a role in sensitizing cells (presumably granulocytes) to release pyrogen on contact with tuberculin) both in vitro and in vivo. Release of endogenous pyrogen in vitro may be a sensitive means of detecting immunologic reactions between antigen and specifically sensitized blood cells-in other allergic states accompanied by fever.

  20. Fluoride release and recharge behavior of a nano-filled resin-modified glass ionomer compared with that of other fluoride releasing materials.

    Science.gov (United States)

    Mitra, Sumita B; Oxman, Joe D; Falsafi, Afshin; Ton, Tiffany T

    2011-12-01

    To compare the long-term fluoride release kinetics of a novel nano-filled two-paste resin-modified glass-ionomer (RMGI), Ketac Nano (KN) with that of two powder-liquid resin-modified glass-ionomers, Fuji II LC (FLC) and Vitremer (VT) and one conventional glass-ionomer, Fuji IX (FIX). Fluoride release was measured in vitro using ion-selective electrodes. Kinetic analysis was done using regression analysis and compared with existing models for GIs and compomers. In a separate experiment the samples of KN and two conventional glass-ionomers, FIX and Ketac Molar (KM) were subjected to a treatment with external fluoride source (Oral-B Neutra-Foam) after 3 months of fluoride release and the recharge behavior studied for an additional 7-day period. The cumulative amount of fluoride released from KN, VT and FLC and the release profiles were statistically similar but greater than that for FIX at P coating of KN with its primer and of DY with its adhesive did not significantly alter the fluoride release behavior of the respective materials. The overall rate for KN was significantly higher than for the compomer DY. DY showed a linear rate of release vs. t and no burst effect as expected for compomers. The nanoionomer KN showed fluoride recharge behavior similar to the conventional glass ionomers FIX and KM. Thus, it was concluded that the new RMGI KN exhibits fluoride ion release behavior similar to typical conventional and RMGIs and that the primer does not impede the release of fluoride.

  1. 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 ...

  2. 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.

  3. A reproducible accelerated in vitro release testing method for PLGA microspheres.

    Science.gov (United States)

    Shen, Jie; Lee, Kyulim; Choi, Stephanie; Qu, Wen; Wang, Yan; Burgess, Diane J

    2016-02-10

    The objective of the present study was to develop a discriminatory and reproducible accelerated in vitro release method for long-acting PLGA microspheres with inner structure/porosity differences. Risperidone was chosen as a model drug. Qualitatively and quantitatively equivalent PLGA microspheres with different inner structure/porosity were obtained using different manufacturing processes. Physicochemical properties as well as degradation profiles of the prepared microspheres were investigated. Furthermore, in vitro release testing of the prepared risperidone microspheres was performed using the most common in vitro release methods (i.e., sample-and-separate and flow through) for this type of product. The obtained compositionally equivalent risperidone microspheres had similar drug loading but different inner structure/porosity. When microsphere particle size appeared similar, porous risperidone microspheres showed faster microsphere degradation and drug release compared with less porous microspheres. Both in vitro release methods investigated were able to differentiate risperidone microsphere formulations with differences in porosity under real-time (37 °C) and accelerated (45 °C) testing conditions. Notably, only the accelerated USP apparatus 4 method showed good reproducibility for highly porous risperidone microspheres. These results indicated that the accelerated USP apparatus 4 method is an appropriate fast quality control tool for long-acting PLGA microspheres (even with porous structures). Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Accelerated in vitro release testing of implantable PLGA microsphere/PVA hydrogel composite coatings.

    Science.gov (United States)

    Shen, Jie; Burgess, Diane J

    2012-01-17

    Dexamethasone loaded poly(lactic-co-glycolic acid) (PLGA) microsphere/PVA hydrogel composites have been investigated as an outer drug-eluting coating for implantable devices such as glucose sensors to counter negative tissue responses to implants. The objective of this study was to develop a discriminatory, accelerated in vitro release testing method for this drug-eluting coating using United States Pharmacopeia (USP) apparatus 4. Polymer degradation and drug release kinetics were investigated under "real-time" and accelerated conditions (i.e. extreme pH, hydro-alcoholic solutions and elevated temperatures). Compared to "real-time" conditions, the initial burst and lag phases were similar using hydro-alcoholic solutions and extreme pH conditions, while the secondary apparent zero-order release phase was slightly accelerated. Elevated temperatures resulted in a significant acceleration of dexamethasone release. The accelerated release data were able to predict "real-time" release when applying the Arrhenius equation. Microsphere batches with faster and slower release profiles were investigated under "real-time" and elevated temperature (60°C) conditions to determine the discriminatory ability of the method. The results demonstrated both the feasibility and the discriminatory ability of this USP apparatus 4 method for in vitro release testing of drug loaded PLGA microsphere/PVA hydrogel composites. This method may be appropriate for similar drug/device combination products and drug delivery systems. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Preparation, characterization, and in vitro release study of albendazole-encapsulated nanosize liposomes

    Science.gov (United States)

    Panwar, Preety; Pandey, Bhumika; Lakhera, P C; Singh, K P

    2010-01-01

    The purpose of the present study was to formulate effective and controlled release albendazole liposomal formulations. Albendazole, a hydrophobic drug used for the treatment of hydatid cysts, was encapsulated in nanosize liposomes. Rapid evaporation method was used for the preparation of albendazole-encapsulated conventional and PEGylated liposomes consisting of egg phosphatidylcholine (PC) and cholesterol (CH) in the molar ratios of (6:4) and PC:CH: polyethylene glycol (PEG) (5:4:1), respectively. In this study, PEGylated and conventional liposomes containing albendazole were prepared and their characteristics, such as particle size, encapsulation efficiency, and in vitro drug release were investigated. The drug encapsulation efficiency of PEGylated and conventional liposomes was 81% and 72%, respectively. The biophysical characterization of both conventional and PEG-coated liposomes were done by transmission electron microscopy and UV-vis spectrophotometry. Efforts were made to study in vitro release of albendazole. The drug release rate showed decrease in albendazole release in descending order: free albendazole, albendazole-loaded conventional liposomes, and least with albendazole-loaded PEG-liposomes. Biologically relevant vesicles were prepared and in vitro release of liposome-entrapped albendazole was determined. PMID:20309396

  6. PIXE investigation of in vitro release of chloramphenicol across polyvinyl alcohol/acrylamide hydrogel

    International Nuclear Information System (INIS)

    Rihawy, M.S.; Alzier, A.; Allaf, A.W.

    2011-01-01

    Hydrogels based on polyvinyl alcohol and different amounts of acrylamide monomer were prepared by thermal cross-linking in the solid state. The hydrogels were investigated for drug delivery system applications. Chloramphenicol was adopted as a model drug to study its release behavior. Particle induced X-ray emission was utilized to study the drug release behavior across the hydrogels and a comparison study with ultraviolet measurements was performed. Fourier Transform Infrared measurements were carried out for molecular characterization. The releasing behavior of the drug exhibits a decrease and a subsequent increase in the release rate, as the acrylamide monomer increases. Characterization of the hydrogels has shown a competitive behavior between crosslinking with AAm acrylamide monomer or oligomerized version, depending on the amount added to prepare the hydrogels.

  7. Liquid crystalline systems for transdermal delivery of celecoxib: in vitro drug release and skin permeation studies.

    Science.gov (United States)

    Estracanholli, Eder André; Praça, Fabíola Silva Garcia; Cintra, Ana Beatriz; Pierre, Maria Bernadete Riemma; Lara, Marilisa Guimarães

    2014-12-01

    Liquid crystalline systems of monoolein/water could be a promising approach for the delivery of celecoxib (CXB) to the skin because these systems can sustain drug release, improve drug penetration into the skin layers and minimize side effects. This study evaluated the potential of these systems for the delivery of CXB into the skin based on in vitro drug release and skin permeation studies. The amount of CXB that permeated into and/or was retained in the skin was assayed using an HPLC method. Polarizing light microscopy studies showed that liquid crystalline systems of monoolein/water were formed in the presence of CXB, without any changes in the mesophases. The liquid crystalline systems decreased drug release when compared to control solution. Drug release was independent of the initial water content of the systems and CXB was released from cubic phase systems, irrespective of the initial water content. The systems released the CXB following zero-order release kinetics. In vitro drug permeation studies showed that cubic phase systems allowed drug permeation and retention in the skin layers. Cubic phase systems of monoolein/water may be promising vehicles for the delivery of CXB in/through the skin because it improved CXB skin permeation compared with the control solution.

  8. Optimization of the in vitro release of zomepirac from suspensions and suppositories

    NARCIS (Netherlands)

    Blaey, C.J. de; Fokkens, J.G.; Niederer, R.R.; Zulliger, H.W.

    1984-01-01

    In an in vitro study the release rates of zomepirac acid (I) and zomepirac sodium dihydrate (II) from suspensions in liquid paraffin towards an aqueous phase were determined. When calcium was added to the aqueous phase a cake of zomepiraecalcium was formed at the interface paraffin/buffer and the

  9. 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. Pieces...

  10. Swelling Studies and in vitro Release of Acemetacin and BSA from Alginate Gel Beads Crosslinked with Ca2+ or Ba2+

    Institute of Scientific and Technical Information of China (English)

    YUAN Pei; JIA Yuntao; ZHANG Liangke; ZHANG Jingqing; HU Wenjing; WANG Chengyuan

    2012-01-01

    The aim of the present work was to investigate the swelling behavior and the in vitro release of acemetacin and bovine serum albumin from alginate gel beads crosslinked with Ca2+ or Ba2+.The release profiles suggested that the extent of swelling of the alginate beads played an important role in the release of drug.Small drugs are mainly released via diffusion through the alginate gel matrix.Compared with small drugs,large molecule drugs are difficult to diffuse through the pores of the matrix bead until the beads swell to a certain extent to provide enough large pores.The Ba2+ crosslinked alginate beads showed slower release rate compared with the Ca2+ crosslinked alginate beads,whether loaded the large molecules or small drugs.In conclusion,the Ba2+ crosslinked alginate beads are considered more suitable than Ca2+ crosslinked alginate beads for using as a sustained release vehicle especially for large molecule drugs.

  11. Formulation and in vitro evaluation of sustained release matrix tablets using cross-linked natural gum.

    Science.gov (United States)

    Jamil, Qurratul Ain; Masood, Muhammad Irfan; Jamil, Muhammad Nauman; Masood, Imran; Iqbal, Shahid Muhammad

    2017-03-01

    Polysaccharide gums because of their biocompatibility, biodegradability and non-immunogenic properties are considered as the best choice for preparing sustained release tablets as compared to their synthetic counterpart. The cross linking of natural gums in matrix tablets increase the sustained release property of matrix tablets. Isoniazid is a first line therapy of tuberculosis, belongs to BCS I with half-life of 3-4 hours. These characteristics make isoniazid a good candidate for sustained release dosage form. Karaya gum crossed linked with trisodium tri metaphosphate was used as release rate retardant for preparing isoniazid cross-linked matrix tablet. Total 8 sustained release formulations were prepared. Both granules and tablets were evaluated under in vitro condition against different parameters. Dissolution studies were performed with all eight formulations for 12 hours using USP apparatus I. Four formulations designated as F1, F2, F3, F4 have drug and karaya gum while other four formulations F5, F6, F7, F8 have drug and crossed linked polymer in ratios of 1:1, 1:2, 1:3 and 1:4 respectively. Dissolution data was analyzed by using different kinetic models. Best fit model for most efficient formulation was zero order while release mechanism was super case I. Formulation 8 showed sufficiently slow release kinetics and about 83% of drug was released in 10 hours, indicating that cross-linked karaya gum proved efficient in preparing sustained release tablets.

  12. In vitro labelled neurotransmitters release for the study of neuro toxins

    International Nuclear Information System (INIS)

    Camillo, Maria A.P.; Rogero, Jose R.; Troncone, Lanfranco R.P.

    1995-01-01

    There is an increasing concern in the replacement of in vivo by in vitro methods in Pharmacology. Looking for a method which involves the most of the physiological aspects related to neural functions, a super fusion system designed to evaluate in vitro neurotransmitter release from brain striatal tissue is here described. The method is based on the basal and stimulated release of pre-loaded tritium-labelled neurotransmitters. This procedure bears an active uptake/release function which is fairly changed by membrane polarisation state, ion channel activation and enzymatic activity, as well as other still unknown steps involved in neurotransmission. Calcium dependency of dopamine and acetylcholine release induced by high potassium depolarization or glutamate (Glu) stimulation was demonstrated employing calcium-free (+EGTA) super fusion or lanthanum/cadmium addition. Glutamate stimulation involved NMDA receptors since magnesium or MK801 blocks stimulated release. Uptake of DA and Ach was evidenced by using bupropione or hemicolinium-3. presynaptic inhibition of Ach release was evidenced by physostigmine-induced inhibitions of acetylcholinesterase. (author). 3 refs., 6 figs

  13. In vitro evaluation of extemporaneously compounded slow-release capsules containing morphine sulfate or oxycodone hydrochloride.

    Science.gov (United States)

    Glowiak, Dana L; Green, Julie L; Bowman, Bill J

    2005-01-01

    The in vitro performance of extemporaneously compounded morphine sulfate and oxycodone hydrochloride slow-release capsules was evaluated. Capsules containing varying amoutns of morphine sulfate (15, 60, 200 mg) or oxycodone hydrochloride (10, 80, 200 mg) were prepared and provided by a Phoenix, Arizona, pharmacy. The capsules also contained 40% Methocel E4M Premium to slow the release of their active ingredient and sufficient lactose to fill the capsules. Three batches of each capsule strength were prepared, and replicates from each batch were evlauated using United Stated Pharmacopeia dissolution apparatus II. Samples were taken at regular time intervals over 24 hours. After 1 hour the pH of the dissolution medium was adjusted form 1.2 to 4.0, and after 2 hours the pH was adjusted to 6.8. The amount of drug released at each time point was determined spectrophotometrically. The compounded capsules released 14% to 23%, 67% to 85% and 93% to 98% of their active ingredient after 0.5, 4 and 12 hours, respectively. The relative standard deviations between the replicates from each batch were less than 10% for most time points. The percent of drug released over the first 4 hours was linear (r squared = 0.9409-0.9999) when plotted versus time 1/2, indicating adherence to the simplified Higuchi model. Statistical analysis of the Higuchi dissolution constants indicated a significant difference (P less than 0.05) between batch No.3 and the other two batches of 200-mg oxycodone hydrochloride capsules. There was also a statistical difference between most of the Higuchi dissolution constants for the different-strength slow-release capsules and most slow-release capsules and equivalent strength controlled-release manufactured tablets (P less than 0.05). Using 40% Methocel E4M Premium slowed the release of morphine sulfate and oxycodone hydrochloride from extemporaneously compounded capsules. The in vitro performance of the slow-release capsules showed little intrabatch variation

  14. Fabrication of ketoprofen controlled-release tablets using biopolymeric hydrophilic matrices: in-vitro studies

    International Nuclear Information System (INIS)

    Rashid, S.; Khan, B.A.; Khan, G.M.

    2017-01-01

    Ketoprofen is propionic acid derivative and belongs to the Non-Steroidal anti-inflammatory group of drugs. Due to the short half-life, dosage frequency, patient non-compliance and side effects such as gastrointestinal disturbance, peptic ulceration and gastro intest inal bleeding, it is considered to be good candidate for formulation into controlled release dosage forms. Directly compressed controlled released ( CR) tablets using Acrylic acid derivatives were prepared and evaluated. In-Vitro Physicochemical assessment of the formulated tablets were performed using different physicochemical, dimensional and quality control tests such as weight variation, thickness and diameter, hardness test, friability test, content uniformity, disintegration and dissolution testing. Results of all these tests were formed within acceptable range. The effect of carbomer polymers on the tablet characteristics, drug release rates, release patterns and release kinetics were investigated. The F2-metric technique was applied to compare dissolution profiles of ketoprofen and carbopol tablets with ketoprofen SR - tablets taken as standard preparation. Acrylic acid derivatives when used as polymers resulted in an extended release profile of about 12 h. Using Higuchi's model and the Korsmeyer equation, the drug release mechanism from the tablets was found to be an anomalous type involving diffusion and erosion. Controlled- release Ketoprofen tablets appear to be a good choice for the symptomatic treatment of rheumatoid arthritis and osteoarthritis. Convenient once-daily administration may help improve patient's compliance. (author)

  15. Release of an endogenous pyrogen in vitro from rabbit mononuclear cells.

    Science.gov (United States)

    Atkins, E; Bodel, P; Francis, L

    1967-08-01

    The capacity of rabbit mononuclear cells to release an endogenous pyrogen (EP) in vitro has been studied. After incubation with tuberculin, preparations of predominantly monocytic cells, derived from the respiratory passages of the lungs of rabbits sensitized with BCG, were activated to release EP. Pyrogen production occurred more slowly with lung monocytes than with blood leukocytes of similarly sensitized rabbits and 9 to 10 hr incubation in a fully supportive medium was required to produce clear-cut results. As previously reported with blood leukocytes, mononuclear cells from the lungs of normal animals were also activated by tuberculin but to a lesser degree than were those from specifically sensitized rabbits. Under a variety of conditions, mononuclear cells from either spleen or lymph nodes of the same sensitized rabbits failed to release detectable amounts of pyrogen when incubated with tuberculin in vitro but were activated in a majority of instances when phagocytosis of heat-killed staphylococci was used as the stimulus. Release of pyrogen from lung monocytes appears to be an active process that is both temperature-dependent and requires protein synthesis. Neither serum antibody nor complement appears to play a role in this process. Evidence is presented that the granulocyte is the main source of pyrogen evolved by blood leukocytes incubated in vitro with OT or heat-killed staphylococci, whereas the lung macrophage and/or monocyte is responsible for most of the pyrogen released from the lung cell preparations. From these studies, it is concluded that mononuclear cells can be activated in vitro by several microbial stimuli and must be considered an additional cellular source of EP. The clinical implications of these findings for the pathogenesis of fever in granulomatous diseases where the monocyte is the predominant cell are discussed.

  16. 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

    A non-randomized cross-over study was performed with bupivacaine HCl (5 mg x ml(-1)) aqueous solution and bupivacaine free base (4.44 mg x ml(-1)) in Viscoleo/castor oil 2:1 (v/v) administered s.c. to male Wistar rats. Plasma levels were analyzed by LC-MS. Plasma profiles obtained after...... 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......) and 25,000+/-3000 ng min x ml(-1), respectively, while the corresponding data for the oil solution were 368+/-89 min, 334+/-186 min, 36+/-25 ng x ml(-1) and 25,000+/-6000 ng x min x ml(-1). The present data indicate the potential of designing an oil formulation of bupivacaine with a prolonged local...

  17. Release behavior of triazine residues in stabilised contaminated soils

    International Nuclear Information System (INIS)

    Ying, G.G.; Kookana, R.S.; Mallavarpu, M.

    2005-01-01

    This paper reports the release behavior of two triazines (atrazine and simazine) in stabilised soils from a pesticide-contaminated site in South Australia. The soils were contaminated with a range of pesticides, especially with triazine herbicides. With multiple extractions of each soil sample with deionised water (eight in total), 15% of atrazine and 4% of simazine residues were recovered, resulting in very high concentrations of the two herbicides in leachate. The presence of small fractions of surfactants was found to further enhance the release of the residues. Methanol content up to 10% did not substantially influence the concentration of simazine and atrazine released. The study demonstrated that while the stabilisation of contaminated soil with particulate activated carbon (5%) and cement mix (15%) was effective in locking the residues of some pesticides, it failed to immobilise triazine herbicides residues completely. Given the higher water solubility of these herbicides than other compounds more effective strategies to immobilise their residues is needed. - Stabilisation of contaminated soil with a mix of activated carbon and cement may fail to immobilise some contaminants like triazines

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

    International Nuclear Information System (INIS)

    Tomic, S.Lj.; Micic, M.M.; Filipovic, J.M.; Suljovrujic, E.H.

    2007-01-01

    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

  19. In vitro release of cholecystokinin octapeptide-like immunoreactivity from rat brain synaptosomes

    International Nuclear Information System (INIS)

    Klaff, L.J.; Hudson, A.; Sheppard, M.; Tyler, M.

    1981-01-01

    Enriched synaptosome fractions prepared by differential centrifugation and ultracentrifugation of homogenates of rat cortex, striatum, thalamus and hypothalamus contained over 65% of the total immunoreactive cholecystokinin octapeptide (CCK-8) in each area. A calcium dependent release of immunoreactive CCK-8 from these fractions in vitro in response to 2 depolarizing stimuli (60 mM KCl and 75 μM veratrine) has been demonstrated. Released CCK-8 immunoreactivity showed parallelism when serial dilutions were compared with the CCK-8 dose-response curve and eluted similarly to synthetic CCK-8 on Sephadex G-50 superfine chromatography. These results provide further evidence for a neurotransmitter or neuromodulator role for CCK-8 in brain

  20. Possibilities for in-vitro testing of controlled-release parenterals.

    OpenAIRE

    Kožák, Jan

    2014-01-01

    The objective of this study was to start with the development of a gel-based medium simulating intramuscular environment for in-vitro drug release testing as an alternative to currently used water-based media. A pork meat was selected as a model of the muscle tissue. At the first part of the study, diffusion rate was proposed as the most determining factor of drug release in gel-based medium. Consequently, the diffusion rate of sodium fluorescein in pork meat was compared with the diffusion r...

  1. In vitro assay for ACTH-releasing activity using ACTH radioimmunoassay. ACTH releasing activities by various drugs

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, K; Takahara, J; Hosogi, H; Ofuji, N; Yasuhara, T [Okayama Univ. (Japan). School of Medicine

    1976-02-01

    This report deals with an in vitro assay of ACTH releasing activity utilizing pituitary incubation combined with ACTH radioimmunoassay. Half of a rat pituitary was preincubated in 2ml Krebs Ringer bicarbonate buffer containing 0.2% glucose and 0.25% BSA (KRBG-BSA) for 1.5 hr (45 min x 2). The medium was replaced by 1 ml KRBG-BSA and incubated for 30 min. Then the medium was again replaced by 1 ml KRBG-BSA or KRBG-BSA containing test materials and incubated for another 30 min. The amount of ACTH assayed by radioimmunoassay in the 2nd 30 min incubation was compared with that in the 1st 30 min incubation, and the result was expressed as a percentage. In the ACTH radioimmunoassay, anti-ACTH serum was diluted to 1:1,500-3,000. The /sup 125/I-..cap alpha../sup 1 -24/ACTH-antibody system was not affected by lysine-vasopressin (LVP), arginine-vasopressin (AVP), rat's pituitary LH, GH or prolactin. Human /sup 1 -39/ACTH was used as the ACTH standard. The dilution curve of the incubation medium was parallel to the standard curve. Reproducibility of immunoassayable ACTH within-assay was 174 +- 5.0 pg/tube (CV=2.9%). A log dose-relationship was observed between the amounts of stalk median eminence extracts (SME; NIAMDD) added to the incubation medium and its ACTH releasing activities. The sensitivity of this assay method was at least 0.1 SME or 10 mU of LVP and AVP. Using this method, it was found that LVP, AVP, norepinephrine (100 ng/ml--200 ng/ml) and 5-hydroxytryptophane (1 ..mu..g/ml) had ACTH releasing activities, but LH-RH, TRH, glucagon, dopamine, phentolamine, propranolol, haloperidol, prostaglandin E/sub 1/ and indomethacin did not affect the release of ACTH.

  2. Flavonoids released naturally from alfalfa promote development of symbiotic glomus spores in vitro.

    Science.gov (United States)

    Tsai, S M; Phillips, D A

    1991-05-01

    Because flavonoids from legumes induce transcription of nodulation genes in symbiotic rhizobial bacteria, it is reasonable to test whether these compounds alter the development of vesicular-arbuscular mycorrhizal (VAM) fungi that infect those plants. Quercetin-3-O-galactoside, the dominant flavonoid released naturally from alfalfa (Medicago sativa L.) seeds, promoted spore germination of Glomus etunicatum and Glomus macrocarpum in vitro. Quercetin produced the maximum increases in spore germination, hyphal elongation, and hyphal branching in G. etunicatum at 1 to 2.5 muM concentrations. Two flavonoids exuded from alfalfa roots, 4',7-dihydroxyflavone and 4',7-dihydroxyflavanone, also enhanced spore germination of this fungal species. Formononetin, an isoflavone that is released from stressed alfalfa roots, inhibited germination of both Glomus species. These in vitro results suggest that plant flavonoids may facilitate or regulate the development of VAM symbioses and offer new hope for developing pure, plant-free cultures of VAM fungi.

  3. Bioactive peptides released from in vitro digestion of human milk with or without pasteurization.

    Science.gov (United States)

    Wada, Yasuaki; Lönnerdal, Bo

    2015-04-01

    Pasteurized donor human milk (HM) serves as the best alternative for breast-feeding when availability of mother's milk is limited. Pasteurization is also applied to mother's own milk for very low birth weight infants, who are vulnerable to microbial infection. Whether pasteurization affects protein digestibility and therefore modulates the profile of bioactive peptides released from HM proteins by gastrointestinal digestion, has not been examined to date. HM with and without pasteurization (62.5 °C for 30 min) were subjected to in vitro gastrointestinal digestion, followed by peptidomic analysis to compare the formation of bioactive peptides. Some of the bioactive peptides, such as caseinophosphopeptide homologues, a possible opioid peptide (or propeptide), and an antibacterial peptide, were present in undigested HM and showed resistance to in vitro digestion, suggesting that these peptides are likely to exert their bioactivities in the gastrointestinal lumen, or be stably transported to target organs. In vitro digestion of HM released a large variety of bioactive peptides such as angiotensin I-converting enzyme-inhibitory, antioxidative, and immunomodulatory peptides. Bioactive peptides were released largely in the same manner with and without pasteurization. Provision of pasteurized HM may be as beneficial as breast-feeding in terms of milk protein-derived bioactive peptides.

  4. On the intracellular release mechanism of hydrophobic cargo and its relation to the biodegradation behavior of mesoporous silica nanocarriers.

    Science.gov (United States)

    von Haartman, Eva; Lindberg, Desiré; Prabhakar, Neeraj; Rosenholm, Jessica M

    2016-12-01

    The intracellular release mechanism of hydrophobic molecules from surface-functionalized mesoporous silica nanoparticles was studied in relation to the biodegradation behavior of the nanocarrier, with the purpose of determining the dominant release mechanism for the studied drug delivery system. To be able to follow the real-time intracellular release, a hydrophobic fluorescent dye was used as model drug molecule. The in vitro release of the dye was investigated under varying conditions in terms of pH, polarity, protein and lipid content, presence of hydrophobic structures and ultimately, in live cancer cells. Results of investigating the drug delivery system show that the degradation and drug release mechanisms display a clear interdependency in simple aqueous solvents. In pure aqueous media, the cargo release was primarily dependent on the degradation of the nanocarrier, while in complex media, mimicking intracellular conditions, the physicochemical properties of the cargo molecule itself and its interaction with the carrier and/or surrounding media were found to be the main release-governing factors. Since the material degradation was retarded upon loading with hydrophobic guest molecules, the cargo could be efficiently delivered into live cancer cells and released intracellularly without pronounced premature release under extracellular conditions. From a rational design point of view, pinpointing the interdependency between these two processes can be of paramount importance considering future applications and fundamental understanding of the drug delivery system. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Involvement of arachidonate metabolism in neurotensin-induced prolactin release in vitro

    International Nuclear Information System (INIS)

    Canonico, P.L.; Speciale, C.; Sortino, M.A.; Scapagnini, U.

    1985-01-01

    Neurotensin increased in a concentration-dependent manner the level of hypophyseal [ 3 H]arachidonic acid in vitro as well as prolactin release from hemipituitary glands. The effect of 1 microM neurotensin on arachidonate release was already present at 2.5 min, maximal at 5, and disappeared after a 10-min incubation. Neurotensin analogues produced an enhancement of hypophyseal arachidonate similar to their relative potencies in other cellular systems, whereas other peptides (somatostatin and vasoactive intestinal peptide) were devoid of any effect on the concentration of the fatty acid in the pituitary. Seventy micromoles RHC 80267, a rather selective inhibitor of diacylglycerol lipase, completely prevented the neurotensin-stimulated prolactin release and decreased arachidonate release both in basal or in neurotensin-induced conditions. Similar results were obtained with 50 microM quinacrine, a phospholipase A2 inhibitor. To clarify whether arachidonate released by neurotensin requires a further metabolism through specific pathways to stimulate prolactin release, the authors used indomethacin and BW 755c, two blockers of cyclooxygenase and lipoxygenase pathways. Thirty micromoles indomethacin, a dose active to inhibit cyclooxygenase, did not affect unesterified arachidonate levels either in basal or in neurotensin-induced conditions; moreover, the drug did not modify basal prolactin release but slightly potentiated the stimulatory effect of neurotensin on the release of the hormone. On the other hand, 250 microM BW 755c, an inhibitor of both cyclooxygenase and lipoxygenase pathways, significantly inhibited both basal and neurotensin-stimulated prolactin release and further potentiated the increase of the fatty acid concentrations produced by 1 microM neurotensin

  6. In vitro efficacy and release study with anti-inflammatory drugs incorporated in adhesive transdermal drug delivery systems.

    Science.gov (United States)

    Meyer, Stefanie; Peters, Nils; Mann, Tobias; Wolber, Rainer; Pörtner, Ralf; Nierle, Jens

    2014-04-01

    The topical application of two different anti-inflammatory extracts incorporated in adhesive transdermal drug delivery systems (TDDSs) was investigated. Therefore, anti-inflammatory properties and percutaneous absorption behavior of adhesive TDDSs were characterized in vitro conducting experiments with a dermatologically relevant human skin model. Anti-inflammatory efficacy against UV irradiation of both TDDSs was determined in vitro with EpiDerm™. The reduction of the release of proinflammatory cytokines by topically applied TDDSs was compared with the reduction during the presence of the specific cyclooxygenase inhibitor diclofenac in the culture medium. A similar anti-inflammatory efficacy of the topically applied TDDSs in comparison with the use of diclofenac in the culture medium should be achieved. Furthermore, percutaneous absorption in efficacy tests was compared with percutaneous absorption in diffusion studies with porcine cadaver skin. Both the topically applied TDDSs showed a significant anti-inflammatory activity. Permeation coefficients through the stratum corneum and the epidermis gained from the release studies on porcine cadaver skin (Magnolia: 2.23·10(-5) cm/h, licorice: 4.68·10(-6) cm/h) were approximately five times lower than the permeation coefficients obtained with the EpiDerm™ skin model (Magnolia: 9.48·10(-5) cm/h, licorice: 24.0·10(-6) cm/h). Therefore, an adjustment of drug doses during experiments with the EpiDerm™ skin model because of weaker skin barrier properties should be considered.

  7. RANKL release from self-assembling nanofiber hydrogels for inducing osteoclastogenesis in vitro.

    Science.gov (United States)

    Xing, James Z; Lu, Lei; Unsworth, Larry D; Major, Paul W; Doschak, Michael R; Kaipatur, Neelambar R

    2017-02-01

    To develop a nanofiber hydrogel (NF-hydrogel) for sustained and controlled release of the recombinant receptor activator of NF-kB ligand; (RANKL) and to characterize the release kinetics and bioactivity of the released RANKL. Various concentrations of fluorescently-labelled RANKL protein were added to NF-hydrogels, composed of Acetyl-(Arg-Ala-Asp-Ala) 4 -CONH 2 [(RADA) 4 ] of different concentrations, to investigate the resulting in vitro release rates. The nano-structures of NF-hydrogel, with and without RANKL, were determined using atomic force microscopy (AFM). Released RANKL was further analyzed for changes in secondary and tertiary structure using CD spectroscopy and fluorescent emission spectroscopy, respectively. Bioactivity of released RANKL protein was determined using NFATc1 gene expression and tartrate resistant acid phosphatase (TRAP) activity of osteoclast cells as biomarkers. NF-hydrogel concentration dependent sustained release of RANKL protein was measured at concentrations between 0.5 and 2%(w/v). NF-hydrogel at 2%(w/v) concentration exhibited a sustained and slow-release of RANKL protein up to 48h. Secondary and tertiary structure analyses confirmed no changes to the RANKL protein released from NF-hydrogel in comparison to native RANKL. The results of NFATc1 gene mRNA expression and TRAP activities of osteoclast, showed that the release process did not affect the bioactivity of released RANKL. This novel study is the first of its kind to attempt in vitro characterization of NF-hydrogel based delivery of RANKL protein to induce osteoclastogenesis. We have shown the self-assembling NF-hydrogel peptide system is amenable to the sustained and controlled release of RANKL locally; that could in turn increase local concentration of RANKL to induce osteoclastogenesis, for application to the controlled mobilization of tooth movement in orthodontic procedures. Orthodontic tooth movement (OTM) occurs through controlled application of light forces to teeth

  8. 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.

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

    International Nuclear Information System (INIS)

    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 + evoked 3 H-5-HT release from superfused HYP slices by 25%. Bacitracin, a nonspecific peptidase inhibitor, reversed the inhibitory effect of BN on K + evoked 3 H-5-HT release. Phosphoramidon (PAN, 10 μM) an endopeptidase 24.11 inhibitor, abolished the inhibitory effect of BN, but not NM-C, on K + evoked 3 H-5-HT release. The peptidyl dipeptidase A inhibitor enalaprilat (ENP, 10 μM), enhanced both BN and NM-C inhibition of 3 H-5-HT release. Bestatin (BST, 10 μM) had no effect on BN or NM-C inhibitory activity on 3 H-5-HT release. Neither BN, NM-C nor NM-B affected reuptake of 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 3 H-5-HT uptake

  10. In vitro studies of copper release from powder particles in synthetic biological media

    International Nuclear Information System (INIS)

    Midander, Klara; Wallinder, Inger Odnevall; Leygraf, Christofer

    2007-01-01

    The aim of this paper is to provide quantitative data on copper release from powder particles of different copper materials, including artificial copper patina, Cu 2 O and metallic Cu, when exposed to different synthetic biological media to simulate an inhalation scenario and/or skin contact. Generated data may contribute in risk assessment of potential health effects following exposure to and handling of various copper materials. All tests were performed in vitro to determine total copper concentrations, release rates of total copper, and to elucidate its time-dependence. The copper release process was interpreted in terms of specific surface area, surface morphology-, and composition. All powder materials show a time-dependent release process with total copper release rates less than 3 μg/cm 2 per hour at steady state conditions, for all media investigated. The importance of using relevant test media when simulating different interstitial lung conditions and difficulties encountered when comparing powder particles of essentially different properties are thoroughly discussed. - Copper release rates from particles are essential to assess potential health aspects

  11. Lyophilized sustained release mucoadhesive chitosan sponges for buccal buspirone hydrochloride delivery: formulation and in vitro evaluation.

    Science.gov (United States)

    Kassem, Mohamed A A; ElMeshad, Aliaa N; Fares, Ahmed R

    2015-06-01

    This work aims to prepare sustained release buccal mucoadhesive lyophilized chitosan sponges of buspirone hydrochloride (BH) to improve its systemic bioavailability. Chitosan sponges were prepared using simple casting/freeze-drying technique according to 3(2) factorial design where chitosan grade was set at three levels (low, medium, and high molecular weight), and concentration of chitosan solution at three levels (0.5, 1, and 2%). Mucoadhesion force, ex vivo mucoadhesion time, percent BH released after 8 h (Q8h), and time for release of 50% BH (T50%) were chosen as dependent variables. Additional BH cup and core buccal chitosan sponge were prepared to achieve uni-directional BH release toward the buccal mucosa. Sponges were evaluated in terms of drug content, surface pH, scanning electron microscopy, swelling index, mucoadhesion strength, ex vivo mucoadhesion time, and in vitro drug release. Cup and core sponge (HCH 0.5E) were able to adhere to the buccal mucosa for 8 h. It showed Q8h of 68.89% and exhibited a uni-directional drug release profile following Higuchi diffusion model.

  12. A mathematical model for interpreting in vitro rhGH release from laminar implants.

    Science.gov (United States)

    Santoveña, A; García, J T; Oliva, A; Llabrés, M; Fariña, J B

    2006-02-17

    Recombinant human growth hormone (rhGH), used mainly for the treatment of growth hormone deficiency in children, requires daily subcutaneous injections. The use of controlled release formulations with appropriate rhGH release kinetics reduces the frequency of medication, improving patient compliance and quality of life. Biodegradable implants are a valid alternative, offering the feasibility of a regular release rate after administering a single dose, though it exists the slight disadvantage of a very minor surgical operation. Three laminar implant formulations (F(1), F(2) and F(3)) were produced by different manufacture procedures using solvent-casting techniques with the same copoly(D,L-lactic) glycolic acid (PLGA) polymer (Mw=48 kDa). A correlation in vitro between polymer matrix degradation and drug release rate from these formulations was found and a mathematical model was developed to interpret this. This model was applied to each formulation. The obtained results where explained in terms of manufacture parameters with the aim of elucidate whether drug release only occurs by diffusion or erosion, or by a combination of both mechanisms. Controlling the manufacture method and the resultant changes in polymer structure facilitates a suitable rhGH release profile for different rhGH deficiency treatments.

  13. In vitro effect of Δ9-tetrahydrocannabinol to stimulate somatostatin release and block that of luteinizing hormone-releasing hormone by suppression of the release of prostaglandin E2

    International Nuclear Information System (INIS)

    Rettori, V.; Aguila, M.C.; McCann, S.M.; Gimeno, M.F.; Franchi, A.M.

    1990-01-01

    Previous in vivo studies have shown that Δ 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 2 (PGE 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 2 suppresses somatostatin release, this enhancement may also be related to the suppressive effect of THC on PGE 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

  14. 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.

  15. Ciprofloxacin-intercalated Zinc Layered Hydroxides Hybrid Material: Synthesis and in Vitro Release Profiles of an Antibiotic Compound

    International Nuclear Information System (INIS)

    Mohd Zobir Hussein; Mohd Zobir Hussein; Stanslas, J.; Abdul Halim Abdullah

    2011-01-01

    The intriguing anion exchange properties of layered hydroxides salts, combined with its high layer charge density have provided strong motivations for the potential use of the inorganic layered host material in drug delivery applications. Ciprofloxacin (CFX), a wide spectrum antibiotic has been anion exchanged with nitrate of zinc hydroxide nitrate (ZHN), which belongs to the LHS family, resulted in the expansion of the basal spacing from 9.92 Amstrom of ZHN to 21.5 Angstrom of ZCFX, the obtained hybrid material. Other characterizations, such as Fourier transform infra red spectroscopy (FTIR), CHNS analysis and TGA/ DTG have further corroborated this finding. Electron microscopy study reveals the plate-like structure of the nano hybrid material. The in vitro release of CFX was performed in phosphate saline buffer at pH 7.4 and it behaves in a slow and sustained release profile over a period of 72 hours. This study suggests that ZHN, which demonstrates a controlled release behavior, could be a potential host material in the drug delivery applications. (author)

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

    International Nuclear Information System (INIS)

    Tan, Donna; Zhao Bin; Moochhala, Shabbir; Yang Yiyan

    2006-01-01

    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

  17. The in vitro antibiotic release from anti-washout apatite cement using chitosan.

    Science.gov (United States)

    Takechi, Masaaki; Miyamoto, Youji; Momota, Yukihiro; Yuasa, Tetsuya; Tatehara, Seikou; Nagayama, Masaru; Ishikawa, Kunio; Suzuki, Kazuomi

    2002-10-01

    The in vitro antibiotic release from anti-washout apatite cement using chitosan (aw-AC(chi)) was investigated in a preliminary evaluation. Flomoxef sodium was employed as the antibiotic and was incorporated into the powder phase aw-AC(chi) at up to 10%. The setting times were measured for aw-AC(chi) containing various amounts of flomoxef sodium. X-ray diffraction (XRD) analysis was also conducted for the identification of products. To evaluate the drug release profile, set aw-AC was immersed in saline and the released flomoxef sodium was determined at regular intervals. The setting time was prolonged slightly with the addition of flomoxef sodium. The difference at 10% flomoxef sodium (0% vs. 10%) was not significant (p>0.05), and can be negligible in clinic. The XRD analysis revealed that formation of hydroxyapatite (HAP) from aw-AC(chi) was reduced, even after 24 h, when the aw-AC(chi) contained flomoxef sodium at 8% or more. The flomoxef sodium release from aw-AC(chi) showed the typical profile observed in skeleton type drug delivery system (DDS). Changing the concentration of chitosan can control the rate of drug release from aw-AC. Therefore, we conclude that aw-AC(chi) is a good candidate for potential use as a DDS carrier that may be useful in surgical operations.

  18. 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.

  19. Release of Fluconazole from Contact Lenses Using a Novel In Vitro Eye Model.

    Science.gov (United States)

    Phan, Chau-Minh; Bajgrowicz, Magdalena; Gao, Huayi; Subbaraman, Lakshman N; Jones, Lyndon W

    2016-04-01

    Rapid drug release followed by a plateau phase is a common observation with drug delivery from contact lenses (CLs) when evaluated in a vial. The aim of this study was to compare the release of fluconazole from seven commercially available daily disposable CLs using a conventional vial-based method with a novel in vitro eye model. An eye model was created using two 3-dimensional printed molds, which were filled with polydimethylsiloxane to obtain an inexpensive model that would mimic the eyeball and eyelid. The model was integrated with a microfluidic syringe pump, and the flow-through was collected in a 12-well microliter plate. Four commercial daily disposable conventional hydrogels (nelfilcon A, omafilcon A, etafilcon A, ocufilcon B) and three silicone hydrogels (somofilcon A, narafilcon A, delefilcon A) were evaluated. These CLs were incubated with fluconazole for 24 h. The drug release was measured in a vial containing 4.8 mL of phosphate-buffered saline and in the polydimethylsiloxane eye model with a 4.8-mL tear flow across 24 h. Overall, conventional hydrogel CLs had a higher uptake and release of fluconazole than silicone hydrogel CLs (p eye model (p eye model under low tear volume was sustained and did not reach a plateau across 24 h (p eyes with fungal keratitis may have increased tearing, which would significantly accelerate drug release.

  20. 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.

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

    International Nuclear Information System (INIS)

    Dou Xiaochen; Zhu Xiaopeng; Zhou Jian; Cai Huaqiong; Li Quanli; Tang Jian

    2011-01-01

    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.

  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

    2017-01-01

    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. PMID:29187697

  3. Development of novel diclofenac potassium controlled release tablets by wet granulation technique and the effect of co-excipients on in vitro drug release rates.

    Science.gov (United States)

    Shah, Shefaatullah; Khan, Gul Majid; Jan, Syed Umer; Shah, Kifayatullah; Hussain, Abid; Khan, Haroon; Khan, Haroon; Khan, Haroon; Khan, Kamran Ahmad

    2012-01-01

    The aim of the present study was the formulation and evaluation of controlled release polymeric tablets of Diclofenac Potassium by wet granulation method for the release rate, release pattern and the mechanism involved in drug release. Formulations having three grades of polymer Ethocel (7P; 7FP, 10P, 10FP, 100P, 100FP) in several drugs to polymer ratios (10:3 and 10:1) were compressed into tablets using wet granulation method. Co-excipients were added to some selected formulations to investigate their enhancement effect on in vitro drug release patterns. In vitro drug release studies were performed using USP Method-1 (Rotating Basket method) and Phosphate buffer (pH 7.4) was used as a dissolution medium. The similarities and dissimilarities of release profiles of test formulations with reference standard were checked using f2 similarity factor and f1 dissimilarity factor. Mathematical/Kinetic models were employed to determine the release mechanism and drug release kinetics.

  4. Pyrogen release in vitro by lymphoid tissues from patients with Hodgkin's disease.

    Science.gov (United States)

    Bodel, P

    1974-01-01

    The mechanism of fever in patients with Hodgkin's disease was investigated by examining endogenous pyrogen production by blood, spleen, and lymph node cells incubated in vitro. Blood leucocytes from febrile or afebrile patients with Hodgkin's disease did not produce pyrogen spontaneously. Spleen cells, however, frequently released pyrogen during initial incubations, unlike spleen cells from patients with non-malignant diseases. Pyrogen production occurred from spleens without observed pathologic infiltrates of Hodgkin's disease. Lymph nodes involved with Hodgkin's disease produced pyrogen more frequently than did nodes involved with other diseases. Pyrogen production by tissue cells was prolonged, required protein synthesis, and in some cases was due to mononuclear cells; it did not correlate with fever in the patient. These studies demonstrate spontaneous production of endogenous pyrogen in vitro by lymphoid tissue cells from patients with Hodgkin's disease.

  5. Incorporation of zinc oxide to dispersions of biopolymers and release of the metallic ion in vitro

    International Nuclear Information System (INIS)

    Barreto, Marina S.R.; Ferreira, Willian H.; Andrade, Cristina T.

    2015-01-01

    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"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"2"+ release. (author)

  6. Multi-kinetics and site-specific release of gabapentin and flurbiprofen from oral fixed-dose combination: in vitro release and in vivo food effect.

    Science.gov (United States)

    Sonvico, Fabio; Conti, Chiara; Colombo, Gaia; Buttini, Francesca; Colombo, Paolo; Bettini, Ruggero; Barchielli, Marco; Leoni, Barbara; Loprete, Luca; Rossi, Alessandra

    2017-09-28

    In this work, a fixed-dose combination of gabapentin and flurbiprofen formulated as multilayer tablets has been designed, developed and studied in vitro and in vivo. The aim was to construct a single dosage form of the two drugs, able to perform a therapeutic program involving three release kinetics and two delivery sites, i.e., immediate release of gabapentin, intra-gastric prolonged release of gabapentin and intestinal (delayed) release of flurbiprofen. An oblong three-layer tablet was manufactured having as top layer a floating hydrophilic polymeric matrix for gastric release of gabapentin, as middle layer a disintegrating formulation for immediate release of a gabapentin loading dose and as bottom layer, an uncoated hydrophilic polymeric matrix, swellable but insoluble in gastric fluids, for delayed and prolonged release of flurbiprofen in intestinal environment. The formulations were studied in vitro and in vivo in healthy volunteers. The in vitro release rate assessment confirmed the programmed delivery design. A significant higher bioavailability of gabapentin administered 30min after meal, compared to fasting conditions or to dose administration 10min before meal, argued in favor of the gastro-retention of gabapentin prolonged release layer. The two drugs were delivered at different anatomical sites, since the food presence prolonged the gastric absorption of gabapentin from the floating layer and delayed the flurbiprofen absorption. The attainment of a successful delayed release of flurbiprofen was realized by a matrix based on a polymers' combination. The combined use of three hydrophilic polymers with different pH sensitivity provided the dosage form layer containing flurbiprofen with gastro-resistant characteristics without the use of film coating. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Preparation of berbamine loaded chitosan-agarose microspheres and in vitro release study

    Directory of Open Access Journals (Sweden)

    Zhang Hu

    2012-01-01

    Full Text Available Berbamine loaded chitosan-agarose microspheres were prepared using a water-in-oil emulsion technique. Optimum preparing parameters were determined by orthogonal experiments as follows: ratio of berbamine to chitosan (w/w is 1:10; percentage of emulsifier (span 80, v/v is 6%; volume of glutaraldehyde is 2 mL; and reaction temperature is 70 ºC. Under these optimal conditions, the encapsulation efficiency and loading capacity of microspheres are 84.57% and 8.44%, respectively. The swelling tests showed that the microspheres possessed higher swelling ratio at pH 7.4 than at pH 1.2. FTIR indicated that berbamine had been successfully loaded in the chitosan-agarose microspheres by physical entrapment. In vitro release studies showed that berbamine was released from microspheres in a significantly sustained fashion.

  8. Fuel behavior and fission product release under HTGR accident conditions

    International Nuclear Information System (INIS)

    Fukuda, K.; Hayashi, K.; Shiba, K.

    1990-01-01

    In early 1989 a final decision was made over construction of a 30 MWth HTGR called the High Temperature Engineering Test Reactor, HTTR, in Japan in order to utilize it for high temperature gas engineering tests and various nuclear material tests. The HTTR fuel is a pin-in-block type fuel element which is composed of a hexagonal graphite block with dimension of 580 mm in length and 360 mm in face-to-face distance and about 30 of the fuel rods inserted into the coolant channels drilled in the block. The TRISO coated fuel particles for HTTR are incorporated with graphite powder and phenol resin into the fuel compacts, 19 of which are encased into a graphite sleeve as a fuel rod. It is necessary for the HTTR licensing to prove the fuel stability under predicted accidents related to the high temperature events. Therefore, the release of the fission products and the fuel failure have been investigated in the irradiation---and the heating experiments simulating these conditions at JAERI. This report describes the HTTR fuel behavior at extreme temperature, made clear in these experiments

  9. 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.

  10. Physico-chemical state influences in vitro release profile of curcumin from pectin beads.

    Science.gov (United States)

    Nguyen, An Thi-Binh; Winckler, Pascale; Loison, Pauline; Wache, Yves; Chambin, Odile

    2014-09-01

    Curcumin is a polyphenolic compound with diverse effects interesting to develop health benefit products but its formulation in functional foods or in food supplement is hampered by its poor water solubility and susceptibility to alkaline conditions, light, oxidation and heat. Encapsulation of curcumin could be a mean to overcome these difficulties. In this paper, curcumin was encapsulated by ionotropic gelation method in low methoxyl pectin beads associated with different surfactants: Solutol(®), Transcutol(®) and sodium caseinate. After encapsulation, physico-chemical properties of encapsulated curcumin such as its solubility, physical state, tautomeric forms and encapsulation efficiency as well as encapsulation yield were characterized. In vitro dissolution of curcumin from beads displayed different kinetic profiles according to bead composition due to different matrix network. As Solutol(®) was a good solvent for curcumin, the drug was present into amorphous form in these beads inducing a rapid release of curcumin in the simulated digestive fluids. In contrast, drug release was slower from sodium caseinate beads since curcumin was not totally dissolved during the manufacturing process. Moreover, the FLIM studies showed that a part of curcumin was encapsulated in caseinate micelles and that 34% of this drug was in keto form which may delay the curcumin release. The Transcutol beads showed also a slow drug release because of the low curcumin solubility and the high density of the matrix. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. In vitro selection of shape-changing DNA nanostructures capable of binding-induced cargo release.

    Science.gov (United States)

    Oh, Seung Soo; Plakos, Kory; Xiao, Yi; Eisenstein, Michael; Soh, H Tom

    2013-11-26

    Many biological systems employ allosteric regulatory mechanisms, which offer a powerful means of directly linking a specific binding event to a wide spectrum of molecular functionalities. There is considerable interest in generating synthetic allosteric regulators that can perform useful molecular functions for applications in diagnostics, imaging and targeted therapies, but generating such molecules through either rational design or directed evolution has proven exceptionally challenging. To address this need, we present an in vitro selection strategy for generating conformation-switching DNA nanostructures that selectively release a small-molecule payload in response to binding of a specific trigger molecule. As an exemplar, we have generated a DNA nanostructure that hybridizes with a separate 'cargo strand' containing an abasic site. This abasic site stably sequesters a fluorescent cargo molecule in an inactive state until the DNA nanostructure encounters an ATP trigger molecule. This ATP trigger causes the nanostructure to release the cargo strand, thereby liberating the fluorescent payload and generating a detectable fluorescent readout. Our DNA nanostructure is highly sensitive, with an EC50 of 30 μM, and highly specific, releasing its payload in response to ATP but not to other chemically similar nucleotide triphosphates. We believe that this selection approach could be generalized to generate synthetic nanostructures capable of selective and controlled release of other small-molecule cargos in response to a variety of triggers, for both research and clinical applications.

  12. Formulation and In Vitro Release Kinetics of Mucoadhesive Blend Gels Containing Matrine for Buccal Administration.

    Science.gov (United States)

    Chen, Xiaojin; Yan, Jun; Yu, Shuying; Wang, Pingping

    2018-01-01

    Enterovirus 71 (EV71) is a pathogenic factor of severe hand, foot, and mouth disease (HFMD). No vaccine or specific treatment is currently available for EV71 infection. Hence, we developed a buccal mucoadhesive gel containing matrine to protect against HFMD. Mucoadhesive gels were prepared by Carbopol 974P and were combined with Carbopol 971P, sodium carboxymethyl cellulose (CMC-Na), or hydroxypropylmethy cellulose (HPMC K100M). The formulations were characterized in terms of tensile testing and continuous flow techniques for mucoadhesion. The rheological studies and in vitro drug release characteristics were also investigated. The results showed that combinations of two polymers significantly improved mucoadhesion, especially Carbopol 974P blended with HPMC. Carbopol 974P to HPMC blend ratios of 1:1 and 2:1 induced better mucoadhesion in the tensile test and continuous flow method, respectively. The most sustained release was obtained at a Carbopol 974P to HPMC ratio of 2.5:1. A predominantly non-Fickian diffusion release mechanism was obtained. The gel containing 2.5% Carbopol 974P combined with 1% HPMC showed good mucoadhesion properties and sustained drug release.

  13. Modulation of the formation and release of bovine SRS-A in vitro by several anti-anaphylactic drugs.

    Science.gov (United States)

    Burka, J F; Eyre, P

    1975-01-01

    Slow-reacting substance of anaphylaxis (SRS-A) is released immunologically from bovine lung in vitro. Various drugs known to protect calves and other animals during anaphylaxis were tested to investigate their modulation of the formation and release of SRS-A. The anti-inflammatory drugs, meclofenamate and aspirin, potentiated SRS-A release. Chlorphenesin and diethylcarbamazine citrate at high concentrations both inhibited SRS-A release. Two new anti-anaphylactic drugs, PR-D-92-EA and M&B 22,948, were particularly effective in inhibiting SRS-A release at low concentrations. The possible modes of actions of these drugs are discussed.

  14. Serotonin binding in vitro by releasable proteins from human blood platelets

    International Nuclear Information System (INIS)

    Heemstra, V.L.

    1983-11-01

    Among the substances released from human blood platelets are serotonin and various proteins. It was hypothesized that one of these proteins binds serotonin and that serotonin might be important to the protein's function or that the protein might be important to serotonin's function. Two platelet-specific proteins, platelet factor 4 (PF4) and β-thromboglobulin (βTG) were found to bind serotonin in vitro. Endogenous PF4 was isolated by serotonin-affinity chromatography and was identified by radioimmunoassay. Purified [ 125 I] -PF4 and native PF4 bound to and eluted from a serotonin-affinity column similarly. Ultrafiltration of the homologous protein, βTG, with [ 14 C]-serotonin demonstrated binding of about 8 moles serotonin per mole tetrameric βTG with a dissociation constant of about 4 X 10(sup-8) M. Equilibrium dialysis of PF4 with radiolabelled serotonin was attempted, but no binding constant values were obtained because serotonin apparently bound to the dialysis membrane. Since EDTA was one of the two agents that eluted PF4 from the serotonin-affinity gel, calcium binding by PF4 was investigated by equilibrium dialysis. Evidence was obtained for positively cooperative binding of calcium ions by PF4. It is concluded that PF4 and βTG bind serotonin in vitro, that they may also bind in vivo when platelets undergo release, and that the functions of serotonin, PF4 and βTG may be mediated in part by serotonin-protein associations

  15. Nanodiamond-based injectable hydrogel for sustained growth factor release: Preparation, characterization and in vitro analysis.

    Science.gov (United States)

    Pacelli, Settimio; Acosta, Francisca; Chakravarti, Aparna R; Samanta, Saheli G; Whitlow, Jonathan; Modaresi, Saman; Ahmed, Rafeeq P H; Rajasingh, Johnson; Paul, Arghya

    2017-08-01

    Nanodiamonds (NDs) represent an emerging class of carbon nanomaterials that possess favorable physical and chemical properties to be used as multifunctional carriers for a variety of bioactive molecules. Here we report the synthesis and characterization of a new injectable ND-based nanocomposite hydrogel which facilitates a controlled release of therapeutic molecules for regenerative applications. In particular, we have formulated a thermosensitive hydrogel using gelatin, chitosan and NDs that provides a sustained release of exogenous human vascular endothelial growth factor (VEGF) for wound healing applications. Addition of NDs improved the mechanical properties of the injectable hydrogels without affecting its thermosensitive gelation properties. Biocompatibility of the generated hydrogel was verified by in vitro assessment of apoptotic gene expressions and anti-inflammatory interleukin productions. NDs were complexed with VEGF and the inclusion of this complex in the hydrogel network enabled the sustained release of the angiogenic growth factor. These results suggest for the first time that NDs can be used to formulate a biocompatible, thermosensitive and multifunctional hydrogel platform that can function both as a filling agent to modulate hydrogel properties, as well as a delivery platform for the controlled release of bioactive molecules and growth factors. One of the major drawbacks associated with the use of conventional hydrogels as carriers of growth factors is their inability to control the release kinetics of the loaded molecules. In fact, in most cases, a burst release is inevitable leading to diminished therapeutic effects and unsuccessful therapies. As a potential solution to this issue, we hereby propose a strategy of incorporating ND complexes within an injectable hydrogel matrix. The functional groups on the surface of the NDs can establish interactions with the model growth factor VEGF and promote a prolonged release from the polymer network

  16. 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.

  17. 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.

  18. Release of axonally transported material from an in vitro amphibian sciatic nerve preparation

    International Nuclear Information System (INIS)

    Snyder, R.E.

    1988-01-01

    The rapid axonal transport of a pulse of [35S]methionine-labelled material was used to study the release of transported material from amphibian nerve maintained in vitro. Following creation of a moving pulse of activity in a dorsal root ganglion-sciatic nerve preparation, the ganglion was removed and the nerve placed in a three-compartment tray, the section of nerve in the middle compartment containing no truncated branches (unbranched section). All three compartments were filled with a saline solution that in some studies contained nonradioactive methionine (1.0 mmol/L). Analysis of studies in which nonradioactive methionine was absent revealed that labelled material appeared in the bathing solution of the end compartments that contained truncated branches, but not in the solution of the middle (unbranched) compartment. The quantity of label released in the branched compartments was approximately 6% of that remaining in the corresponding section of nerve following an 18-20 h incubation period. However, when nonradioactive methionine was present, all compartments showed an additional activity in the bathing solution of approximately 10% of that remaining in the nerve. In another study in which a position-sensitive detector of ionizing radiation was used to monitor progress of the pulse, it was found that activity did not enter the bathing solution of a compartment prior to the pulse of activity. It is concluded that in the absence of methionine from the bathing solution, axonally transported material is released only from regions of nerve that contain severed axons; however, the presence of methionine allows transported material to be released from nerve containing intact axons. Ultrafiltration studies and thin-layer chromatography revealed the majority of material released to be of low-molecular weight (less than 30,000 daltons) and not free [35S]methionine

  19. Role of hemolysis in red cell adenosine triphosphate release in simulated exercise conditions in vitro.

    Science.gov (United States)

    Mairbäurl, Heimo; Ruppe, Florian A; Bärtsch, Peter

    2013-10-01

    Specific adenosine triphosphate (ATP) release from red blood cells has been discussed as a possible mediator controlling microcirculation in states of decreased tissue oxygen. Because intravascular hemolysis might also contribute to plasma ATP, we tested in vitro which portion of ATP release is due to hemolysis in typical exercise-induced strains to the red blood cells (shear stress, deoxygenation, and lactic acidosis). Human erythrocytes were suspended in dextran-containing media (hematocrit 10%) and were exposed to shear stress in a rotating Couette viscometer at 37°C. Desaturation (oxygen saturation of hemoglobin ∼20%) was achieved by tonometry with N2 before shear stress exposure. Cells not exposed to shear stress were used as controls. Na lactate (15 mM), lactic acid (15 mM, pH 7.0), and HCl (pH 7.0) were added to simulate exercise-induced lactic acidosis. After incubation, extracellular hemoglobin was measured to quantify hemolysis. ATP was measured with the luciferase assay. Shear stress increased extracellular ATP in a stress-related and time-dependent manner. Hypoxia induced a ∼10-fold increase in extracellular ATP in nonsheared cells and shear stress-exposed cells. Lactic acid had no significant effect on ATP release and hemolysis. In normoxic cells, approximately 20%-50% of extracellular ATP was due to hemolysis. This proportion decreased to less than 10% in hypoxic cells. Our results indicate that when exposing red blood cells to typical strains they encounter when passing through capillaries of exercising skeletal muscle, ATP release from red blood cells is caused mainly by deoxygenation and shear stress, whereas lactic acidosis had only a minor effect. Hemolysis effects were decreased when hemoglobin was deoxygenated. Together, by specific release and hemolysis, extracellular ATP reaches values that have been shown to cause local vasodilatation.

  20. Tuning the Hydrophilic/Hydrophobic Balance to Control the Structure of Chitosan Films and Their Protein Release Behavior.

    Science.gov (United States)

    Becerra, Jose; Sudre, Guillaume; Royaud, Isabelle; Montserret, Roland; Verrier, Bernard; Rochas, Cyrille; Delair, Thierry; David, Laurent

    2017-05-01

    The control over the crystallinity of chitosan and chitosan/ovalbumin films can be achieved via an appropriate balance of the hydrophilic/hydrophobic interactions during the film formation process, which then controls the release kinetics of ovalbumin. Chitosan films were prepared by solvent casting. The presence of the anhydrous allomorph can be viewed as a probe of the hydrophobic conditions at the neutralization step. The semicrystalline structure, the swelling behavior of the films, the protein/chitosan interactions, and the release behavior of the films were impacted by the DA and the film processing parameters. At low DAs, the chitosan films neutralized in the solid state corresponded to the most hydrophobic environment, inducing the crystallization of the anhydrous allomorph with and without protein. The most hydrophilic conditions, leading to the hydrated allomorph, corresponded to non-neutralized films for the highest DAs. For the non-neutralized chitosan acetate (amorphous) films, the swelling increased when the DA decreased, whereas for the neutralized chitosan films, the swelling decreased. The in vitro release of ovalbumin (model protein) from chitosan films was controlled by their swelling behavior. For fast swelling films (DA = 45%), a burst effect was observed. On the contrary, a lag time was evidenced for DA = 2.5% with a limited release of the protein. Furthermore, by blending chitosans (DA = 2.5% and 45%), the release behavior was improved by reducing the burst effect and the lag time. The secondary structure of ovalbumin was partially maintained in the solid state, and the ovalbumin was released under its native form.

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

    Science.gov (United States)

    Kau, Yi-Chuan; Liao, Chia-Chih; Chen, Ying-Chi; Liu, Shih-Jung

    2014-09-16

    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.

  2. 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.

  3. Characterisation, in vitro release study, and antibacterial activity of montmorillonite-gentamicin complex material

    International Nuclear Information System (INIS)

    Rapacz-Kmita, A.; Bućko, M.M.; Stodolak-Zych, E.; Mikołajczyk, M.; Dudek, P.; nd Department of Surgery, Kopernika 21, 31-501 Krakow (Poland))" data-affiliation=" (Jagiellonian University, Medical College, 2nd Department of Surgery, Kopernika 21, 31-501 Krakow (Poland))" >Trybus, M.

    2017-01-01

    The present paper concerns the potential use of montmorillonite as a drug carrier and focusses on the intercalation of the studied clay with gentamicin (an aminoglycoside antibiotic) at various temperatures (20, 50 and 80 °C). The experiments were performed to identify the temperature required for the optimum intercalation of gentamicin into the interlayer of montmorillonite. The structural and microstructural properties of gentamicin and the potential for introducing it between smectite clay layers were investigated by means of X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopic techniques, and SEM with EDS analysis. Additionally, the in vitro drug release behaviour of the montmorillonite-gentamicin complex and its antibacterial activity against Escherichia coli (E. coli) bacteria was investigated. Based on these studies, the impact of temperature on the intercalation of the drug between layers of smectite was evaluated. It was found that an intercalation temperature of 50 °C resulted in the highest shift in the position of principle peak d (001) as measured by XRD, suggesting, that the greatest amount of gentamicin had been introduced into the interlayer space of montmorillonite at this temperature. Subsequently, the montmorillonite-gentamicin complex material obtained at 50 °C revealed the greatest capacity for killing E. coli bacteria during an in vitro test. - Highlights: • A novel montmorillonite-gentamicin hybrid materials was prepared as potential drug carrier. • Optimal conditions for the intercalation of gentamicin into the interlayer space of montmorillonite were tested. • The MMT-G complex material obtained at 50 °C revealed the greatest capacity for killing E. coli during the inhibitory zone test. • Modulating drug delivery was monitored and confirmed in in vitro drug release study.

  4. Characterisation, in vitro release study, and antibacterial activity of montmorillonite-gentamicin complex material

    Energy Technology Data Exchange (ETDEWEB)

    Rapacz-Kmita, A., E-mail: kmita@agh.edu.pl [AGH University of Science and Technology, Faculty of Materials Science and Ceramics, Mickiewicza 30, 30-059 Krakow (Poland); Bućko, M.M.; Stodolak-Zych, E. [AGH University of Science and Technology, Faculty of Materials Science and Ceramics, Mickiewicza 30, 30-059 Krakow (Poland); Mikołajczyk, M. [The University Hospital in Krakow, Division of Microbiology, Kopernika 19, 31-501 Krakow (Poland); Dudek, P. [AGH University of Science and Technology, Faculty of Mechanical Engineering and Robotics, Mickiewicza 30, 30-059 Krakow (Poland); Trybus, M. [Jagiellonian University, Medical College, 2" n" d Department of Surgery, Kopernika 21, 31-501 Krakow (Poland)

    2017-01-01

    The present paper concerns the potential use of montmorillonite as a drug carrier and focusses on the intercalation of the studied clay with gentamicin (an aminoglycoside antibiotic) at various temperatures (20, 50 and 80 °C). The experiments were performed to identify the temperature required for the optimum intercalation of gentamicin into the interlayer of montmorillonite. The structural and microstructural properties of gentamicin and the potential for introducing it between smectite clay layers were investigated by means of X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopic techniques, and SEM with EDS analysis. Additionally, the in vitro drug release behaviour of the montmorillonite-gentamicin complex and its antibacterial activity against Escherichia coli (E. coli) bacteria was investigated. Based on these studies, the impact of temperature on the intercalation of the drug between layers of smectite was evaluated. It was found that an intercalation temperature of 50 °C resulted in the highest shift in the position of principle peak d{sub (001)} as measured by XRD, suggesting, that the greatest amount of gentamicin had been introduced into the interlayer space of montmorillonite at this temperature. Subsequently, the montmorillonite-gentamicin complex material obtained at 50 °C revealed the greatest capacity for killing E. coli bacteria during an in vitro test. - Highlights: • A novel montmorillonite-gentamicin hybrid materials was prepared as potential drug carrier. • Optimal conditions for the intercalation of gentamicin into the interlayer space of montmorillonite were tested. • The MMT-G complex material obtained at 50 °C revealed the greatest capacity for killing E. coli during the inhibitory zone test. • Modulating drug delivery was monitored and confirmed in in vitro drug release study.

  5. Release of metal ions from fixed orthodontic appliance: an in vitro study in continuous flow system.

    Science.gov (United States)

    Mikulewicz, Marcin; Chojnacka, Katarzyna; Wołowiec, Paulina

    2014-01-01

    To evaluate the release of metal ions from fixed orthodontic appliances. A new system for in vitro testing of dental materials was constructed and consisted of a thermostatic glass reactor that enabled immersion of the studied material. Experimental conditions reflected the human oral cavity, with a temperature of 37°C and a saliva flow rate of 0.5mL/min. The simulated fixed orthodontic appliance made of stainless steel was evaluated. Sampling was performed at several time points during the 28-day study, and the metal ion concentration was determined by inductively coupled plasma optical emission spectrometry. The total mass of released metal ions from the appliance during 4 weeks of the experiment was as follows nickel 18.7 μg, chromium 5.47 μg, copper 31.3 μg. The estimated doses of nickel, chromium, and copper determined by extrapolation of experimental data released during the treatment period were far below the toxic dose to humans. This shows that orthodontic treatment might not be a significant source of exposure to these metal ions.

  6. Risk based In Vitro Performance Assessment of Extended Release Abuse Deterrent Formulations

    Science.gov (United States)

    Xu, Xiaoming; Gupta, Abhay; Al-Ghabeish, Manar; Calderon, Silvia N.; Khan, Mansoor A.

    2016-01-01

    High strength extended release opioid products, which are indispensable tools in the management of pain, are associated with serious risks of unintentional and potentially fatal overdose, as well as of misuse and abuse that might lead to addiction. The issue of drug abuse becomes increasingly prominent when the dosage forms can be readily manipulated to release a high amount of opioid or to extract the drug in certain products or solvents. One approach to deter opioid drug abuse is by providing novel abuse deterrent formulations (ADF), with properties that may be viewed as barriers to abuse of the product. However, unlike regular extended release formulations, assessment of ADF technologies are challenging, in part due to the great variety of formulation designs available to achieve deterrence of abuse by oral, parenteral, nasal and respiratory routes. With limited prior history or literature information, and lack of compendial standards, evaluation and regulatory approval of these novel drug products become increasingly difficult. The present article describes a risk-based standardized in-vitro approach that can be utilized in general evaluation of abuse deterrent features for all ADF products. PMID:26784976

  7. Synthesis, characterization, and in vitro release of diclofenac sodium from hybrid nanostructured magnetite–calcium pectinate

    International Nuclear Information System (INIS)

    Dutta, Raj Kumar; Sahu, Saurabh; Reddy, V. R.

    2012-01-01

    A stable spherical nanostructured calcium pectinate loaded with diclofenac sodium (DS) and functionalized by superparamagnetic iron oxide nanoparticles, referred as MCPDS, was developed as a potential magnetically targeted drug delivery system. The sizes of the MCPDS were in the range of 100–200 nm in dried condition, confirmed by scanning electron microscopy and transmission electron microscopy. In the aqueous medium, the sizes of MCPDS were in the range 300 ± 50 nm, measured by dynamic light scattering technique. The X-ray diffraction and 57 Fe Mössbauer spectroscopy confirmed magnetite phase in MCPDS. The magnetic property of the MCPDS nanostructures was confirmed from high saturation magnetization (44.05 emu/g), measured using a vibrating sample magnetometer. The superparamagnetic property of MCPDS was characterized by superconducting quantum unit interference device magnetometry and corroborated by Mössbauer spectroscopy. The loading efficiency of DS in MCPDS was measured by UV–Vis spectrophotometry and corroborated by thermal analysis. The in vitro release of the drug from MCPDS in simulated gastrointestinal fluids and in phosphate buffer solution was found to be pH sensitive and exhibited sustained release property. The cumulative drug release agreed well with that of swelling controlled diffusion mechanism, given by the Korsemeyer Peppas model.

  8. Synthesis, characterization, and in vitro release of diclofenac sodium from hybrid nanostructured magnetite-calcium pectinate

    Energy Technology Data Exchange (ETDEWEB)

    Dutta, Raj Kumar, E-mail: duttafcy@iitr.ernet.in; Sahu, Saurabh, E-mail: saurabhsahu12@gmail.com [Indian Institute of Technology Roorkee, Analytical Chemistry Laboratory, Department of Chemistry (India); Reddy, V. R., E-mail: vrreddy@csr.res.in [UGC-DAE Consortium for Scientific Research (India)

    2012-08-15

    A stable spherical nanostructured calcium pectinate loaded with diclofenac sodium (DS) and functionalized by superparamagnetic iron oxide nanoparticles, referred as MCPDS, was developed as a potential magnetically targeted drug delivery system. The sizes of the MCPDS were in the range of 100-200 nm in dried condition, confirmed by scanning electron microscopy and transmission electron microscopy. In the aqueous medium, the sizes of MCPDS were in the range 300 {+-} 50 nm, measured by dynamic light scattering technique. The X-ray diffraction and {sup 57}Fe Moessbauer spectroscopy confirmed magnetite phase in MCPDS. The magnetic property of the MCPDS nanostructures was confirmed from high saturation magnetization (44.05 emu/g), measured using a vibrating sample magnetometer. The superparamagnetic property of MCPDS was characterized by superconducting quantum unit interference device magnetometry and corroborated by Moessbauer spectroscopy. The loading efficiency of DS in MCPDS was measured by UV-Vis spectrophotometry and corroborated by thermal analysis. The in vitro release of the drug from MCPDS in simulated gastrointestinal fluids and in phosphate buffer solution was found to be pH sensitive and exhibited sustained release property. The cumulative drug release agreed well with that of swelling controlled diffusion mechanism, given by the Korsemeyer Peppas model.

  9. Synthesis, characterization, and in vitro release of diclofenac sodium from hybrid nanostructured magnetite-calcium pectinate

    Science.gov (United States)

    Dutta, Raj Kumar; Sahu, Saurabh; Reddy, V. R.

    2012-08-01

    A stable spherical nanostructured calcium pectinate loaded with diclofenac sodium (DS) and functionalized by superparamagnetic iron oxide nanoparticles, referred as MCPDS, was developed as a potential magnetically targeted drug delivery system. The sizes of the MCPDS were in the range of 100-200 nm in dried condition, confirmed by scanning electron microscopy and transmission electron microscopy. In the aqueous medium, the sizes of MCPDS were in the range 300 ± 50 nm, measured by dynamic light scattering technique. The X-ray diffraction and 57Fe Mössbauer spectroscopy confirmed magnetite phase in MCPDS. The magnetic property of the MCPDS nanostructures was confirmed from high saturation magnetization (44.05 emu/g), measured using a vibrating sample magnetometer. The superparamagnetic property of MCPDS was characterized by superconducting quantum unit interference device magnetometry and corroborated by Mössbauer spectroscopy. The loading efficiency of DS in MCPDS was measured by UV-Vis spectrophotometry and corroborated by thermal analysis. The in vitro release of the drug from MCPDS in simulated gastrointestinal fluids and in phosphate buffer solution was found to be pH sensitive and exhibited sustained release property. The cumulative drug release agreed well with that of swelling controlled diffusion mechanism, given by the Korsemeyer Peppas model.

  10. 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.

  11. 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.

  12. MAGNOLOL ENTRAPPED ULTRA-FINE FIBROUS MATS ELECTROSPUN FROM POLY(ETHYLENE GLYCOL)-b-POLY(L-LACTIDE) AND IN VITRO RELEASE

    Institute of Scientific and Technical Information of China (English)

    Hao Wang; Hong-rui Song; Yong Cui; Ying-jie Deng; Xue-si Chen

    2011-01-01

    Ultra-fine fibrous mats with magnolol entrapped have been prepared by electrospinning biodegradable copolymer poly(ethylene glycol) blocked poly(L-lactide). Drug entrapment was perfect which was confirmed by scanning electron microscopy and differential scanning calorimetry. According to in vitro drug release investigation by high performance liquid chromatography, it was found that fibers with 10%, 20% and 30% drug entrapped respect to polymer (mass ratio) presented dramatically different drug release behavior and degradation behavior under the effect of proteinase K. The reason may be that fibers with 10% drug entrapped was more easily affected by enzyme while, to some degree, magnolol in fibers with 20% and 30% entrapped prevented polymer from being degraded by enzyme.

  13. 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.

  14. In vitro atrazine-exposure inhibits human natural killer cell lytic granule release

    International Nuclear Information System (INIS)

    Rowe, Alexander M.; Brundage, Kathleen M.; Barnett, John B.

    2007-01-01

    The herbicide atrazine is a known immunotoxicant and an inhibitor of human natural killer (NK) cell lytic function. The precise changes in NK cell lytic function following atrazine exposure have not been fully elucidated. The current study identifies the point at which atrazine exerts its affect on the stepwise process of human NK cell-mediated lyses of the K562 target cell line. Using intracellular staining of human peripheral blood lymphocytes, it was determined that a 24-h in vitro exposure to atrazine did not decrease the level of NK cell lytic proteins granzyme A, granzyme B or perforin. Thus, it was hypothesized that atrazine exposure was inhibiting the ability of the NK cells to bind to the target cell and subsequently inhibit the release of lytic protein from the NK cell. To test this hypothesis, flow cytometry and fluorescent microscopy were employed to analyze NK cell-target cell co-cultures following atrazine exposure. These assays demonstrated no significant decrease in the level of target cell binding. However, the levels of NK intracellular lytic protein retained and the amount of lytic protein released were assessed following a 4-h incubation with K562 target cells. The relative level of intracellular lytic protein was 25-50% higher, and the amount of lytic protein released was 55-65% less in atrazine-treated cells than vehicle-treated cells following incubation with the target cells. These results indicate that ATR exposure inhibits the ability of NK cells to lyse target cells by blocking lytic granule release without affecting the ability of the NK cell to form stable conjugates with target cells

  15. 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

  16. Starch and antioxidant compound release during in vitro gastrointestinal digestion of gluten-free pasta.

    Science.gov (United States)

    Camelo-Méndez, Gustavo A; Agama-Acevedo, Edith; Rosell, Cristina M; de J Perea-Flores, Maria; Bello-Pérez, Luis A

    2018-10-15

    The microstructure of cooked gluten-free pasta depends on the ingredients used, and this microstructure affects the starch hydrolysis (SH), the release of phenolic compounds (PC) and their antioxidant capacity (AC). The aim of this study was to evaluate the SD and bioaccessibility of PC during in vitro gastrointestinal digestion of gluten-free pasta and its relationship with the microstructure. The highest SH was during the intestinal phase (≈60%), but pasta with the highest content of unripe plantain and chickpea presented the lowest release of PC (≈60%). The insoluble dietary fibre could be responsible (≈12.5%) for these effects. The cooked pasta showed high AC in the intestinal phase. Regions with gelatinized starch granules in a less dense protein network and other regions with intact or swollen granules surrounded by a protein network were observed. The starch digestion and bioaccessibility of PC were related to the structure of the matrix. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Thermal release behavior of helium from copper irradiated by He+ ions

    International Nuclear Information System (INIS)

    Yamauchi, T.; Tokura, S.; Yamanaka, S.; Miyake, M.

    1988-01-01

    Thermal release behavior of helium from copper irradiated by 20 keV He + ions with a dose of 2x10 15 to 3x10 17 ions/cm 2 has been studied. The shape of the thermal release curves and thew number of helium release peaks strongly depend on the irradiation dose. Results from SEM surface observastion after post-irradiation heating suggested that helium release caused various surface damages such as blistering, flaking, and hole formation. Helium release resulting in small holes was analyzed and helium bubble growth mechanisms are discussed. (orig.)

  18. Effect of surface water on tritium release behavior from Li4SiO4

    International Nuclear Information System (INIS)

    Hanada, T.; Fukada, S.; Nishikawa, M.; Suematsu, K.; Yamashita, N.; Kanazawa, T.

    2010-01-01

    The tritium release model to represent the release behavior of bred tritium from solid breeder materials has been developed by the blanket group of Kyushu University. It has been found that water is released to the purge gas from solid breeder materials and that this water affects the tritium release behavior. In this study, the amount of surface water released from Li 4 SiO 4 is quantified by the experiment. In addition, the tritium release behavior from Li 4 SiO 4 are estimated based on the tritium release model using parameters obtained in our studies under conditions of commercial reactor operation and ITER test blanket module operation. The effect of the surface water on tritium release behavior is discussed from the obtained results. Moreover, the tritium inventory of Li 4 SiO 4 is discussed based on calculation under the unsteady state condition. Further, the effects of grain size and temperature on distribution of tritium inventory under the steady state condition are evaluated, and the optimal grain size is discussed from the view point of tritium release from Li 4 SiO 4 .

  19. "Effect of nano-filled surface coating agent on fluoride release from conventional glass ionomer cement: An in vitro trial"

    OpenAIRE

    S Tiwari; B Nandlal

    2013-01-01

    Context: To overcome the drawbacks of glass ionomer cement of sensitivity to initial desiccation and moisture contamination the use of surface coating agent is recommended. The search in this area led to invent of use of nanofillers in surface coating agent, but its effect on fluoride release is not clear. Aim: The aim of this study is to evaluate and compare the fluoride release from conventional glass ionomer cement with and without surface coating agent. Settings and Design: This in vitro ...

  20. 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...... these regions with in situ electrodes and demonstrates the utility of fast-scan cyclic voltammetry to investigate the mechanisms and possible non-classical functions of somato-dendritic DA release....

  1. 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.

  2. The in vitro sustained release profile and antitumor effect of etoposide-layered double hydroxide nanohybrids

    Directory of Open Access Journals (Sweden)

    Qin LL

    2013-05-01

    Full Text Available Lili Qin,1 Mei Wang,2 Rongrong Zhu,3 Songhui You,1 Ping Zhou,1 Shilong Wang31Department of Physical Education, Tongji University, Shanghai, People's Republic of China; 2Department of Chemistry, Tongji University, Shanghai, People's Republic of China; 3School of Life Science and Technology, Tongji University, Shanghai, People's Republic of ChinaAbstract: Magnesium-aluminum layered double hydroxides intercalated with antitumor drug etoposide (VP16 were prepared for the first time using a two-step procedure. The X-ray powder diffraction data suggested the intercalation of VP16 into layers with the increased basal spacing from 0.84–1.18 nm was successful. Then, it was characterized by X-ray powder diffraction, Fourier transform infrared spectroscopy, thermogravimetry and differential thermal analysis, and transmission electron microscopy. The prepared nanoparticles, VP16-LDH, showed an average diameter of 62.5 nm with a zeta potential of 20.5 mV. Evaluation of the buffering effect of VP16-LDH indicated that the nanohybrids were ideal for administration of the drugs that treat human stomach irritation. The loading amount of intercalated VP16 was 21.94% and possessed a profile of sustained release. The mechanism of VP16-LDH release in the phosphate buffered saline solution at pH 7.4 is likely controlled by the diffusion of VP16 anions from inside to the surface of LDH particles. The in vitro cytotoxicity and antitumor assays indicated that VP16-LDH hybrids were less toxic to GES-1 cells while exhibiting better antitumor efficacy on MKN45 and SGC-7901 cells. These results imply that VP16-LDH is a potential antitumor drug for a broad range of gastric cancer therapeutic applications.Keywords: layered double hydroxides, etoposide, drug delivery, antitumor effect, sustained release

  3. 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.

  4. Behavior of fission products released from severely damaged fuel during the PBF severe fuel damage tests

    International Nuclear Information System (INIS)

    Osetek, D.J.; Cronenberg, A.W.; Hagrman, D.L.; Broughton, J.M.; Rest, J.

    1984-01-01

    The results of fission product release behavior during the first two Power Burst Facility Severe Fuel Damage tests are presented. Measured fission product release is compared with calculated release using temperature dependent release rate correlations and FASTGRASS analysis. The test results indicate that release from fuel of the high volatility fission products (Xe, Kr, I, Cs, and Te) is strongly influenced by parameters other than fuel temperature; namely fuel/fission product morphology, fuel and cladding oxidation state, extent of fuel liquefaction, and quench induced fuel shattering. Fission product transport from the test fuel through the sample system was strongly influenced by chemical effects. Holdup of I and Cs was affected by fission product chemistry, and transport time while Te release was primarily influenced by the extent of zircaloy oxidation. Analysis demonstrates that such integral test data can be used to confirm physical, chemical, and mechanistic models of fission product behavior for severe accident conditions

  5. 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

  6. 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.

  7. Oral matrix tablet formulations for concomitant controlled release of anti-tubercular drugs: design and in vitro evaluations.

    Science.gov (United States)

    Hiremath, Praveen S; Saha, Ranendra N

    2008-10-01

    The aim of the present investigation was to develop controlled release (C.R.) matrix tablet formulations of rifampicin and isoniazid combination, to study the design parameters and to evaluate in vitro release characteristics. In the present study, a series of formulations were developed with different release rates and duration using hydrophilic polymers hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC). The duration of rifampicin and isoniazid release could be tailored by varying the polymer type, polymer ratio and processing techniques. Further, Eudragit L100-55 was incorporated in the matrix tablets to compensate for the pH-dependent release of rifampicin. Rifampicin was found to follow linear release profile with time from HPMC formulations. In case of formulations with HPC, there was an initial higher release in simulated gastric fluid (SGF) followed by zero order release profiles in simulated intestinal fluid (SIFsp) for rifampicin. The release of isoniazid was found to be predominantly by diffusion mechanism in case of HPMC formulations, and with HPC formulations release was due to combination of diffusion and erosion. The initial release was sufficiently higher for rifampicin from HPC thus ruling out the need to incorporate a separate loading dose. The initial release was sufficiently higher for isoniazid in all formulations. Thus, with the use of suitable polymer or polymer combinations and with the proper optimization of the processing techniques it was possible to design the C.R. formulations of rifampicin and isoniazid combination that could provide the sufficient initial release and release extension up to 24h for both the drugs despite of the wide variations in their physicochemical properties.

  8. 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

    Leucocyte expression of the urokinase receptor [urokinase-type plasminogen activator receptor (uPAR)] is regulated by inflammatory mediators. This study investigated the in vivo effect of endotoxin, interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha on uPAR-release in vivo and in vitro in ...

  9. 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

  10. Effect of thickening agent in the in vitro mouth, stomach and intestine release of tyrosol from enriched custards

    NARCIS (Netherlands)

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

    2006-01-01

    Custards prepared with four thickeners (two modified starches: waxy maize and tapioca, and two derives of cellulose: CMC and HPMC) and at two levels of consistency were enriched with a water-soluble functional ingredient (tyrosol) and its release evaluated after in vitro mouth, stomach and small

  11. Experimental study of PLLA/INH slow release implant fabricated by three dimensional printing technique and drug release characteristics in vitro.

    Science.gov (United States)

    Wu, Gui; Wu, Weigang; Zheng, Qixin; Li, Jingfeng; Zhou, Jianbo; Hu, Zhilei

    2014-07-19

    Local slow release implant provided long term and stable drug release in the lesion. The objective of this study was to fabricate biodegradable slow release INH/PLLA tablet via 3 dimensional printing technique (3DP) and to compare the drug release characteristics of three different structured tablets in vitro. Three different drug delivery systems (columnar-shaped tablet (CST), doughnut-shaped tablet (DST) and multilayer doughnut-shaped tablet (MDST)) were manufactured by the three dimensional printing machine and isoniazid was loaded into the implant. Dynamic soaking method was used to study the drug release characteristics of the three implants. MTT cytotoxicity test and direct contact test were utilized to study the biocompatibility of the implant. The microstructures of the implants' surfaces were observed with electron microscope. The PLLA powder in the tablet could be excellently combined through 3DP without disintegration. Electron microscope observations showed that INH distributed evenly on the surface of the tablet in a "nest-shaped" way, while the surface of the barrier layer in the multilayer doughnut shaped tablet was compact and did not contain INH. The concentration of INH in all of the three tablets were still higher than the effective bacteriostasis concentration (Isoniazid: 0.025 ~ 0.05 μg/ml) after 30 day's release in vitro. All of the tablets showed initial burst release of the INH in the early period. Drug concentration of MDST became stable and had little fluctuation starting from the 6th day of the release. Drug concentration of DST and CST decreased gradually and the rate of decrease in concentration was faster in DST than CST. MTT cytotoxicity test and direct contact test indicated that the INH-PLLA tablet had low cytotoxicity and favorable biocompatibility. Three dimensional printing technique was a reliable technique to fabricate complicated implants. Drug release pattern in MDST was the most stable among the three implants. It was

  12. 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.

  13. Characterization of modified allergen extracts by in vitro beta-hexosaminidase release from rat basophils.

    Science.gov (United States)

    Gehlhar, Kirsten; Peters, Marcus; Brockmann, Kirsten; van Schijndel, Hans; Bufe, Albrecht

    2005-04-01

    To date, there is no well-established test available that can be used to measure functional properties of modified allergens (allergoids). Due to the cross-linking process, the IgE-binding capacity of the allergens, normally necessary for their characterization, is lost. The aim of this study was to test whether the rat basophilic leukaemia (RBL) cell assay (beta-hexosaminidase release by rat basophils upon allergen stimulation) can be adopted to characterize allergoids and to evaluate the assay for testing allergoids and native allergens as well. Mice were immunized with native and modified Phleumpratense extracts in the presence of alum. Their sera were used to sensitize RBL-2H3 cells and measure basophil stimulation induced by different allergen extracts in the presence or absence of various additives. Sera containing specific IgE against both extract formulations were obtained. Native as well as modified extracts induced dose-dependent beta-hexosaminidase release from RBL cells. Both extracts were used to evaluate the characteristics of the assay, which showed high precision. Storage conditions were chosen to enhance extract degradation, which could be read directly from the altered stimulatory capacity of the extracts. Additives turned out to have diverse effects on the assay, whereas phenol had no measurable effect, alum had an inhibitory effect and glycerol elevated basophil activation. For the first time, a reliable, precise in vitro assay is available that is able to directly measure the properties of modified allergen extracts after their production process. The test is well evaluated and its advantages and limitations are discussed in this report. Copyright (c) 2005 S. Karger AG, Basel

  14. Release of atrial natriuretic peptide from rat myocardium in vitro: effect of minoxidil-induced hypertrophy.

    Science.gov (United States)

    Kinnunen, P.; Taskinen, T.; Leppäluoto, J.; Ruskoaho, H.

    1990-01-01

    1. Ventricular hypertrophy is characterized by stimulation of ventricular synthesis of atrial natriuretic peptide (ANP). To examine the role of ventricular ANP levels in the secretion of ANP into the circulation, atrial and ventricular levels of immunoreactive-ANP (IR-ANP) as well as ANP messenger RNA (mRNA), and the release of IR-ANP from isolated perfused hearts, both before and after atrialectomy, were measured simultaneously in control and minoxidil-treated Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. 2. IR-ANP levels in the ventricles of untreated, 12 month-old SHR with severe ventricular hypertrophy were increased when compared to age-matched WKY rats. Minoxidil treatment for 8 weeks in both strains resulted in a decrease in mean arterial pressure and increases in ventricular weight to body weight ratios, plasma IR-ANP concentrations (in WKY from 133 +/- 20 to 281 +/- 34 pg ml-1, P less than 0.01; in SHR from 184 +/- 38 to 339 +/- 61 pg ml-1, P less than 0.05), and in ventricular IR-ANP contents (in WKY: 53%; in SHR: 41%). A highly significant correlation was found between ventricular IR-ANP content and ventricular weight to body weight ratio (r = 0.59, P less than 0.001, n = 26). 3. When studied in vitro, in isolated perfused heart preparations, the hypertrophied ventricular tissue after atrialectomy secreted more ANP into the perfusate than ventricles of the control hearts; ventricles contributed 28%, 22%, 18% and 15% of the total ANP release to perfusate in the minoxidil-treated SHR, control SHR, minoxidil-treated WKY and control WKY, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2141796

  15. Assessment of Aprotinin Loaded Microemulsion Formulations for Parenteral Drug Delivery: Preparation, Characterization, in vitro Release and Cytotoxicity Studies.

    Science.gov (United States)

    Okur, Neslihan Üstündağ; Özdemir, Derya İlem; Kahyaoğlu, Şennur Görgülü; Şenyiğit, Zeynep Ay; Aşıkoğlu, Makbule; Genç, Lütfi; Karasulu, H Yeşim

    2015-01-01

    The object of the current study was to prepare novel microemulsion formulations of aprotinin for parenteral delivery and to compare in vitro characteristics and release behaviour of different Technetium-99m ((99m)Tc)-Aprotinin loaded microemulsion formulations. In addition, cytotoxicity of microemulsion formulation was evaluated with cell culture studies on human immortalized pancreatic duct epithelial-like cells. For this aim, firstly, pseudo-ternary phase diagrams were plotted to detect the formulation region and optimal microemulsions were characterized for their thermodynamic stability, conductivity, particle size, zeta potential, viscosity, pH and in vitro release properties. For in vitro release studies aprotinin was labelled with (99m)Tc and labelling efficiency, radiochemical purity and stability of the radiolabeled complex were determined by several chromatography techniques. Radiolabeling efficiency of (99m)Tc-Aprotinin was found over than 90% without any significant changes up to 6 hours after labelling at room temperature. After that, in vitro release studies of (99m)Tc-Aprotinin loaded microemulsions were performed with two different methods; dissolution from diffusion cells and dialysis bags. Both methods showed that release rate of (99m)Tc- Aprotinin from microemulsion could be controlled by microemulsion formulations. Drug release from the optimized microemulsion formulations was found lower compared to drug solution at the end of six hours. According to stability studies, the optimized formulation was found to be stable over a period of 12 months. Also, human immortalized pancreatic duct epithelial-like cells were used to evaluate the cytotoxicity of optimum formulation. Developed microemulsion did not reveal cytotoxicity. In conclusion the present study indicated that the M1-APT microemulsion is appropriate for intravenous application of aprotinin.

  16. New oral dosage form for elderly patients. II. Release behavior of benfotiamine from silk fibroin gel.

    Science.gov (United States)

    Hanawa, T; Watanabe, A; Tsuchiya, T; Ikoma, R; Hidaka, M; Sugihara, M

    1995-05-01

    Silk fibroin gel (SFG) containing benfotiamine (BTMP) was prepared. The release behavior of BTMP from SFG was studied as a function of silk fibroin (SF) content and glycerol content, and the influence of the existence of beta-cyclodextrin (beta-CD) on the physicochemical properties of SFG were investigated. The release rate of BTMP from SFG was retarded by an increase in SF concentration. The addition of beta-CD affected both the release properties and rheological properties of the SFG. It was found from the results of the "paddle-bead method" that the release profiles of BTMP from SFG were inversely proportional to the SFG firmness.

  17. Preparation of ionic-crosslinked chitosan-based gel beads and effect of reaction conditions on drug release behaviors.

    Science.gov (United States)

    Chen, Shilan; Liu, Mingzhu; Jin, Shuping; Wang, Bin

    2008-02-12

    Drug-loaded chitosan (CS) beads were prepared under simple and mild condition using trisodium citrate as ionic crosslinker. The beads were further coated with poly(methacrylic acid) (PMAA) by dipping the beads in PMAA aqueous solution. The surface and cross-section morphology of these beads were observed by scanning electron microscopy and the observation showed that the coating beads had core-shell structure. In vitro release of model drug from these beads obtained under different reaction conditions was investigated in buffer medium (pH 1.8). The results showed that the rapid drug release was restrained by PMAA coating and the optimum conditions for preparing CS-based drug-loaded beads were decided through the effect of reaction conditions on the drug release behaviors. In addition, the drug release mechanism of CS-based drug-loaded beads was analyzed by Peppa's potential equation. According to this study, the ionic-crosslinked CS beads coated by PMAA could serve as suitable candidate for drug site-specific carrier in stomach.

  18. Growth factor release by vesicular phospholipid gels: in-vitro results and application for rotator cuff repair in a rat model.

    Science.gov (United States)

    Buchmann, Stefan; Sandmann, Gunther H; Walz, Lars; Reichel, Thomas; Beitzel, Knut; Wexel, Gabriele; Tian, Weiwei; Battmann, Achim; Vogt, Stephan; Winter, Gerhard; Imhoff, Andreas B

    2015-04-10

    Biological augmentation of rotator cuff repair is of growing interest to improve biomechanical properties and prevent re-tearing. But intraoperative single shot growth factor application appears not sufficient to provide healing support in the physiologic growth factor expression peaks. The purpose of this study was to establish a sustained release of granulocyte-colony stimulating factor (G-CSF) from injectable vesicular phospholipid gels (VPGs) in vitro and to examine biocompatibility and influence on histology and biomechanical behavior of G-CSF loaded VPGs in a chronic supraspinatus tear rat model. G-CSF loaded VPGs were produced by dual asymmetric centrifugation. In vitro the integrity, stability and release rate were analyzed. In vivo supraspinatus tendons of 60 rats were detached and after 3 weeks a transosseous refixation with G-CSF loaded VPGs augmentation (n = 15; control, placebo, 1 and 10 μg G-CSF/d) was performed. 6 weeks postoperatively the healing site was analyzed histologically (n = 9; H&E by modified MOVIN score/Collagen I/III) and biomechanically (n = 6). In vitro testing revealed stable proteins after centrifugation and a continuous G-CSF release of up to 4 weeks. Placebo VPGs showed histologically no negative side effects on the healing process. Histologically in vivo testing demonstrated significant advantages for G-CSF 1 μg/d but not for G-CSF 10 μg/d in Collagen III content (p = 0.035) and a higher Collagen I/III ratio compared to the other groups. Biomechanically G-CSF 1 μg/d revealed a significant higher load to failure ratio (p = 0.020) compared to control but no significant differences in stiffness. By use of VPGs a continuous growth factor release could be obtained in vitro. The in vivo results demonstrate an improvement of immunohistology and biomechanical properties with a low dose G-CSF application via VPG. The VPG itself was well tolerated and had no negative influence on the healing behavior. Due to the favorable properties

  19. The effect of amperozide on uptake and release of [3H]-dopamine in vitro from perfused rat striatal and limbic brain areas

    International Nuclear Information System (INIS)

    Eriksson, E.; Christensson, E.

    1990-01-01

    Amperozide, a putatively antipsychotic drug, was studied for its effects on uptake and release of [ 3 H]-dopamine in rat brain in vitro. Amperozide inhibited uptake of [ 3 H]-dopamine in striatal chopped tissue in vitro with an IC 50 of 18 μM. It also increased basal release of [ 3 H]-dopamine from perfused rat striatal and limbic tissue in vitro at concentrations above 5 μM. Release of [ 3 H]-dopamine from perfused rat striatal and limbic tissue stimulated with 5 μM amphetamine, was inhibited by 1 μM amperozide to 46%. No significant difference was found for the effect of amperozide on in vitro release of [ 3 H]-dopamine from corpus striatum compared to tissue from limbic grain regions; neither on basal release nor on amphetamine-stimulated release of dopamine. (author)

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

    Science.gov (United States)

    Malana, Muhammad A; Zohra, Rubab

    2013-01-18

    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. 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. 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 the systems indicate that these co-polymeric hydrogels have a great potential to

  1. The impact of manufacturing variables on in vitro release of clobetasol 17-propionate from pilot scale cream formulations.

    Science.gov (United States)

    Fauzee, Ayeshah Fateemah Beebee; Khamanga, Sandile Maswazi; Walker, Roderick Bryan

    2014-12-01

    The purpose of the study was to evaluate the effect of different homogenization speeds and times, anchor speeds and cooling times on the viscosity and cumulative % clobetasol 17-propionate released per unit area at 72 h from pilot scale cream formulations. A 2(4) full factorial central composite design for four independent variables were investigated. Thirty pilot scale batches of cream formulations were manufactured using a Wintech® cream/ointment plant. The viscosity and in vitro release of CP were monitored and compared to an innovator product that is commercially available on the South African market, namely, Dermovate® cream. Contour and three-dimensional response surface plots were produced and the viscosity and cumulative % CP released per unit area at 72 h were found to be primarily dependent on the homogenization and anchor speeds. An increase in the homogenization and anchor speeds appeared to exhibit a synergistic effect on the resultant viscosity of the cream whereas an antagonistic effect was observed for the in vitro release of CP from the experimental cream formulations. The in vitro release profiles were best fitted to a Higuchi model and diffusion proved to be the dominant mechanism of drug release that was confirmed by use of the Korsmeyer-Peppas model. The research was further validated and confirmed by the high prognostic ability of response surface methodology (RSM) with a resultant mean percentage error of (±SD) 0.17 ± 0.093 suggesting that RSM may be an efficient tool for the development and optimization of topical formulations.

  2. Comparison of WTC Dust Size on Macrophage Inflammatory Cytokine Release In vivo and In vitro

    Science.gov (United States)

    Weiden, Michael D.; Naveed, Bushra; Kwon, Sophia; Segal, Leopoldo N.; Cho, Soo Jung; Tsukiji, Jun; Kulkarni, Rohan; Comfort, Ashley L.; Kasturiarachchi, Kusali J.; Prophete, Colette; Cohen, Mitchell D.; Chen, Lung-Chi; Rom, William N.; Prezant, David J.; Nolan, Anna

    2012-01-01

    Background The WTC collapse exposed over 300,000 people to high concentrations of WTC-PM; particulates up to ∼50 mm were recovered from rescue workers’ lungs. Elevated MDC and GM-CSF independently predicted subsequent lung injury in WTC-PM-exposed workers. Our hypotheses are that components of WTC dust strongly induce GM-CSF and MDC in AM; and that these two risk factors are in separate inflammatory pathways. Methodology/Principal Findings Normal adherent AM from 15 subjects without WTC-exposure were incubated in media alone, LPS 40 ng/mL, or suspensions of WTC-PM10–53 or WTC-PM2.5 at concentrations of 10, 50 or 100 µg/mL for 24 hours; supernatants assayed for 39 chemokines/cytokines. In addition, sera from WTC-exposed subjects who developed lung injury were assayed for the same cytokines. In the in vitro studies, cytokines formed two clusters with GM-CSF and MDC as a result of PM10–53 and PM2.5. GM-CSF clustered with IL-6 and IL-12(p70) at baseline, after exposure to WTC-PM10–53 and in sera of WTC dust-exposed subjects (n = 70) with WTC lung injury. Similarly, MDC clustered with GRO and MCP-1. WTC-PM10–53 consistently induced more cytokine release than WTC-PM2.5 at 100 µg/mL. Individual baseline expression correlated with WTC-PM-induced GM-CSF and MDC. Conclusions WTC-PM10–53 induced a stronger inflammatory response by human AM than WTC-PM2.5. This large particle exposure may have contributed to the high incidence of lung injury in those exposed to particles at the WTC site. GM-CSF and MDC consistently cluster separately, suggesting a role for differential cytokine release in WTC-PM injury. Subject-specific response to WTC-PM may underlie individual susceptibility to lung injury after irritant dust exposure. PMID:22815721

  3. Comparison of WTC dust size on macrophage inflammatory cytokine release in vivo and in vitro.

    Directory of Open Access Journals (Sweden)

    Michael D Weiden

    Full Text Available BACKGROUND: The WTC collapse exposed over 300,000 people to high concentrations of WTC-PM; particulates up to ∼50 mm were recovered from rescue workers' lungs. Elevated MDC and GM-CSF independently predicted subsequent lung injury in WTC-PM-exposed workers. Our hypotheses are that components of WTC dust strongly induce GM-CSF and MDC in AM; and that these two risk factors are in separate inflammatory pathways. METHODOLOGY/PRINCIPAL FINDINGS: Normal adherent AM from 15 subjects without WTC-exposure were incubated in media alone, LPS 40 ng/mL, or suspensions of WTC-PM(10-53 or WTC-PM(2.5 at concentrations of 10, 50 or 100 µg/mL for 24 hours; supernatants assayed for 39 chemokines/cytokines. In addition, sera from WTC-exposed subjects who developed lung injury were assayed for the same cytokines. In the in vitro studies, cytokines formed two clusters with GM-CSF and MDC as a result of PM(10-53 and PM(2.5. GM-CSF clustered with IL-6 and IL-12(p70 at baseline, after exposure to WTC-PM(10-53 and in sera of WTC dust-exposed subjects (n = 70 with WTC lung injury. Similarly, MDC clustered with GRO and MCP-1. WTC-PM(10-53 consistently induced more cytokine release than WTC-PM(2.5 at 100 µg/mL. Individual baseline expression correlated with WTC-PM-induced GM-CSF and MDC. CONCLUSIONS: WTC-PM(10-53 induced a stronger inflammatory response by human AM than WTC-PM(2.5. This large particle exposure may have contributed to the high incidence of lung injury in those exposed to particles at the WTC site. GM-CSF and MDC consistently cluster separately, suggesting a role for differential cytokine release in WTC-PM injury. Subject-specific response to WTC-PM may underlie individual susceptibility to lung injury after irritant dust exposure.

  4. Bioaccessible peptides released by in vitro gastrointestinal digestion of fermented goat milks.

    Science.gov (United States)

    Moreno-Montoro, Miriam; Jauregi, Paula; Navarro-Alarcón, Miguel; Olalla-Herrera, Manuel; Giménez-Martínez, Rafael; Amigo, Lourdes; Miralles, Beatriz

    2018-06-01

    In this study, ultrafiltered goat milks fermented with the classical starter bacteria Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus salivarus subsp. thermophilus or with the classical starter plus the Lactobacillus plantarum C4 probiotic strain were analyzed using ultra-high performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) and/or high performance liquid chromatography-ion trap (HPLC-IT-MS/MS). Partial overlapping of the identified sequences with regard to fermentation culture was observed. Evaluation of the cleavage specificity suggested a lower proteolytic activity of the probiotic strain. Some of the potentially identified peptides had been previously reported as angiotensin-converting enzyme (ACE) inhibitory, antioxidant, and antibacterial and might account for the in vitro activity previously reported for these fermented milks. Simulated digestion of the products was conducted in the presence of a dialysis membrane to retrieve the bioaccessible peptide fraction. Some sequences with reported physiological activity resisted digestion but were found in the non-dialyzable fraction. However, new forms released by digestion, such as the antioxidant α s1 -casein 144 YFYPQL 149 , the antihypertensive α s2 -casein 90 YQKFPQY 96 , and the antibacterial α s2 -casein 165 LKKISQ 170 , were found in the dialyzable fraction of both fermented milks. Moreover, in the fermented milk including the probiotic strain, the k-casein dipeptidyl peptidase IV inhibitor (DPP-IV) 51 INNQFLPYPY 60 as well as additional ACE inhibitory or antioxidant sequences could be identified. With the aim of anticipating further biological outcomes, quantitative structure activity relationship (QSAR) analysis was applied to the bioaccessible fragments and led to potential ACE inhibitory sequences being proposed. Graphical abstract Ultrafiltered goat milks were fermented with the classical starter bacteria (St) and with St plus the

  5. Influence of different test parameters on in vitro drug release from topical diclofenac formulations in a vertical diffusion cell setup.

    Science.gov (United States)

    Klein, S

    2013-07-01

    In the past decades, the vertical diffusion cell has emerged as a useful device for testing drug release of topical dosage forms. However, to date neither a general USP method nor formulation-related monographs have been published in international pharmacopoeia. The purpose of the present work was to examine the influence of different test parameters in a vertical diffusion cell setup on in vitro drug release from semi-solid preparations for cutaneous application. Diclofenac was selected as the model compound. Release experiments were performed in a 7 ml Microett vertical diffusion cell system. Various test parameters, including the media composition and pH, degassing, membrane material and pore size, stirring speed and stirrer type, were varied. Results obtained with different test parameter settings clearly indicate that both drug properties and instrumental details can have a huge impact on the outcome of in vitro diffusion/drug release studies with the vertical diffusion cell. Thus, the selection of adequate test parameters is crucial for the success of the release experiments and, as shown in the present study, optimal test parameters/conditions need to be established and validated on a case by case study.

  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 F 10 composed of 28.5% Eudragit RSPM, 3% NaHCO 3 , and 7% citric acid provided sustained drug release. In vitro results showed sustained release of F 10 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 (AUC 0-∞ ) 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 F 10 increased to 187.80% ( P =0.022). The prepared floating tablets of ITO HCl (F 10 ) could be a promising drug delivery system with sustained-release action and enhanced drug bioavailability.

  7. "Effect of nano-filled surface coating agent on fluoride release from conventional glass ionomer cement: an in vitro trial".

    Science.gov (United States)

    Tiwari, S; Nandlal, B

    2013-01-01

    To overcome the drawbacks of glass ionomer cement of sensitivity to initial desiccation and moisture contamination the use of surface coating agent is recommended. The search in this area led to invent of use of nanofillers in surface coating agent, but its effect on fluoride release is not clear. The aim of this study is to evaluate and compare the fluoride release from conventional glass ionomer cement with and without surface coating agent. This in vitro study comprised of total 80 samples (40 samples of each with and without surface coating). Specimens were prepared, G coat plus was applied and light cured. Fluoride release of the sample was measured every 24 h for 7 days and weekly from 7th to 21 st day using Sension4 pH/ISE/MV Meter. Descriptive Statistics, Repeated Measure ANOVA, Paired Sample t-test, Independent Sample t-test, Scheffe post hoc test. Mean values clearly reveal a significant decrease in the fluoride release from day 1 to day 21 for both groups. Non-coated group released significantly more fluoride than surface coated group (Pagent will reduce the amount of fluoride released into oral environment as compared to non-coated group and at the same time releasing fluoride into surrounding cavity walls to create zones of inhibition into the cavity floor to help internal remineralization.

  8. 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.

  9. Investigating the correlation between in vivo absorption and in vitro release of fenofibrate from lipid matrix particles in biorelevant medium.

    Science.gov (United States)

    Borkar, Nrupa; Xia, Dengning; Holm, René; Gan, Yong; Müllertz, Anette; Yang, Mingshi; Mu, Huiling

    2014-01-23

    Lipid matrix particles (LMP) may be used as better carriers for poorly water-soluble drugs than liquid lipid carriers because of reduced drug mobilization in the formulations. However, the digestion process of solid lipid particles and their effect on the absorption of poorly water-soluble drugs are not fully understood. This study aimed at investigating the effect of particle size of LMP on drug release in vitro as well as absorption in vivo in order to get a better understanding on the effect of degradation of lipid particles on drug solubilisation and absorption. Fenofibrate, a model poorly water-soluble drug, was incorporated into LMP in this study using probe ultrasound sonication. The resultant LMP were characterised in terms of particle size, size distribution, zeta potential, entrapment efficiency, in vitro lipolysis and in vivo absorption in rat model. LMP of three different particle sizes i.e. approximately 100 nm, 400 nm, and 10 μm (microparticles) were produced with high entrapment efficiencies. The in vitro lipolysis study showed that the recovery of fenofibrate in the aqueous phase for 100 nm and 400 nm LMP was significantly higher (pmicroparticles>control. In summary, the present study demonstrated the particle size dependence of bioavailability of fenofibrate loaded LMP in rat model which correlates well with the in vitro drug release performed in the biorelevant medium. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Induction of histamine release in vitro from rat peritoneal mast cells by extracts of grain dust.

    Science.gov (United States)

    Warren, C P; Holford-Strevens, V

    1986-01-01

    The ability of extracts of grain dust and wheat to induce histamine release from rat peritoneal cells was investigated. Some grain dusts, with a high endotoxin content, were found to produce cytotoxic histamine release. Extract of wheat dust, with a low endotoxin release, produced noncytotoxic histamine release from peritoneal cells but not from purified mast cells. This reaction was dependent on the presence of phosphatidyl serine. The agent did not appear to be a lectin because histamine release was not enhanced by passive sensitization of mast cells with IgE. The activity occurred only over a narrow range of concentrations of the extract of wheat. The cause was unclear. PMID:2423321

  11. Innovation of novel 'Tab in Tab' system for release modulation of milnacipran HCl: optimization, formulation and in vitro investigations.

    Science.gov (United States)

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

    2013-11-01

    The study was aimed toward development of modified release oral drug delivery system for highly water soluble drug, Milnacipran HCl (MH). Novel Tablet in Tablet system (TITs) comprising immediate and extended release dose of MH in different parts was fabricated. The outer shell was composed of admixture of MH, lactose and novel herbal disintegrant obtained from seeds of Lepidium sativum. In the inner core, MH was matrixed with blend of hydrophilic (Benecel®) and hydrophobic (Compritol®) polymers. 3² full factorial design and an artificial neuron network (ANN) were employed for correlating effect of independent variables on dependent variables. The TITs were characterized for pharmacopoeial specifications, in vitro drug release, SEM, drug release kinetics and FTIR study. The release pattern of MH from batch A10 containing 25.17% w/w Benecel® and 8.21% w/w of Compritol® exhibited drug release pattern close proximal to the ideal theoretical profile (t(50%) = 5.92 h, t(75%) = 11.9 h, t(90%) = 18.11 h). The phenomenon of drug release was further explained by concept of percolation and the role of Benecel® and Compritol® in drug release retardation was studied. The normalized error obtained from ANN was less, compared with the multiple regression analysis, and exhibits the higher accuracy in prediction. The results of short-term stability study revealed stable chataracteristics of TITs. SEM study of TITs at different dissolution time points confirmed both diffusion and erosion mechanisms to be operative during drug release from the batch A10. Novel TITs can be a succesful once a day delivery system for highly water soluble drugs.

  12. 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.

  13. Antibiotic-loaded acrylic bone cements: An in vitro study on the release mechanism and its efficacy

    Energy Technology Data Exchange (ETDEWEB)

    Miola, Marta, E-mail: marta.miola@polito.it [Applied Science and Technology Department, Politecnico di Torino (Italy); Bistolfi, Alessandro [Department of Orthopaedics, Traumatology and HM, University of Turin (Italy); AO CTO, M Adelaide Hospital, Turin (Italy); Valsania, Maria Carmen; Bianco, Carlotta [Department of Orthopaedics, Traumatology and HM, University of Turin (Italy); Fucale, Giacomo [Chemical, Clinical and Microbiological Analyses Dept., CTO, Turin (Italy); Verné, Enrica [Applied Science and Technology Department, Politecnico di Torino (Italy)

    2013-07-01

    An in vitro study was carried out in order to investigate the antibiotic release mechanism and the antibacterial properties of commercially (Palacos® R + G and Palacos® LV + G) and manually (Palacos® R + GM and Palacos® LV + GM) blended gentamicin-loaded bone cements. Samples were characterized by means of scanning electron microscopy (SEM) and compression strength was evaluated. The antibiotic release was investigated by dipping sample in simulated body fluid (SBF) and periodically analyzing the solution by means of high pressure liquid chromatography (HPLC). Different antibacterial tests were performed to investigate the possible influence of blending technique on antibacterial properties. Only some differences were observed between gentamicin manually added and commercial ones, in the release curves, while the antibacterial effect and the mechanical properties seem to not feel the blending technique. Highlights: • The efficacy of commercially and manually mixed antibiotic-loaded cements is studied. • Exhaustive mechanical, drug release and antibacterial studies are carried out. • The blending technique does not affect the antibacterial and mechanical properties. • The blending process influences only the release curve, not the released drug amount.

  14. Antibiotic-loaded acrylic bone cements: An in vitro study on the release mechanism and its efficacy

    International Nuclear Information System (INIS)

    Miola, Marta; Bistolfi, Alessandro; Valsania, Maria Carmen; Bianco, Carlotta; Fucale, Giacomo; Verné, Enrica

    2013-01-01

    An in vitro study was carried out in order to investigate the antibiotic release mechanism and the antibacterial properties of commercially (Palacos® R + G and Palacos® LV + G) and manually (Palacos® R + GM and Palacos® LV + GM) blended gentamicin-loaded bone cements. Samples were characterized by means of scanning electron microscopy (SEM) and compression strength was evaluated. The antibiotic release was investigated by dipping sample in simulated body fluid (SBF) and periodically analyzing the solution by means of high pressure liquid chromatography (HPLC). Different antibacterial tests were performed to investigate the possible influence of blending technique on antibacterial properties. Only some differences were observed between gentamicin manually added and commercial ones, in the release curves, while the antibacterial effect and the mechanical properties seem to not feel the blending technique. Highlights: • The efficacy of commercially and manually mixed antibiotic-loaded cements is studied. • Exhaustive mechanical, drug release and antibacterial studies are carried out. • The blending technique does not affect the antibacterial and mechanical properties. • The blending process influences only the release curve, not the released drug amount

  15. 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.

  16. Preparation and In-Vitro Evaluation of Sustained Release Matrix Diclofenac Sodium Tablets Using HPMC KM 100 and Gums

    Directory of Open Access Journals (Sweden)

    Zafar Iqbal, Raza Khan, Fazli Nasir, Jamshaid Ali Khan, Lateef Ahmad, Abad Khan, Yaser Shah

    2010-12-01

    Full Text Available Objectives: The impact of hydroxypropylmethyl cellulose(HPMC K 100M alone and in combination with the guar gum,xanthan gum and gum tragacanth on the release of the diclofenac sodium matrix tablets were evaluated.Materials and Methods: The granules were prepared using wet granulation method and compressed into tablets using different ratio of drug and gum ratio. The physical properties of the tablets were within acceptable pharmacopeial limits.The release profiles of the matrix tablets were evaluated in vitro,using USP dissolution apparatus II (paddle method.Results: The formulations containing HPMC K 100M drug ratio1:1.3 and 1:1.6 and formulations containing HPMC, gum and drug with different ratio also sustained the release of diclofenac sodium for 12 hours. The mechanism of drug release from the matrix tablets was studied using Zero order, First order, Higuchi and Korsmeyer’s models using regression coefficient method. The stability of the selected formulations was evaluated at 40˚C and 70% RH for 6 months.Conclusions: HPMC K100M alone and in combination with natural gums as the retarding material retarded the release upto 12 hours and showed little deviation from the theoretical release pattern.

  17. Hormonal induction of gamete release, and in-vitro fertilisation, in the critically endangered Southern Corroboree Frog, Pseudophryne corroboree

    Directory of Open Access Journals (Sweden)

    Silla Aimee J

    2010-11-01

    Full Text Available Abstract Background Conservation Breeding Programs (CBP's are playing an important role in the protection of critically endangered anuran amphibians, but for many species recruitment is not successful enough to maintain captive populations, or provide individuals for release. In response, there has been an increasing focus on the use of Assisted Reproductive Technologies (ART, including the administration of reproductive hormones to induce gamete release followed by in vitro fertilisation. The objective of this study was to test the efficacy of two exogenous hormones to induce gamete release, for the purpose of conducting in vitro fertilisation (IVF, in one of Australia's most critically endangered frog species, Pseudophryne corroboree. Methods Male frogs were administered a single dose of either human chorionic gonadotropin (hCG or luteinizing hormone-releasing hormone (LHRHa, while female frogs received both a priming and ovulatory dose of LHRHa. Spermiation responses were evaluated at 3, 7, 12, 24, 36, 48, 60 and 72 h post hormone administration (PA, and sperm number and viability were quantified using fluorescent microscopy. Ovulation responses were evaluated by stripping females every 12 h PA for 5 days. Once gametes were obtained, IVF was attempted by combining spermic urine with oocytes in a dilute solution of simplified amphibian ringer (SAR. Results Administration of both hCG and LHRHa induced approximately 80% of males to release sperm over 72 h. Peak sperm release occurred at 12 h PA for hCG treated males and 36 h PA for LHRHa treated males. On average, LHRHa treated males released a significantly higher total number of live sperm, and a higher concentration of sperm, over a longer period. In female frogs, administration of LHRHa induced approximately 30% of individuals to release eggs. On average, eggs were released between 24 and 48 h PA, with a peak in egg release at 36 h PA. IVF resulted in a moderate percentage (54.72% of eggs

  18. 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.

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

    International Nuclear Information System (INIS)

    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 (∼100 m 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

  20. Effect of stage of development and sex on gonadotropin-releasing hormone secretion in in vitro hypothalamic perifusion.

    Science.gov (United States)

    Lacau-Mengido, I M; González Iglesias, A; Díaz-Torga, G; Thyssen-Cano, S; Libertun, C; Becú-Villalobos, D

    1998-04-01

    Marked sexual and ontogenic differences have been described in gonadotropin regulation in the rat. These could arise from events occurring both at the hypothalamic or hypophyseal levels. The present experiments were designed to evaluate the capacity of the hypothalamus in releasing GnRH in vitro, basally and in response to depolarization with KCl, during ontogeny in the rat. To that end we chose two well-defined developmental ages that differ markedly in sexual and ontogenic characteristics of gonadotropin regulation, 15 and 30 days. We compared GnRH release from hypothalami of females, neonatal androgenized females and males. Mediobasal hypothalami were perifused in vitro, and GnRH measured in the effluent. Basal secretion of the decapeptide increased with age in the three groups with no sexual differences encountered. When studying GnRH release induced by membrane depolarization, no differences within sex or age were encountered. On the other hand FSH serum levels decreased with age in females and increased in males, and in neonatal androgenized females followed a similar pattern to that of females. LH levels were higher in infantile females than in age-matched males or androgenized females. Such patterns of gonadotropin release were therefore not correlated to either basal or K+-induced GnRH release from the hypothalamus. We conclude that sexual and ontogenic differences in gonadotropin secretion in the developing rat are not dependent on the intrinsic capability of the hypothalamus to release GnRH in response to membrane depolarization. The hormonal differences observed during development and between sexes are probably related to differences in the sensitivity of the GnRH neuron to specific secretagogue and neurotransmitter regulation, and/or to differences in hypophyseal GnRH receptors and gonadotrope sensitivity.

  1. In Vitro Inhibition of Enamel Demineralisation by Fluoride-releasing Restorative Materials and Dental Adhesives.

    Science.gov (United States)

    Dionysopoulos, Dimitrios; Koliniotou-Koumpia, Eugenia; Helvatzoglou-Antoniades, Maria; Kotsanos, Nikolaos

    2016-01-01

    To determine the ability of 5 contemporary fluoride-releasing restoratives and 3 fluoride-releasing adhesives to inhibit enamel demineralisation surrounding restorations, and the associations between inhibition and the levels of fluoride released from these materials. Five fluoride-releasing restoratives (Fuji IX GP, Ketac N100, Dyract Extra, Beautifil II and Wave) and 3 fluoride-releasing adhesives (Stae, Prime & Bond NT and Fluoro Bond II) were investigated. Eight disks of each material were prepared. Fluoride release was measured daily using a fluoride-ion-selective electrode for 15 days. Twenty-four cavities for each group were restored with a restorative and an adhesive. Specimens were subjected to thermal stress and stored for 30 days in saline solution. After a 15-day pH-cycling regimen, two 150-μm-thick sections were derived from each specimen. Enamel lesion depth was measured at 0, 100, and 200 μm from each restoration's margin via polarised light microscopy. Of the restoratives investigated, Fuji IX GP released the most fluoride. The fluoride-releasing restoratives tested exhibited shallower enamel lesions than did the control group at all distances tested (p < 0.05). Fuji IX GP yielded significantly lower enamel lesion depth than did the other experimental materials. The depths of enamel lesions did not differ significantly when comparing restoratives applied with a fluoride-releasing adhesive with those applied with a non-fluoride-releasing adhesive. The fluoride-releasing materials tested reduced enamel demineralisation but to different extents, depending on their levels of fluoride release. Fluoride-releasing adhesives did not influence enamel lesion formation.

  2. Influence of diphenylhydantoin on lysosomal enzyme release during bone resorption in vitro

    International Nuclear Information System (INIS)

    Lerner, U.; Haenstroem, L.

    1980-01-01

    The effect of diphenylhydantoin (DPH) on the release of lysosomal enzymes during resorption of cultured mouse calvarial bone was studied. The enzyme activities of β-glucuronidase and β-galactosidase in the culture medium was taken as indicators for lysosomal enzyme release. In concentrations 50 μg/ml or higher, DPH inhibited the release of β-glucuronidase and β-galactosidase in parallel with bone resorption as indicated by reduced release of 4 Ca, Ca 2 , Psub(i) and hydroxyproline. The release of the cytosolic enzyme lactate dehydrogenase was not influenced by concentrations of DPH up to 50 μg/ml but higher concentrations caused an increased release indicating cell injury. When bone resorption was stimulated by prostaglandin E 2 , DPH(50 μg/ml) also reduced the mobilization of bone mineral and the release of β- glucuronidase without influencing the release of lactate dehydrogenase. It is suggested that DPH by interfering with cellular release processes reduces the resorption on bone. (author)

  3. Inhibition of histamine and eicosanoid release from dispersed human lung cells in vitro by quinotolast.

    Science.gov (United States)

    Okayama, Y; Hiroi, J; Lau, L C; Church, M K

    1995-12-01

    We have examined the effects of a new anti-allergic drug, quinotolast [sodium 5-(4-oxo-1-phenoxy-4H-quinolizine-3-carboxamido) yetrazolate monohydrate], in inhibiting the release of histamine and the generation of leukotriene (LT) C4 and prostaglandin (PG) D2 from dispersed human lung cells and compared this with those of its active metabolite in the rat, hydroxy quinotolast, and reference drugs, tranilast and sodium cromoglycate (SCG). Quinotolast in the concentration range of 1-100 micrograms/ml inhibited histamine and LTC4 release in a concentration-dependent manner. The inhibitory effect of quinotolast on histamine release from dispersed lung cells was largely independent of the preincubation period, no tachyphylaxis being observed. Hydroxy quinotolast and tranilast showed a weak inhibition of histamine release only when the drugs were added to the cells simultaneously with anti-IgE challenge. Quinotolast, 100 micrograms/ml, and SCG, 1 mM, significantly inhibited PGD2 and LTC4 release. Quinotolast inhibited PGD2 release by 100% and LTC4 release by 54%, whereas SCG inhibited PDG2 release by 33% and LTC4 release by 100%. No cross-tachyphylaxis between quinotolast and SCG was observed. The results demonstrated that quinotolast showed a significant inhibition of inflammatory mediators from human dispersed lung cells, suggesting that quinotolast is a good candidate for a clinical anti-allergic drug.

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

    International Nuclear Information System (INIS)

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

    1985-01-01

    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 [ 3 H]glucosamine (glycosylation) and [ 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 [ 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

  5. Gas retention and release behavior in Hanford double-shell waste tanks

    Energy Technology Data Exchange (ETDEWEB)

    Meyer, P.A.; Brewster, M.E.; Bryan, S.A. [and others

    1997-05-01

    This report describes the current understanding of flammable gas retention and release in Hanford double-shell waste tanks AN-103, AN-104, AN-105, AW-101, SY-101, and SY-103. This knowledge is based on analyses, experimental results, and observations of tank behavior. The applicable data available from the void fraction instrument, retained gas sampler, ball rheometer, tank characterization, and field monitoring are summarized. Retained gas volumes and void fractions are updated with these new data. Using the retained gas compositions from the retained gas sampler, peak dome pressures during a gas burn are calculated as a function of the fraction of retained gas hypothetically released instantaneously into the tank head space. Models and criteria are given for gas generation, initiation of buoyant displacement, and resulting gas release; and predictions are compared with observed tank behavior.

  6. Gas retention and release behavior in Hanford double-shell waste tanks

    International Nuclear Information System (INIS)

    Meyer, P.A.; Brewster, M.E.; Bryan, S.A.

    1997-05-01

    This report describes the current understanding of flammable gas retention and release in Hanford double-shell waste tanks AN-103, AN-104, AN-105, AW-101, SY-101, and SY-103. This knowledge is based on analyses, experimental results, and observations of tank behavior. The applicable data available from the void fraction instrument, retained gas sampler, ball rheometer, tank characterization, and field monitoring are summarized. Retained gas volumes and void fractions are updated with these new data. Using the retained gas compositions from the retained gas sampler, peak dome pressures during a gas burn are calculated as a function of the fraction of retained gas hypothetically released instantaneously into the tank head space. Models and criteria are given for gas generation, initiation of buoyant displacement, and resulting gas release; and predictions are compared with observed tank behavior

  7. Nifedipine-loaded polymeric nanocapsules: validation of a stability-indicating HPLC method to evaluate the drug entrapment efficiency and in vitro release profiles.

    Science.gov (United States)

    Granada, Andréa; Tagliari, Monika Piazzon; Soldi, Valdir; Silva, Marcos António Segatto; Zanetti-Ramos, Betina Ghiel; Fernandes, Daniel; Stulzer, Hellen Karine

    2013-01-01

    A simple stability-indicating analytical method was developed and validated to quantify nifedipine in polymeric nanocapsule suspensions; an in vitro drug release study was then carried out. The analysis was performed using an RP C18 column, UV-Vis detection at 262 nm, and methanol-water (70 + 30, v/v) mobile phase at a flow rate of 1.2 mL/min. The method was validated in terms of specificity, linearity and range, LOQ, accuracy, precision, and robustness. The results obtained were within the acceptable ranges. The nanocapsules, made of poly(epsilon-caprolactone), were prepared by the solvent displacement technique and showed high entrapment efficiency. The entrapment efficiency was 97.6 and 98.2% for the nifedipine-loaded polymeric nanocapsules prepared from polyvinyl alcohol (PVA) and Pluronic F68 (PF68), respectively. The particle size and zeta potential of nanocapsules were found to be influenced by the nature of the stabilizer used. The mean diameter and zeta potential for nanocapsules with PVA and PF68 were 290.9 and 179.9 nm, and -17.7 mV and -32.7 mV, respectively. The two formulations prepared showed a drug release of up to 70% over 4 days. This behavior indicates the viability of this drug delivery system for use as a controlled-release system.

  8. Preparation and evaluation of a timolol maleate drug-resin ophthalmic suspension as a sustained-release formulation in vitro and in vivo.

    Science.gov (United States)

    Qin, Fuhong; Zeng, Li; Zhu, Yongtao; Cao, Jingjing; Wang, Xiaohui; Liu, Wei

    2016-01-01

    The aim of this work was to assess the performance of resin as an ocular delivery system. Timolol maleate (TM) was chosen as the model drug and an ion exchange resin (IER) as the carrier. The drug-resin complex was prepared using an oscillation method and then characterized regarding particle size, zeta potential, morphology, and drug content. After in vitro drug release study and corneal permeation study were performed, in vivo studies were performed in New Zealand albino rabbits using a suspension with particles sized 4.8 ± 1.2 μm and drug loading at 43.00 ± 0.09%. The results indicate that drug released from the drug-resin ophthalmic suspension permeated the cornea and displayed a sustained-release behavior. Drug levels in the ocular tissues after administration of the drug-resin ophthalmic suspension were significantly higher than after treatment with an eye drop formulation but were lower in body tissues and in the plasma. In conclusion, resins have great potential as effective ocular drug delivery carriers to increase ocular bioavailability of timolol while simultaneously reducing systemic drug absorption.

  9. Novel Polyurethane Matrix Systems Reveal a Particular Sustained Release Behavior Studied by Imaging and Computational Modeling.

    Science.gov (United States)

    Campiñez, María Dolores; Caraballo, Isidoro; Puchkov, Maxim; Kuentz, Martin

    2017-07-01

    The aim of the present work was to better understand the drug-release mechanism from sustained release matrices prepared with two new polyurethanes, using a novel in silico formulation tool based on 3-dimensional cellular automata. For this purpose, two polymers and theophylline as model drug were used to prepare binary matrix tablets. Each formulation was simulated in silico, and its release behavior was compared to the experimental drug release profiles. Furthermore, the polymer distributions in the tablets were imaged by scanning electron microscopy (SEM) and the changes produced by the tortuosity were quantified and verified using experimental data. The obtained results showed that the polymers exhibited a surprisingly high ability for controlling drug release at low excipient concentrations (only 10% w/w of excipient controlled the release of drug during almost 8 h). The mesoscopic in silico model helped to reveal how the novel biopolymers were controlling drug release. The mechanism was found to be a special geometrical arrangement of the excipient particles, creating an almost continuous barrier surrounding the drug in a very effective way, comparable to lipid or waxy excipients but with the advantages of a much higher compactability, stability, and absence of excipient polymorphism.

  10. 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.

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

    International Nuclear Information System (INIS)

    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 -4 M AA was administered for 20 min before a 10 min, 10 -10 M GnRH pulse. Like cortisol, chloroquine also failed to inhibit AA-induced LH release. Perifusion with 10 -6 M cortisol for 6.0 hours significantly (p 3 ]AA release 24% below the basal (100%) [ 3 H]AA secretion. Reduction of [ 3 H]AA release was accompanied by decreased GnRH-stimulated LH secretion

  12. 3D bioprinting matrices with controlled pore structure and release function guide in vitro self-organization of sweat gland.

    Science.gov (United States)

    Liu, Nanbo; Huang, Sha; Yao, Bin; Xie, Jiangfan; Wu, Xu; Fu, Xiaobing

    2016-10-03

    3D bioprinting matrices are novel platforms for tissue regeneration. Tissue self-organization is a critical process during regeneration that implies the features of organogenesis. However, it is not clear from the current evidences whether 3D printed construct plays a role in guiding tissue self-organization in vitro. Based on our previous study, we bioprinted a 3D matrix as the restrictive niche for direct sweat gland differentiation of epidermal progenitors by different pore structure (300-μm or 400-μm nozzle diameters printed) and reported a long-term gradual transition of differentiated cells into glandular morphogenesis occurs within the 3D construct in vitro. At the initial 14-day culture, an accelerated cell differentiation was achieved with inductive cues released along with gelatin reduction. After protein release completed, the 3D construct guide the self-organized formation of sweat gland tissues, which is similar to that of the natural developmental process. However, glandular morphogenesis was only observed in 300-μm-printed constructs. In the absence of 3D architectural support, glandular morphogenesis was not occurred. This striking finding made us to identify a previously unknown role of the 3D-printed structure in glandular tissue regeneration, and this self-organizing strategy can be applied to forming other tissues in vitro.

  13. Metal release profiles of orthodontic bands, brackets, and wires: an in vitro study.

    Science.gov (United States)

    Wendl, B; Wiltsche, H; Lankmayr, E; Winsauer, H; Walter, A; Muchitsch, A; Jakse, N; Wendl, M; Wendl, T

    2017-11-01

    The present study evaluated the temporal release of Co Cr, Mn, and Ni from the components of a typical orthodontic appliance during simulated orthodontic treatment. Several commercially available types of bands, brackets, and wires were exposed to an artificial saliva solution for at least 44 days and the metals released were quantified in regular intervals using inductively coupled plasma quadrupole mass spectrometry (ICP-MS, Elan DRC+, Perkin Elmer, USA). Corrosion products encountered on some products were investigated by a scanning electron microscope equipped with an energy dispersive X-ray microanalyzer (EDX). Bands released the largest quantities of Co, Cr, Mn, and Ni, followed by brackets and wires. Three different temporal metal release profiles were observed: (1) constant, though not necessarily linear release, (2) saturation (metal release stopped after a certain time), and (3) an intermediate release profile that showed signs of saturation without reaching saturation. These temporal metal liberation profiles were found to be strongly dependent on the individual test pieces. The corrosion products which developed on some of the bands after a 6-month immersion in artificial saliva and the different metal release profiles of the investigated bands were traced back to different attachments welded onto the bands. The use of constant release rates will clearly underestimate metal intake by the patient during the first couple of days and overestimate exposure during the remainder of the treatment which is usually several months long. While our data are consistent with heavy metal release by orthodontic materials at levels well below typical dietary intake, we nevertheless recommend the use of titanium brackets and replacement of the band with a tube in cases of severe Ni or Cr allergy.

  14. In vitro histamine release from basophils of asthmatic and atopic individuals in D2O

    International Nuclear Information System (INIS)

    Tung, R.; Lichtenstein, L.M.

    1982-01-01

    It was found that spontaneous histamine release from human basophils in H 2 O-based buffers is negligible; in D 2 O-based buffers, however, release is observed with the cells of some donors. Analysis of this phenomenon revealed release from the basophils of 1 of 22 control individuals (5%), 15 of 47 patients with allergic rhinitis (32%), and 14 of 20 asthmatic patients (70%). The difference between both patient groups and controls and between atopics and asthmatics was highly significant. That D 2 O release was not cytotoxic is suggested by the finding that 37 0 was optimal, with inhibition at 4 0 C or 46 0 C as well as by EDTA, 2-deoxyglucose, and dibromoacetophenone, an inhibitor of phospholipase A 2 . The release mechanism was unusual in that dibutyryl cAMP and agonists that cause an increase in cAMP lead to no inhibition. No correlation was noted between the total serum IgE level (and thus the number of IgE receptors on the basophil surface) and the magnitude of D 2 O release. No increase in D 2 O release was observed in 17 ragweed-sensitive patients through a ragweed season. A unique property of D 2 O release was the loss of reactivity by preincubating cells at 37 0 C for 30 min before adding D 2 O. Non-D 2 O-reactive cells could be ''converted'' to D 2 O-reactive cells by incubation with antigen in the whole blood phase during leukocyte isolation; these cells showed the same loss of releaseability at 37 0 C and an inhibitor profile similar to D 2 O-responsive cells from ragweed allergic or asthmatic patients. We suggest that D 2 O-based buffers reveal, in atopic and asthmatic patients, in vivo basophil activation; whether this is due to IgE cross-links, to C split products, or to other stimuli is not yet clear

  15. UV imaging for in vitro dissolution and release studies: Initial experiences

    DEFF Research Database (Denmark)

    Østergaard, Jesper; Lenke, James; Jensen, Sabrine Smedegaard

    2014-01-01

    UV imaging has recently been introduced as a method in drug dissolution and release testing. Spatially and temporally resolved mapping of drug oncentrations in a 7 × 9 mm imaging area provides new opportunities for visualization and study of drug dissolution and release. This review describes...... in hydrogels with relevance for characterization of parenteral depots. UV imaging may be of particular use when the amounts of material are sparse and detailed insights into dissolution and release processes are required, that is in solid form screening, preformulation, and early drug development....

  16. Comparison of in vitro histamine release by ionic and nonionic radiographyic contrast media

    International Nuclear Information System (INIS)

    Faraj, B.A.; Martin, L.G.

    1989-01-01

    This paper discusses a study whose results showed that in 53 hospitalized patients undergoing cardiovascular catheterization, incubation of their blood samples with varying concentrations of an ionic contrast medium (Angiovist-370, 60--631 mM) induced a significant (P < .005) amount of histamine release from whole blood (3.5%--10%), as compared with the histamine release following incubation with a nonionic contrast medium. Data suggest that the use of nonionic contrast media may induce minimal histamine release and thereby involve less patient risk from the histamine-mediated allergic and hemodynamic side effects associated with radiographic contrast media procedures

  17. In vitro chemopreventive properties of peptides released from quinoa (Chenopodium quinoa Willd.) protein under simulated gastrointestinal digestion.

    Science.gov (United States)

    Vilcacundo, Rubén; Miralles, Beatriz; Carrillo, Wilman; Hernández-Ledesma, Blanca

    2018-03-01

    Because of the continuous and direct interaction between the digestive tract and foods, dietary compounds represent an interesting source of chemopreventive agents for gastrointestinal health. In this study, the influence of a standardized static in vitro gastrointestinal digestion model on the release of peptides with chemopreventive potential from quinoa protein was investigated. Gastroduodenal digests and fractions collected by ultrafiltration were evaluated for their in plate oxygen radical absorbance capacity and in vitro colon cancer cell viability inhibitory activity. Highest effects were observed in the digests obtained during the intestinal phase, with fraction containing peptides 5kDa showing the greatest anti-cancer effects. Seventeen potential bioactive peptides derived from quinoa proteins have been identified. These proteins might be utilized as new ingredients in the development of functional foods or nutraceuticals with the aim of reducing oxidative stress-associated diseases, including cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    African Journals Online (AJOL)

    HP

    applied to study the effect of polymers used on drug release from the DHL. The tablets were ... A fair correlation between the dissolution profile and bioavailability for ... The results also indicate that the approach used could lead to a successful.

  19. PIXE investigation of in-vitro release of chloramphenicol across polyvinyl alcohol/ acrylamide hydrogel

    International Nuclear Information System (INIS)

    Rihawi, M.; Al-Zeer, A.; Allaf, A.

    2012-01-01

    Hydrogels based on polyvinyl alcohol (PVA) and different amounts of acrylamide monomer (AAm) were prepared by thermal crosslinking process in solid state. The PVA/AAm hydrogels were investigated for drug delivery system applications. Chloramphenicol was adopted as a model drug to study its release behaviour across the prepared hydrogels. Particle induced X-ray emission (PIXE) analytical technique was utilized to study the drug release behaviour across the hydrogels. A comparison study between PIXE and UV measurements was performed. FTIR measurements were carried out to perform the molecular characterization. The releasing behaviour of the drug across the hydrogels demonstrates a decrease and a subsequent increase in the drug release rate, as the AAm amount increases. The FTIR characterization of the prepared hydrogels has shown a competitive behaviour between the crosslinking of PVA with AAm monomer or oligomerized AAm, depending on the amount of AAm added to prepare the PVA/AAm hydrogels. (author)

  20. The effect of additives on release and in vitro skin retention of flavonoids from emulsion and gel semisolid formulations.

    Science.gov (United States)

    Dyja, R; Jankowski, A

    2017-08-01

    To assess the effect of two different additives (propylene glycol (PG) and polyethylene glycol 400 (PEG 400)) on release and in vitro skin retention of quercetin and chrysin from semisolid bases (amphiphilic creams and acidic carbomer gels). For obtaining semisolid formulations, flavonoids were pre-dissolved in the liquid (PG or PEG 400) or directly suspended in the semisolid base. Three chrysin formulations ('cream 0', 'PG-cream' and 'PEG 400-cream') and five quercetin formulations ('cream 0', 'PG cream', 'PEG 400 cream', 'gel 0' and 'PG gel') were prepared. The release studies were carried out in Franz diffusion cells by means of a cellulose membrane. The porcine ear skin was used in in vitro skin retention studies. The dissolution was a prerequisite to increase the release rates of tested flavonoids from obtained semisolid formulations. The cumulative amount of chrysin released after 6 h from 'PEG 400 cream' containing partly dissolved form of that flavonoid was higher than that from 'cream 0' or 'PG cream' containing its suspended form. The formulations containing quercetin dissolved in PG ('PG cream', 'PG gel') or PEG 400 ('PEG 400 cream') exhibited higher release rates of that flavonoid than corresponding semisolid suspensions ('cream 0' or 'gel 0'). The effects of both liquid additives (PG and PEG 400) on the cumulative amount of quercetin released after 6 h were comparable. However, there was no correlation between the release rate and the skin retention. The amounts of the flavonoids found in the skin were strongly affected by the type of the used solvent. While PG increased the skin retention of both flavonoids, PEG 400 had no effect on chrysin skin retention and delayed quercetin skin absorption. The proper choice of the solvent added to the semisolid base is crucial for enhanced skin delivery of the tested flavonoids. PG is more efficient absorption promoter than PEG 400 of both chrysin and quercetin. © 2017 Society of Cosmetic Scientists and the Soci

  1. Fabrication, characterization, in vitro drug release and glucose uptake activity of 14-deoxy, 11, 12-didehydroandrographolide loaded polycaprolactone nanoparticles

    Directory of Open Access Journals (Sweden)

    Nagalakshmi Kamaraj

    2017-07-01

    Full Text Available Biodegradable polymer based novel drug delivery systems brought a considerable attention in enhancing the therapeutic efficacy and bioavailability of various drugs. 14-deoxy 11, 12-didehydro andrographolide (poorly water soluble compound loaded polycaprolactone (nano-DDA was synthesized using the solvent evaporation technique. Nano-DDA was characterized by scanning electron microscopy (SEM and dynamic light scattering (DLS studies. Fourier Transform InfraRed Spectroscopy (FTIR was used to investigate the structural interaction between the drug and the polymer. Functional characterization of the formulation was determined using drug content, cellular uptake and in vitro drug release. 2-deoxy-D-[1-3H] glucose uptake assay was carried out to assess the antidiabetic potential of nano-DDA in L6 myotubes. The nano-DDA displayed spherical shape with a smooth surface (252.898 nm diameter, zeta potential, encapsulation and loading efficiencies of −38.9 mV, 91.98 ± 0.13% and 15.09 ± 0.18% respectively. No structural alteration between the drug and the polymer was evidenced (FTIR analysis. Confocal microscopy studies with rhodamine 123 loaded polycaprolactone nanoparticles (Rh123-PCL NPs revealed the internalization of Rh123-PCL NPs in a time dependent manner in L6 myoblasts. A dose dependent increase in glucose uptake was observed for nano-DDA with a maximal uptake of 108.54 ± 1.42% at 100 nM on L6 myotubes, thereby proving its anti-diabetic efficacy. A biphasic pattern of in vitro drug release demonstrated an initial burst release at 24 h followed by a sustained release for up to 11 days. To conclude, our results revealed that nano-DDA formulation can be a potent candidate for antidiabetic drug delivery.

  2. 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

  3. In vitro study of vancomycin release and osteoblast-like cell growth on structured calcium phosphate-collagen

    International Nuclear Information System (INIS)

    Pon-On, Weeraphat; Charoenphandhu, Narattaphol; Teerapornpuntakit, Jarinthorn; Thongbunchoo, Jirawan; Krishnamra, Nateetip; Tang, I-Ming

    2013-01-01

    A drug delivery vehicle consisting of spherical calcium phosphate-collagen particles covered by flower-like (SFCaPCol) blossoms composed of nanorod building blocks and their cellular response is studied. The spherical structure was achieved by a combination of sonication and freeze-drying. The SFCaPCol blossoms have a high surface area of approximately 280 m 2 g −1 . The blossom-like formation having a high surface area allows a drug loading efficiency of 77.82%. The release profile for one drug, vancomycin (VCM), shows long term sustained release in simulated body fluid (SBF), in a phosphate buffer saline (PBS, pH 7.4) solution and in culture media over 2 weeks with a cumulative release ∼ 53%, 75% and 50%, respectively, over the first 7 days. The biocompatibility of the VCM-loaded SFCaPCol scaffold was determined by in vitro cell adhesion and proliferation tests of rat osteoblast-like UMR-106 cells. MTT tests indicated that UMR-106 cells were viable after exposure to the VCM loaded SFCaPCol, meaning that the scaffold (the flower-like blossoms) did not impair the cell's viability. The density of cells on the substrate was seen to increase with increasing cultured time. - Graphical abstract: A spherical calcium phosphate-collagen with flower-like blossoms consisting of nanorod building blocks (SFCaPCol) particles was achieved by a combination of sonication and freeze-drying. In vitro drug release profile and the biocompatibility of the VCM-loaded SFCaPCol composite cell adhesion and proliferation in rat osteoblast-like UMR-106 cells were determined for biomaterial applications. Highlights: ► SFCaPCol and VCM-loaded SFCaPCol composite were synthesized by a combination of ultra sonication and freeze-drying. ► VCM drug-loaded SFCaPCol composite was used as substrate for the growth of rat osteoblast-like UMR-106 cells. ► Controlled release of VCM from the composite is critically medium dependent. ► The VCM-loaded SFCaPCol composite is also bioactive by in

  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. Microemulsion-Based Mucoadhesive Buccal Wafers: Wafer Formation, In Vitro Release, and Ex Vivo Evaluation.

    Science.gov (United States)

    Pham, Minh Nguyet; Van Vo, Toi; Tran, Van-Thanh; Tran, Phuong Ha-Lien; Tran, Thao Truong-Dinh

    2017-10-01

    Microemulsion has the potentials to enhance dissolution as well as facilitate absorption and permeation of poorly water-soluble drugs through biological membranes. However, its application to govern a controlled release buccal delivery for local treatment has not been discovered. The aim of this study is to develop microemulsion-based mucoadhesive wafers for buccal delivery based on an incorporation of the microemulsion with mucoadhesive agents and mannitol. Ratio of oil to surfactant to water in the microemulsion significantly impacted quality of the wafers. Furthermore, the combination of carbopol and mannitol played a key role in forming the desired buccal wafers. The addition of an extra 50% of water to the formulation was suitable for wafer formation by freeze-drying, which affected the appearance and distribution of carbopol in the wafers. The amount of carbopol was critical for the enhancement of mucoadhesive properties and the sustained drug release patterns. Release study presented a significant improvement of the drug release profile following sustained release for 6 h. Ex vivo mucoadhesive studies provided decisive evidence to the increased retention time of wafers along with the increased carbopol content. The success of this study indicates an encouraging strategy to formulate a controlled drug delivery system by incorporating microemulsions into mucoadhesive wafers.

  6. In vitro release of metformin hydrochloride from sodium alginate/polyvinyl alcohol hydrogels.

    Science.gov (United States)

    Martínez-Gómez, Fabián; Guerrero, Juan; Matsuhiro, Betty; Pavez, Jorge

    2017-01-02

    Hydrogels, based on polysaccharides have found a number of applications as drug delivery carriers. In this work, hydrogels of full characterized sodium alginate (Mn 87,400g/mol) and commercial poly(vinyl alcohol) (PVA) sensitive to pH and temperature stimuli were obtained using a simple, controlled, green, low cost method based on freeze-thaw cycles. Stable hydrogels of sodium alginate/PVA with 0.5:1.5 and 1.0:1.0w/v concentrations showed very good swelling ratio values in distilled water (14 and 20g/g, respectively). Encapsulation and release of metformin hydrochloride in hydrogels of 1.0:1.0w/v sodium alginate/PVA was followed by UV spectroscopy. The hydrogel released a very low amount of metformin hydrochloride at pH 1.2; the highest release value (55%) was obtained after 6h at pH 8.0. Also, the release of metformin hydrochloride was studied by 1 H NMR spectroscopy, the temporal evolution of methyl group signals of metformin showed 30% of drug release after 3h. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. In vitro release of arachidonic acid and in vivo responses to respirable fractions of cotton dust

    International Nuclear Information System (INIS)

    Thomson, T.A.; Edwards, J.H.; Al-Zubaidy, T.S.; Brown, R.C.; Poole, A.; Nicholls, P.J.

    1986-01-01

    It was considered that the fall in lung function seen after exposure to cotton dust may be attributable in part to the activity of arachidonic acid metabolites, such as leucotrienes as well as to the more established release of histamine by cotton dust. However, we found that cotton and barley dusts elicited poor release of arachidonic acid from an established macrophage like cell line compared with that observed with other organic dusts. In the experimental animal, pulmonary cellular responses to both cotton and barley dust were similar to those evoked by moldy hay and pigeon dropping dusts, although after multiple doses a more severe response was seen to cotton and barley. Since both moldy hay and pigeon droppings elicit a greater arachidonic acid release than cotton or barley, a role for arachidonic acid in inducing the cellular response is less likely than other factors. There are limitations to our conclusions using this system, i.e., the arachidonic acid may be released in a nonmetabolized form, although it is noted that the two dusts with the greatest arachidonic acid release produce their clinical responses in humans largely by hypersensitivity mechanisms

  8. Growth factor delivery: How surface interactions modulate release in vitro and in vivo

    Science.gov (United States)

    King, William J.; Krebsbach, Paul H.

    2013-01-01

    Biomaterial scaffolds have been extensively used to deliver growth factors to induce new bone formation. The pharmacokinetics of growth factor delivery has been a critical regulator of their clinical success. This review will focus on the surface interactions that control the non-covalent incorporation of growth factors into scaffolds and the mechanisms that control growth factor release from clinically relevant biomaterials. We will focus on the delivery of recombinant human bone morphogenetic protein-2 from materials currently used in the clinical practice, but also suggest how general mechanisms that control growth factor incorporation and release delineated with this growth factor could extend to other systems. A better understanding of the changing mechanisms that control growth factor release during the different stages of preclinical development could instruct the development of future scaffolds for currently untreatable injuries and diseases. PMID:22433783

  9. Models for recurrent gas release event behavior in hazardous waste tanks

    International Nuclear Information System (INIS)

    Anderson, D.N.; Arnold, B.C.

    1994-08-01

    Certain radioactive waste storage tanks at the United States Department of Energy Hanford facilities continuously generate gases as a result of radiolysis and chemical reactions. The congealed sludge in these tanks traps the gases and causes the level of the waste within the tanks to rise. The waste level continues to rise until the sludge becomes buoyant and ''rolls over'', changing places with heavier fluid on top. During a rollover, the trapped gases are released, resulting, in a sudden drop in the waste level. This is known as a gas release event (GRE). After a GRE, the wastes leading to another GRE. We present nonlinear time waste re-congeals and gas again accumulates leading to another GRE. We present nonlinear time series models that produce simulated sample paths that closely resemble the temporal history of waste levels in these tanks. The models also imitate the random GRE, behavior observed in the temporal waste level history of a storage tank. We are interested in using the structure of these models to understand the probabilistic behavior of the random variable ''time between consecutive GRE's''. Understanding the stochastic nature of this random variable is important because the hydrogen and nitrous oxide gases released from a GRE, are flammable and the ammonia that is released is a health risk. From a safety perspective, activity around such waste tanks should be halted when a GRE is imminent. With credible GRE models, we can establish time windows in which waste tank research and maintenance activities can be safely performed

  10. 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

  11. Corticotropine-releasing hormone and/or corticosterone differentially affect behavior of rat

    Czech Academy of Sciences Publication Activity Database

    Valeš, Karel; Řezáčová, Lenka; Stuchlík, Aleš

    2008-01-01

    Roč. 11, Suppl.1 (2008), s. 118-118 ISSN 1461-1457. [CINP Congress /26./. 13.07.2008-17.07.2008, Munich] R&D Projects: GA MŠk(CZ) 1M0517; GA MZd NR9180; GA ČR(CZ) GA309/07/0341 Institutional research plan: CEZ:AV0Z50110509 Keywords : cpo1 * corticotropine-releasing hormone * corticosterone * behavior Subject RIV: FH - Neurology

  12. 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.

  13. Metal release behavior of surface oxidized stainless steels into flowing high temperature pure water

    International Nuclear Information System (INIS)

    Fujiwara, Kazuo; Tomari, Haruo; Nakayama, Takenori; Shimogori, Kazutoshi; Ishigure, Kenkichi; Matsuura, Chihiro; Fujita, Norihiko; Ono, Shoichi.

    1987-01-01

    In order to clarify the effect of oxidation treatment of Type 304 SS on the inhibition of metal release into high temperature pure water, metal release rate of individual alloying element into flowing deionized water containing 50 ppb dissolved oxygen was measured as the function of exposure time on representative specimens oxidized in air and steam. The behavior of metal release was also discussed in relation to the structure of surface films. Among the alloying elements the amount of Fe ion, Cr ion and Fe crud in high temperature pure water tended to saturate with the exposure time and that of Ni ion and Co ion tended to increase monotonously with the exposure time for all specimens tested. And the treatment of steam-oxidation was the most effective to decrease the metal release of alloying elements and the treatment by air-oxidation also decreased the metal release. These tendencies were confirmed to correlate well with the structure of the surface films as it was in the results in the static autoclave test. (author)

  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. 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.

  16. 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.

  17. 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...

  18. 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.

  19. 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®.

  20. The effects of cyclodextrins on drug release from fatty suppository bases : I. In vitro observations

    NARCIS (Netherlands)

    Frijlink, H.W.; Eissens, Anko; Schoonen, Adelbert; Lerk, C.F.

    The effect of cyclodextrins on suppository drug release was investigated. Complexes of several lipophilic drugs with β- and/or γ-cyclodextrin were prepared using the coprecipitation method. The formation of true complexes was confirmed by DSC and an 'ether-wash' method. Witepsol H15 suppositories

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

    African Journals Online (AJOL)

    HP

    ISSN: 1596-5996 (print); 1596-9827 (electronic). © Pharmacotherapy ... (DHL). Methods: DHL tablets were prepared by direct compression and consisted of .... subjected to 3D response surface methodology to determine the .... Table 3: Release of diltiazem HCl from the test formulations as per factorial design. Formulation ...

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

    African Journals Online (AJOL)

    HP

    2013-07-15

    Jul 15, 2013 ... They are generally used to treat high blood pressure ... extending drug release for highly water-soluble drugs is limited ..... by the high water permeability of Kollidon SR while the ... due to the extremely low water solubility of.

  3. 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.

  4. 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.

  5. In vitro drug release and biological evaluation of biomimetic polymeric micelles self-assembled from amphiphilic deoxycholic acid–phosphorylcholine–chitosan conjugate

    International Nuclear Information System (INIS)

    Wu, Minming; Guo, Kai; Dong, Hongwei; Zeng, Rong; Tu, Mei; Zhao, Jianhao

    2014-01-01

    Novel biomimetic amphiphilic chitosan derivative, deoxycholic acid–phosphorylcholine–chitosan conjugate (DCA–PCCs) was synthesized based on the combination of Atherton–Todd reaction for coupling phosphorylcholine (PC) and carbodiimide coupling reaction for linking deoxycholic acid (DCA) to chitosan. The chemical structure of DCA–PCCs was characterized by 1 H and 31 P nuclear magnetic resonance (NMR). The self-assembly of DCA–PCCs in water was analyzed by fluorescence measurements, dynamic laser light-scattering (DLS), zeta potential and transmission electron microscopy (TEM) technologies. The results confirmed that the amphiphilic DCA–PCCs can self-assemble to form nanosized spherical micelles with biomimetic PC shell. In vitro biological evaluation revealed that DCA–PCCs micelles had low toxicity against NIH/3T3 mouse embryonic fibroblasts as well as good hemocompatibility. Using quercetin as a hydrophobic model drug, drug loading and release study suggested that biomimetic DCA–PCCs micelles could be used as a promising nanocarrier avoiding unfavorable biological response for hydrophobic drug delivery applications. - Highlights: • DCA–PCCs with phosphorylcholine and deoxycholic acid was synthesized. • DCA–PCCs can self-assemble to form spherical micelles in aqueous system. • DCA–PCCs micelles had excellent cytocompatibility and hemocompatibility. • DCA–PCCs micelles loaded with quercetin exhibited a sustained drug release behavior

  6. In vitro drug release and biological evaluation of biomimetic polymeric micelles self-assembled from amphiphilic deoxycholic acid–phosphorylcholine–chitosan conjugate

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Minming; Guo, Kai; Dong, Hongwei; Zeng, Rong, E-mail: tzengronga@jnu.edu.cn; Tu, Mei; Zhao, Jianhao

    2014-12-01

    Novel biomimetic amphiphilic chitosan derivative, deoxycholic acid–phosphorylcholine–chitosan conjugate (DCA–PCCs) was synthesized based on the combination of Atherton–Todd reaction for coupling phosphorylcholine (PC) and carbodiimide coupling reaction for linking deoxycholic acid (DCA) to chitosan. The chemical structure of DCA–PCCs was characterized by {sup 1}H and {sup 31}P nuclear magnetic resonance (NMR). The self-assembly of DCA–PCCs in water was analyzed by fluorescence measurements, dynamic laser light-scattering (DLS), zeta potential and transmission electron microscopy (TEM) technologies. The results confirmed that the amphiphilic DCA–PCCs can self-assemble to form nanosized spherical micelles with biomimetic PC shell. In vitro biological evaluation revealed that DCA–PCCs micelles had low toxicity against NIH/3T3 mouse embryonic fibroblasts as well as good hemocompatibility. Using quercetin as a hydrophobic model drug, drug loading and release study suggested that biomimetic DCA–PCCs micelles could be used as a promising nanocarrier avoiding unfavorable biological response for hydrophobic drug delivery applications. - Highlights: • DCA–PCCs with phosphorylcholine and deoxycholic acid was synthesized. • DCA–PCCs can self-assemble to form spherical micelles in aqueous system. • DCA–PCCs micelles had excellent cytocompatibility and hemocompatibility. • DCA–PCCs micelles loaded with quercetin exhibited a sustained drug release behavior.

  7. A Status of Art-Report on the Fission Products Behavior Released from Spent Fuel at High Temperature Conditions

    International Nuclear Information System (INIS)

    Park, Geun Il; Kim, J. H.; Lee, J. W.

    2003-04-01

    The experiments on the fission products release behavior from spent fuel at high temperature assuming reactor accident conditions have been carried out at Oak Ridge Nation Laboratory of USA in HI/VI tests, CEA of France in HEVA/VERCOS tests, AEA of England and CRNL of Canada in HOX test. The VEGA program to study the fission product release behavior from LWR irradiated fuel was recently initiated at JAERI. The key parameter affecting the fission product(FP) release behavior is temperature. In addition, other parameters such as fuel oxidation, burnup, pre-transient conditions are found to affect the FP releases considerably in the earlier tests. The atmosphere conditions such as oxidizing atmosphere (steam or air) or reducing atmosphere (hydrogen) can cause significant change of FPs release and transport behavior due to chemical forms of the reactive FPs which is dependent on the oxidation potential. The effect of fuel burnup on the Kr-85 or Cs-137 release showed that the release rates of these radionuclides increased with the increase of burnup, meaning that release rates are dominated by the atomic diffusions in the grains and they are primarily a function of temperature. However, the data on FPs release behavior using higher burnups above 50,000 MWD/MTU are not so many reported up to now. This report summarizes the test results of FPs release behavior in reactor accident conditions produced from other countries mentioned above. This review and analysis on earlier studies would be useful for predicting the release characteristics of FPs from domestic spent fuel. The release rates of fission gas or FPs from spent fuel at high temperature conditions during fabrication process of dry recycling fuel were also analyzed using many data obtained from earlier tests

  8. 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.

  9. 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.

  10. The content of DNA and RNA in microparticles released by Jurkat and HL-60 cells undergoing in vitro apoptosis

    International Nuclear Information System (INIS)

    Reich, Charles F.; Pisetsky, David S.

    2009-01-01

    Microparticles are small membrane-bound vesicles that are released from apoptotic cells during blebbing. These particles contain DNA and RNA and display important functional activities, including immune system activation. Furthermore, nucleic acids inside the particle can be analyzed as biomarkers in a variety of disease states. To elucidate the nature of microparticle nucleic acids, DNA and RNA released in microparticles from the Jurkat T and HL-60 promyelocytic cell lines undergoing apoptosis in vitro were studied. Microparticles were isolated from culture media by differential centrifugation and characterized by flow cytometry and molecular approaches. In these particles, DNA showed laddering by gel electrophoresis and was present in a form that allowed direct binding by a monoclonal anti-DNA antibody, suggesting antigen accessibility even without fixation. Analysis of RNA by gel electrophoresis showed intact 18s and 28s ribosomal RNA bands, although lower molecular bands consistent with 28s ribosomal RNA degradation products were also present. Particles also contained messenger RNA as shown by RT-PCR amplification of sequences for β-actin and GAPDH. In addition, gel electrophoresis showed the presence of low molecular weight RNA in the size range of microRNA. Together, these results indicate that microparticles from apoptotic Jurkat and HL-60 cells contain diverse nucleic acid species, indicating translocation of both nuclear and cytoplasmic DNA and RNA as particle release occurs during death

  11. Impact of human milk pasteurization on the kinetics of peptide release during in vitro dynamic term newborn digestion.

    Science.gov (United States)

    Deglaire, Amélie; De Oliveira, Samira C; Jardin, Julien; Briard-Bion, Valérie; Emily, Mathieu; Ménard, Olivia; Bourlieu, Claire; Dupont, Didier

    2016-07-01

    Holder pasteurization (62.5°C, 30 min) ensures sanitary quality of donor's human milk but also denatures beneficial proteins. Understanding whether this further impacts the kinetics of peptide release during gastrointestinal digestion of human milk was the aim of the present paper. Mature raw (RHM) or pasteurized (PHM) human milk were digested (RHM, n = 2; PHM, n = 3) by an in vitro dynamic system (term stage). Label-free quantitative peptidomics was performed on milk and digesta (ten time points). Ascending hierarchical clustering was conducted on "Pasteurization × Digestion time" interaction coefficients. Preproteolysis occurred in human milk (159 unique peptides; RHM: 91, PHM: 151), mostly on β-casein (88% of the endogenous peptides). The predicted cleavage number increased with pasteurization, potentially through plasmin activation (plasmin cleavages: RHM, 53; PHM, 76). During digestion, eight clusters resumed 1054 peptides from RHM and PHM, originating for 49% of them from β-casein. For seven clusters (57% of peptides), the kinetics of peptide release differed between RHM and PHM. The parent protein was significantly linked to the clustering (p-value = 1.4 E-09), with β-casein and lactoferrin associated to clusters in an opposite manner. Pasteurization impacted selectively gastric and intestinal kinetics of peptide release in term newborns, which may have further nutritional consequences. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Modelling of fission product release behavior from HTR spherical fuel elements under accident conditions

    International Nuclear Information System (INIS)

    Verfondern, K.; Mueller, D.

    1991-01-01

    Computer codes for modelling the fission product release behavior of spherical fuel elements for High Temperature Reactors (HTR) have been developed for the purpose of being used in risk analyses for HTRs. An important part of the validation and verification procedure for these calculation models is the theoretical investigation of accident simulation experiments which have been conducted in the KueFA test facility in the Hot Cells at KFA. The paper gives a presentation of the basic modeling and the calculational results of fission product release from modern German HTR fuel elements in the temperature range 1600-1800 deg. C using the TRISO coated particle failure model PANAMA and the diffusion model FRESCO. Measurements of the transient release behavior for cesium and strontium and of their concentration profiles after heating have provided informations about diffusion data in the important retention barriers of the fuel: silicon carbide and matrix graphite. It could be shown that the diffusion coefficients of both cesium and strontium in silicon carbide can significantly be reduced using a factor in the range of 0.02 - 0.15 compared to older HTR fuel. Also in the development of fuel element graphite, a tendency towards lower diffusion coefficients for both nuclides can be derived. Special heating tests focussing on the fission gases and iodine release from the matrix contamination have been evaluated to derive corresponding effective diffusion data for iodine in fuel element graphite which are more realistic than the iodine transport data used so far. Finally, a prediction of krypton and cesium release from spherical fuel elements under heating conditions will be given for fuel elements which at present are irradiated in the FRJ2, Juelich, and which are intended to be heated at 1600/1800 deg. C in the KueFA furnace in near future. (author). 7 refs, 11 figs

  13. 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

  14. Preparation, characterization, and in vitro release study of albendazole-encapsulated nanosize liposomes

    OpenAIRE

    Panwar, Preety; Pandey, Bhumika; Lakhera, P C; Singh, K P

    2010-01-01

    Preety Panwar1, Bhumika Pandey1, P C Lakhera2, K P Singh11Biophysics and Nanotechnology Research Laboratory, CBSH, G.B. Pant University of Agriculture and Technology, Pantnagar, Uttarakhand, India; 2Department of Biotechnology, H.N.B. Garhwal University, Srinagar Garhwal, Uttarakhand, IndiaAbstract: The purpose of the present study was to formulate effective and controlled release albendazole liposomal formulations. Albendazole, a hydrophobic drug used for the treatment of hydatid cysts, was ...

  15. The enhanced radiation response of an in vitro tumour model by cyanide released from hydrolysed amygdalin

    International Nuclear Information System (INIS)

    Biaglow, J.E.; Durand, R.E.

    1978-01-01

    Any inhibition of oxygen consumption by respiring cells should result in indirect radiosensitization of the more centrally located hypoxic cells of a tumour. Amygdalin (D-mandelonitrile-β-D-glucosido-6-β-D-glucoside) when hydrolysed by the enzyme β-D-glucoside glycohydrolase (β-glucosidase) releases the respiratory inhibitor cyanide. A study has been made of the conditions for enhancing the gamma radiation response of multi-cell spheroids of V79 cells by cyanide or by cyanide released by enzymatic hydrolysis of amygdalin. Amygdalin hydrolysis was monitored by the increase in absorbancy at 250nm (production of benzaldehyde). Oxygen utilization was recorded by an oxygen electrode. The respiratory effects produced by the additon of amygdalin to cell suspensions containing β-glucosidase were immediate and essentially the same as those obtained by adding the equivalent amounts of KCN to the cell suspensions. The radio-resistant 'tail' of the survival curve of multi-cell spheroids was reduced in the presence of cyanide (added directly or secondarily released). The radiation response of the spheroids in the presence of cyanide was slightly greater than that for reoxygenation alone. (U.K.)

  16. 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

  17. Development and in vitro evaluation of sustained release multiparticulate tablet of freely water soluble drug

    Directory of Open Access Journals (Sweden)

    Ashlesha Pravin Pandit

    2010-09-01

    Full Text Available Blends of aqueous dispersion of a hydrophobic and hydrophilic polymer, namely Surelease®: hydroxypropyl methylcellulose (Surelease®: HPMC E15 were used as coating materials to control the drug release from coated pellets of the highly water soluble drug metoprolol succinate. Varying the polymer blends, ranges of drug release patterns were obtained at pH 6.8. The present study dealt with diffusion of drug through plasticized Surelease®/ hydroxypropyl methylcellulose (HPMC E15 films prepared by coating of drug and polymers onto non-pareil seeds using the solution layering technique. The release of metoprolol succinate from coated pellets was decreased with increased coating load of polymer. The optimized formulation was obtained by 3² full factorial design. The release profile revealed that the optimized formulation follows zero order release kinetics. The stability data showed no interaction for storage at 25ºC and 60% relative humidity.Misturas das dispersões aquosas de polímero hidrofóbico e de polímero hidrofílico, a saber, Surelease®: hidroxipropil metilcelulose (Surelease®: HPMC E15, foram utilizadas como material de revestimento para controlar a liberação de fármacos de péletes revestidos de fármaco altamente solúvel, o succinato de metoprolol. Variando as misturas de polímeros, obtiveram-se faixas de padrão de liberação do fármaco em pH 6,8. O presente estudo tratou da difusão do fármaco através de filmes de Surelease®/hidroxipropil metilcelulose(HPMC E15, preparados pelo revestimento do fármaco e dos polímeros em sementes nonpareil, utilizando técnica de solução em camada. A liberação de succinato de metoprolol dos péletes revestidos diminuiu com o aumento da carga de polímero de revestimento. A formulação otimizada foi obtida por planejamento fatorial 3². O perfil de liberação revelou que a formulação otimizada segue a cinética de liberação de ordem zero. Os dados de estabilidade mostraram n

  18. 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.

  19. In vitro study revealed different size behavior of different nanoparticles

    International Nuclear Information System (INIS)

    Schaudien, Dirk; Knebel, Jan; Creutzenberg, Otto

    2012-01-01

    Toxicity of nanoparticles is depending not only on the size of the primary particles but on the size of their agglomerates. Therefore, further studies are needed to examine the behavior of nanoparticles after they have gotten in contact with cells. The presented study investigated the change of size of different commercially available nanoparticles after applying them to different cell lines such as A549, Calu-3, 16HBE14o and LK004 representative for the different parts of the human lung. The different nanoparticles exhibited differences in behavior of size. TiO 2 P25 showed a tendency to increase, whereas TiO 2 T805 and Printex ® 90 remained more or less at the same size. In contrast, ZnO < 50 nm particles showed a significant decrease of size.

  20. Exposure of alveolar macrophages to polybrominated diphenyl ethers suppresses the release of pro-inflammatory products in vitro.

    Science.gov (United States)

    Hennigar, Stephen R; Myers, Jay L; Tagliaferro, Anthony R

    2012-04-01

    Inhalation of chemical pollutants has been associated with a reduced immune response in humans. Inhalation of dust is a major route of exposure for one endocrine-disrupting chemical and suspected xenoestrogen, polybrominated diphenyl ethers (PBDEs); however, the impact of PBDEs on immune function is unclear. The objective of this study was to investigate the action of PBDEs on cytokine and eicosanoid release by alveolar macrophages and determine whether the effects are mediated via the estrogen receptor. The production of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, IL-10 and prostaglandin E(2) (PGE(2)) by porcine alveolar macrophages exposed to different concentrations of the pentabrominated diphenyl ether mixture, DE-71, were measured; cells were also exposed to varying concentrations of 17β-estradiol and the selective estrogen receptor-modulating agent, tamoxifen. Cells exposed to PBDEs released significantly less pro-inflammatory cytokines (TNF-α and IL-6) and PGE(2) compared with controls; IL-1β and IL-10 were not detected in the culture medium. Cells exposed to 17β-estradiol released significantly less TNF-α compared with controls, an effect that was reversed by the addition of tamoxifen; tamoxifen had no effect on the inhibition of TNF-α release by PBDEs. Although the suppression of TNF-α with DE-71 was similar to that of estrogen, the inhibitory effects of DE-71 were not found to be dependent on the estrogen receptor. Findings of this study suggest that chronic exposure to PBDEs suppressed innate immunity in vitro. Whether the immunosuppressant effects of PBDEs occur in vivo, remains to be determined.

  1. 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 t 1/2 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 t 1/2 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.

  2. Effect of thermocycling on nickel release from orthodontic arch wires: an in vitro study.

    Science.gov (United States)

    Sheibaninia, Ahmad

    2014-12-01

    The amount of daily intake of metals from orthodontic appliances over time is a matter of great concern. Nickel results in one of the most common metal-induced allergic contact dermatitis in humans; it produces more allergic reactions than all the other metals combined together. The purpose of this study was to evaluate the effects of thermocycling on the nickel release from orthodontic arch wires stored in artificial saliva with different pH values. Forty new wire pieces were selected. Each wire piece was placed in a special capillary Pyrex tube filled with artificial saliva, which was sealed and immersed in deionized water at 37 °C. The samples were divided into four groups of ten. Group I received no treatment; group II was subjected to thermocycling. The pH of storage in groups III and IV was reduced to 4.5, and group IV was subjected to thermocycling. Thermocycling was carried out between 5 and 55 °C for 500 cycles. The release of nickel ions was statistically analyzed by two-way ANOVA for the effects of two variables: pH and thermocycling. The interaction between pH and thermocycling was found to be statistically significant (F = 12.127, P = 0.001). Two-way ANOVA showed that different storage media or pH and thermocycling had a significant effect on the nickel release (F = 52.812, P nickel from orthodontic wires, while thermocycling is clearly the dominant factor.

  3. In vitro controlled release of cisplatin from gold-carbon nanobottles via cleavable linkages

    Directory of Open Access Journals (Sweden)

    Li J

    2015-12-01

    Full Text Available Jian Li,1 Sia Lee Yoong,2 Wei Jiang Goh,2 Bertrand Czarny,1 Zhi Yang,1 Kingshuk Poddar,2,3 Michal M Dykas,2,3 Abhijeet Patra,2,3 T Venkatesan,2,3 Tomasz Panczyk,4 Chengkuo Lee,5 Giorgia Pastorin1–3 1Department of Pharmacy, National University of Singapore, 2NUS Graduate School for Integrative Sciences and Engineering, Centre for Life Sciences (CeLS, 3NUSNNI-NanoCore, National University of Singapore, Singapore; 4Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, Cracow, Poland; 5Department of Electrical and Computer Engineering, National University of Singapore, Singapore Abstract: Carbon nanotubes’ (CNTs hollow interior space has been explored for biomedical applications, such as drug repository against undesirable inactivation. To further devise CNTs as smart material for controlled release of cargo molecules, we propose the concept of “gold-carbon nanobottles”. After encapsulating cis-diammineplatinum(II dichloride (cisplatin, CDDP in CNTs, we covalently attached gold nanoparticles (AuNPs at the open-tips of CNTs via different cleavable linkages, namely hydrazine, ester, and disulfide-containing linkages. Compared with our previous study in which more than 80% of CDDP leaked from CNTs in 2 hours, AuNPs were found to significantly decrease such spontaneous release to <40%. In addition, CDDP release from AuNP-capped CNTs via disulfide linkage was selectively enhanced by twofolds in reducing conditions (namely with 1 mM dithiothreitol [DTT], which mimic the intracellular environment. We treated human colon adenocarcinoma cells HCT116 with our CDDP-loaded gold-carbon nanobottles and examined the cell viability using lactate dehydrogenase assay. Interestingly, we found that our nanobottles with cleavable disulfide linkage exerted stronger cytotoxic effect in HCT116 compared with normal human fetal lung fibroblast cells IMR-90. Therefore, we infer that our nanobottles strategy with inbuilt disulfide linkage could

  4. An Ilustrative Nuclide Release Behavior from an HLW Repository due to an Earthquake Event

    International Nuclear Information System (INIS)

    Lee, Youn-Myoung; Hwang, Yong-Soo; Choi, Jong-Won

    2008-01-01

    Program for the evaluation of a high-level waste repository which is conceptually modeled. During the last few years, programs developed with the aid of AMBER and GoldSim by which nuclide transports in the near- and far-field of a repository as well as transport through the biosphere under various normal and disruptive release scenarios could be modeled and evaluated, have been continuously demonstrated. To show its usability, as similarly done for the natural groundwater flow scheme, influence of a possible disruptive event on a nuclide release behavior from an HLW repository system caused naturally due to an earthquake has been investigated and illustrated with the newly developed GoldSim program

  5. Surface Modification of NiTi Alloy via Cathodic Plasma Electrolytic Deposition and its Effect on Ni Ion Release and Osteoblast Behaviors

    International Nuclear Information System (INIS)

    Yan Ying; Cai Kaiyong; Yang Weihu; Liu Peng

    2013-01-01

    To reduce Ni ion release and improve biocompatibility of NiTi alloy, the cathodic plasma electrolytic deposition (CPED) technique was used to fabricate ceramic coating onto a NiTi alloy surface. The formation of a coating with a rough and micro-textured surface was confirmed by X-ray diffraction, scanning electron microscopy, and energy-dispersive X-ray spectroscopy, respectively. An inductively coupled plasma mass spectrometry test showed that the formed coating significantly reduced the release of Ni ions from the NiTi alloy in simulated body fluid. The influence of CPED treated NiTi substrates on the biological behaviors of osteoblasts, including cell adhesion, cell viability, and osteogenic differentiation function (alkaline phosphatase), was investigated in vitro. Immunofluorescence staining of nuclei revealed that the CPED treated NiTi alloy was favorable for cell growth. Osteoblasts on CPED modified NiTi alloy showed greater cell viability than those for the native NiTi substrate after 4 and 7 days cultures. More importantly, osteoblasts cultured onto a modified NiTi sample displayed significantly higher differentiation levels of alkaline phosphatase. The results suggested that surface functionalization of NiTi alloy with ceramic coating via the CPED technique was beneficial for cell proliferation and differentiation. The approach presented here is useful for NiTi implants to enhance bone osteointegration and reduce Ni ion release in vitro

  6. Surface Modification of NiTi Alloy via Cathodic Plasma Electrolytic Deposition and its Effect on Ni Ion Release and Osteoblast Behaviors

    Science.gov (United States)

    Yan, Ying; Cai, Kaiyong; Yang, Weihu; Liu, Peng

    2013-07-01

    To reduce Ni ion release and improve biocompatibility of NiTi alloy, the cathodic plasma electrolytic deposition (CPED) technique was used to fabricate ceramic coating onto a NiTi alloy surface. The formation of a coating with a rough and micro-textured surface was confirmed by X-ray diffraction, scanning electron microscopy, and energy-dispersive X-ray spectroscopy, respectively. An inductively coupled plasma mass spectrometry test showed that the formed coating significantly reduced the release of Ni ions from the NiTi alloy in simulated body fluid. The influence of CPED treated NiTi substrates on the biological behaviors of osteoblasts, including cell adhesion, cell viability, and osteogenic differentiation function (alkaline phosphatase), was investigated in vitro. Immunofluorescence staining of nuclei revealed that the CPED treated NiTi alloy was favorable for cell growth. Osteoblasts on CPED modified NiTi alloy showed greater cell viability than those for the native NiTi substrate after 4 and 7 days cultures. More importantly, osteoblasts cultured onto a modified NiTi sample displayed significantly higher differentiation levels of alkaline phosphatase. The results suggested that surface functionalization of NiTi alloy with ceramic coating via the CPED technique was beneficial for cell proliferation and differentiation. The approach presented here is useful for NiTi implants to enhance bone osseointegration and reduce Ni ion release in vitro.

  7. Simulation of tritium behavior after intended tritium release in ventilated room

    International Nuclear Information System (INIS)

    Iwai, Yasunori; Hayashi, Takumi; Yamanishi, Toshihiko; Kobayashi, Kazuhiro; Nishi, Masataka

    2001-01-01

    At the Tritium Process Laboratory (TPL) at the Japan Atomic Energy Research Institute (JAERI), Caisson Assembly for Tritium Safety study (CATS) with 12 m 3 of large airtight vessel (Caisson) was fabricated for confirmation and enhancement of fusion reactor safety to estimate tritium behavior in the case where a tritium leak event should happen. One of the principal objectives of the present studies is the establishment of simulation method to predict the tritium behavior after the tritium leak event should happen in a ventilated room. The RNG model was found to be valid for eddy flow calculation in the 50 m 3 /h ventilated Caisson with acceptable engineering precision. The calculated initial and removal tritium concentration histories after intended tritium release were consistent with the experimental observations in the 50 m 3 /h ventilated Caisson. It is found that the flow near a wall plays an important role for the tritium transport in the ventilated room. On the other hand, tritium behavior intentionally released in the 3,000 m 3 of tritium handling room was investigated experimentally under a US-Japan collaboration. The tritium concentration history calculated with the same method was consistent with the experimental observations, which proves that the present developed method can be applied to the actual scale of tritium handling room. (author)

  8. 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...... of buffy-coat-depleted red cell (SAGM) blood were donated by healthy blood donors. Subsequently, half of every unit was leucocyte depleted by filtration, and all 32 half-units were stored under standard conditions for 35 days. Just after storage, and on days 7, 21 and 35 during storage, aliquots...

  9. 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.

  10. Growth inhibition and chemosensitization of exogenous nitric oxide released from NONOates in glioma cells in vitro.

    Science.gov (United States)

    Weyerbrock, Astrid; Baumer, Brunhilde; Papazoglou, Anna

    2009-01-01

    Exogenous nitric oxide (NO) from NO donors has cytotoxic, chemosensitizing, and radiosensitizing effects, and increases vascular permeability and blood flow in tumors. Yet little is known about whether these cytotoxic and chemosensitizing effects can be observed in glioma cells at doses that alter tumor physiological characteristics in vivo and whether these effects are tumor selective. The effect of NO released from proline NONOate, diethylamine NONOate, spermine NONOate, and sodium nitrite on cell proliferation, apoptosis, and chemosensitivity to carboplatin of cultured glioma cells was studied in C6, U87 glioma cells, human glioblastoma cells, and human astrocytes and fibroblasts. Although proline NONOate failed to induce cell death, the other NO donors induced growth arrest when present in high concentrations (10(-2) M) in all cell lines. Chemosensitization was observed after concomitant incubation with spermine NONOate and carboplatin in C6 and human glioblastoma cells. There is strong evidence that cell death occurs primarily by necrosis and to a lesser degree by apoptosis. The NO doses, which altered tumor physiology in vivo, were not cytotoxic, indicating that NO alters vascular permeability and cell viability in vivo by different mechanisms. The authors found that NO-generating agents at high concentrations are potent growth inhibitors and might also be useful as chemosensitizers in glioma cells. These data corroborate the theory that the use of NOgenerating agents may play a role in the multimodal treatment of malignant gliomas but that the NO release must be targeted more specifically to tumor cells to improve selectivity and efficacy.

  11. In-vitro release of diclofenac diethylammonium from lipid-based formulations.

    Science.gov (United States)

    Parsaee, Siamak; Sarbolouki, Mohammad N; Parnianpour, Mohamad

    2002-07-08

    This article presents the preparation and topical performance of some new lipid-based formulations of diclofenac, namely (a) a diclofenac aqueous gel containing mixed micelles (sodium cholate:egg lecithin molar ratio 0.55); (b) diclofenac lotion that contains soya lecithin, ethanol and buffer; and (c) diclofenac lipogel containing egg lecithin, isopropyl myristate, propylene glycol and ethanol. Gel formulations were prepared using Carbomer 934. Release of diclofenac from all formulations was monitored via dialysis through Spectra/por membrane into phosphate buffer (0.2 M pH=7.4) using a Franz cell. Drug release profile and diffusion coefficients were compared with brand formulation (Geigy's Vlotaren Emulgel). Statistical analysis of data show that the diffusion coefficient of the drug from these formulations rank according to the following order: Diclofenac lotion (D=5.308x10(-7) cm(2)/s) >lipogel (D=2.102 x 10(-7) cm(2)/s) >Voltaren Emulgel (1.518 x 10(-7) cm(2)/s) >aqueous gel mixed micelle (0.966 x 10(-7) cm(2)/s). These results show that diclofenac lotion and lipogel maybe more suitable formulations than the conventional topical dosage form.

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

    Science.gov (United States)

    Feng, Shun; Zhu, Lijun; Huang, Zhisheng; Wang, Haojia; Li, Hong; Zhou, Hua; Lu, Linlin; Wang, Ying; Liu, Zhongqiu; Liu, Liang

    2017-01-01

    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 20.84 ng/mL after treatment with electroporation. Therefore, electroporation with optimized parameters could significantly enhance transdermal permeation of SH. The mechanism by which electroporation promoted permeation was that the electronic pulses made the skin structure looser. To summarize, electroporation may be an effective complementary method for transdermal permeation of SH. The controlled release of electroporation may be a promising clinical method for transdermal drug administration. PMID:28670109

  13. 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

  14. Hydrogen sulphide-releasing diclofenac derivatives inhibit breast cancer-induced osteoclastogenesis in vitro and prevent osteolysis ex vivo.

    Science.gov (United States)

    Frantzias, J; Logan, J G; Mollat, P; Sparatore, A; Del Soldato, P; Ralston, S H; Idris, A I

    2012-03-01

    Hydrogen sulphide (H(2)S) and prostaglandins are both involved in inflammation, cancer and bone turnover, and non-steroidal anti-inflammatory drugs (NSAIDs) and H(2)S donors exhibit anti-inflammatory and anti-tumour properties. H(2)S-releasing diclofenac (S-DCF) derivatives are a novel class of NSAIDs combining the properties of a H(2)S donor with those of a conventional NSAID. We studied the effects of the S-DCF derivatives ACS15 and ACS32 on osteoclast and osteoblast differentiation and activity in vitro, human and mouse breast cancer cells support for osteoclast formation and signalling in vitro, and osteolysis ex vivo. The S-diclofenac derivatives ACS15 and ACS32 inhibited the increase in osteoclast formation induced by human MDA-MB-231 and MCF-7 and mouse 4T1 breast cancer cells without affecting breast cancer cell viability. Conditioned media from human MDA-MB-231 cells enhanced IκB phosphorylation and osteoclast formation and these effects were significantly inhibited following treatment by ACS15 and ACS32, whereas the parent compound diclofenac had no effects. ACS15 and ACS32 inhibited receptor activator of NFκB ligand-induced osteoclast formation and resorption, and caused caspase-3 activation and apoptosis in mature osteoclasts via a mechanism dependent on IKK/NFκB inhibition. In calvaria organ culture, human MDA-MB-231 cells caused osteolysis, and this effect was completely prevented following treatment with ACS15 and ACS32. S-diclofenac derivatives inhibit osteoclast formation and activity, suppress breast cancer cell support for osteoclastogenesis and prevent osteolysis. This suggests that H(2)S-releasing diclofenac derivatives exhibit anti-resorptive properties, which might be of clinical value in the treatment of osteolytic bone disease. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  15. Caffeine alleviates the deterioration of Ca2+ release mechanisms and fragmentation of in vitro aged mouse eggs

    Science.gov (United States)

    Zhang, Nan; Wakai, Takuya; Fissore, Rafael. A.

    2011-01-01

    The developmental competence of mammalian eggs is compromised by postovulatory aging. We and others found that in these eggs the intracellular calcium ([Ca2+]i) responses required for egg activation and initiation of development are altered. Nevertheless, the mechanism(s) underlying this defective Ca2+ release is not well known. Here, we investigated if the function of IP3R1, the major Ca2+ release channel at fertilization, was undermined in in vitro aged mouse eggs. We found that in aged eggs IP3R1 displayed reduced function, as many of the changes acquired during maturation that enhance IP3R1 Ca2+ conductivity such as phosphorylation, receptor reorganization and increased Ca2+ store content ([Ca2+]ER) were lost with increasing postovulatory time. IP3R1 fragmentation, possibly associated with the activation of caspase-3, was also observed in these eggs. Many of these changes were prevented when the postovulatory aging of eggs was carried out in the presence of caffeine, which minimized the decline in IP3R1 function and maintained [Ca2+]ER content. Caffeine also maintained mitochondrial membrane potential as measured by JC-1 fluorescence. We therefore conclude that [Ca2+]i responses in aged eggs are undermined by reduced IP3R1 sensitivity, decreased [Ca2+]ER and compromised mitochondrial function, and that addition of caffeine ameliorates most of these aging-associated changes. Understanding the molecular basis of the protective effects of caffeine will be useful in elucidating, and possibly reversing, the signaling pathway(s) compromised by in vitro culture of eggs. PMID:22095868

  16. Quantification of peptides released during in vitro digestion of cooked meat.

    Science.gov (United States)

    Sayd, T; Chambon, C; Santé-Lhoutellier, V

    2016-04-15

    We aimed to identify and quantify the peptides generated during in vitro digestion of cooked meat by liquid chromatography coupled with high resolution mass spectrometer. A total of 940 non-redundant peptides in the gastric compartment and 989 non-redundant peptides in the intestinal compartment were quantified and identified. Among the 71 different proteins identified, 43 meat proteins were found in the two digestive compartments, 20 proteins were specific to the gastric compartment and 8 proteins to the intestinal compartment. In terms of estimation, the proteins involved in muscle contraction and structure were preferentially enzymatically hydrolyzed in the small intestine. The effect of cooking provided different but less clear patterns of digestion. To the best of our knowledge, this constitutes the highest number of peptides identified in beef meat digests and provides a comprehensive database for meat protein digestion associated with cooking conditions. Such quantitative and qualitative differences may have important nutritional consequences. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Surfacing behavior and gas release of the physostome sprat (Sprattus sprattus) in ice-free and ice-covered waters

    KAUST Repository

    Solberg, Ingrid; Kaartvedt, Stein

    2013-01-01

    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

  18. Influence of charge on encapsulation and release behavior of small molecules in self-assembled layer-by-layer microcapsules.

    Science.gov (United States)

    Mandapalli, Praveen K; Labala, Suman; Vanamala, Deekshith; Koranglekar, Manali P; Sakimalla, Lakshmi A; Venuganti, Venkata Vamsi K

    2014-12-01

    The objective of this study is to investigate the influence of charge of model small molecules on their encapsulation and release behavior in layer-by-layer microcapsules (LbL-MC). Poly(styrene sulfonate) and poly(ethylene imine) were sequentially adsorbed on calcium carbonate sacrificial templates to prepare LbL-MC. Model molecules with varying charge, anionic - ascorbic acid, cationic - imatinib mesylate (IM) and neutral - 5-fluorouracil were encapsulated in LbL-MC. Free and encapsulated LbL-MC were characterized using zetasizer, FTIR spectroscope and differential scanning calorimeter. The influence of IM-loaded LbL-MC on cell viability was studied in B16F10 murine melanoma cells. Furthermore, biodistribution of IM-loaded LbL-MC with and without PEGylation was studied in BALB/c mice. Results showed spherical LbL-MC of 3.0 ± 0.4 μm diameter. Encapsulation efficiency of LbL-MC increased linearly (R(2 )= 0.89-0.99) with the increase in solute concentration. Increase in pH from 2 to 6 increased the encapsulation of charged molecules in LbL-MC. Charged molecules showed greater encapsulation efficiency in LbL-MC compared with neutral molecule. In vitro release kinetics showed Fickian and non-Fickian diffusion of small molecules, depending on the nature of molecular interactions with LbL-MC. At 50 μM concentration, free IM showed significantly (p < 0.05) more cytotoxicity compared with IM-loaded LbL-MC. Biodistribution studies showed that PEGylation of LbL-MC decreased the liver and spleen uptake of IM-encapsulated LbL-MC. In conclusion, LbL-MC can be developed as a potential carrier for small molecules depending on their physical and chemical properties.

  19. 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

  20. 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

  1. 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.

  2. Tumor necrosis factor-alpha release from rat pulmonary leukocytes exposed to ultrafine cobalt: in vivo and in vitro studies

    International Nuclear Information System (INIS)

    Zhang Qunwei; Kusaka, Yukinori; Sato, Kazuhiro; Wang Deweng; Donaldson, Kenneth

    1999-01-01

    Ultrafine cobalt (Uf-Co), one of the new category of ultrafine particles, is generated in some industrial situations and it also exists in environmental particles. The aim of this study was to investigate the ability of rat pulmonary leukocytes to release tumor necrosis factor alpha (TNF-alpha) after exposure to Uf-Co in vivo and in vitro. Rats were intratracheally instilled with 1 mg of Uf-Co, and then wet lung weight and bronchoalveolar lavage fluid (BASF) profile were analysed 1, 3, 7, 15, and 30 days later. The effects of Uf-Co on indices that can be presumed to reflect epithelial injury and permeability (lactate dehydrogenase (LDH) and total protein (TP)) were increased throughout the 30 day post-exposure period. Furthermore, at 3 days after exposure, leukocytes were collected by bronchoalveolar lavage (BAL). After 3, 6, 12, 24, 48, and 72 hours of incubation, TNF-alpha in supernatants were determined by ELISA method. The results showed that TNF-alpha secretion by activated leukocytes from rats instilled with Uf-Co was significantly higher than that of the controls. BAL leucocytes from the lung of exposed rats revealed time-and dose-related increases in TNF-alpha release. In conclusion, our results reveal, for the first time to our knowledge, that exposure to Uf-Co can stimulate leukocytes to secrete TNF-alpha. These data suggest that the TNF-alpha release from pulmonary leukocytes probably plays a role in the pathogenesis of 'cobalt lung'. (author)

  3. Release of transgenic progranulin from a living hyaline cartilage graft model: An in vitro evaluation on anti-inflammation.

    Science.gov (United States)

    Lau, Ting Ting; Zhang, Feng; Tang, Wei; Wang, Dong-An

    2016-12-01

    Osteoarthritis (OA) is a prevalent condition that compromises and even jeopardizes the life quality of millions of people. Common symptoms in OA includes joint stiffness and soreness, and they are often associated with inflammations to various extend. Due to the avascular and aneural nature of articular hyaline cartilage, it has limited self-repair capabilities; especially under inflammatory conditions, damages inflicted on cartilage are often irreversible. Hence, treatment approaches focus on anti-inflammation or articular cartilage replacement. In this study, an engineered, dual-functional living hyaline cartilage graft (LhCG), capable of releasing transgenic anti-inflammatory cytokine-progranulin (PGRN) is developed and envisioned to simultaneously fulfil both requirements. The therapeutic functionality of PGRN releasing LhCG is evaluated by co-culturing the constructs with tumor necrosis factor-alpha (TNFα) secreting THP-1 cells to simulate the inflammatory condition in arthritis. Non-transgenic LhCG constructs and non-coculture sample groups were set up as controls. Gene expression and ECM composition changes across samples were assessed to understand the effects of PGRN as well as inflammatory environment on the cartilage graft. Collectively, the results in this study suggest that in situ release of transgenic recombinant PGRN protects LhCG from induced inflammation in vitro; contrastively, in the absence of PGRN, cartilage grafts are at risk of being degraded and mineralized under exposure to TNFα signaling. This shows that cartilage graft itself can be at risk of degradation or calcification when implanted in arthritic microenvironment. Hence, the inflammatory microenvironment has to be considered in cartilage replacement therapy to increase chances of successful joint mobility restoration. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2968-2977, 2016. © 2016 Wiley Periodicals, Inc.

  4. Pectin/anhydrous dibasic calcium phosphate matrix tablets for in vitro controlled release of water-soluble drug.

    Science.gov (United States)

    Mamani, Pseidy Luz; Ruiz-Caro, Roberto; Veiga, María Dolores

    2015-10-15

    Different pectin/anhydrous dibasic calcium phosphate (ADCP) matrix tablets have been developed in order to obtain controlled release of a water-soluble drug (theophylline). Swelling, buoyancy and dissolution studies have been carried out in different aqueous media (demineralized water, progressive pH medium, simulated gastric fluid, simulated intestinal fluid and simulated colonic fluid), to characterize the matrix tablets. When the pectin/ADCP ratio was ≥0.26 (P1, P2, P3 and P4 tablets) a continuous swelling and low theophylline dissolution rate from the matrices were observed. So, pectin gel forming feature predominated over the ADCP properties, yielding pH-independent drug release behavior from these matrices. On the contrary, pectin/ADCP ratios ≤0.11 (P5 and P6 tablets) allowed to achieve drug dissolution pH dependent. Consequently, the suitable selection of the pectin/ADCP ratio will allow to tailor matrix tablets for controlled release of water-soluble drugs in a specific manner in the gastrointestinal tract. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Zhang Y

    2011-04-01

    Full Text Available Yue Zhang1,2, Jungang Gao1, Hetang Zheng2, Ran Zhang3, Yucui Han21College of Chemistry and Enviromental Science, Hebei University, Baoding, China; 2School of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, Shijiazhuang, China; 3College of Chemical Engineering, East China University of Science and Technology, Shanghai, ChinaAbstract: 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.Keywords: nanoemulsion, 3,5-dihydroxy-4-isopropylstilbene, DHPS, pseudo-ternary phase diagram

  6. Platelet-released growth factors inhibit proliferation of primary keratinocytes in vitro.

    Science.gov (United States)

    Bayer, Andreas; Tohidnezhad, Mersedeh; Berndt, Rouven; Lippross, Sebastian; Behrendt, Peter; Klüter, Tim; Pufe, Thomas; Jahr, Holger; Cremer, Jochen; Rademacher, Franziska; Simanski, Maren; Gläser, Regine; Harder, Jürgen

    2018-01-01

    Autologous thrombocyte concentrate lysates as platelet-released growth factors (PRGF) or Vivostat Platelet Rich Fibrin (PRF ® ) represent important tools in modern wound therapy, especially in the treatment of chronic, hard-to-heal or infected wounds. Nevertheless, underlying cellular and molecular mechanisms of the beneficial clinical effects of a local wound therapy with autologous thrombocyte concentrate lysates are poorly understood. Recently, we have demonstrated that PRGF induces antimicrobial peptides in primary keratinocytes and accelerates keratinocytes' differentiation. In the present study we analyzed the influence of PRGF on primary human keratinocytes' proliferation. Using the molecular proliferation marker Ki-67 we observed a concentration- and time dependent inhibition of Ki-67 gene expression in PRGF treated primary keratinocytes. These effects were independent from the EGFR- and the IL-6-R pathway. Inhibition of primary keratinocytes' proliferation by PRGF treatment was confirmed in colorimetric cell proliferation assays. Together, these data indicate that the clinically observed positive effects of autologous thrombocytes concentrates in the treatment of chronic, hard-to-heal wounds are not based on an increased keratinocytes proliferation. Copyright © 2017 Elsevier GmbH. All rights reserved.

  7. Effect of corticotropin-releasing factor receptor antagonist on psychologically suppressed masculine sexual behavior in rats.

    Science.gov (United States)

    Miwa, Yoshiji; Nagase, Keiko; Oyama, Nobuyuki; Akino, Hironobu; Yokoyama, Osamu

    2011-03-01

    Corticotropin-releasing factor (CRF) coordinates various responses of the body to stress, and CRF receptors are important targets of treatment for stress-related disorders. To investigate the effect of a nonselective CRF receptor antagonist, astressin, on suppression of masculine sexual behavior by psychological stress in rats. First, we investigated the influence of psychological stress, induced 2 hours per day for three consecutive days, on sexual behavior. Then, rats were divided into 4 groups: a control group, an astressin administration group (A), a psychological stress loading group (PS), and a psychological stress loading and astressin administration group (PS + A). The rats were exposed to sham or psychological stress for three consecutive days. After the last stress loading, the rats were injected with vehicle or astressin, and their sexual behavior was observed. We also measured serum levels of adrenocorticotropic hormone (ACTH). The effects of astressin on sexual behavior and serum levels of ACTH in rats affected by psychological stress were determined. Sexual behavior was reduced after psychological stress loading. The PS rats had significantly longer mount, intromission, and ejaculation latencies and lower ejaculation frequency than did the control, A, and PS + A rats. The intromission latency and ejaculation frequency in the PS + A rats did not achieve the level observed in the controls. There was no significant difference in these parameters between the control and A rats. Serum ACTH levels were significantly lower in PS + A rats than in PS rats. Psychologically suppressed masculine sexual behavior could be partially recovered with astressin administration in rats. These data provide a rationale for the further study of CRF receptor antagonists as novel agents for treating psychological sexual disorders. © 2010 International Society for Sexual Medicine.

  8. Tritium recapture behavior at a nuclear power reactor due to airborne releases.

    Science.gov (United States)

    Harris, Jason T; Miller, David W; Foster, Doug W

    2008-08-01

    This paper describes the initiatives taken by Cook Nuclear Plant to study the on-site behavior of recaptured tritium released in its airborne effluents. Recapture is the process where a released radioactive effluent, in this case tritium, is brought back on-site through some mechanism. Precipitation, shifts in wind direction, or anthropogenic structures that restrict or alter effluent movement can all lead to recapture. The investigation was started after tritium was detected in the north storm drain outfall. Recent inadvertent tritium releases by several other nuclear power plants, many of which entered the groundwater, have led to increased surveillance and scrutiny by regulatory authorities and the general public. To determine the source of tritium in the outfall, an on-site surface water, well water, rainwater and air-conditioning condensate monitoring program was begun. Washout coefficients were also determined to compare with results reported by other nuclear power plants. Program monitoring revealed detectable tritium concentrations in several precipitation sample locations downwind of the two monitored containment building release vents. Tritium was found in higher concentrations in air-conditioning condensate, with a mean value of 528 Bq L(-1) (14,300 pCi L(-1)). The condensate, and to a lesser extent rainwater, were contributing to the tritium found in the north storm drain outfall. Maximum concentration values for each sample type were used to estimate the most conservative dose. A maximum dose of 1.1 x 10(-10) mSv (1.1 x 10(-8) mrem) total body was calculated to determine the health impact of the tritium detected.

  9. Fission Product Release Behavior of Individual Coated Fuel Particles for High-Temperature Gas-Cooled Reactors

    Energy Technology Data Exchange (ETDEWEB)

    Minato, Kazuo [Japan Atomic Energy Research Institute (Japan); Sawa, Kazuhiro [Japan Atomic Energy Research Institute (Japan); Koya, Toshio [Japan Atomic Energy Research Institute (Japan); Tomita, Takeshi [Japan Atomic Energy Research Institute (Japan); Ishikawa, Akiyoshi [Japan Atomic Energy Research Institute (Japan); Baldwin, Charles A; Gabbard, William Alexander [Oak Ridge National Laboratory (United States); Malone, Charlie M [Oak Ridge National Laboratory (United States)

    2000-07-15

    Postirradiation heating tests of TRISO-coated UO{sub 2} particles at 1700 and 1800degC were performed to understand fission product release behavior at accident temperatures. The inventory measurements of the individual particles were carried out before and after the heating tests with gamma-ray spectrometry to study the behavior of the individual particles. The time-dependent release behavior of {sup 85}Kr, {sup 110m}Ag, {sup 134}Cs, {sup 137}Cs, and {sup 154}Eu were obtained with on-line measurements of fission gas release and intermittent measurements of metallic fission product release during the heating tests. The inventory measurements of the individual particles revealed that fission product release behavior of the individual particles was not uniform, and large particle-to-particle variations in the release behavior of {sup 110m}Ag, {sup 134}Cs, {sup 137}Cs, and {sup 154}Eu were found. X-ray microradiography and ceramography showed that the variations could not be explained by only the presence or absence of cracks in the SiC coating layer. The SiC degradation may have been related to the variations.

  10. Fission Product Release Behavior of Individual Coated Fuel Particles for High-Temperature Gas-Cooled Reactors

    International Nuclear Information System (INIS)

    Minato, Kazuo; Sawa, Kazuhiro; Koya, Toshio; Tomita, Takeshi; Ishikawa, Akiyoshi; Baldwin, Charles A.; Gabbard, William Alexander; Malone, Charlie M.

    2000-01-01

    Postirradiation heating tests of TRISO-coated UO 2 particles at 1700 and 1800degC were performed to understand fission product release behavior at accident temperatures. The inventory measurements of the individual particles were carried out before and after the heating tests with gamma-ray spectrometry to study the behavior of the individual particles. The time-dependent release behavior of 85 Kr, 110m Ag, 134 Cs, 137 Cs, and 154 Eu were obtained with on-line measurements of fission gas release and intermittent measurements of metallic fission product release during the heating tests. The inventory measurements of the individual particles revealed that fission product release behavior of the individual particles was not uniform, and large particle-to-particle variations in the release behavior of 110m Ag, 134 Cs, 137 Cs, and 154 Eu were found. X-ray microradiography and ceramography showed that the variations could not be explained by only the presence or absence of cracks in the SiC coating layer. The SiC degradation may have been related to the variations

  11. Influence of cell culture medium composition on in vitro dissolution behavior of a fluoride-containing bioactive glass.

    Science.gov (United States)

    Shah, Furqan A; Brauer, Delia S; Wilson, Rory M; Hill, Robert G; Hing, Karin A

    2014-03-01

    Bioactive glasses are used clinically for bone regeneration, and their bioactivity and cell compatibility are often characterized in vitro, using physiologically relevant test solutions. The aim of this study was to show the influence of varying medium characteristics (pH, composition, presence of proteins) on glass dissolution and apatite formation. The dissolution behavior of a fluoride-containing bioactive glass (BG) was investigated over a period of one week in Eagle's Minimal Essential Medium with Earle's Salts (MEM), supplemented with either, (a) acetate buffer, (b) 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer, (c) HEPES + carbonate, or (d) HEPES + carbonate + fetal bovine serum. Results show pronounced differences in pH, ion release, and apatite formation over 1 week: Despite its acidic pH (pH 5.8 after BG immersion, as compared to pH 7.4-8.3 for HEPES-containing media), apatite formation was fastest in acetate buffered (HEPES-free) MEM. Presence of carbonate resulted in formation of calcite (calcium carbonate). Presence of serum proteins, on the other hand, delayed apatite formation significantly. These results confirm that the composition and properties of a tissue culture medium are important factors during in vitro experiments and need to be taken into consideration when interpreting results from dissolution or cell culture studies. Copyright © 2013 Wiley Periodicals, Inc.

  12. Loss of hypothalamic corticotropin-releasing hormone markedly reduces anxiety behaviors in mice

    Science.gov (United States)

    Zhang, Rong; Asai, Masato; Mahoney, Carrie E; Joachim, Maria; Shen, Yuan; Gunner, Georgia; Majzoub, Joseph A

    2016-01-01

    A long-standing paradigm posits that hypothalamic corticotropin-releasing hormone (CRH) regulates neuroendocrine functions such as adrenal glucocorticoid release, while extra-hypothalamic CRH plays a key role in stressor-triggered behaviors. Here we report that hypothalamus-specific Crh knockout mice (Sim1CrhKO mice, created by crossing Crhflox with Sim1Cre mice) have absent Crh mRNA and peptide mainly in the paraventricular nucleus of the hypothalamus (PVH) but preserved Crh expression in other brain regions including amygdala and cerebral cortex. As expected, Sim1CrhKO mice exhibit adrenal atrophy as well as decreased basal, diurnal and stressor-stimulated plasma corticosterone secretion and basal plasma ACTH, but surprisingly, have a profound anxiolytic phenotype when evaluated using multiple stressors including open field, elevated plus maze, holeboard, light-dark box, and novel object recognition task. Restoring plasma corticosterone did not reverse the anxiolytic phenotype of Sim1CrhKO mice. Crh-Cre driver mice revealed that PVHCrh fibers project abundantly to cingulate cortex and the nucleus accumbens shell, and moderately to medial amygdala, locus coeruleus, and solitary tract, consistent with the existence of PVHCrh-dependent behavioral pathways. Although previous, nonselective attenuation of CRH production or action, genetically in mice and pharmacologically in humans, respectively, has not produced the anticipated anxiolytic effects, our data show that targeted interference specifically with hypothalamic Crh expression results in anxiolysis. Our data identify neurons that express both Sim1 and Crh as a cellular entry point into the study of CRH-mediated, anxiety-like behaviors and their therapeutic attenuation. PMID:27595593

  13. 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...

  14. Food-dependent disintegration of immediate release fosamprenavir tablets: In vitro evaluation using magnetic resonance imaging and a dynamic gastrointestinal system

    NARCIS (Netherlands)

    Brouwers, J.; Anneveld, B.; Goudappel, G.J.; Duchateau, G.; Annaert, P.; Augustijns, P.; Zeijdner, E.

    2011-01-01

    In the present study, we demonstrated the value of two advanced tools, the TNO gastric and small Intestinal Model (TIM-1) and magnetic resonance imaging (MRI), for the in vitro evaluation of food-dependent disintegration of immediate release fosamprenavir tablets. Upon introduction of a tablet with

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

    International Nuclear Information System (INIS)

    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 α-modified Eagles medium followed by 24h in fresh medium +/- estradiol (E 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 2 (10 -11 to 10 -8 M) on 3 H-glucosamine ( 3 H-Gln) and 35 S-methionine ( 35 S-Met) incorporation into LH +/- 1 nM GnRH (4h) were investigated. GnRH (10 -9 M) and E 2 (all doses) significantly increased total 3 H-Gln LH. Moreover, E 2 at 10 -9 M and 10 -8 M significantly enhanced GnRH stimulated LH glycosylation. In contrast, addition of GnRH and/or E 2 did not significantly increase 35 S-Met incorporation into LH over a 4h period. The effects of various GnRH concentrations (10 -11 to 10 -9 M; 8h) +/- E 2 (0.05 nM) on 3 H-Gln LH and 35 S-Met LH production were also investigated. In the absence of E 2 , only 10 -9 M GnRH was effective in increasing total 3 H-Gln LH and 35 S-Met LH synthesis. However, in the presence of E 2 , all concentrations of GnRH stimulated LH synthesis with 3 H-Gln LH production responding in a dose related manner whereas 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 3 H-Gln or 35 S-Met +/- GnRH. Removal of extracellular calcium completely inhibited GnRH stimulated 3 H-Gln LH and 35 S-Met LH production

  16. Food-dependent disintegration of immediate release fosamprenavir tablets: in vitro evaluation using magnetic resonance imaging and a dynamic gastrointestinal system.

    Science.gov (United States)

    Brouwers, Joachim; Anneveld, Bart; Goudappel, Gert-Jan; Duchateau, Guus; Annaert, Pieter; Augustijns, Patrick; Zeijdner, Evelijn

    2011-02-01

    In the present study, we demonstrated the value of two advanced tools, the TNO gastric and small Intestinal Model (TIM-1) and magnetic resonance imaging (MRI), for the in vitro evaluation of food-dependent disintegration of immediate release fosamprenavir tablets. Upon introduction of a tablet with the nutritional drink Scandishake Mix® in the stomach compartment of TIM-1, simulating the fed state, disintegration and fosamprenavir dissolution were significantly postponed compared to the fasted state (lag time 80 ± 23 min). This resulted in a lag in the appearance of bioaccessible fosamprenavir (tablet disintegration and subsequent amprenavir absorption in healthy volunteers. Therefore, TIM-1 can be used in tablet development to identify food-induced disintegration issues causing unexpected clinical behavior. From a mechanistic perspective, we applied MRI to illustrate impaired water ingress in fosamprenavir tablets immersed in the nutritional drink compared to simulated gastric fluid. This effect may be attributed to both competition between nutritional components and the tablet for the available water (indicated by reduced rotational and translational diffusion) as well as the possible formation of a food-dependent precipitation layer on the HPMC-coated tablet. Copyright © 2010 Elsevier B.V. All rights reserved.

  17. The effect of anti-IgE treatment on in vitro leukotriene release in children with seasonal allergic rhinitis.

    Science.gov (United States)

    Kopp, Matthias Volkmar; Brauburger, Jens; Riedinger, Frank; Beischer, Dorothee; Ihorst, Gabriele; Kamin, Wolfgang; Zielen, Stefan; Bez; Friedrichs, Frank; Von Berg, Andrea; Gerhold, Kerstin; Hamelmann, Eckard; Hultsch; Kuehr, Joachim

    2002-11-01

    Binding of allergens with IgE to the IgE receptors on mast cells and basophils results in the release of inflammatory mediators as sulfidoleukotrienes (SLTs), triggering allergic cascades that result in allergic symptoms, such as asthma and rhinitis. We sought to investigate whether anti-IgE (Oma-lizumab), a humanized monoclonal anti-IgE antibody, in addition to specific immunotherapy (SIT) affects the leukotriene pathway. Ninety-two children (age range, 6-17 years) with sensitization to birch and grass pollens and with seasonal allergic rhinitis were included in a phase III, placebo- controlled, multicenter clinical study. All subjects were randomized to one of 4 treatment groups. Two groups subcutaneously received birch SIT and 2 groups received grass SIT for at least 14 weeks before the start of the birch pollen season. After 12 weeks of SIT titration, placebo or anti-IgE was added for 24 weeks. The primary clinical efficacy variable was symptom load (ie, the sum of daily symptom severity score and rescue medication score during pollen season). Blood samples taken at baseline and at the end of study treatment after the grass pollen season were used for separation of leukocytes in this substudy. After in vitro stimulation of the blood cells with grass and birch pollen allergens, SLT release (LTC4, LTD4, and LTE4) was quantified by using the ELISA technique. Before the study treatment, SLT release to birch and grass pollen exposure did not differ significantly among the 4 groups. Under treatment with anti-IgE + SIT-grass (n = 23), a lower symptom load occurred during the pollen season compared to placebo + SIT-grass (n = 24, P =.012). The same applied to both groups receiving birch SIT (n = 23 and n = 22, respectively; P =.03). At the end of treatment, the combination of anti-IgE plus grass SIT, as well as anti-IgE plus birch SIT, resulted in significantly lower SLT release after stimulation with the corresponding allergen (416 ng/L [5th-95th percentile, 1

  18. 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.

  19. 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.

  20. Preparation and in-vitro in-vivo evaluation of sustained release matrix diclofenac sodium tablets using PVP-K90 and natural gums.

    Science.gov (United States)

    Iqbal, Zafar; Khan, Raza; Nasir, Fazli; Khan, Jamshaid Ali; Rashid, Abdur; Khan, Abbas; Khan, Abad

    2011-10-01

    Conventional dosage form is nowadays mostly replaced by sustained release formulation in order to increase drug efficacy and patient compliance. The sustained release properties of the PVP K90 alone and in combination with guar gum, xanthan gum and gum tragacanth were evaluated using diclofenac sodium (100 mg/tablet) as a model drug. Tablets were processed using wet granulation method and evaluated for sustained drug release properties. The drug release from the formulations was studied in relationship with Commercially available Diclofenac Sodium SR, used as a reference tablets and results were expressed as similarity (f1) and differential factor (f2). The tablets prepared using PVP K90 160 mg/tablet sustained the release of diclofenac sodium for 12 hours. Formulations where the PVP K90 was partially replaced with different gums also sustained the release of drug for 12 hours. The release of the drug from these formulations mainly followed Higuchi model and super case-II and Non-Fickian diffusion. The in-vivo drug release was studied in healthy human volunteers using non-blinded cross over, two period design using Diclofenac Sodium SR Tablets as a reference drug. The relative bioavailability of the formulation containing PVP K90 and gum tragacanth was 0.91. The studies showed that the use of the PVP K90 in combination with gum tragacanth both in-vitro and in-vivo sustained the release of the drug.

  1. Integrated performance assessment model for waste policy package behavior and radionuclide release

    International Nuclear Information System (INIS)

    Kossik, R.; Miller, I.; Cunnane, M.

    1992-01-01

    Golder Associates Inc. (GAI) has developed a probabilistic total system performance assessment and strategy evaluation model (RIP) which can be applied in an iterative manner to evaluate repository site suitability and guide site characterization. This paper describes one component of the RIP software, the waste package behavior and radionuclide release model. The waste package component model considers waste package failure by various modes, matrix alteration/dissolution, and radionuclide mass transfer. Model parameters can be described as functions of local environmental conditions. The waste package component model is coupled to component models for far-field radionuclide transport and disruptive events. The model has recently been applied to the proposed repository at Yucca Mountain

  2. Integrated performance assessment model for waste package behavior and radionuclide release

    International Nuclear Information System (INIS)

    Kossik, R.; Miller, I.; Cunnane, M.

    1992-01-01

    Golder Associates Inc. (GAI) has developed a probabilistic total system performance assessment and strategy evaluation model (RIP) which can be applied in an iterative manner to evaluate repository site suitability and guide site characterization. This paper describes one component of the RIP software, the waste package behavior and radionuclide release model. The waste package component model considers waste package failure by various modes, matrix alteration/dissolution, and radionuclide mass transfer. Model parameters can be described as functions of local environmental conditions. The waste package component model is coupled to component models for far-field radionuclide transport and disruptive events. The model has recently been applied to the proposed repository at Yucca Mountain

  3. Regulation of feeding behavior and psychomotor activity by corticotropin-releasing hormone (CRH in fish

    Directory of Open Access Journals (Sweden)

    Kouhei eMatsuda

    2013-05-01

    Full Text Available Corticotropin-releasing hormone (CRH is a hypothalamic neuropeptide belonging to a family of neuropeptides that includes urocortins, urotensin I and sauvagine in vertebrates. CRH and urocortin act as anorexigenic factors for satiety regulation in fish. In a goldfish model, intracerebroventricular (ICV administration of CRH has been shown to affect not only food intake, but also locomotor and psychomotor activities. In particular, CRH elicits anxiety-like behavior as an anxiogenic neuropeptide in goldfish, as is the case in rodents. This paper reviews current knowledge of CRH and its related peptides derived from studies of teleost fish, as representative non-mammals, focusing particularly on the role of the CRH system, and examines its significance from a comparative viewpoint.

  4. Tandem mass spectrometry of nitric oxide and hydrogen sulfide releasing aspirins: a hint into activity behavior.

    Science.gov (United States)

    Crestoni, Maria Elisa; Chiavarino, Barbara; Guglielmo, Stefano; Lilla, Valentina; Fornarini, Simonetta

    2013-01-01

    Aspirin (acetylsalicylic acid, ASA) is the most popular non-steroidal anti-inflammatory drug. However, due to its action on cyclooxygenase and its acid nature, aspirin is associated with adverse gastrointestinal effects. In an effort to minimize these side effects, NO-donor and H2S-donor ASA co-drugs have been designed and tested. Their mass spectrometric behavior is now analyzed and reported. Positive ions were obtained by electrospray ionization involving protonation or alkali metal attachment. Their dissociation processes have been studied by collision induced dissociation in a triple quadrupole instrument. High mass accuracy measurements have been recorded on a Fourier transform ion cyclotron resonance mass spectrometer. The protonated molecules dissociate by an exclusive or largely prevailing path leading to acetyloxy-substituted benzoyl cation, namely an ASA unit. The process is reminiscent of the enzymatic hydrolysis, releasing intact ASA to a large extent. Only at higher collision energy does the formal ketene loss disrupt the ASA moiety. The gas phase chemistry of protonated ASA-releasing drugs develops along elementary dissociation steps analogous to the reactive processes in complex biological environments. This notion may provide a tool for preliminary testing of new compounds.

  5. Tritium behavior on a cultivated plot in the 1994 chronic HT release experiment at Chalk River

    International Nuclear Information System (INIS)

    Noguchi, H.; Yokoyama, S.; Kinouchi, N.; Murata, M.; Amano, H.; Atarashi, M.; Ichimasa, Y.; Ichimasa, M.

    1995-01-01

    The behavior of HT and HTO in air and surface soil has been studied extensively in the chronic HT release experiment carried out at Chalk River during the summer of 1994. HTO concentrations in air moisture and soil water collected in a cultivated plot showed similar time-variations, increasing rapidly during the first and second days and becoming gradual after the first 3-4 days. The air HTO concentration decreased during and following rainfall but recovered within a day. The rainfall reduced the HTO concentrations in ridge soil water but little in furrows. Time histories of HTO concentrations in air moisture and soil water suggest that the system was near steady-state within a continuous HT release period of 12 days, in spite of the presence of rain during the period. The air HTO concentrations on clear days showed diurnal cycles that were higher during daytime than at night. The experimental field had a very complex soil regime with respect to HT deposits. The deposits to soil surface varied depending on soil conditions. 12 refs., 5 figs

  6. 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.

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

    International Nuclear Information System (INIS)

    Numpilai, Thanapha; Muenmee, Suthaporn; Witoon, Thongthai

    2016-01-01

    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 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.

  8. Surface chemical functionalities affect the behavior of human adipose-derived stem cells in vitro

    International Nuclear Information System (INIS)

    Liu, Xujie; Feng, Qingling; Bachhuka, Akash; Vasilev, Krasimir

    2013-01-01

    This study examines the effect of surface chemical functionalities on the behavior of human adipose-derived stem cells (hASCs) in vitro. Plasma polymerized films rich in amine (-NH 2 ), carboxyl (-COOH) and methyl (-CH 3 ), were generated on hydroxyapatite (HAp) substrates. The surface chemical functionalities were characterized by X-ray photoelectron spectroscopy (XPS). The ability of different substrates to absorb proteins was evaluated. The results showed that substrates modified with hydrophilic functional group (-COOH and -NH 2 ) can absorb more proteins than these modified with more hydrophobic functional group (-CH 3 ). The behavior of human adipose-derived stem cells (hASCs) cultured on different substrates was investigated in vitro: cell counting kit-8 (CCK-8) analysis was used to characterize cell proliferation, scanning electronic microscopy (SEM) analysis was used to characterize cell morphology and alkaline phosphatase (ALP) activity analysis was used to account for differentiation. The results of this study demonstrated that the -NH 2 modified surfaces encourage osteogenic differentiation; the -COOH modified surfaces promote cell adhesion and spreading and the -CH 3 modified surfaces have the lowest ability to induce osteogenic differentiation. These findings confirmed that the surface chemical states of biomaterials can affect the behavior of hASCs in vitro.

  9. Surface chemical functionalities affect the behavior of human adipose-derived stem cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xujie [State key laboratory of new ceramics and fine processing, School of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Feng, Qingling, E-mail: biomater@mail.tsinghua.edu.cn [State key laboratory of new ceramics and fine processing, School of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Bachhuka, Akash [Mawson Institute, University of South Australia, Mawson Lakes 5095 (Australia); Vasilev, Krasimir [Mawson Institute, University of South Australia, Mawson Lakes 5095 (Australia); School of Advanced Manufacturing, University of South Australia, Mawson Lakes 5095 (Australia)

    2013-04-01

    This study examines the effect of surface chemical functionalities on the behavior of human adipose-derived stem cells (hASCs) in vitro. Plasma polymerized films rich in amine (-NH{sub 2}), carboxyl (-COOH) and methyl (-CH{sub 3}), were generated on hydroxyapatite (HAp) substrates. The surface chemical functionalities were characterized by X-ray photoelectron spectroscopy (XPS). The ability of different substrates to absorb proteins was evaluated. The results showed that substrates modified with hydrophilic functional group (-COOH and -NH{sub 2}) can absorb more proteins than these modified with more hydrophobic functional group (-CH{sub 3}). The behavior of human adipose-derived stem cells (hASCs) cultured on different substrates was investigated in vitro: cell counting kit-8 (CCK-8) analysis was used to characterize cell proliferation, scanning electronic microscopy (SEM) analysis was used to characterize cell morphology and alkaline phosphatase (ALP) activity analysis was used to account for differentiation. The results of this study demonstrated that the -NH{sub 2} modified surfaces encourage osteogenic differentiation; the -COOH modified surfaces promote cell adhesion and spreading and the -CH{sub 3} modified surfaces have the lowest ability to induce osteogenic differentiation. These findings confirmed that the surface chemical states of biomaterials can affect the behavior of hASCs in vitro.

  10. Environmental behavior of the radionuclides released from the Fukushima Daiichi Nuclear Power Plant accident

    International Nuclear Information System (INIS)

    Yamazaki, Hideo

    2014-01-01

    The environmental behavior of radioactive nuclides released from the Fukushima Daiichi Nuclear Power Station (FDNPS) accident in eastern Japan was investigated. The radioactive pollution of environmental samples, including airborne dust, soil, sediment, fish, and other organisms was described. It was evaluated for environmental behavior and fate of the radioactive material from the spatial and temporal distribution of the radioactive nuclides. In Higashiosaka City about 600 km away from FDNPS, it begins to detect the radioactive nuclides in the airborne dust from 25th March 2011. Radioactive fission products 95 Zr- 95 Nb was detected on 18th April. The concentrations of 131 I, 134 Cs, and 137 Cs in the soil collected from Fukushima City were 126000, 14000, and 14200 Bq/kg on 19th March 2011 and 12800, 13200, and 13700 Bq/kg on 26th March 2011, respectively. The concentrations of 131 I, 134 Cs, and 137 Cs in the soil samples collected from March-June 2011 from study sites in metropolitan area and Kanto region ranged from nd to 91900, 59 to 16100, and 69 to 17600 Bq/kg, respectively. (Concentrations of 131 I were done decay correction to the value of 16th March) Radioactivities in fish samples collected from off FDNPS, Tokyo Bay, and Kejonuma Pond were measured. The radioactive contamination of forest ecosystem was also investigated. Two processes are involved in the radioactive contamination of the environment from the FDNPS accident. One is contamination by radioactive nuclides released from the hydrogen explosion. Leakage of contaminated cooling water to the ocean is in other important environmental pollution. We must continue carefully monitoring of radioactive nuclides in the environment. (author)

  11. Properties and in vitro drug release of hyaluronic acid-hydroxyethyl cellulose hydrogels for transdermal delivery of isoliquiritigenin.

    Science.gov (United States)

    Kong, Bong Ju; Kim, Ayoung; Park, Soo Nam

    2016-08-20

    In the present study, the properties of hydrogel systems based on hyaluronic acid (HA)-hydroxyethyl cellulose (HEC) were investigated for effective transdermal delivery of isoliquiritigenin (ILTG). Hydrogels were synthesized by chemical cross-linking, and network structures were characterised using scanning electron microscopy (SEM) and surface area analyser. Texture properties and swelling of HA-HEC hydrogels were found to be closely linked to cross-linker concentration and swelling medium. Water in HA-HEC hydrogels was found to exist mostly in the form of free water. The viscoelasticity and the network stabilization of the hydrogels were analysed via rheological studies. The release kinetics of the hydrogel followed Fickian diffusion mechanism. In an in vitro skin penetration study, the system substantially improved the delivery of ILTG into the skin. These results indicate that the hydrogel system composed of HA and HEC has potential as a transdermal delivery system, with cross-linking density and the swelling medium influencing the properties. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Comparative study of kanamycin sulphate microparticles and nanoparticles for intramuscular administration: preparation in vitro release and preliminary in vivo evaluation.

    Science.gov (United States)

    Mustafa, Sanaul; Devi, V Kusum; Pai, Roopa S

    2016-11-01

    Kanamycin sulphate (KS) is a Mycobacterium tuberculosis protein synthesis inhibitor. KS is polycationic, a property responsible for KS poor oral absorption half-life (2.5 h) and rapid renal clearance, which results in serious nephrotoxicity/ototoxicity. The current study aimed to develop KS-loaded PLGA vitamin-E-TPGS microparticles (MPs) and nanoparticles (NPs) to reduce the dosing frequency and dose-related adverse effect. In vitro release was sustained up to 10 days for KS PLGA-TPGS MPs and 13 days for KS PLGA-TPGS NPs in phosphate-buffered saline (PBS) pH 7.4. The in vivo pharmacokinetic test in Wistar rats showed that the AUC 0-∞ of KS PLGA-TPGS NPs (280.58 μg/mL*min) was about 1.62-fold higher than that of KS PLGA-TPGS MPs (172.30 μg/mL*min). Further, in vivo protein-binding assay ascribed 1.20-fold increase in the uptake of KS PLGA-TPGS NPs through the alveolar macrophage (AM). The studies, therefore, could provide another useful tool for successful development of KS MPs and NPs.

  13. 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.

  14. Low dietary protein is associated with an increase in food intake and a decrease in the in vitro release of radiolabeled glutamate and GABA from the lateral hypothalamus.

    Science.gov (United States)

    White, B D; Du, F; Higginbotham, D A

    2003-12-01

    Moderately low-protein diets lead to a rapid increase in food intake and body fat. The increase in feeding is associated with a decrease in the concentration of serum urea nitrogen, suggesting that the low-protein-induced increase in food intake may be related to the decreased metabolism of nitrogen from amino acids. We hypothesized that low dietary protein would be associated with a decrease in the synaptic release of two nitrogen-containing neurotransmitters, GABA and glutamate, whose nitrogen can be derived from amino acids. In this study, we examined the effects of a low-protein diet (10% casein) in Sprague-Dawley rats on the in vitro release of 3H-GABA and 14C-glutamate from the lateral and medial hypothalamus. The low-protein diet increased food intake by about 25% after one day. After four days, the in vitro release of radiolabeled GABA and glutamate was assessed. The calcium-dependent, potassium-stimulated release of radiolabeled GABA and glutamate from the lateral hypothalamus was decreased in rats fed the low-protein diet. The magnitude of neurotransmitter release from the lateral hypothalamus inversely correlated with food intake. No dietary differences in the release of neurotransmitters from the medial hypothalamus were observed. These results support the contention that alterations in nitrogen metabolism are associated with low-protein-induced feeding.

  15. alpha7 and non-alpha7 nicotinic acetylcholine receptors modulate dopamine release in vitro and in vivo in the rat prefrontal cortex.

    Science.gov (United States)

    Livingstone, Phil D; Srinivasan, Jayaraman; Kew, James N C; Dawson, Lee A; Gotti, Cecilia; Moretti, Milena; Shoaib, Mohammed; Wonnacott, Susan

    2009-02-01

    Nicotine enhances attentional and working memory aspects of executive function in the prefrontal cortex (PFC) where dopamine plays a major role. Here, we have determined the nicotinic acetylcholine receptor (nAChR) subtypes that can modulate dopamine release in rat PFC using subtype-selective drugs. Nicotine and 5-Iodo-A-85380 (beta2* selective) elicited [(3)H]dopamine release from both PFC and striatal prisms in vitro and dopamine overflow from medial PFC in vivo. Blockade by dihydro-beta-erythroidine supports the participation of beta2* nAChRs. However, insensitivity of nicotine-evoked [(3)H]dopamine release to alpha-conotoxin-MII in PFC prisms suggests no involvement of alpha6beta2* nAChRs, in contrast to the striatum, and this distinction is supported by immunoprecipitation of nAChR subunits from these tissues. The alpha7 nAChR-selective agonists choline and Compound A also promoted dopamine release from PFC in vitro and in vivo, and their effects were enhanced by the alpha7 nAChR-selective allosteric potentiator PNU-120596 and blocked by specific antagonists. DNQX and MK801 inhibited [(3)H]dopamine release evoked by choline and PNU-120596, suggesting crosstalk between alpha7 nAChRs, glutamate and dopamine in the PFC. In vivo, systemic (but not local) administration of PNU-120596, in the absence of agonist, facilitated dopamine overflow in the medial PFC, consistent with the activation of extracortical alpha7 nAChRs by endogenous acetylcholine or choline. These data establish that both beta2* and alpha7 nAChRs can modulate dopamine release in the PFC in vitro and in vivo. Through their distinct actions on dopamine release, these nAChR subtypes could contribute to executive function, making them specific therapeutic targets for conditions such as schizophrenia and attention deficit hyperactivity disorder.

  16. Some effects of gas adsorption on the high temperature volatile release behavior of a terrestrial basalt, tektite and lunar soil

    Science.gov (United States)

    Graham, D. G.; Muenow, D. W.; Gibson, E. K., Jr.

    1979-01-01

    Mass pyrograms obtained from high-temperature, mass psectrometric pyrolysis of a glassy theoleiitic submarine basalt and a tektite, ground in air to less than 64 microns, have shown N2 and SO release patterns very similar to those from the pyrolysis of mature lunar soil fines. The N2 and CO release behavior from the terrestrial samples reproduces the biomodal, high-temperature (approximately 700 and 1050 C) features from the lunar samples. Unground portions of the basalt and tektite show no release of N2 and CO during pyrolysis. Grinding also alters the release behavior and absolute amounts of H2O and CO2. It is suggested that adsorption of atmospheric gases in addition to solar wind implantation of ions may account for the wide range of values in previously reported concentrations of carbon and nitrogen from lunar fines.

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

    Science.gov (United States)

    Uvnäs-Moberg, Kerstin; Handlin, Linda; Petersson, Maria

    2014-01-01

    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 adults 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Sustained-release diclofenac potassium-loaded solid lipid microparticle based on solidified reverse micellar solution: in vitro and in vivo evaluation.

    Science.gov (United States)

    Chime, Salome Amarachi; Attama, Anthony Amaechi; Builders, Philip F; Onunkwo, Godswill C

    2013-01-01

    To formulate sustained-release diclofenac potassium-loaded solid lipid microparticles (SLMs) based on solidified reverse micellar solution (SRMS) and to evaluate the in vitro and in vivo properties. SRMS consisting of mixtures of Phospholipon® 90H and Softisan® 154 were used to formulate diclofenac potassium-loaded SLMs. Characterization based on the particle size and morphology, stability and encapsulation efficiency (EE%) were carried out on the SLMs. In vitro release was carried out in simulated intestinal fluid (pH 7.5). Anti-inflammatory and ulcerogenic properties were studied using rats. Maximum EE% of 95%, 94% and 93% were obtained for SLMs formulated with SRMS 1:1, 2:1 and 1:2, respectively. In vitro release showed about 85-90% drug release at 13 h. Diclofenac potassium-loaded SLMs showed good anti-inflammatory and gastro-protective properties. Diclofenac potassium-loaded SLMs based on SRMS could be used orally or parenterally under controlled conditions, for once daily administration.

  20. 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.

  1. Effects of Agar Gel Strength and Fat on Oral Breakdown, Volatile Release, and Sensory Perception Using in Vivo and in Vitro Systems.

    Science.gov (United States)

    Frank, Damian; Eyres, Graham T; Piyasiri, Udayasika; Cochet-Broch, Maeva; Delahunty, Conor M; Lundin, Leif; Appelqvist, Ingrid M

    2015-10-21

    The density and composition of a food matrix affect the rates of oral breakdown and in-mouth flavor release as well as the overall sensory experience. Agar gels of increasing concentration (1.0, 1.7, 2.9, and 5% agarose) with and without added fat (0, 2, 5, and 10%) were spiked with seven aroma volatiles. Differences in oral processing and sensory perception were systematically measured by a trained panel using a discrete interval time intensity method. Volatile release was measured in vivo and in vitro by proton transfer reaction mass spectrometry. Greater oral processing was required as agar gel strength increased, and the intensity of flavor-related sensory attributes decreased. Volatile release was inversely related to gel strength, showing that physicochemical phenomena were the main mechanisms underlying the perceived sensory changes. Fat addition reduced the amount of oral processing and had differential effects on release, depending on the fat solubility or lipophilicity of the volatiles.

  2. A targeted liposome delivery system for combretastatin A4: formulation optimization through drug loading and in vitro release studies.

    Science.gov (United States)

    Nallamothu, Ramakrishna; Wood, George C; Kiani, Mohammad F; Moore, Bob M; Horton, Frank P; Thoma, Laura A

    2006-01-01

    Efficient liposomal therapeutics require high drug loading and low leakage. The objective of this study is to develop a targeted liposome delivery system for combretastatin A4 (CA4), a novel antivascular agent, with high loading and stable drug encapsulation. Liposomes composed of hydrogenated soybean phosphatidylcholine (HSPC), cholesterol, and distearoyl phosphoethanolamine-PEG-2000 conjugate (DSPE-PEG) were prepared by the lipid film hydration and extrusion process. Cyclic arginine-glycine-aspartic acid (RGD) peptides with affinity for alphav beta3-integrins overexpressed on tumor vascular endothelial cells were coupled to the distal end of polyethylene glycol (PEG) on the liposomes sterically stabilized with PEG (non-targeted liposomes; LCLs). Effect of lipid concentration, drug-to-lipid ratio, cholesterol, and DSPE-PEG content in the formulation on CA4 loading and its release from the liposomes was studied. Total liposomal CA4 levels obtained increased with increasing lipid concentration in the formulation. As the drug-to-lipid ratio increased from 10:100 to 20:100, total drug in the liposome formulation increased from 1.05+/-0.11 mg/mL to 1.55+/-0.13 mg/mL, respectively. When the drug-to-lipid ratio was further raised to 40:100, the total drug in liposome formulation did not increase, but the amount of free drug increased significantly, thereby decreasing the percent of entrapped drug. Increasing cholesterol content in the formulation decreased drug loading. In vitro drug leakage from the liposomes increased with increase in drug-to-lipid ratio or DSPE-PEG content in the formulation; whereas increasing cholesterol content of the formulation up to 30 mol-percent, decreased CA4 leakage from the liposomes. Ligand coupling to the liposome surface increased drug leakage as a function of ligand density. Optimized liposome formulation with 100 mM lipid concentration, 20:100 drug-to-lipid ratio, 30 mol-percent cholesterol, 4 mol-percent DSPE-PEG, and 1 mol

  3. Dopamine Release and Uptake Impairments and Behavioral Alterations Observed in Mice that Model Fragile X Mental Retardation Syndrome.

    Science.gov (United States)

    Fulks, Jenny L; O'Bryhim, Bliss E; Wenzel, Sara K; Fowler, Stephen C; Vorontsova, Elena; Pinkston, Jonathan W; Ortiz, Andrea N; Johnson, Michael A

    2010-10-20

    In this study we evaluated the relationship between amphetamine-induced behavioral alterations and dopamine release and uptake characteristics in Fmr1 knockout (Fmr1 KO) mice, which model fragile X syndrome. The behavioral analyses, obtained at millisecond temporal resolution and 2 mm spatial resolution using a force-plate actometer, revealed that Fmr1 KO mice express a lower degree of focused stereotypy compared to wild type (WT) control mice after injection with 10 mg/kg (ip) amphetamine. To identify potentially related neurochemical mechanisms underlying this phenomenon, we measured electrically-evoked dopamine release and uptake using fast-scan cyclic voltammetry at carbon-fiber microelectrodes in striatal brain slices. At 10 weeks of age, dopamine release per pulse, which is dopamine release corrected for differences in uptake, was unchanged. However, at 15 (the age of behavioral testing) and 20 weeks of age, dopamine per pulse and the maximum rate of dopamine uptake was diminished in Fmr1 KO mice compared to WT mice. Dopamine uptake measurements, obtained at different amphetamine concentrations, indicated that dopamine transporters in both genotypes have equal affinities for amphetamine. Moreover, dopamine release measurements from slices treated with quinpirole, a D2-family receptor agonist, rule out enhanced D2 autoreceptor sensitivity as a mechanism of release inhibition. However, dopamine release, uncorrected for uptake and normalized against the corresponding pre-drug release peaks, increased in Fmr1 KO mice, but not in WT mice. Collectively, these data are consistent with a scenario in which a decrease in extracellular dopamine levels in the striatum result in diminished expression of focused stereotypy in Fmr1 KO mice.

  4. Effects of an Antagonistic Analog of Growth Hormone-Releasing Hormone on Endometriosis in a Mouse Model and In Vitro.

    Science.gov (United States)

    Köster, Frank; Jin, Li; Shen, Yuanming; Schally, Andrew V; Cai, Ren-Zhi; Block, Norman L; Hornung, Daniela; Marschner, Gabriele; Rody, Achim; Engel, Jörg B; Finas, Dominique

    2017-11-01

    Endometriosis is a benign gynecologic disorder causing dysmenorrhea, pelvic pain, and subfertility. Receptors for the growth hormone-releasing hormone (GHRH) were found in endometriotic tissues. Antagonists of GHRH have been used to inhibit the growth of endometriotic endometrial stromal cells. In this study, the GHRH receptor splice variant (SV) 1 was detected in human endometrial tissue samples by Western blots and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The highest messenger RNA (mRNA) and protein levels of SV1 were found in eutopic endometrium from patients with endometriosis compared to ectopic endometriotic tissues and endometrium from normal patients. The highest expression for GHRH mRNA was found by qRT-PCR in ectopic endometriosis lesions. In an in vivo mouse model with human endometrial explants from patients with endometriosis, 10 μg MIA-602 per day resulted in significantly smaller human endometrial xenotransplants after 4 weeks compared to mice treated with vehicle. The endometrial tissues expressed SV1 before and after xenotransplantation. The proliferation of endometrial stromal cells as well as the endometriosis cell lines 12-Z and 49-Z was decreased by exposure to 1 μM MIA-602 after 72 hours. The protein levels of epithelial growth factor receptors in 12-Z and 49-Z cell lines were reduced 48 and 72 hours after the administration of 1 μM MIA-602. MIA-602 decreased the activation of the MAP-kinases ERK-1/2. Our study demonstrates the presence of SV1 receptor as a target for treatment with GHRH antagonist in endometriosis. Endometrial tissues respond to MIA-602 with inhibition of proliferation in vitro and in vivo. The use of MIA-602 could be an effective supplement to the treatment strategies in endometriosis.

  5. Long-Acting Diclofenac Ester Prodrugs for Joint Injection: Kinetics, Mechanism of Degradation, and In Vitro Release From Prodrug Suspension.

    Science.gov (United States)

    Mertz, Nina; Larsen, Susan Weng; Kristensen, Jesper; Østergaard, Jesper; Larsen, Claus

    2016-10-01

    A prodrug approach for local and sustained diclofenac action after injection into joints based on ester prodrugs having a pH-dependent solubility is presented. Inherent ester prodrug properties influencing the duration of action include their pH-dependent solubility and charge state, as well as susceptibility to undergo esterase facilitated hydrolysis. In this study, physicochemical properties and pH rate profiles of 3 diclofenac ester prodrugs differing with respect to the spacer carbon chain length between the drug and the imidazole-based promoiety were determined and a rate equation for prodrug degradation in aqueous solution in the pH range 1-10 was derived. In the pH range 6-10, the prodrugs were subject to parallel degradation to yield diclofenac and an indolinone derivative. The prodrug degradation was found to be about 6-fold faster in 80% (vol/vol) human plasma as compared to 80% (vol/vol) human synovial fluid with 2-(1-methyl-1H-imidazol-2-yl)ethyl 2-(2-(2,6 dichlorophenyl)amino)phenylacetate being the poorest substrate toward enzymatic cleavage. The conversion and release of parent diclofenac from prodrug suspensions in vitro were studied using the rotating dialysis model. The results suggest that it is possible to alter and control dissolution and reconversion behavior of the diclofenac prodrugs, thus making the prodrug approach feasible for local and sustained diclofenac action after joint injection. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  6. 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

  7. Application of isotope tracer technique on the study of the filling and release behavior of carbon nanotubes

    International Nuclear Information System (INIS)

    Wu Shengwei; Guo Jinxue; Li Yan; Li Yulan; Li Wenxin; Liu Shiyuan

    2004-01-01

    The behaviors of washing and release of 110 Ag m -AgNO 3 from carbon nanotubes (CNTs), following soak of opened CNTs in 110 Ag m -AgNO 3 solutions are investigated with the isotope tracer technique. The filled CNTs samples are characterized by HREM, SEM, XRD and EDS. The amount of filled materials is also estimated by the isotope tracer technique. It shows that there are silver materials filled in the CNTs and would not release from the cavities. The results indicate that radioactive tracer is an effective and powerful technique to be applied into study of filling and release behaviors of CNTs as well as estimating the amount of filled materials. (authors)

  8. In-vitro release and permeation studies of ketoconazole from optimized dermatological vehicles using powder, nanoparticles and solid dispersion forms of drug

    Science.gov (United States)

    Mohammed, Irfan A.

    study for its drug release/permeation profile using the human cadaver skin as the diffusion barrier. Here, as expected, the drug release from both the formulations tested was significantly reduced due to the resistance posed by the skin. After 6 hours, the drug release form the commercial product was 0.17% when compared to 2.80% from the optimum formulation. Once again, this indicated that the experimental formulation exhibits superior drug release dynamics. The selected formulations were further evaluated for their in-vitro anti-fungal activities using yeast microorganisms. The results correlated to the in-vitro drug release profile, where HPMC based formulations exhibited a greater area of zone of inhibition for the growth of microorganisms when compared to diminutive area of zone of inhibition for the commercial product. The release data from all the samples were treated to calculate various physical parameters including: diffusion co-efficient, partition co-efficient, steady state flux and lag period etc. Interestingly, the values for the steady state flux and diffusion coefficient were found to be the highest from the optimum formulation and the values for the lag time and partition coefficient were observed to be the lowest. This supports the evidence that the drug from this formulation is readily diffusible to the skin at a steady rate after its application at the site. In-vitro drug diffusion studies and in-vitro anti-fungal studies proved useful in screening various dermatological formulations of ketoconazole compared to the commercial product containing 2% w/w drug. The HPMC based optimum formulation with reduced level of drug represents 15 folds increase through human cadaver skin and also exhibited augmented anti-fungal activity. This supports that by using an appropriate vehicle and proper incorporation of drug, one can optimize the drug release from topical formulation for maximum therapeutic effect.

  9. 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.

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

    Science.gov (United States)

    Numpilai, Thanapha; Muenmee, Suthaporn; Witoon, Thongthai

    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 N2-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 5nm to 10nm increased the ibuprofen loading from 0.74 to 0.85mmol/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 92wt.% 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. 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

  12. 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.

  13. A simple and rapid approach to evaluate the in vitro in vivo role of release controlling agent ethyl cellulose ether derivative polymer.

    Science.gov (United States)

    Akhlaq, Muhammad; Khan, Gul Majid; Jan, Syed Umer; Wahab, Abdul; Hussain, Abid; Nawaz, Asif; Abdelkader, Hamdy

    2014-11-01

    Diclofenac sodium (DCL-Na) conventional oral tablets exhibit serious side effects when given for a longer period leading to noncompliance. Controlled release matrix tablets of diclofenac sodium were formulated using simple blending (F-1), solvent evaporation (F-2) and co-precipitation techniques (F-3). Ethocel® Standard 7 FP Premium Polymer (15%) was used as a release controlling agent. Drug release study was conducted in 7.4 pH phosphate buffer solutions as dissolution medium in vitro. Pharmacokinetic parameters were evaluated using albino rabbits. Solvent evaporation technique was found to be the best release controlling technique thereby prolonging the release rate up to 24 hours. Accelerated stability studies of the optimized test formulation (F-2) did not show any significant change (prelease rate when stored for six months. A simple and rapid method was developed for DCL-Na active moiety using HPLC-UV at 276nm. The optimized test tablets (F-2) significantly (prelease. The study showed that once-daily controlled release matrix tablets of DCL-Na were successfully developed using Ethocel® Standard 7 FP Premium.

  14. 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.

  15. 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).

  16. Evaluation of Fatigue Behavior in Dental Implants from In Vitro Clinical Tests: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Rosa Rojo

    2018-05-01

    Full Text Available In the area of dentistry, there is a wide variety of designs of dental implant and materials, especially titanium, which aims to avoid failures and increase their clinical durability. The purpose of this review was to evaluate fatigue behavior in different connections and implant materials, as well as their loading conditions and response to failure. In vitro tests under normal and dynamic loading conditions evaluating fatigue at implant and abutment connection were included. A search was conducted in PubMed, Scopus, and Science Direct. Data extraction was performed independently by two reviewers. The quality of selected studies was assessed using the Cochrane Handbook proposed by the tool for clinical trials. Nineteen studies were included. Fourteen studies had an unclear risk and five had high risk of bias. Due to the heterogeneity of the data and the evaluation of the quality of the studies, meta-analysis could not be performed. Evidence from this study suggests that both internal and morse taper connections presented a better behavior to failure. However, it is necessary to unify criteria in the methodological design of in vitro studies, following methodological guidelines and establishing conditions that allow the homogenization of designs in ISO (International Organization for Standardization standards.

  17. Nanostructural drug-inorganic clay composites: Structure, thermal property and in vitro release of captopril-intercalated Mg-Al-layered double hydroxides

    International Nuclear Information System (INIS)

    Zhang Hui; Zou Kang; Guo Shaohuan; Duan Xue

    2006-01-01

    A nanostructural drug-inorganic clay composite involving a pharmaceutically active compound captopril (Cpl) intercalated Mg-Al-layered double hydroxides (Cpl-LDHs) with Mg/Al molar ratio of 2.06 has been assembled by coprecipitation method. Powder X-ray diffraction (XRD), Fourier transform infrared spectra (FT-IR) and Raman spectra analysis indicate a successful intercalation of Cpl between the layers with a vertical orientation of Cpl disulphide-containing S-S linkage. SEM photo indicates that as-synthesized Cpl-LDHs possess compact and non-porous structure with approximately and linked elliptical shape particles of ca. 50 nm. TG-DTA analyses suggest that the thermal stability of intercalated organic species is largely enhanced due to host-guest interaction involving the hydrogen bond compared to pure form before intercalation. The in vitro release studies show that both the release rate and release percentages markedly decrease with increasing pH from 4.60 to 7.45 due to possible change of release mechanism during the release process. The kinetic simulation for the release data, and XRD and FT-IR analyses for samples recovered from release media indicate that the dissolution mechanism is mainly responsible for the release behaviour of Cpl-LDHs at pH 4.60, while the ion-exchange one is responsible for that at pH 7.45. - Graphical abstract: Based on XRD, FT-IR and Raman spectra analyses, it is suggested that captopril (Cpl) exists as its disulphide metabolites in the interlayer of Mg-Al-LDHs via hydrogen bonding between guest carboxylate function and hydroxyl group of the host layers. A schematic supramolecular structure of Cpl intercalates involving a vertical orientation of Cpl disulphide-containing S-S bond between the layers with carboxylate anions pointing to both hydroxide layers is presented

  18. 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.

  19. The in Vitro Release of Indomethacin from Suppositories: Effects of Bases and Comparison of Different Dissolution Methods.

    Science.gov (United States)

    Mori, Kenji; Hori, Seiichi; Kawata, Tsubasa; Kogure, Sanae; Matsumoto, Kaori; Hasegawa, Tetsuya; Akimoto, Masayuki

    2017-01-01

    The suitability of apparatuses for the quality control of indomethacin (IND, 50 mg) compounded suppositories was evaluated and the effects of the type of suppository base on release profiles was investigated. The release characteristics of hydrophilic and lipophilic suppositories containing IND were compared using four types of dissolution methods: basket (RB), paddle (PD), dialysis tubing (DT) and flow-through cell (FTC). The release process was evaluated using the following model independent parameters: the mean dissolution time (MDT), cumulative percent of drug released (Q) at the end of the sampling time, and dissolution efficiency (DE). The fastest and most reproducible release profiles were observed for a hydrophilic base (macrogols), which resulted in more than 90% of the drug being released in 30 min using PD, RB and FTC. After 90 min, 90% of the total amount of the drug was released from a mixture of hydrophilic bases with a lipophilic base (macrogols and hard fat) in compendial dissolution methods and the mixture base was the second fastest only to the hydrophilic base. The slowest release profiles in each method were observed for the lipophilic base (hard fat). Poor drug release from any type of suppository base was noted using DT. Based on the results of the present study, FTC may be regarded as an adequate technique allowing sufficient discriminating power for the quality control of IND compounded suppositories.

  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. 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 (pH M -SD) for the poorly water-soluble model drug Toltrazuril (TOL). Various pH M -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 (TOLSO 2 ). The in-vitro dissolution profiles and in-vivo absorption, distribution and metabolism behaviors of the pH M -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 pH M -SDs prepared with various polymers. Therefore, a non-sink in-vitro dissolution method can be used to predict the in-vivo performance of pH M -SDs formulated with various polymers with trend consistency. In-vitro and in-vivo screening procedures revealed that the pH M -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.

  3. Biodegradable drug-eluting nanofiber-enveloped implants for sustained release of high bactericidal concentrations of vancomycin and ceftazidime: in vitro and in vivo studies

    Directory of Open Access Journals (Sweden)

    Hsu YH

    2014-09-01

    Full Text Available Yung-Heng Hsu,1,2 Dave Wei-Chih Chen,1 Chun-Der Tai,3 Ying-Chao Chou,1,2 Shih-Jung Liu,2 Steve Wen-Neng Ueng,1 Err-Cheng Chan4 1Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Guishan Township, 2Department of Mechanical Engineering, Chang Gung University, Guishan Township, 3Graduate Institute of Medical Mechatronics, Chang Gung University, Guishan Township, 4School of Medical Technology, Chang Gung University, Guishan Township, Taiwan Abstract: We developed biodegradable drug-eluting nanofiber-enveloped implants that provided sustained release of vancomycin and ceftazidime. To prepare the biodegradable nanofibrous membranes, poly(D,L-lactide-co-glycolide and the antibiotics were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol. They were electrospun into biodegradable drug-eluting membranes, which were then enveloped on the surface of stainless plates. An elution method and a high-performance liquid chromatography assay were employed to characterize the in vivo and in vitro release rates of the antibiotics from the nanofiber-enveloped plates. The results showed that the biodegradable nanofiber-enveloped plates released high concentrations of vancomycin and ceftazidime (well above the minimum inhibitory concentration for more than 3 and 8 weeks in vitro and in vivo, respectively. A bacterial inhibition test was carried out to determine the relative activity of the released antibiotics. The bioactivity ranged from 25% to 100%. In addition, the serum creatinine level remained within the normal range, suggesting that the high vancomycin concentration did not affect renal function. By adopting the electrospinning technique, we will be able to manufacture biodegradable drug-eluting implants for the long-term drug delivery of different antibiotics. Keywords: biodegradable nanofiber-enveloped plates, electrospinning, antibiotics, release characteristics

  4. Effect of a controlled-release drug delivery system made of oleanolic acid formulated into multivesicular liposomes on hepatocellular carcinoma in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Luo YL

    2016-07-01

    Full Text Available Yuling Luo, Zhongbing Liu, Xiaoqin Zhang, Juan Huang, Xin Yu, Jinwei Li, Dan Xiong, Xiaoduan Sun, Zhirong Zhong Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan,People’s Republic of ChinaAbstract: The aim of the present study was to develop a novel dosage form of multivesicular liposomes for oleanolic acid (OA to overcome its poor solubility, prolong therapeutic drug levels in the blood, and enhance the antitumor effect on hepatocellular carcinoma. OA-encapsulated multivesicular liposomes (OA-MVLs were prepared by a double-emulsion method, and the formulation was optimized by the central composite design. The morphology, particle size, and drug-loading efficiency of OA-MVLs were investigated. Furthermore, OA-MVLs were also characterized both in vitro and in vivo. The results showed that OA-MVLs were spherical particles with an average particle size of 11.57 µm and an encapsulation efficiency of 82.3%±0.61%. OA-MVLs exhibited a sustained-release pattern in vitro, which was fitted to Ritger–Peppas equation. OA-MVLs inhibited the growth of human HepG2 cells which was confirmed by the MTT assay and fluorescence microscopy detection. The in vivo release of OA from OA-MVLs exhibited a sustained manner, indicating a longer circulation time compared to OA solution. The in vivo toxicity study indicated that medium-dose OA-MVLs exerted no toxic effect on the hosts. Importantly, OA-MVLs suppressed the growth of murine H22 hepatoma and prolonged the survival of tumor-bearing mice. In conclusion, the poorly soluble OA could be encapsulated into MVLs to form a novel controlled-release drug delivery system. The present study may hold promise for OA-MVLs as a new dosage form for sustained-release drug delivery in cancer therapy.Keywords: oleanolic acid, multivesicular liposomes, murine hepatocellular carcinoma, controlled release, cancer therapy

  5. Evaluation of the effect of physical variables on in vitro release of diclofenac pellets using Box-Behnken design

    Directory of Open Access Journals (Sweden)

    Reza Enayatifard

    2015-07-01

    Full Text Available Objective(s: A Box-Behnken design was used for evaluation of Eudragit coated diclofenac pellets. The purpose of this work was to optimize diclofenac pellets to improve the physicochemical properties using experimental design. Materials and Methods: Diclofenac was loaded onto the non-pareil beads using conventional coating pan. Film coating of pellets was done at the same pan. The effect of plasticizer level, curing temperature and curing time was determined on the release of diclofenac from pellets coated with polymethacrylates. Results: Increasing the plasticizer in the coating formula led to decrease in drug release and increasing the curing temperature and time resulted in higher drug release. The optimization process generated an optimum of 35% drug release at 3 hr. The level of plasticizer concentration, curing temperature and time were 20% w/w, 55 °C and 24 hr, respectively. Conclusion: This study showed that by controllinig the physical variables optimum drug release were obtained.

  6. Evaluation of the effect of physical variables on in vitro release of diclofenac pellets using Box-Behnken design

    Science.gov (United States)

    Enayatifard, Reza; Mahjoob, Aiding; Ebrahimi, Pouneh; Ebrahimnejad, Pedram

    2015-01-01

    Objective(s): A Box-Behnken design was used for evaluation of Eudragit coated diclofenac pellets. The purpose of this work was to optimize diclofenac pellets to improve the physicochemical properties using experimental design. Materials and Methods: Diclofenac was loaded onto the non-pareil beads using conventional coating pan. Film coating of pellets was done at the same pan. The effect of plasticizer level, curing temperature and curing time was determined on the release of diclofenac from pellets coated with polymethacrylates. Results: Increasing the plasticizer in the coating formula led to decrease in drug release and increasing the curing temperature and time resulted in higher drug release. The optimization process generated an optimum of 35% drug release at 3 hr. The level of plasticizer concentration, curing temperature and time were 20% w/w, 55 °C and 24 hr, respectively. Conclusion: This study showed that by controllinig the physical variables optimum drug release were obtained. PMID:26351563

  7. The control of beads diameter of bead-on-string electrospun nanofibers and the corresponding release behaviors of embedded drugs

    Energy Technology Data Exchange (ETDEWEB)

    Li, Tingxiao [Key Laboratory of Textile Science and Technology (Donghua University), Ministry of Education of China, Shanghai 201620 (China); College of Textiles, Donghua University, Shanghai 201620 (China); Ding, Xin, E-mail: xding@dhu.edu.cn [Key Laboratory of Textile Science and Technology (Donghua University), Ministry of Education of China, Shanghai 201620 (China); College of Textiles, Donghua University, Shanghai 201620 (China); Tian, Lingling, E-mail: lingling_tian@nus.edu.sg [Center of Nanofibers & Nanotechnology, Department of Mechanical Engineering, National University of Singapore, 117576 (Singapore); Hu, Jiyong; Yang, Xudong [Key Laboratory of Textile Science and Technology (Donghua University), Ministry of Education of China, Shanghai 201620 (China); College of Textiles, Donghua University, Shanghai 201620 (China); Ramakrishna, Seeram [Center of Nanofibers & Nanotechnology, Department of Mechanical Engineering, National University of Singapore, 117576 (Singapore); Guangdong-Hongkong-Macau Institute of CNS Regeneration (GHMICR), Jinan University, Guangzhou 510632 (China)

    2017-05-01

    Bead-on-string nanofibers, with appropriate control of the beads diameter, are potential fibrous structures for efficient encapsulation of particle drugs in micron scales and could achieve controlled drug release for tissue engineering applications. In this study, the beads diameter of electrospun bead-on-string nanofibers was controlled by adjusting the concentration of spinning polymer, poly (lactic-co-glycolic acid) (PLGA), and the solvent ratio of chloroform to acetone. The images of the scanning electron microscopy (SEM) suggested that bead-on-string nanofibers could be successfully obtained only with a certain range of PLGA solution concentration. Moreover, with the decrease in the solvent ratio of chloroform to acetone, the range was left-shifted towards a smaller concentration. In addition, increase in the PLGA solution concentration within the range the beads diameter became greater and the shape of the beads changed from oval to slender when increasing the PLGA concentration within the range. The bead-on-string nanofibers with different beads diameter were further used to load micro-particle drugs of tetracycline hydrochloride, as a model drug, to examine the release behavior of nanofibers scaffold. The release profiles of drug loaded bead-on-string nanofibers demonstrated the possibility to alleviate the burst drug release by means of beads diameter control. - Highlights: • Bead diameter of bead-on-string electrospun nanofibers was controlled by varying solvent ratio and polymer concentration. • The effect of the addition of particle drugs on BD of bead-on-string electrospun nanofibers was studied. • The corresponding release behaviors of nanofibers with different BD loading micro-particle drugs were investigated. • Bead-on-string nanofibers with bigger BD could alleviate the initial burst release.

  8. The control of beads diameter of bead-on-string electrospun nanofibers and the corresponding release behaviors of embedded drugs

    International Nuclear Information System (INIS)

    Li, Tingxiao; Ding, Xin; Tian, Lingling; Hu, Jiyong; Yang, Xudong; Ramakrishna, Seeram

    2017-01-01

    Bead-on-string nanofibers, with appropriate control of the beads diameter, are potential fibrous structures for efficient encapsulation of particle drugs in micron scales and could achieve controlled drug release for tissue engineering applications. In this study, the beads diameter of electrospun bead-on-string nanofibers was controlled by adjusting the concentration of spinning polymer, poly (lactic-co-glycolic acid) (PLGA), and the solvent ratio of chloroform to acetone. The images of the scanning electron microscopy (SEM) suggested that bead-on-string nanofibers could be successfully obtained only with a certain range of PLGA solution concentration. Moreover, with the decrease in the solvent ratio of chloroform to acetone, the range was left-shifted towards a smaller concentration. In addition, increase in the PLGA solution concentration within the range the beads diameter became greater and the shape of the beads changed from oval to slender when increasing the PLGA concentration within the range. The bead-on-string nanofibers with different beads diameter were further used to load micro-particle drugs of tetracycline hydrochloride, as a model drug, to examine the release behavior of nanofibers scaffold. The release profiles of drug loaded bead-on-string nanofibers demonstrated the possibility to alleviate the burst drug release by means of beads diameter control. - Highlights: • Bead diameter of bead-on-string electrospun nanofibers was controlled by varying solvent ratio and polymer concentration. • The effect of the addition of particle drugs on BD of bead-on-string electrospun nanofibers was studied. • The corresponding release behaviors of nanofibers with different BD loading micro-particle drugs were investigated. • Bead-on-string nanofibers with bigger BD could alleviate the initial burst release.

  9. Hot Experiment on Fission Gas Release Behavior from Voloxidation Process using Spent Fuel

    International Nuclear Information System (INIS)

    Park, Geun Il; Park, J. J.; Jung, I. H.; Shin, J. M.; Cho, K. H.; Yang, M. S.; Song, K. C.

    2007-08-01

    Quantitative analysis of the fission gas release characteristics during the voloxidation and OREOX processes of spent PWR fuel was carried out by spent PWR fuel in a hot-cell of the DFDF. The release characteristics of 85 Kr and 14 C fission gases during voloxidation process at 500 .deg. C is closely linked to the degree of conversion efficiency of UO 2 to U 3 O 8 powder, and it can be interpreted that the release from grain-boundary would be dominated during this step. Volatile fission gases of 14 C and 85 Kr were released to near completion during the OREOX process. Both the 14 C and 85 Kr have similar release characteristics under the voloxidation and OREOX process conditions. A higher burn-up spent fuel showed a higher release fraction than that of a low burn-up fuel during the voloxidation step at 500 .deg. C. It was also observed that the release fraction of semi-volatile Cs was about 16% during a reduction at 1,000 .deg. C of the oxidized powder, but over 90% during the voloxidation at 1,250 .deg. C

  10. Three-dimensional, two-species magnetohydrodynamic studies of the early time behaviors of the Combined Release and Radiation Effects Satellite G2 barium release

    International Nuclear Information System (INIS)

    Xie, Lianghai; Li, Lei; Wang, Jingdong; Zhang, Yiteng

    2014-01-01

    We present a three-dimensional, two-species (Ba + and H + ) MHD model to study the early time behaviors of a barium release at about 1 R E like Combined Release and Radiation Effects Satellite G2, with emphasis placed on the three-dimensional evolution of the barium cloud and its effects on the ambient plasma environment. We find that the perturbations caused by the cloud are the combined results of the initial injection, the radial expansion, and the diamagnetic effect and propagate as fast MHD waves in the magnetosphere. In return, the transverse expansion and the cross-B motion of barium ions are constrained by the magnetic force, which lead to a field-aligned striation of ions and the decoupling of these ions from the neutrals. Our simulation shows the formation and collapse of the diamagnetic cavity in the barium cloud. The estimated time scale for the cavity evolution might be much shorter if photoionization time scale and field aligned expansion of barium ions are considered. In addition, our two species MHD simulation also finds the snowplow effect resulting from the momentum coupling between barium ions and background H + , which creates density hole and bumps in the background H + when barium ions expanding along the magnetic field lines

  11. 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.

  12. 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.

  13. Effect of hydroxyapatite-containing microspheres embedded into three-dimensional magnesium phosphate scaffolds on the controlled release of lysozyme and in vitro biodegradation

    Directory of Open Access Journals (Sweden)

    Lee JM

    2014-09-01

    Full Text Available Jongman Lee, Hui-suk YunPowder and Ceramics Division, Korea Institute of Materials Science, Changwon, Republic of KoreaAbstract: The functionality of porous three-dimensional (3D magnesium phosphate (MgP scaffold was investigated for the development of a novel protein delivery system and biomimetic bone tissue engineering scaffold. This enhancement can be achieved by incorporation of hydroxyapatite (HA-containing polymeric microspheres (MSs into a bulk MgP matrix, and a paste-extruding deposition (PED system. In this work, the amount of MS and HA was precisely controlled when manufacturing MS-embedded MgP (MS/MgP composite scaffolds. The main influence was researched in terms of in vitro lysozyme-release, in vitro biodegradation, mechanical properties, and in vitro calcification. The controlled release of lysozyme was indicated, while showing graded release patterns according to HA content. The composite scaffolds degraded gradually with MS content and degradation time. Due to the effect of HA inclusion, the higher HA-containing MS/MgP scaffolds could, not only delay the biodegradation process but also, compensate for the possible loss of mechanical properties. In this regard, it is reasonable to confirm the inverse relationship between biodegradation and corresponding compressive properties. In order to encourage bioactivity and osteoconductivity, the MS/MgP composite scaffolds were subjected to simulated body fluid treatment. Calcium deposition was, in turn, improved with increasing MS and HA content over time. This quantitative result was also proved using morphological and elemental analysis. In summary, a significant transformation of a monolithic MgP scaffold was directed toward a multifunctional bone tissue engineering scaffold equipped with controlled protein delivery, biodegradability, and bioactivity.Keywords: protein delivery, bone tissue engineering

  14. Microstructure, mechanical property, corrosion behavior, and in vitro biocompatibility of Zr-Mo alloys.

    Science.gov (United States)

    Zhou, F Y; Wang, B L; Qiu, K J; Li, L; Lin, J P; Li, H F; Zheng, Y F

    2013-02-01

    In this study, the microstructure, mechanical properties, corrosion behaviors, and in vitro biocompatibility of Zr-Mo alloys as a function of Mo content after solution treatment were systemically investigated to assess their potential use in biomedical application. The experimental results indicated that Zr-1Mo alloy mainly consisted of an acicular structure of α' phase, while ω phase formed in Zr-3Mo alloy. In Zr-5Mo alloy, retained β phase and a small amount of precipitated α phase were observed. Only the retained β phase was obtained in Zr-10Mo alloy. Zr-1Mo alloy exhibited the greatest hardness, bending strength, and modulus among all experimental Zr-Mo alloys, while β phase Zr-10Mo alloy had a low modulus. The results of electrochemical corrosion indicated that adding Mo into Zr improved its corrosion resistance which resulted in increasing the thermodynamic stability and passivity of zirconium. The cytotoxicity test suggested that the extracts of the studied Zr-Mo alloys produced no significant deleterious effect to fibroblast cells (L-929) and osteoblast cells (MG 63), indicating an excellent in vitro biocompatibility. Based on these facts, certain Zr-Mo alloys potentially suitable for different biomedical applications were proposed. Copyright © 2012 Wiley Periodicals, Inc.

  15. Gastrointestinal and in vitro release of copper, cadmium, indium, mercury and zinc from conventional and copper-rich amalgams

    International Nuclear Information System (INIS)

    Brune, D.; Gjerdet, N.; Paulsen, G.

    1983-01-01

    Particles of a conventional lathe-cut, a spherical non-gamma 2 and a copper amalgam have been gastrointestinally administered to rats for the purpose of evaluation of the dissolution resistance. The animals were sacrificed after 20 hrs. The contents of copper, cadmium, indium, mercury and zinc in kidney, liver, lung or blood were measured using nuclear tracer techniques. From a copper amalgam an extreme release of copper was demonstrated. This study simulates the clinical conditions of elemental release from swallowed amalgam particles after amalgam insertion or after removal of old amalgam fillings. Specimens of the same types of amalgams were also exposed to artificial saliva for a period of 10 days. The amounts of copper and mercury released were measured with flame and flameless atomic absorption spectrophotometry respectively. The levels of copper and mercury released from the copper amalgam were approximately 50 times those of the two other amalgam types studied. (author)

  16. In vitro characterization of a formulation of butorphanol tartrate in a poloxamer 407 base intended for use as a parenterally administered slow-release analgesic agent.

    Science.gov (United States)

    Laniesse, Delphine; Smith, Dale A; Knych, Heather K; Mosley, Cornelia; Guzman, David Sanchez-Migallon; Beaufrère, Hugues

    2017-06-01

    OBJECTIVE To assess rheological properties and in vitro diffusion of poloxamer 407 (P407) and butorphanol-P407 (But-P407) hydrogels and to develop a sustained-release opioid formulation for use in birds. SAMPLE P407 powder and a commercially available injectable butorphanol tartrate formulation (10 mg/mL). PROCEDURES P407 and But-P407 gels were compounded by adding water or butorphanol to P407 powder. Effects of various concentrations of P407 (20%, 25% and 30% [{weight of P407/weight of diluent} × 100]), addition of butorphanol, and sterilization through a microfilter on rheological properties of P407 were measured by use of a rheometer. In vitro diffusion of butorphanol from But-P407 25% through a biological membrane was compared with that of a butorphanol solution. RESULTS P407 20% and 25% formulations were easily compounded, whereas it was difficult to obtain a homogenous P407 30% formulation. The P407 was a gel at avian body temperature, although its viscosity was lower than that at mammalian body temperature. The But-P407 25% formulation (butorphanol concentration, 8.3 mg/mL) was used for subsequent experiments. Addition of butorphanol to P407 as well as microfiltration did not significantly affect viscosity. Butorphanol diffused in vitro from But-P407, and its diffusion was slower than that from a butorphanol solution. CONCLUSIONS AND CLINICAL RELEVANCE But-P407 25% had in vitro characteristics that would make it a good candidate for use as a sustained-release analgesic medication. Further studies are needed to characterize the pharmacokinetic and pharmacodynamic properties of But-P407 25% in vivo before it can be recommended for use in birds.

  17. 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.

  18. 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

  19. pH responsive N-succinyl chitosan/Poly (acrylamide-co-acrylic acid hydrogels and in vitro release of 5-fluorouracil.

    Directory of Open Access Journals (Sweden)

    Shahid Bashir

    Full Text Available There has been significant progress in the last few decades in addressing the biomedical applications of polymer hydrogels. Particularly, stimuli responsive hydrogels have been inspected as elegant drug delivery systems capable to deliver at the appropriate site of action within the specific time. The present work describes the synthesis of pH responsive semi-interpenetrating network (semi-IPN hydrogels of N-succinyl-chitosan (NSC via Schiff base mechanism using glutaraldehyde as a crosslinking agent and Poly (acrylamide-co-acrylic acid(Poly (AAm-co-AA was embedded within the N-succinyl chitosan network. The physico-chemical interactions were characterized by Fourier transform infrared (FTIR, X-ray diffraction (XRD, thermogravimetric analysis (TGA, and field emission scanning electron microscope (FESEM. The synthesized hydrogels constitute porous structure. The swelling ability was analyzed in physiological mediums of pH 7.4 and pH 1.2 at 37°C. Swelling properties of formulations with various amounts of NSC/ Poly (AAm-co-AA and crosslinking agent at pH 7.4 and pH 1.2 were investigated. Hydrogels showed higher swelling ratios at pH 7.4 while lower at pH 1.2. Swelling kinetics and diffusion parameters were also determined. Drug loading, encapsulation efficiency, and in vitro release of 5-fluorouracil (5-FU from the synthesized hydrogels were observed. In vitro release profile revealed the significant influence of pH, amount of NSC, Poly (AAm-co-AA, and crosslinking agent on the release of 5-FU. Accordingly, rapid and large release of drug was observed at pH 7.4 than at pH 1.2. The maximum encapsulation efficiency and release of 5-FU from SP2 were found to be 72.45% and 85.99%, respectively. Kinetics of drug release suggested controlled release mechanism of 5-FU is according to trend of non-Fickian. From the above results, it can be concluded that the synthesized hydrogels have capability to adapt their potential exploitation as targeted oral drug

  20. Investigation on Secondary Structure Perturbations of Proteins Embedded in Solid Lipid Matrices as a Novel Indicator of their Biological Activity upon In Vitro Release

    DEFF Research Database (Denmark)

    Zeeshan, Farrukh; Tabbassum, Misbah; Jorgensen, Lene

    2018-01-01

    encased in solid lipid matrices as a novel indicator of their stability upon in vitro release. Model proteins namely catalase and lysozyme were incorporated into lipid namely Precirol® AT05 (glycerol palmitostearate, melting point 58°C) at 30% w/w loading using melting and mixing and wet granulation...... aggregation for catalase which was increased using wet granulation. The biological activity of catalase was statistically different from that of control and was affected by the incorporation method and was found to be in alignment with ATR spectral changes and extent of aggregation. In conclusion, ATR...

  1. Synthesis, characterization, and controlled release antibacterial behavior of antibiotic intercalated Mg–Al layered double hydroxides

    International Nuclear Information System (INIS)

    Wang, Yi; Zhang, Dun

    2012-01-01

    Graphical abstract: The antibiotic anion released from Mg–Al LDHs provides a controlled release antibacterial activity against the growth of Micrococcus lysodeikticus in 3.5% NaCl solution. Highlights: ► Antibiotic anion intercalated LDHs were synthesized and characterized. ► The ion-exchange one is responsible for the release process. ► The diffusion through particle is the release rate limiting step. ► LDHs loaded with antibiotic anion have high antibacterial capabilities. -- Abstract: Antibiotic–inorganic clay composites including four antibiotic anions, namely, benzoate (BZ), succinate (SU), benzylpenicillin (BP), and ticarcillin (TC) anions, intercalated Mg–Al layered double hydroxides (LDHs) were synthesized via ion-exchange. Powder X-ray diffraction and Fourier transform infrared spectrum analyses showed the successful intercalation of antibiotic anion into the LDH interlayer. BZ and BP anions were accommodated in the interlayer region as a bilayer, whereas SU and TC anions were intercalated in a monolayer arrangement. Kinetic simulation of the release data indicated that ion-exchange was responsible for the release process, and the diffusion through the particles was the rate-limiting step. The antibacterial capabilities of LDHs loaded with antibiotic anion toward Micrococcus lysodeikticus growth were analyzed using a turbidimetric method. Significant high inhibition rate was observed when LDH nanohybrid was introduced in 3.5% NaCl solution. Therefore, this hybrid material may be applied as nanocontainer in active antifouling coating for marine equipment.

  2. Drug Loading and Release Behavior Depending on the Induced Porosity of Chitosan/Cellulose Multilayer Nanofilms.

    Science.gov (United States)

    Park, Sohyeon; Choi, Daheui; Jeong, Hyejoong; Heo, Jiwoong; Hong, Jinkee

    2017-10-02

    The ability to control drug loading and release is the most important feature in the development of medical devices. In this research, we prepared a functional nanocoating technology to incorporate a drug-release layer onto a desired substrate. The multilayer films were prepared using chitosan (CHI) and carboxymethyl cellulose (CMC) polysaccharides by the layer-by-layer (LbL) method. By using chemical cross-linking to change the inner structure of the assembled multilayer, we could control the extent of drug loading and release. The cross-linked multilayer film had a porous structure and enhanced water wettability. Interestingly, more of the small-molecule drug was loaded into and released from the non-cross-linked multilayer film, whereas more of the macromolecular drug was loaded into and released from the cross-linked multilayer film. These results indicate that drug loading and release can be easily controlled according to the molecular weight of the desired drug by changing the structure of the film.

  3. 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....

  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. A novel co-processed directly compressible release-retarding polymer: In vitro, solid state and in vivo evaluation

    Directory of Open Access Journals (Sweden)

    Prashant Kumar Choudhari

    2018-06-01

    Full Text Available Directly compressible (DC co-processed excipient capable of providing nearly zero order release with improved functionality was developed without any chemical modification by employed various techniques such as physical mixing, high shear mixer granulation and spray drying. Co-processed excipient was developed by using release retarding polymer Eudragit RSPO, separately, in combination with different concentration of hydroxyl propyl methyl cellulose 100 cps (Methocel K100 LV, HPMC, ethyl cellulose (Ethocel N50, EC and hydroxyl propyl cellulose (Klucel EF, HPC. All co-processed excipients were evaluated for their flow properties in terms of angle of repose, bulk density, tapped density, compressibility index and Hausner's ratio. Out of eighteen combinations, the nine co-processed excipients exhibited promising flow properties were found suitable for direct compression and formulated as tablets. Metoprolol succinate, a BCS Class I drug, was selected as a model drug and the formulation was developed employing direct compression approach. The developed tablets were evaluated for physical parameters like uniformity of weight, thickness, hardness, friability and assay. In vitro dissolution study confirms that formulation prepared using co-processed excipient showed sustained drug release. The optimized tablet formulation was characterized by DSC, FTIR and PXRD which confirms the absence of any chemical change during co-processing. The optimized formulation was kept for stability study for six months as per ICH guidelines and found to be stable. In vivo pharmacokinetic study of optimized formulation in rats showed similar pharmacokinetic behaviour as was observed with the marketed brand. Study revealed that co-processed excipient has advantage over polymers with single property and can be utilised for sustained release formulation. Keywords: Co-processed excipient, Metoprolol succinate, Extended-release, Direct compression, Zero-order release

  6. 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)

  7. Analgesic and anti-inflammatory controlled-released injectable microemulsion: Pseudo-ternary phase diagrams, in vitro, ex vivo and in vivo evaluation.

    Science.gov (United States)

    Pineros, Isabel; Slowing, Karla; Serrano, Dolores R; de Pablo, Esther; Ballesteros, Maria Paloma

    2017-04-01

    Development of analgesic and anti-inflammatory controlled-released injectable microemulsions utilising lysine clonixinate (LC) as model drug and generally regarded as safe (GRAS) excipients. Different microemulsions were optimised through pseudo-ternary phase diagrams and characterised measuring droplet size, viscosity, ex vivo haemolytic activity and in vitro drug release. The anti-inflammatory and analgesic activity was tested in mice (Hot plate test) and rats (Carrageenan-induced paw edema test) respectively and their activity was compared to an aqueous solution of LC salt. The aqueous solution showed a faster and shorter response whereas the optimised microemulsion increased significantly (p<0.01) the potency and duration of the analgesic and anti-inflammatory activity after deep intramuscular injection. The droplet size and the viscosity were key factors to control the drug release from the systems and enhance the effect of the formulations. The microemulsion consisting of Labrafil®/Lauroglycol®/Polysorbate 80/water with LC (56.25/18.75/15/10, w/w) could be a promising formulation after buccal surgery due to its ability to control the drug release and significantly achieve greater analgesic and anti-inflammatory effect over 24h. Copyright © 2016. Published by Elsevier B.V.

  8. Collagen induced aggregation of platelets and release of 14C serotonin from platelets depending on temperature and pH during in vitro storage of platelets

    International Nuclear Information System (INIS)

    Krause, J.

    1978-01-01

    The paper investigates collagen-induced platelet aggregation and 14 C serotonin release in dependence of age, temperature, and pH value during the storage of the conserved platelets. The optimum pH (with adjusted CO 2 /air mixture) for platelet storage is found to be pH 6.9. The optimum temperature for platelet storage is 4-8 0 C. After 12, 24, or 48 hours of storage at pH 6.9 and 4-8 0 C and subsequent heating of the platelet-rich plasma to 37 0 C for 30 minutes, the values determined for collagen-induced platelet aggregation and 14 C serotonin release rarely differed from the initial values before storage. Cold-induced spontaneous platelet aggregation and serotonin release of the platelets stored at 4-8 0 C can be avoided by 30-60 minutes pre-incubation of the platelets at 37 0 C before transfusions. The in vitro findings for collagen-induced platelet aggregation and 14 C serotonin release indicate that platelet storage for 24-48 hours at pH 6.9 and 4-8 0 C may be permissible also for clinical purposes. The problem remains open whether the clinical effect of these platelets is still sufficient after 48 hours of storage, but literature findings suggest that this may well be the case. (orig.) [de

  9. Release of neuropeptides from a neuro-cutaneous co-culture model: A novel in vitro model for studying sensory effects of ciguatoxins.

    Science.gov (United States)

    Le Garrec, Raphaele; L'herondelle, Killian; Le Gall-Ianotto, Christelle; Lebonvallet, Nicolas; Leschiera, Raphael; Buhe, Virginie; Talagas, Matthieu; Vetter, Irina; Lewis, Richard J; Misery, Laurent

    2016-06-15

    Ciguatoxins are the major toxins responsible for ciguatera fish poisoning, a disease dominated by muco-cutaneous sensory disorders including paresthesiae, cold dysesthesia and pruritus. While the ciguatoxins are well known to target voltage-gated sodium channels (VGSCs), the ensuing molecular mechanisms underlying these sensory disorders remain poorly understood. In this study, we propose a primary sensory neuron-keratinocyte co-culture as an appropriate model to study the neuro-cutaneous effects of ciguatoxins. Using this model, we show for the first time that nanomolar concentrations of Pacific ciguatoxin-2 (P-CTX-2) induced a VGSC-dependent release of substance P (SP) and calcitonin gene-related peptide (CGRP). As these neuropeptides are known mediators of pain and itch sensations, the ciguatoxin-induced sensory disturbances in ciguatera fish poisoning may involve the release of these neuropeptides. We further determined time- and P-CTX-2 concentration-dependence of the release of SP and CGRP from the co-culture model. Moreover, we highlighted the influence of extracellular calcium on the release of neuropeptides elicited by P-CTX-2. These findings underline the usefulness of this novel in vitro model for studying the cellular and molecular mechanisms of the neuro-cutaneous effects of ciguatoxins, which may assist with identifying potential therapeutics for ciguatera fish poisoning. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Cortisol rapidly reduces prolactin release and cAMP and 45Ca2+ accumulation in the cichlid fish pituitary in vitro

    International Nuclear Information System (INIS)

    Borski, R.J.; Helms, L.M.H.; Richman, N.H. III; Grau, E.G.

    1991-01-01

    During in vitro incubation, prolactin release is inhibited in a dose-related manner by cortisol. This action is mimicked by the synthetic glucocorticoid agonist dexamethasone but not by other steroids tested. Perifusion studies indicate that the inhibition of [ 3 H]prolactin release by cortisol occurs within 20 min. Cortisol (50 nM) also inhibits cAMP accumulation and reduces 45 Ca 2+ accumulation in the tilapia rostral pars distalis within 15 min. Cortisol's action on prolactin release is blocked in the presence of either the Ca 2+ ionophore A23187 or a combination of dibutyryl cAMP and 3-isobutyl-1-methylxanthine, which increase intracellular Ca 2+ and cAMP, respectively. Taken together, these findings suggest that cortisol may play a physiologically relevant role in the rapid modulation of prolactin secretion in vivo. These studies also suggest that the inhibition of prolactin release by cortisol is a specific glucocorticoid action that may be mediated, in part, through cortisol's ability to inhibit intracellular cAMP and Ca 2+ metabolism

  11. Preparation and in vitro evaluation of carboxymethylated κ-carrageenan aluminum hydrogel microbeads for prolonged release of mefenamic acid

    International Nuclear Information System (INIS)

    Beron, Pia Maria G.; Cruzado, Shervin T.; Dela Cruz, Sharmaine F.; Estanislao, Fides Mae L.; Evangelista, Charina Joy; Mandocdoc, Larra Minnellie W.; Salas, Sharlaine B.; Tiu, Mark Brian C.; Carigma, Andrea Q.; Bayquen, Aristea V.

    2012-01-01

    Polymers that swell in an aqueous medium have been widely used to formulate controlled-release dosage forms. This study aims to prepare carboxymethyl κ-carrageenan (CMKC) microbeads and evaluate its potential for controlled release of mefenamic acid in comparison to the positive control, carboxymethylcellulose (CMC) microbeads. The powdered κ-carrageenan was carboxymethylated and Fourier-Transform Infrared Spectroscopy confirmed the carboxy methylation. Aqueous solutions of CMC (3% w/v) and CMKC (3%, 4%, 5% w/v) were prepared as microbeads using ionotropic gelation technique. Microbeads were loaded with mefenamic acid by suspending it in the aqueous solution (0.5% w/v) of the drug for 72 hours. Particle size and surface morphology were characterized using scanning electron microscopy. One-way ANOVA was used to determine a significant difference between the release activity of the drug-loaded CMKC and CMC microbeads. Differential Scanning Calorimetry was performed on the drug, drug- free, and drug-loaded microbeads of CMC and CMKC. Two-way ANOVARM showed significant interaction in % drug release of the three groups being analyzed in respect to time effect (p≤0.001) and group effect (p≤0.001). Post Hoc Duncan Multiple Range Test showed that 3% CMC and 4% CMKC has equal average % drug release values and is significantly higher compared to the commercial mefenamic acid. Also, one way ANOVA showed that 3% CMC was able to release the drug with no significant difference in time (p = 0.159), while 4% CMKC (p < 0.001) and the commercial mefenamic acid (p≤0.001) were able to release the drug with significant difference in time (author)

  12. 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.

  13. Release behavior and stability of encapsulated D-limonene from emulsion-based edible films.

    Science.gov (United States)

    Marcuzzo, Eva; Debeaufort, Frédéric; Sensidoni, Alessandro; Tat, Lara; Beney, Laurent; Hambleton, Alicia; Peressini, Donatella; Voilley, Andrée

    2012-12-12

    Edible films may act as carriers of active molecules, such as flavors. This possibility confers to them the status of active packaging. Two different film-forming biopolymers, gluten and ι-carrageenans, have been compared. D-Limonene was added to the two film formulations, and its release kinetics from emulsion-based edible films was assessed with HS-SPME. Results obtained for edible films were compared with D-limonene released from the fatty matrix called Grindsted Barrier System 2000 (GBS). Comparing ι-carrageenans with gluten-emulsified film, the latter showed more interesting encapsulating properties: in fact, D-limonene was retained by gluten film during the process needed for film preparation, and it was released gradually during analysis time. D-Limonene did not show great affinity to ι-carrageenans film, maybe due to high aroma compound hydrophobicity. Carvone release from the three different matrices was also measured to verify the effect of oxygen barrier performances of edible films to prevent D-limonene oxidation. Further investigations were carried out by FT-IR and liquid permeability measurements. Gluten film seemed to better protect D-limonene from oxidation. Gluten-based edible films represent an interesting opportunity as active packaging: they could retain and release aroma compounds gradually, showing different mechanical and nutritional properties from those of lipid-based ingredients.

  14. Disintegration mediated controlled release supersaturating solid dispersion formulation of an insoluble drug: design, development, optimization, and in vitro evaluation.

    Science.gov (United States)

    Verma, Sanjay; Rudraraju, Varma S

    2015-02-01

    The objective of this study was to develop a solid dispersion based controlled release system for drug substances that are poorly soluble in water. A wax-based disintegration mediated controlled release system was designed based on the fact that an amorphous drug can crystallize out from hydrophilic matrices. For this study, cilostazol (CIL) was selected as the model drug, as it exhibits poor aqueous solubility. An amorphous solid dispersion was prepared to assist the drug to attain a supersaturated state. Povidone was used as carrier for solid dispersion (spray drying technique), hydrogenated vegetable oil (HVO) as wax matrix former, and sodium carboxymethyl cellulose (NaCMC) as a disintegrant. The extreme vertices mixture design (EVMD) was applied to optimize the designed and developed composition. The optimized formulation provided a dissolution pattern which was equivalent to the predicted curve, ascertaining that the optimal formulation could be accomplished with EVMD. The release profile of CIL was described by the Higuchi's model better than zero-order, first-order, and Hixson-Crowell's model, which indicated that the supersaturation state of CIL dominated to allow drug release by diffusion rather than disintegration regulated release as is generally observed by Hixson-Crowell's model. The optimized composition was evaluated for disintegration, dissolution, XRD, and stability studies. It was found that the amorphous state as well as the dissolution profile of CIL was maintained under the accelerated conditions of 40°C/75% RH for 6 months.

  15. Effect of aging treatment on the in vitro nickel release from porous oxide layers on NiTi

    Energy Technology Data Exchange (ETDEWEB)

    Huan, Z.; Fratila-Apachitei, L.E., E-mail: e.l.fratila-apachitei@tudelft.nl; Apachitei, I.; Duszczyk, J.

    2013-06-01

    Despite the ability of creating porous oxide layers on nickel–titanium alloy (NiTi) surface for biofunctionalization, the use of plasma electrolytic oxidation (PEO) has raised concerns over the possible increased levels of Ni release. Therefore, the primary aim of this study was to investigate the effect of aging in boiling water on Ni release from porous NiTi surfaces that have been formed by the PEO process. Based on different oxidation conditions, e.g. electrolyte composition and electrical parameters, three kinds of oxide layers with various characteristics were prepared on NiTi substrate. The process was followed by aging in boiling water for different durations. The Ni release was assessed by immersion tests in phosphate buffer saline and the Ni concentration was measured using the flame atomic absorption spectrometry. The results showed that aging in boiling water can significantly reduce the Ni release from oxidized porous samples, given that the duration of the treatment is finely adjusted according to the parameters of the as-formed oxide layer. Surface examination of the samples before and after aging in boiling water suggested that such a treatment is non-destructive while improving the corrosion resistance of oxidized samples, as evidenced by potentiodynamic polarization tests. The results of this study indicate that water boiling may be a suitable post-treatment required to minimize Ni release from porous oxides produced on NiTi by PEO for biomedical applications.

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

    DEFF Research Database (Denmark)

    Boutrup Stephansen, Karen; García-Díaz, María; Jessen, Flemming

    2016-01-01

    , 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...

  17. Uncovering cancer cell behavioral phenotype in 3-D in vitro metastatic landscapes

    Science.gov (United States)

    Liu, Liyu; Sun, Bo; Duclos, Guillaume; Kam, Yoonseok; Gatenby, Robert; Stone, Howard; Austin, Robert

    2012-02-01

    One well-known fact is that cancer cell genetics determines cell metastatic potentials. However, from a physics point of view, genetics as cell properties cannot directly act on metastasis. An agent is needed to unscramble the genetics first before generating dynamics for metastasis. Exactly this agent is cell behavioral phenotype, which is rarely studied due to the difficulties of real-time cell tracking in in vivo tissue. Here we have successfully constructed a micro in vitro environment with collagen based Extracellular Matrix (ECM) structures for cell 3-D metastasis. With stable nutrition (glucose) gradient inside, breast cancer cell MDA-MB-231 is able to invade inside the collagen from the nutrition poor site towards the nutrition rich site. Continuous confocal microscopy captures images of the cells every 12 hours and tracks their positions in 3-D space. The micro fluorescent beads pre-mixed inside the ECM demonstrate that invasive cells have altered the structures through mechanics. With the observation and the analysis of cell collective behaviors, we argue that game theory may exist between the pioneering cells and their followers in the metastatic cell group. The cell collaboration may explain the high efficiency of metastasis.

  18. Free amino acids exhibit anthozoan "host factor" activity: they induce the release of photosynthate from symbiotic dinoflagellates in vitro.

    Science.gov (United States)

    Gates, R D; Hoegh-Guldberg, O; McFall-Ngai, M J; Bil, K Y; Muscatine, L

    1995-08-01

    Reef-building corals and other tropical anthozoans harbor endosymbiotic dinoflagellates. It is now recognized that the dinoflagellates are fundamental to the biology of their hosts, and their carbon and nitrogen metabolisms are linked in important ways. Unlike free living species, growth of symbiotic dinoflagellates is unbalanced and a substantial fraction of the carbon fixed daily by symbiont photosynthesis is released and used by the host for respiration and growth. Release of fixed carbon as low molecular weight compounds by freshly isolated symbiotic dinoflagellates is evoked by a factor (i.e., a chemical agent) present in a homogenate of host tissue. We have identified this "host factor" in the Hawaiian coral Pocillopora damicornis as a set of free amino acids. Synthetic amino acid mixtures, based on the measured free amino acid pools of P. damicornis tissues, not only elicit the selective release of 14C-labeled photosynthetic products from isolated symbiotic dinoflagellates but also enhance total 14CO2 fixation.

  19. Stability and in vitro release profile of enalapril maleate from different commercially available tablets: possible therapeutic implications.

    Science.gov (United States)

    Lima, Dione Marçal; dos Santos, Leandro Dias; Lima, Eliana Martins

    2008-08-05

    Stability of enalapril maleate formulations can be affected when the product is exposed to higher temperature and humidity, with the formation of two main degradation products: enalaprilat and a diketopiperazine derivative. In this work, stability and drug release profiles of 20 mg enalapril maleate tablets (reference, generic and similar products) were evaluated. After 180 days of the accelerated stability testing, most products did not exhibit the specified amount of drug. Additionally, drug release profiles were markedly different from that of the reference product, mainly due to drug degradation. Changes in drug concentration and drug release profile of enalapril formulations are strong indicators of a compromised bioavailability, with possible interferences on the therapeutic response for this drug.

  20. Investigation on the ion pair amphiphiles and their in vitro release of amantadine drug based on PLGA–PEG–PLGA gel

    International Nuclear Information System (INIS)

    Yang, Xiaoxia; Ji, Xiaoqing; Shi, Chunhuan; Liu, Jing; Wang, Haiyang; Luan, Yuxia

    2014-01-01

    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 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. Process behavior and environmental assessment of 14C releases from an HTGR fuel reprocessing facility

    International Nuclear Information System (INIS)

    Snider, J.W.; Kaye, S.V.

    1976-01-01

    Large quantities of 14 CO 2 will be evolved when graphite fuel blocks are burned during reprocessing of spent fuel from HTGR reactors. The possible release of some or all of this 14 C to the environment is a matter of concern which is investigated in this paper. Various alternatives are considered in this study for decontaminating and releasing the process off-gas to the environment. Concomitant radiological analyses have been done for the waste process scenarios to supply the necessary feedbacks for process design

  2. 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.

  3. Evaluation of tritium release behavior from Li{sub 2}TiO{sub 3} during DT neutron irradiation by use of an improved tritium collection method

    Energy Technology Data Exchange (ETDEWEB)

    Edao, Yuki, E-mail: edao.yuki@jaea.go.jp [Tritium Technology Group, Department of Blanket Systems Research, Rokkasho Fusion Institute, Sector of Fusion Research and Development, Japan Atomic Energy Agency, 2-4 Shirane Shirakata, Tokai-mura, Naka-gun, Ibaraki 319-1195 (Japan); Kawamura, Yoshinori [Blanket Technology Group, Department of Blanket Systems Research, Rokkasho Fusion Institute, Sector of Fusion Research and Development, Japan Atomic Energy Agency, 801-1 Mukoyama, Naka, Ibaraki 311-0193 (Japan); Hoshino, Tsuyoshi [Breeding Functional Materials Development Group, Department of Blanket Systems Research, Rokkasho Fusion Institute, Sector of Fusion Research and Development, Japan Atomic Energy Agency, 2-166 Omotedate Obuchi, Rokkasho, Aomori 039-3212 (Japan); Ochiai, Kentaro [BA Project Coordination Group, Department of Fusion Power Systems Research, Rokkasho Fusion Institute, Sector of Fusion Research and Development, Japan Atomic Energy Agency, 2-166 Omotedate Obuchi, Rokkasho, Aomori 039-3212 (Japan)

    2016-11-15

    Highlights: • Behavior of tritium released from Li{sub 2}TiO{sub 3} under neutron irradiation was measured. • Tritium collection method with hydrophobic catalyst was demonstrated successfully. • Temperature of Li{sub 2}TiO{sub 3} was dominant to control the chemical form of tritium release. - Abstract: The accurate measurement of behavior of bred tritium released from a tritium breeder is indispensable to understand the behavior for a design of a tritium extraction system. The tritium collection method combined a CuO bed and water bubbles was not suitable to measure transient behavior of tritium released from Li{sub 2}TiO{sub 3} during neutron irradiation because tritium released behavior was changed to be delayed due to adsorption of oxidized tritium on the CuO. Hence, the tritium collection method with hydrophobic catalyst instead of the CuO was demonstrated and succeeded the accurate release measurement of tritium from Li{sub 2}TiO{sub 3}. With the method, we assessed the behavior of tritium release under the various conditions since tritium should be released from Li{sub 2}TiO{sub 3} as the form of HT as much as possible from the view point of the fuel cycle. Our results indicated; promotion of isotopic exchange reaction on the surface of Li{sub 2}TiO{sub 3} by addition of hydrogen in sweep gas is mandatory in order to release tritium smoothly from Li{sub 2}TiO{sub 3} irradiated with neutrons; the favorable sweep gas to release as the form of HT was hydrogen added inert gas; and the temperature of Li{sub 2}TiO{sub 3} was the dominant parameter to control the chemical form of tritium released from the Li{sub 2}TiO{sub 3}.

  4. 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.

  5. GRSIS program to predict fission gas release and swelling behavior of metallic fast reactor fuel

    International Nuclear Information System (INIS)

    Lee, Chan Bock; Lee, Byung Ho; Nam, Cheol; Sohn, Dong Seong

    1999-03-01

    A mechanistic model of fission gas release and swelling for the U-(Pu)-Zr metallic fuel in the fast reactor, GRSIS (Gas Release and Swelling in ISotropic fuel matrix) was developed. Fission gas bubbles are assumed to nucleate isotropically from the gas atoms in the metallic fuel matrix since they can nucleate at both the grain boundaries and the phase boundaries which are randomly distributed inside the grain. Bubbles can grow to larger size by gas diffusion and coalition with other bubbles so that they are classified as three classes depending upon their sizes. When bubble swelling reaches the threshold value, bubbles become interconnected each other to make the open channel to the external free space, that is, the open bubbles and then fission gases inside the interconnected open bubbles are released instantaneously. During the irradiation, fission gases are released through the open bubbles. GRSIS model can take into account the fuel gap closure by fuel bubble swelling. When the fuel gap is closed by fuel swelling, the contact pressure between fuel and cladding in relation to the bubble swelling and temperature is calculated. GRSIS model was validated by comparison with the irradiation test results of U-(Pu)-Zr fuels in ANL as well as the parametric studies of the key variable in the model. (author). 13 refs., 1 tab., 22 figs

  6. GRSIS program to predict fission gas release and swelling behavior of metallic fast reactor fuel

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Chan Bock; Lee, Byung Ho; Nam, Cheol; Sohn, Dong Seong

    1999-03-01

    A mechanistic model of fission gas release and swelling for the U-(Pu)-Zr metallic fuel in the fast reactor, GRSIS (Gas Release and Swelling in ISotropic fuel matrix) was developed. Fission gas bubbles are assumed to nucleate isotropically from the gas atoms in the metallic fuel matrix since they can nucleate at both the grain boundaries and the phase boundaries which are randomly distributed inside the grain. Bubbles can grow to larger size by gas diffusion and coalition with other bubbles so that they are classified as three classes depending upon their sizes. When bubble swelling reaches the threshold value, bubbles become interconnected each other to make the open channel to the external free space, that is, the open bubbles and then fission gases inside the interconnected open bubbles are released instantaneously. During the irradiation, fission gases are released through the open bubbles. GRSIS model can take into account the fuel gap closure by fuel bubble swelling. When the fuel gap is closed by fuel swelling, the contact pressure between fuel and cladding in relation to the bubble swelling and temperature is calculated. GRSIS model was validated by comparison with the irradiation test results of U-(Pu)-Zr fuels in ANL as well as the parametric studies of the key variable in the model. (author). 13 refs., 1 tab., 22 figs.

  7. In vivo drug release behavior and osseointegration of a doxorubicin-loaded tissue-engineered scaffold

    DEFF Research Database (Denmark)

    Sun, Ming; Chen, Muwan; Wang, Miao

    2016-01-01

    Bone tissue-engineered scaffolds with therapeutic effects must meet the basic requirements as to support bone healing at the defect side and to release an effect drug within the therapeutic window. Here, a rapid prototyped PCL scaffold embedded with chitosan/nanoclay/β-tricalcium phosphate...

  8. Balance and behavior of gaseous radionuclides released during initial fast reactor fuel reprocessing operations

    International Nuclear Information System (INIS)

    Leudet, A.; Goumondy, J.P.; Charrier, G.

    1985-10-01

    Five pins from the fast reactor Phenix are cut and dissolved in a specially designed cell for the accurate determination of gas released during the operation. Amount and activity of gaseous radionuclides: Kr, Xe, Kr-85, I, I-129, H-3 and C-14 are determined in the fuel pins and also their distribution between shearing and dissolution [fr

  9. 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

    Directory of Open Access Journals (Sweden)

    Jayanthi Mungara

    2013-01-01

    Full Text Available Aim: 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. Materials and Methods: 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 completed every day prior to their immersion in the demineralizing solution. Media solutions were buffered with equal volumes of total ionic strength adjustment buffer (TISAB II; fluoride levels were measured using a digital ion analyzer and fluoride electrode throughout the 21 day duration of the experiment. Results: Nano-ionomeric glass ionomer showed a better amount of fluoride release than PRG composite irrespective of the fluoride treatment supplementation (P < 0.01. Additional fluoride supplementation improved fluoride release and recharge ability for both the materials when compared to their respective control groups. The fluoride recharge for both materials did not show any sustained pattern of release. Conclusion: Nano-ionomeric glass ionomer demonstrated a greater ability to release and recharge compared with that of PRG composite.

  10. 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.

  11. Formulation design of an HPMC-based sustained release tablet for pyridostigmine bromide as a highly hygroscopic model drug and its in vivo/in vitro dissolution properties.

    Science.gov (United States)

    Huang, Yuh-Tyng; Tsai, Tong-Rong; Cheng, Chun-Jen; Cham, Thau-Ming; Lai, Tsun-Fwu; Chuo, Wen-Ho

    2007-11-01

    Pyridostigmine bromide (PB), a highly hygroscopic drug was selected as the model drug. A sustained-release (SR) tablet prepared by direct compression of wet-extruded and spheronized core pellets with HPMC excipients and exhibited a zero-order sustained release (SR) profile. The 2(3) full factorial design was utilized to search an optimal SR tablet formulation. This optimal formulation was followed zero-order mechanism and had specific release rate at different time intervals (released % of 1, 6, and 12 hr were 15.84, 58.56, and 93.10%). The results of moisture absorption by Karl Fischer meter showed the optimum SR tablet could improve the hygroscopic defect of the pure drug (PB). In the in vivo study, the results of the bioavailability data showed the T(max) was prolonged (from 0.65 +/- 0.082 hr to 4.83 +/- 1.60 hr) and AUC(0-t) (from 734.88 +/- 230.68 ng/ml.hr to 1153.34 +/- 488.08 ng/ml.hr) and was increased respectively for optimum PB-SR tablets when compared with commercial immediate release (IR) tablets. Furthermore, the percentages of in vitro dissolution and in vivo absorption in the rabbits have good correlation. We believe that PB-SR tablets designed in our study would improve defects of PB, decrease the frequency of administration and enhance the retention period of drug efficacy in vivo for personnel exposed to contamination situations in war or terrorist attacks in the future.

  12. Phosphorus release behaviors of poultry litter biochar as a soil amendment

    International Nuclear Information System (INIS)

    Wang, Yue; Lin, Yingxin; Chiu, Pei C.; Imhoff, Paul T.; Guo, Mingxin

    2015-01-01

    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 −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 −1 in raw PL to 27.1 g kg −1 in PL biochar while reduced the water-soluble P level from 2.95 g kg −1 in the former to 0.17 g kg −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 of poultry litter biochar

  13. 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

  14. 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...

  15. Comparative In Vitro Controlled Release Studies on the Chronobiotic Hormone Melatonin from Cyclodextrins-Containing Matrices and Cyclodextrin: Melatonin Complexes.

    Science.gov (United States)

    Vlachou, Marilena; Papamichael, Marianna; Siamidi, Angeliki; Fragouli, Irene; Afroudakis, Pandelis A; Kompogennitaki, Rodanthi; Dotsikas, Yannis

    2017-07-28

    A series of hydrophilic matrix tablets was prepared and tested with respect to their ability to release the hormone melatonin in a controlled manner, in order to alleviate sleep onset and sleep maintenance dysfunctions. Besides the active ingredient, the tablets were comprised of combinations of the following: HPMC K 15M, low viscosity sodium alginate, microcrystalline cellulose (Avicel PH 102), magnesium stearate, and the cyclodextrins, α-CD, β-CD, γ-CD, HP-β-CD, sulfated β-CD, HP-α-CD and HP-γ-CD, and MLT (guest):CD (host) complexes of the above cyclodextrins, in 1:1 ratio. The controlled release studies were conducted in two aqueous dissolution media at pH 1.2 and 7.4. The stoichiometry of the formed complexes was examined by applying the continuous variation method (Job plot), while the stability constants were calculated by monitoring the spectrophotometric properties of free and CD-encapsulated melatonin (UV-Vis). Host-guest interactions were studied by Nuclear Magnetic Resonance (NMR) spectroscopy. The dissolution data suggest that melatonin is released faster from the MLT:CD complexes than from the rest matrix systems. This enhancement in the dissolution rate and the % release of melatonin from the complexes is due to the increased solubility of the MLT:CD complexes.

  16. Nanoparticles of lipid monolayer shell and biodegradable polymer core for controlled release of paclitaxel: effects of surfactants on particles size, characteristics and in vitro performance.

    Science.gov (United States)

    Liu, Yutao; Pan, Jie; Feng, Si-Shen

    2010-08-16

    This work developed a system of nanoparticles of lipid monolayer shell and biodegradable polymer core for controlled release of anticancer drugs with paclitaxel as a model drug, in which the emphasis was given to the effects of the surfactant type and the optimization of the emulsifier amount used in the single emulsion solvent evaporation/extraction process for the nanoparticle preparation on the particle size, characters and in vitro performance. The drug loaded nanoparticles were characterized by laser light scattering (LLS) for size and size distribution, field-emission scanning electron microscopy (FESEM) for surface morphology, X-ray photoelectron spectroscopy (XPS) for surface chemistry, zetasizer for surface charge, and high performance liquid chromatography (HPLC) for drug encapsulation efficiency and in vitro drug release kinetics. MCF-7 breast cancer cells were employed to evaluate the cellular uptake and cytotoxicity. It was found that phospholipids of short chains such as 1,2-dilauroylphosphatidylocholine (DLPC) have great advantages over the traditional emulsifier poly(vinyl alcohol) (PVA), which is used most often in the literature, in preparation of nanoparticles of biodegradable polymers such as poly(D,L-lactide-co-glycolide) (PLGA) for desired particle size, character and in vitro cellular uptake and cytotoxicity. After incubation with MCF-7 cells at 0.250 mg/ml NP concentration, the coumarin-6 loaded PLGA NPs of DLPC shell showed more effective cellular uptake versus those of PVA shell. The analysis of IC(50), i.e. the drug concentration at which 50% of the cells are killed, demonstrated that our DLPC shell PLGA core NP formulation of paclitaxel could be 5.88-, 5.72-, 7.27-fold effective than the commercial formulation Taxol after 24, 48, 72h treatment, respectively. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  17. 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

  18. Synthesis, characterization, and controlled release anticorrosion behavior of benzoate intercalated Zn-Al layered double hydroxides

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yi [Shandong Provincial Key Lab of Corrosion Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071 (China); Zhang, Dun, E-mail: zhangdun@qdio.ac.cn [Shandong Provincial Key Lab of Corrosion Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071 (China)

    2011-11-15

    Graphical abstract: The benzoate anion released from Zn-Al LDHs provides a more effective long-term protection against corrosion of Q235 carbon steel in 3.5% NaCl solution. Highlights: {yields} A benzoate anion corrosion inhibitor intercalated Zn-Al layered double hydroxides (LDHs) has been assembled by coprecipitation method. {yields} The kinetic simulation indicates that the ion-exchange one is responsible for the release process and the diffusion through particle is the rate limiting step. {yields} A significant reduction of the corrosion rate is observed when the LDH nanohybrid is present in the corrosive media. -- Abstract: Corrosion inhibitor-inorganic clay composite including benzoate anion intercalated Zn-Al layered double hydroxides (LDHs) are assembled by coprecipitation. Powder X-ray diffraction (XRD) and Fourier transform infrared (FT-IR) spectrum analyses indicate that the benzoate anion is successfully intercalated into the LDH interlayer and the benzene planes are vertically bilayer-positioned as a quasi-guest ion-pair form in the gallery space. Kinetic simulation for the release data, XRD and FT-IR analyses of samples recovered from the release medium indicate that ion-exchange is responsible for the release process and diffusion through the particle is also indicated to be the rate-limiting step. The anticorrosion capabilities of LDHs loaded with corrosion inhibitor toward Q235 carbon steel are analyzed by polarization curve and electrochemical impedance spectroscopy methods. Significant reduction of corrosion rate is observed when the LDH nanohybrid is present in the corrosive medium. This hybrid material may potentially be applied as a nanocontainer in self-healing coatings.

  19. Release behavior of fission products from irradiated dispersion fuels at high temperatures

    International Nuclear Information System (INIS)

    Iwai, Takashi; Shimizu, Michio; Nakagawa, Tetsuya

    1990-02-01

    As a framework of reduced enrichment fuel program of JMTR Project, the measurements of fission products release rates at high temperatures (600degC - 1100degC) were performed in order to take the data to use for safety evaluation of LEU fuel. Three type miniplates of dispersion silicide and aluminide fuel, 20% enrichment LEU fuel with 4.8 gU/cc (U 3 Si 2 90 %, USi 10 % and U 3 Si 2 50 %, U 3 Si 50 % dispersed in aluminium) and 45 % enrichment MEU fuel with 1.6 gU/cc, were irradiated in JMTR. The burnups attained by one cycle (22 days) irradiation were within 21.6 % - 22.5 % of initial 235 U. The specimens cut down from miniplates were measured on fission products release rates by means of new apparatus specially designed for this experiment. The specimens were heated up within 600degC - 1100degC in dry air. Then fission products such as 85 Kr, 133 Xe, 131 I, 137 Cs, 103 Ru, 129m Te were collected at each temperature and measured on release rates. In the results of measurement, the release rates of 85 Kr, 133 Xe, 131 I, 129m Te from all specimens were slightly less than that of G.W. Parker's data on U-Al alloy fuel. For 137 Cs and 103 Ru from a silicide specimen (U 3 Si 2 90 %, USi 10 % dispersed in aluminium) and 137 Cs from an aluminide specimen, the release rates were slightly higher than that of G.W. Parker's. (author)

  20. Ketoprofen-loaded Eudragit RSPO microspheres: an influence of sodium carbonate on in vitro drug release and surface topology.

    Science.gov (United States)

    Pandit, Sachin S; Hase, Dinesh P; Bankar, Manish M; Patil, Arun T; Gaikwad, Naresh J

    2009-05-01

    Eudragit RSPO microspheres containing ketoprofen as model drug, prepared by solvent evaporation technique using acetone-liquid paraffin (heavy) solvent system were examined. Depending upon polymer concentration in the internal phase, microspheres of particle mean diameter (122.8, 213.6 and 309.5 μm) were obtained. The influence of surface washing of microspheres with n-hexane, i.e. untreated microspheres (UM) on the drug content, drug release and surface topology of microspheres were compared to those of microspheres washed with sodium carbonate, i.e. treated microspheres (TM) in order to make the non-encapsulated surface drug soluble. The significant reduction in encapsulation efficiency (p < 0.001) and drug content (p < 0.001) after treatment, in combination with the small crystalline peaks observed during XRD testing and lack of melting endotherm observed in DSC testing, suggests that the washing process actually removes a significant amount of drug (p < 0.001) from the surface and encapsulated near to the surface of the microsphere polymer matrix. Scanning electron microscopy (SEM) examination revealed that the removal of surface drug did not affect the size of microspheres but the topology of treated smallest microspheres was modified. The ketoprofen release profiles were examined in phosphate buffer pH 7.4, using USPXXIII paddle type dissolution apparatus. In general both UM and TM result in biphasic release patterns, but the initial burst effect (first release phase) of TM was lower than that of UM. The second release phase did not change for the bigger size but increased for the smallest microspheres, probably owing to the modification of matrix porosity.

  1. Investigating the correlation between in vivo absorption and in vitro release of fenofibrate from lipid matrix particles in biorelevant medium

    DEFF Research Database (Denmark)

    Borkar, Nrupa Nitin; Xia, Dengning; Holm, René

    2014-01-01

    Lipid matrix particles (LMP) may be used as better carriers for poorly water-soluble drugs than liquid lipid carriers because of reduced drug mobilization in the formulations. However, the digestion process of solid lipid particles and their effect on the absorption of poorly water-soluble drugs......-soluble drug, was incorporated into LMP in this study using probe ultrasound sonication. The resultant LMP were characterised in terms of particle size, size distribution, zeta potential, entrapment efficiency, in vitro lipolysis and in vivo absorption in rat model. LMP of three different particle sizes i.......e. approximately 100 nm, 400 nm, and 10 μm (microparticles) were produced with high entrapment efficiencies. The in vitro lipolysis study showed that the recovery of fenofibrate in the aqueous phase for 100 nm and 400 nm LMP was significantly higher (p

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

    OpenAIRE

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

    2012-01-01

    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 ce...

  3. Minor corral changes and adoption of good handling practices can improve the behavior and reduce cortisol release in Nellore cows.

    Science.gov (United States)

    Lima, Maria Lúcia Pereira; Negrão, João Alberto; de Paz, Claudia Cristina Paro; Grandin, Temple

    2018-03-01

    Inadequate corral facilities and improper handling are major causes of stress in beef cattle. The purpose of this study was to evaluate the effects of minor changes in the corral and adoption of good handling practices on the behavior, cortisol release, and time spent taking blood samples in Nellore cows. Minor corral changes included obstructing the cow's vision when the handler walked deep into the animal's flight zone and the elimination of bright objects, color contrasts, puddles, shadows, and darkness in the corral. Handling was improved by eliminating dogs, electric goads (prods), and yelling, as well as adopting a calm behavior. A total of 141 Nellore cows from two typical extensive livestock farms were studied. The cows were evaluated individually before and after the corral changes. Blood samples were collected in the restraint device for cortisol measurement. The minor corral changes and the adoption of good handling practices result in better results for all variables studied. The results showed differences in the interactions between treatment and ranch for chute score (P = 0.0091) and exit score (P good handling practices were effective in improving cow behavior in the chute and in reducing exit velocity, cortisol released, and the time spent taking blood samples.

  4. 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.

  5. 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

  6. 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.

  7. THE STUDY ON THE EFFECT OF FORMULATION VARIABLES ON IN VITRO FLOATING TIME AND THE RELEASE PROPERTIES OF A FLOATING DRUG DELIVERY SYSTEM BY A STATISTICAL OPTIMIZATION TECHNIQUE

    Directory of Open Access Journals (Sweden)

    C. NARENDRA

    2008-03-01

    Full Text Available The present investigation concerns the evaluation of the effect of formulation variables on in vitro floating time and the release properties in developing a floating drug delivery system (FDDS containing a highly water soluble drug metoprolol tartrate (MT in the presence of a gas generating agent. A 32 full factorial design was employed in formulating the FDDS containing hydroxyl propylmethylcellulose (HPMC K4M and sodium carboxymethylcellulose (NaCMC as swellable polymers. Drug-to-polymer ratio and polymer-to-polymer ratio were included as independent variables. The main effect and the interaction terms were quantitatively evaluated by a quadratic model to predict formulations with the floating time desired, and the release properties. It was found that only drug-to-polymer ratio and its quadratic term were found to be significantly affective for all the response variables. Non-Fickian transport was confirmed as a release mechanism from the optimized formulations. The desirability function was used to optimize the response variables, each having a different target, and the observed responses were highly agreed with experimental values. The results demonstrate the feasibility of the model in the development of FDDS containing a highly water-soluble drug MT.

  8. Polyamide nanocapsules and nano-emulsions containing Parsol® MCX and Parsol® 1789: in vitro release, ex vivo skin penetration and photo-stability studies.

    Science.gov (United States)

    Hanno, Ibrahim; Anselmi, Cecilia; Bouchemal, Kawthar

    2012-02-01

    To prepare polyamide nanocapsules for skin photo-protection, encapsulating α-tocopherol, Parsol®MCX (ethylhexyl methoxycinnamate) and/or Parsol®1789 (butyl methoxydibenzoylmethane). Nanocapsules were obtained by combining spontaneous emulsification and interfacial polycondensation reaction between sebacoyl chloride and diethylenetriamine. Nano-emulsions used as control were obtained by the same process without monomers. The influence of carrier on release rate was studied in vitro with a membrane-free model. Epidermal penetration of encapsulated sunscreens was ex vivo evaluated using Franz diffusion cells. Ability of encapsulated sunscreens to improve photo-stability was verified by comparing percentage of degradation after UV radiation exposure. Sunscreen-containing nanocapsules (260-400 nm) were successfully prepared; yield of encapsulation was >98%. Parsol®MCX and Parsol®1789 encapsulation led to decreased release rate by up to 60% in comparison with nano-emulsion and allowed minimum penetration through pig ear epidermis. Presence of polyamide shell protected encapsulated sunscreen filters from photo-degradation without affecting their activity. Encapsulation of Parsol®MCX and Parsol®1789 into oil-core of polyamide nanocapsules allowed protection from photo-degradation, controlled release from nanocapsules, and limited penetration through pig ear epidermis.

  9. In vitro and in vivo evidence of the cytotoxic and genotoxic effects of metal ions released by orthodontic appliances: A review.

    Science.gov (United States)

    Martín-Cameán, Ana; Jos, Ángeles; Mellado-García, Pilar; Iglesias-Linares, Alejandro; Solano, Enrique; Cameán, Ana M

    2015-07-01

    Intraoral fixed orthodontic appliances are frequently used in the clinical practice of dentistry. They are made from alloys containing different metals at various percentages. The use of these appliances leads to the long-term exposure of patients to these materials, and the potential toxic effects of this exposure raises concerns about patient safety. Thus, the biocompatibility (corrosion behaviour and toxicity) of these materials has to be evaluated prior to clinical use. In the present report, the most recent studies in the scientific literature examining metal ion release from orthodontic appliances and the toxic effects of these ions have been reviewed with a special focus on cytotoxicity and genotoxicity. Previous studies suggest that a case-by-case safety evaluation is required to take into account the increasing variability of materials, their composition and the manufacturing processes. Moreover, in vivo toxicity studies in regard to metal release, cytotoxicity and genotoxicity are still scarce. Therefore, in vitro and in vivo monitoring studies are needed to establish cause-effect relationships between metal ion release and biomarkers of cytotoxicity and genotoxicity. Further investigations could be performed to elucidate the toxic mechanisms involved in the observed effects with a special emphasis on oxidative damage. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. 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.

  11. Synthesis and in vitro anti-cancer evaluation of luteinizing hormone-releasing hormone-conjugated peptide.

    Science.gov (United States)

    Deng, Xin; Qiu, Qianqian; Ma, Ke; Huang, Wenlong; Qian, Hai

    2015-11-01

    Luteinizing hormone-releasing hormone (LHRH) is a decapeptide hormone released from the hypothalamus and shows high affinity binding to the LHRH receptors. It is reported that several cancer cells also express LHRH receptors such as breast, ovarian, prostatic, bladder and others. In this study, we linked B1, an anti-cancer peptide, to LHRH and its analogs to improve the activity against cancer cells with LHRH receptor. Biological evaluation revealed that TB1, the peptide contains triptorelin sequence, present favorable anti-cancer activity as well as plasma stability. Further investigations disclosed that TB1 trigger apoptosis by activating the mitochondria-cytochrome c-caspase apoptotic pathway, it also exhibited the anti-migratory effect on cancer cells.

  12. In vitro characterizations of mesoporous hydroxyapatite as a controlled release delivery device for VEGF in orthopedic applications.

    Science.gov (United States)

    Poh, Chye Khoon; Ng, Suxiu; Lim, Tee Yong; Tan, Hark Chuan; Loo, Joachim; Wang, Wilson

    2012-11-01

    Following bone implant surgery, prolonged ischemic conditions at the implant site often result in postsurgical complications like failure of osseointegration at the bone-implant interface which can lead to implant failure. Thus, restoration of the vascular supply is paramount to the proper development of the bone. High surface area mesostructured materials have been shown to be attractive candidates for bone regeneration to enhance cell adhesion and cell proliferation. This study uses hydroxyapatite, a naturally occurring mineral in the bone, fabricated to a range of suitable pore sizes, infused with vascular endothelial growth factor (VEGF), to be progressively released to stimulate revascularization. In this study, several characterizations including nitrogen adsorption analysis, Fourier-transformed infrared spectroscopy, X-ray diffraction, field emission scanning electron microscope, and transmission electron microscope were used to evaluate the synthesized mesoporous hydroxyapatite (MHA). The results showed that MHA can gradually release VEGF for enhancing revascularization, which is beneficial for orthopedic applications. Copyright © 2012 Wiley Periodicals, Inc.

  13. In vitro release of ketoprofen suppositories using the USP basket and the flow-through cell dissolution methods.

    Science.gov (United States)

    Medina, José Raúl; Padilla, Adrián Roberto; Hurtado, Marcela; Cortés, Alma Rosa; Domínguez-Ramírez, Adriana Miriam

    2014-05-01

    In order to study the release characteristics of ketoprofen suppositories under the hydrodynamic environment generated by USP Apparatus 1 and 4, the dissolution profiles of the Mexican reference product (100 mg) were determined. Phosphate buffer pH 8 and 1% sodium lauryl sulfate (SLS) aqueous solutions were proved as dissolution mediums. Baskets were rotated at 100 rpm with USP Apparatus 1 and different flow rates from 16-32 mL/min with USP Apparatus 4 were used. Drug samples were taken and quantified during 60 min by UV analysis at 260 nm. Mean dissolution time (MDT) and dissolution efficiency (DE) were calculated by model-independent methods. Data were also fitted to several kinetic models. Poor dissolution was found in both dissolution mediums when USP basket method was used ( 0.99). The results suggest the need to establish an adequate dissolution method to evaluate the release kinetics of ketoprofen from suppositories.

  14. Lipid nanoparticles for topical and transdermal application for alopecia treatment: development, physicochemical characterization, and in vitro release and penetration studies

    DEFF Research Database (Denmark)

    Gomes, M. J.; Martins, S.; Ferreira, D.

    2014-01-01

    with few side effects, new drug-delivery systems able to improve alopecia therapy are urgently required. With this purpose in mind, the present study aimed to develop lipid nanoparticles (nanostructured lipid carriers) with the ability to incorporate and deliver anti-alopecia active compounds (minoxidil...... less than 30% was achieved for minoxidil nanoparticles, over 28 days. Controlled release assays in physiological conditions demonstrated that nanoparticles loaded with minoxidil yielded a prolonged release, as desired. Penetration assays through pig ear skin demonstrated that nanoparticles loaded...... with minoxidil and finasteride had low levels of penetration. These results suggest that the proposed novel formulation presents several good characteristics indicating their suitability for dermal delivery of anti-alopecia active compounds....

  15. Behavior of strontium-90 and cesium-137 released into the pond of Office of Atomic Energy for Peace

    International Nuclear Information System (INIS)

    Milintawisamai, Mesak; Panyathipsakul, Yureeporn

    1989-01-01

    Strontium-90 and cesium-137 in liquid waste released from the waste disposal plant of Office of Atomic Energy for Peace(OAEP) have been followed since 1984. The concentration of both nuclides in surface water outside OAEP boundary is 2 to 30 times less than in the OAEP pond, the reservoir of liquid waste. This indicates that most of the nuclides are effectively absorbed by clay in the bottom of the pond. The nuclide concentration in fresh-water organisms in the pond such as fish, prawn and snail is also investigated to elucidate the behavior of strontium-90 and cesium-137 in a static fresh-water ecological system

  16. Adequate Measuring Technology and System of Fission Gas release Behavior from Voloxidation Process

    International Nuclear Information System (INIS)

    Park, Geun Il; Park, J. J.; Jung, I. H.; Shin, J. M.; Yang, M. S.; Song, K. C.

    2006-09-01

    Based on the published literature and an understanding of available hot cell technologies, more accurate measuring methods for each volatile fission product released from voloxidation process were reviewed and selected. The conceptual design of an apparatus for measuring volatile and/or semi-volatile fission products released from spent fuel was prepared. It was identified that on-line measurement techniques can be applied for gamma-emitting fission products, and off-line measurement such as chemical/or neutron activation analysis can applied for analyzing beta-emitting fission gases. Collection methods using appropriate material or solutions were selected to measure the release fraction of beta-emitting gaseous fission products at IMEF M6 hot cell. Especially, the on-line gamma-ray counting system for monitoring of 85Kr and the off-line measuring system of 14C was established. On-line measuring system for obtaining removal ratios of the semi-volatile fission products, mainly gamma-emitting fission products such as Cs, Ru etc., was also developed at IMEF M6 hot cell which was based on by measuring fuel inventory before and after the voloxidation test through gamma measuring technique. The development of this measurement system may enable basic information to be obtained to support design of the off-gas treatment system for the voloxidation process at INL, USA

  17. Characterization and in vitro release studies of oral microbeads containing thiolated pectin–doxorubicin conjugates for colorectal cancer treatment

    Directory of Open Access Journals (Sweden)

    Kamonrak Cheewatanakornkool

    2017-11-01

    Full Text Available Novel oral microbeads were developed based on a biopolymer–drug conjugate of doxorubicin (DOX conjugated with thiolated pectin via reducible disulfide bonds. The microbeads were fabricated by ionotropic gelation with cations such as Al3+, Ca2+ and Zn2+. The results showed that using zinc acetate can produce the strongest microbeads with spherical shape. However, the microbeads prepared from thiolated pectin–DOX conjugate were very soft and irregular in shape. To produce more spherical microbeads with suitable strength, the native pectin was then added to the formulations. The particle size of the microbeads ranged from 0.87 to 1.14 mm. The morphology of the microbeads was characterized by optical and scanning electron microscopy. DOX was still in crystalline form when used in preparing the microbeads, as confirmed by powder X-ray diffractometry. Drug release profiles showed that the microbeads containing thiolated pectin–DOX conjugate exhibited reduction-responsive character; in reducing environments, the thiolated pectin–DOX conjugate could uncouple resulting from a cleavage of the disulfide linkers and consequently release the DOX. The best-fit release kinetics of the microbeads containing thiolated pectin–DOX conjugate, in the medium without reducing agent, fit the Korsmeyer–Peppas model while those in the medium with reducing agent fit a zero-order release model. These results suggested that the microbeads containing thiolated pectin–DOX conjugate may be a promising platform for cancer-targeted delivery of DOX, exploiting the reducing environment typically found in tumors.

  18. In vitro dissolution study of acetylsalicylic acid solid dispersions. Tunable drug release allowed by the choice of polymer matrix

    Czech Academy of Sciences Publication Activity Database

    Policianová, Olivia; Brus, Jiří; Hrubý, Martin; Urbanová, Martina

    2015-01-01

    Roč. 20, č. 8 (2015), s. 935-940 ISSN 1083-7450 R&D Projects: GA ČR(CZ) GA14-03636S; GA ČR GPP106/11/P426 Grant - others:AV ČR(CZ) M200501201 Program:M Institutional support: RVO:61389013 Keywords : acetylsallicylic acid * controlled drug release * polymers Subject RIV: CD - Macromolecular Chemistry Impact factor: 1.566, year: 2015

  19. 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.

  20. Fluoxetine Alleviates Behavioral Depression while Decreasing Acetylcholine Release in the Nucleus Accumbens Shell

    OpenAIRE

    Chau, David T; Rada, Pedro V; Kim, Kay; Kosloff, Rebecca A; Hoebel, Bartley G

    2011-01-01

    Selective serotonin reuptake inhibitors, such as fluoxetine, have demonstrated the ability to alleviate behavioral depression in the forced swim test; however, the sites and mechanisms of their actions remain to be further elucidated. Previous studies have suggested that behavioral depression in the swim test is mediated in part by acetylcholine (ACh) stimulating the cholinergic M1 receptors in the nucleus accumbens (NAc) shell. The current study tested whether acute, local, and chronic, subc...

  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. In-vitro evaluation of ion-exchange microspheres for the sustained release of liposomal-adenoviral conjugates.

    Science.gov (United States)

    Steel, Jason C; Cavanagh, Heather M A; Burton, Mark A; Dingwall, Daniel; Kalle, Wouter H J

    2004-03-24

    This study looks at the development of a novel combination vector consisting of adenovirus conjugated to liposomes (AL complexes) bound to cation-exchanging microspheres (MAL complexes). With adenovirus having a net negative charge and the liposomes a net positive charge it was possible to modify the net charge of the AL complexes by varying the concentrations of adenovirus to liposomes. The modification of the net charge resulted in altered binding and release characteristics. Of the complexes tested, the 5:1 and 2:1 ratio AL complexes were able to be efficiently bound by the microspheres and exhibited sustained release over 24 h. The 1:1 and 1:2 AL complexes, however, bound poorly to the microspheres and were rapidly released. In addition the MAL complexes also were able to reduce the toxicity of the AL complexes, which was seen with the 10:1 ratio. The AL complexes showed considerably more toxicity alone than in combination with microspheres, highlighting a potential benefit of this vector.

  3. Sub-100 nm biodegradable nanoparticles: in vitro release features and toxicity testing in 2D and 3D cell cultures

    International Nuclear Information System (INIS)

    Biondi, Marco; Guarnieri, Daniela; Yu Hui; Belli, Valentina; Netti, Paolo Antonio

    2013-01-01

    A big challenge in tumor targeting by nanoparticles (NPs), taking advantage of the enhanced permeability and retention effect, is the fabrication of small size devices for enhanced tumor penetration, which is considered fundamental to improve chemotherapy efficacy. The purposes of this study are (i) to engineer the formulation of doxorubicin-loaded poly(d,l-lactic-co-glycolic acid) (PLGA)–block–poly(ethylene glycol) (PEG) NPs to obtain <100 nm devices and (ii) to translate standard 2D cytotoxicity studies to 3D collagen systems in which an initial step gradient of the NPs is present. Doxorubicin release can be prolonged for days to weeks depending on the NP formulation and the pH of the release medium. Sub-100 nm NPs are effectively internalized by HeLa cells in 2D and are less cytotoxic than free doxorubicin. In 3D, <100 nm NPs are significantly more toxic than larger ones towards HeLa cells, and the cell death rate is affected by the contributions of drug release and device transport through collagen. Thus, the reduction of NP size is a fundamental feature from both a technological and a biological point of view and must be properly engineered to optimize the tumor response to the NPs. (paper)

  4. 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.

  5. Involvement of reactive oxygen species in brominated diphenyl ether-47-induced inflammatory cytokine release from human extravillous trophoblasts in vitro

    International Nuclear Information System (INIS)

    Park, Hae-Ryung; Kamau, Patricia W.; Loch-Caruso, Rita

    2014-01-01

    Polybrominated diphenyl ethers (PBDEs) are widely used flame retardant compounds. Brominated diphenyl ether (BDE)-47 is one of the most prevalent PBDE congeners found in human breast milk, serum and placenta. Despite the presence of PBDEs in human placenta, effects of PBDEs on placental cell function are poorly understood. The present study investigated BDE-47-induced reactive oxygen species (ROS) formation and its role in BDE-47-stimulated proinflammatory cytokine release in a first trimester human extravillous trophoblast cell line, HTR-8/SVneo. Exposure of HTR-8/SVneo cells for 4 h to 20 μM BDE-47 increased ROS generation 1.7 fold as measured by the dichlorofluorescein (DCF) assay. Likewise, superoxide anion production increased approximately 5 fold at 10 and 15 μM and 9 fold at 20 μM BDE-47 with a 1-h exposure, as measured by cytochrome c reduction. BDE-47 (10, 15 and 20 μM) decreased the mitochondrial membrane potential by 47–64.5% at 4, 8 and 24 h as assessed with the fluorescent probe Rh123. Treatment with 15 and 20 μM BDE-47 stimulated cellular release and mRNA expression of IL-6 and IL-8 after 12 and 24-h exposures: the greatest increases were a 35-fold increased mRNA expression at 12 h and a 12-fold increased protein concentration at 24 h for IL-6. Antioxidant treatments (deferoxamine mesylate, (±)α-tocopherol, or tempol) suppressed BDE-47-stimulated IL-6 release by 54.1%, 56.3% and 37.7%, respectively, implicating a role for ROS in the regulation of inflammatory pathways in HTR-8/SVneo cells. Solvent (DMSO) controls exhibited statistically significantly decreased responses compared with non-treated controls for IL-6 release and IL-8 mRNA expression, but these responses were not consistent across experiments and times. Nonetheless, it is possible that DMSO (used to dissolve BDE-47) may have attenuated the stimulatory actions of BDE-47 on cytokine responses. Because abnormal activation of proinflammatory responses can disrupt trophoblast functions

  6. Involvement of reactive oxygen species in brominated diphenyl ether-47-induced inflammatory cytokine release from human extravillous trophoblasts in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hae-Ryung, E-mail: heaven@umich.edu; Kamau, Patricia W.; Loch-Caruso, Rita

    2014-01-15

    Polybrominated diphenyl ethers (PBDEs) are widely used flame retardant compounds. Brominated diphenyl ether (BDE)-47 is one of the most prevalent PBDE congeners found in human breast milk, serum and placenta. Despite the presence of PBDEs in human placenta, effects of PBDEs on placental cell function are poorly understood. The present study investigated BDE-47-induced reactive oxygen species (ROS) formation and its role in BDE-47-stimulated proinflammatory cytokine release in a first trimester human extravillous trophoblast cell line, HTR-8/SVneo. Exposure of HTR-8/SVneo cells for 4 h to 20 μM BDE-47 increased ROS generation 1.7 fold as measured by the dichlorofluorescein (DCF) assay. Likewise, superoxide anion production increased approximately 5 fold at 10 and 15 μM and 9 fold at 20 μM BDE-47 with a 1-h exposure, as measured by cytochrome c reduction. BDE-47 (10, 15 and 20 μM) decreased the mitochondrial membrane potential by 47–64.5% at 4, 8 and 24 h as assessed with the fluorescent probe Rh123. Treatment with 15 and 20 μM BDE-47 stimulated cellular release and mRNA expression of IL-6 and IL-8 after 12 and 24-h exposures: the greatest increases were a 35-fold increased mRNA expression at 12 h and a 12-fold increased protein concentration at 24 h for IL-6. Antioxidant treatments (deferoxamine mesylate, (±)α-tocopherol, or tempol) suppressed BDE-47-stimulated IL-6 release by 54.1%, 56.3% and 37.7%, respectively, implicating a role for ROS in the regulation of inflammatory pathways in HTR-8/SVneo cells. Solvent (DMSO) controls exhibited statistically significantly decreased responses compared with non-treated controls for IL-6 release and IL-8 mRNA expression, but these responses were not consistent across experiments and times. Nonetheless, it is possible that DMSO (used to dissolve BDE-47) may have attenuated the stimulatory actions of BDE-47 on cytokine responses. Because abnormal activation of proinflammatory responses can disrupt trophoblast functions

  7. 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.

  8. Design and evaluation of nicorandil extended-release tablet

    Directory of Open Access Journals (Sweden)

    Ju-Young Kim

    2015-04-01

    Full Text Available The aim of this study was to design and evaluate extended-release formulations of a model drug, nicorandil, in order to achieve the desired steady-state plasma concentration of drug in vivo. Simulation was employed to estimate optimum dissolution and absorption rate of nicorandil. The dissolution test was employed using pH 1.2, 4.0, 6.8 buffer solution, or water, to measure the in vitro release behaviors of nicorandil formulations. A single dose (15 mg of each formulation was orally administered to four beagle dogs under fasted conditions, and the pharmacokinetic parameters were calculated. The in vitro/in vivo relationship of the extended-release formulation was confirmed using in vitro dissolution profiles and plasma concentrations of drug in beagle dogs. Nicorandil was released completely within 30 min from the immediate-release tablets and released for 24 h from the extended-release tablets. The nicorandil plasma concentration could be modified by adjusting the drug release rate from the extended-release formulation. The release rate of nicorandil was the rate-limiting step in the overall absorption of drug from the extended-release formulations. These results highlight the potential of a nicorandil extended-release formulation in the treatment of angina pectoris.

  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. Formulation and in-vitro evaluation of directly compressed controlled release matrices of Losartan Potassium using Ethocel Grade 100 as rate retarding agent.

    Science.gov (United States)

    Khan, Kamran Ahmad; Khan, Gul Majid; Zeeshan Danish, Muhammad; Akhlaq; Khan, Haroon; Rehman, Fazal; Mehsud, Saifullah

    2015-12-30

    Current study was aimed to develop 200mg controlled release matrix tablets of Losartan Potassium using Ethocel 100 Premium and Ethocel 100 FP Premium as rate controlling polymer. In-vitro studies were performed according to USP Method-I in phosphate buffer (PH 6.8) using pharma test dissolution apparatus. The temperature of the dissolution medium was kept constant at 37±0.5°C at 100rpm. Flow properties, physical quality control tests, effect of polymer size and drug-to-polymers ratios were studied using different kinetics models such as 1st-order, zero-order, Hixon Crowell model, Highuchi model and Power law. Difference factor f1 and similarity factor f2 were applied for dissolution profiles against Cardaktin® tablets used as a reference formulation. The matrices with polymer ethocel 100 FP Premiums have prolonged the drug release rate as compared to polymer ethocel 100 Premiums. The n values matrices with polymer ethocel grade 100 ranged from 0.603 to 0.857 indicating that the drug release occurred by anomalous non fickian diffusion kinetics while then value of reference Cardaktin® tablet was measured as 0.125 indicating that these tablets do not follow power law. The dissolution profiles of test formulations were different than that of reference Cardaktin®. This suggests the polymer Ethocel grade 100 can be proficiently incorporated in fabrication and development of once a day controlled release matrix tablets. Copyright © 2015. Published by Elsevier B.V.

  11. A stent for co-delivering paclitaxel and nitric oxide from abluminal and luminal surfaces: Preparation, surface characterization, and in vitro drug release studies

    International Nuclear Information System (INIS)

    Gallo, Annemarie; Mani, Gopinath

    2013-01-01

    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.

  12. 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.

  13. In-vitro bioactivity and electrochemical behavior of polyaniline encapsulated titania nanotube arrays for biomedical applications

    Science.gov (United States)

    Agilan, P.; Rajendran, N.

    2018-05-01

    Titania nanotube arrays (TNTA) have attracted increasing attention due to their outstanding properties and potential applications in biomedical field. Fabrication of titania nanotubes on titanium surface enhances the biocompatibility. Polyaniline (PANI) is one of the best conducting polymers with remarkable corrosion resistance and reasonable biocompatibility. In this work, the corrosion resistance and biocompatibility of polyaniline encapsulated TiO2 nanotubes for orthopaedic applications were investigated. The vertically oriented, highly ordered TiO2 nanotubes were fabricated on titanium by electrochemical anodization process using fluoride containing electrolytes. The anodization parameters viz., voltage, pH, time and electrolyte concentration were optimized to get orderly arranged TNTA. Further, the conducting polymer PANI was encapsulated on TNTA by electropolymerization process to enhance the corrosion resistance. The nanostructure of the fabricated TNTA and polyaniline encapsulated titania nanotube arrays (PANI-TNTA) were investigated by HR SEM analysis. The formed phases and functional groups were find using XRD, ATR-FTIR. The hydrophilic surface of TNTA and PANI-TNTA was identified by water contact angle studies. The corrosion behavior of specimens was evaluated by electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization studies. In-vitro immersion studies were carried out in simulated body fluid solution (Hanks' solution) to evaluate the bioactivity of the TNTA and PANI-TNTA. The surface morphological studies revealed the formation of PANI on the TNTA surface. Formation of hydroxyapatite (HAp) on the surfaces of TNTA and PANI-TNTA enhanced the bioactivity and corrosion resistance.

  14. Platelet concentration in platelet-rich plasma affects tenocyte behavior in vitro.

    Science.gov (United States)

    Giusti, Ilaria; D'Ascenzo, Sandra; Mancò, Annalisa; Di Stefano, Gabriella; Di Francesco, Marianna; Rughetti, Anna; Dal Mas, Antonella; Properzi, Gianfranco; Calvisi, Vittorio; Dolo, Vincenza

    2014-01-01

    Since tendon injuries and tendinopathy are a growing problem, sometimes requiring surgery, new strategies that improve conservative therapies are needed. Platelet-rich plasma (PRP) seems to be a good candidate by virtue of its high content of growth factors, most of which are involved in tendon healing. This study aimed to evaluate if different concentrations of platelets in PRP have different effects on the biological features of normal human tenocytes that are usually required during tendon healing. The different platelet concentrations tested (up to 5 × 10(6) plt/µL) stimulated differently tenocytes behavior; intermediate concentrations (0.5 × 10(6), 1 × 10(6) plt/µL) strongly induced all tested processes (proliferation, migration, collagen, and MMPs production) if compared to untreated cells; on the contrary, the highest concentration had inhibitory effects on proliferation and strongly reduced migration abilities and overall collagen production but, at the same time, induced increasing MMP production, which could be counterproductive because excessive proteolysis could impair tendon mechanical stability. Thus, these in vitro data strongly suggest the need for a compromise between extremely high and low platelet concentrations to obtain an optimal global effect when inducing in vivo tendon healing.

  15. In vivo and in vitro effects of chromium VI on anterior pituitary hormone release and cell viability

    International Nuclear Information System (INIS)

    Quinteros, Fernanda A.; Poliandri, Ariel H.B.; Machiavelli, Leticia I.; Cabilla, Jimena P.; Duvilanski, Beatriz H.

    2007-01-01

    Hexavalent chromium (Cr VI) is a highly toxic metal and an environmental pollutant. Different studies indicate that Cr VI exposure adversely affects reproductive functions. This metal has been shown to affect several tissues and organs but Cr VI effects on pituitary gland have not been reported. Anterior pituitary hormones are central for the body homeostasis and have a fundamental role in reproductive physiology. The aim of this study was to evaluate the effect of Cr VI at the pituitary level both in vivo and in vitro. We showed that Cr VI accumulates in the pituitary and hypothalamus, and decreases serum prolactin levels in vivo but observed no effects on LH levels. In anterior pituitary cells in culture, the effect of Cr VI on hormone secretion followed the same differential pattern. Besides, lactotrophs were more sensitive to the toxicity of the metal. As a result of oxidative stress generation, Cr VI induced apoptosis evidenced by nuclear fragmentation and caspase 3 activation. Our results indicate that the anterior pituitary gland can be a target of Cr VI toxicity in vivo and in vitro, thus producing a negative impact on the hypothalamic-pituitary-gonadal axis and affecting the normal endocrine function

  16. In vivo and in vitro effects of chromium VI on anterior pituitary hormone release and cell viability.

    Science.gov (United States)

    Quinteros, Fernanda A; Poliandri, Ariel H B; Machiavelli, Leticia I; Cabilla, Jimena P; Duvilanski, Beatriz H

    2007-01-01

    Hexavalent chromium (Cr VI) is a highly toxic metal and an environmental pollutant. Different studies indicate that Cr VI exposure adversely affects reproductive functions. This metal has been shown to affect several tissues and organs but Cr VI effects on pituitary gland have not been reported. Anterior pituitary hormones are central for the body homeostasis and have a fundamental role in reproductive physiology. The aim of this study was to evaluate the effect of Cr VI at the pituitary level both in vivo and in vitro. We showed that Cr VI accumulates in the pituitary and hypothalamus, and decreases serum prolactin levels in vivo but observed no effects on LH levels. In anterior pituitary cells in culture, the effect of Cr VI on hormone secretion followed the same differential pattern. Besides, lactotrophs were more sensitive to the toxicity of the metal. As a result of oxidative stress generation, Cr VI induced apoptosis evidenced by nuclear fragmentation and caspase 3 activation. Our results indicate that the anterior pituitary gland can be a target of Cr VI toxicity in vivo and in vitro, thus producing a negative impact on the hypothalamic-pituitary-gonadal axis and affecting the normal endocrine function.

  17. Behavior and movement of formerly landlocked juvenile coho salmon after release into the free-flowing Cowlitz River, Washington

    Science.gov (United States)

    Kock, Tobias J.; Henning, Julie A.; Liedtke, Theresa L.; Royer, Ida M.; Ekstrom, Brian K.; Rondorf, Dennis W.

    2011-01-01

    Formerly landlocked Coho Salmon (Oncorhynchus kisutch) juveniles (age 2) were monitored following release into the free-flowing Cowlitz River to determine if they remained in the river or resumed seaward migration. Juvenile Coho Salmon were tagged with a radio transmitter (30 fish) or Floy tag (1050 fish) and their behavior was monitored in the lower Cowlitz River. We found that 97% of the radio-tagged fish remained in the Cowlitz River beyond the juvenile outmigration period, and the number of fish dispersing downstream decreased with increasing distance from the release site. None of the tagged fish returned as spawning adults in the 2 y following release. We suspect that fish in our study failed to migrate because they exceeded a threshold in size, age, or physiological status. Tagged fish in our study primarily remained in the Cowlitz River, thus it is possible that these fish presented challenges to juvenile salmon migrating through the system either directly by predation or indirectly by competition for food or habitat. Given these findings, returning formerly landlocked Coho Salmon juveniles to the free-flowing river apparently provided no benefit to the anadromous population. These findings have management implications in locations where landlocked salmon have the potential to interact with anadromous species of concern.

  18. Balance and behavior of gaseous radionuclides released during initial PWR fuel reprocessing operations

    International Nuclear Information System (INIS)

    Leudet, A.; Miquel, P.; Goumondy, P.J.; Charrier, G.

    1982-08-01

    Five fuel pins, taken from a PWR fuel assembly with 32000 MWD/t burn-up were chopped and dissolved in leak-proof equipment designed for accurate determination of the composition and quantity of gaseous elements released in these operations. Analytical methods were specially developped to determine directly the noble gases, tritium and gaseous carbon compounds in the gas phase. Volatile iodine was kept as close as possible to the source by cold traps, then transferred to a caustic solution for quantitative analysis. The quantities and activities of gaseous fission products thus determined were compared with predicted values obtained through computation. Very good agreement was generally observed

  19. Balance and behavior of gaseous radionuclides released during initial PWR fuel reprocessing operations

    International Nuclear Information System (INIS)

    Leudet, A.; Miquel, P.; Goumondy, P.J.; Charrier, G.

    1983-01-01

    Five fuel pins, taken from a PWR fuel assembly with 32,000 MwD/t burn-up were chopped and dissolved in leak-proof equipment designed for accurate determination of the composition and quantity of gaseous elements released in these operations. Analytical methods were specially developed to determine directly the noble gases, tritium and gaseous carbon compounds in the gas phase. Volatile iodine was kept as close as possible to the source by cold traps, then transferred to a caustic solution for quantitative analysis. The quantities and activities of gaseous fission products thus determined were compared with predicted values obtained through computation. Very good agreement was generally observed

  20. Bactericidal Activity of Copper Oxide Nanocomposite/Bioglass for in Vitro Clindamycin Release in Implant Infections Due to Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Alijanian

    2016-08-01

    Full Text Available Background In recent years, bioactive bioceramics such as bioglass and hydroxyapatite (HA have been introduced as a remarkable development in the field of medicine due to their bio-adaptability, non-toxicity, and persistence, in vivo. They have many potential applications in the repair of bone defects and hence they have attracted significant interest from scholars. Objectives The aim of this study was to synthesize inorganic matrix CuO-based bioglasses and evaluate their antibacterial activity against aerobic bacterial infections in bone implants. Methods Nano-composite samples of silica-based bioactive glass, 60S BG with nano-powder CuO, were synthesized using the sol-gel method and then assessed with regard to their antibacterial properties against Staphylococcus aureus using well diffusion agar. The samples included BG58S (58%SiO2, 36%CaO, 6%P2O5, BG/10CuO (58%SiO2, 26%CaO, 6%P2O5, 10%CuO, and BG/20CuO (48%SiO2, 26%CaO, 6%P2O5, 20%CuO. To evaluate their bioactivity, the prepared samples of BG/20CuO, BG/10CuO, and BG58S were immersed in simulated body fluids (SBF. The surface morphology and structure of the samples before and after immersion in the SBF were characterized using scanning electron microscopy (SEM and Fourier transform infrared (FTIR, respectively. Then, the BG/20CuO and BG/10CuO samples were loaded in clindamycin, an antibiotic widely used in the treatment of osteomyelitis, and their release profiles were studied in phosphate buffer solution. Results It was observed that the growth inhibition zone increased through clindamycin release due to the increasing CuO percentage in the nanocomposite of bioactive glass. The bioactivity of the nanocomposite/bioglass with CuO was superior to that of bioglass alone. In this study, the BG/20CuO sample showed a sustained release of clindamycin, which is sufficient for a drug delivery system. Conclusions Increasing the Cu nanoparticles in bioactive glass samples leads to the release of Cu2

  1. Green synthesis of Si-incorporated hydroxyapatite using sodium metasilicate as silicon precursor and in vitro antibiotic release studies.

    Science.gov (United States)

    Abinaya Sindu, P; Kolanthai, Elayaraja; Suganthi, R V; Thanigai Arul, K; Manikandan, E; Catalani, Luiz H; Narayana Kalkura, S

    2017-10-01

    The aim of the current study is to synthesize nanosized silicon incorporated HAp (Si-HAP) using sodium metasilicate as the silicon source. The sol-gel derived samples were further subjected to microwave irradiation. Incorporation of Si into HAp did not alter the HAp phase, as confirmed by the X-ray diffraction analysis (XRD). Moreover, variation in the lattice parameters of the Si-incorporated HAp indicates that Si is substituted into the HAp lattice. The decrease in the intensity of the peaks attributed to hydroxyl groups, which appeared in the FTIR and Raman spectra of Si-HAp, further confirms the Si substitution in HAp lattices. The silicon incorporation enhanced the nanorods length by 70%, when compared to that of pure HAp. Microwave irradiation improved the crystallinity of Si-HAp when compared to as-synthesized Si-HAp samples. As-synthesized Si-incorporated HAp sample showed an intense blue emission under UV excitation. Microwave irradiation reduced the intensity of blue emission and exhibited red shift due to the reduction of defects in the Si-HAp crystal. The morphological change from rod to spherical and ribbon-like forms was observed with an increase in silicon content. Further, Si-HAp exhibited better bioactivity and low dissolution rate. Initially there was a burst release of amoxicillin from all the samples, subsequently it followed a sustained release. The microwave-irradiated HAp showed extended period of sustained release than that of as-synthesized HAp and Si-HAp. Similarly, the microwave-irradiated Si-incorporated samples exhibited prolonged drug release, as compared to that of the as-synthesized samples. Hence, Si-HAp is rapidly synthesized by a simple and cost effective method without inducing any additional phases, as compared to the conventional sintering process. This study provides a new insight into the rapid green synthesis of Si-HAp. Si-HAp could emerge as a promising material for the bone tissue replacement and as a drug delivery system

  2. 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.

  3. In vitro differentiation of human monocytes to macrophages: change of PDE profile and its relationship to suppression of tumour necrosis factor-α release by PDE inhibitors

    Science.gov (United States)

    Gantner, Florian; Kupferschmidt, Rochus; Schudt, Christian; Wendel, Albrecht; Hatzelmann, Armin

    1997-01-01

    During in vitro culture in 10% human AB serum, human peripheral blood monocytes acquire a macrophage-like phenotype. The underlying differentiation was characterized by increased activities of the macrophage marker enzymes unspecific esterase (NaF-insensitive form) and acid phosphatase, as well as by a down-regulation in surface CD14 expression. In parallel, a dramatic change in the phosphodiesterase (PDE) profile became evident within a few days that strongly resembled that previously described for human alveolar macrophages. Whereas PDE1 and PDE3 activities were augmented, PDE4 activity, which represented the major cyclic AMP-hydrolysing activity of peripheral blood monocytes, rapidly declined. Monocytes and monocyte-derived macrophages responded to lipopolysaccharide (LPS) with the release of tumour necrosis factor-α (TNF). In line with the change in CD14 expression, the EC50 value of LPS for induction of TNF release increased from approximately 0.1 ng ml−1 in peripheral blood monocytes to about 2 ng ml−1 in macrophages. Both populations of cells were equally susceptible towards inhibition of TNF release by cyclic AMP elevating agents such as dibutyryl cyclic AMP, prostaglandin E2 (PGE2) or forskolin, which all led to a complete abrogation of TNF production in a concentration-dependent manner and which were more efficient than the glucocorticoid dexamethasone. In monocytes, PDE4 selective inhibitors (rolipram, RP73401) suppressed TNF formation by 80%, whereas motapizone, a PDE3 selective compound, exerted a comparatively weak effect (10–15% inhibition). Combined use of PDE3 plus PDE4 inhibitors resulted in an additive effect and fully abrogated LPS-induced TNF release as did the mixed PDE3/4 inhibitor tolafentrine. In monocyte-derived macrophages, neither PDE3- nor PDE4-selective drugs markedly affected TNF generation when used alone (<15% inhibition), whereas in combination, they led to a maximal inhibition of TNF formation by about 40–50

  4. The antimicrobial efficacy of sustained release silver–carbene complex-loaded l-tyrosine polyphosphate nanoparticles: Characterization, in vitro and in vivo studies

    Science.gov (United States)

    Hindi, Khadijah M.; Ditto, Andrew J.; Panzner, Matthew J.; Medvetz, Douglas A.; Han, Daniel S.; Hovis, Christine E.; Hilliard, Julia K.; Taylor, Jane B.; Yun, Yang H.; Cannon, Carolyn L.; Youngs, Wiley J.

    2009-01-01

    The pressing need to treat multi-drug resistant bacteria in the chronically infected lungs of cystic fibrosis (CF) patients has given rise to novel nebulized antimicrobials. We have synthesized a silver–carbene complex (SCC10) active against a variety of bacterial strains associated with CF and chronic lung infections. Our studies have demonstrated that SCC10-loaded into l-tyrosine polyphosphate nanoparticles (LTP NPs) exhibits excellent antimicrobial activity in vitro and in vivo against the CF relevant bacteria Pseudomonas aeruginosa. Encapsulation of SCC10 in LTP NPs provides sustained release of the antimicrobial over the course of several days translating into efficacious results in vivo with only two administered doses over a 72 h period. PMID:19395021

  5. Strain-dependent release of cytokines modulated by Lactobacillus salivarius human isolates in an in vitro model

    Science.gov (United States)

    2010-01-01

    Background Oral administration of probiotics is known to modulate cytokines profile not only locally, but also systemically. Four strains of Lactobacillus salivarius, LDR0723, BNL1059, RGS1746 and CRL1528, were evaluated for their ability to modulate release of pro- and anti-inflammatory cytokines. Findings Strains were assessed for effects on production of Interleukin-12 (IL-12), Interferon-γ (IFN-γ), Interleukin-4 (IL-4) and Interleukin-5 (IL-5) by incubating bacterial suspensions with THP-1 macrophage like cells. Cytokines were determined by means of specific quantitative enzyme-linked immunosorbent assays. LDR0723 and CRL1528 led to a sustained increment in production of IL-12 and IFN-γ and to a decrease in release of IL-4 and IL-5, while BNL1059 and RGS1746 favoured Th2 response, leading to a decrease in Th1/Th2 ratio with respect to unstimulated cells. Conclusions In conclusion, capability of L. salivarius to modulate immune response was strictly strain dependent and strains of the same species might have opposite effects. Therefore, a careful evaluation of anti-inflammatory properties of lactobacilli should be performed on single strain, before any consideration on potential probiotic use. PMID:20184725

  6. Strain-dependent release of cytokines modulated by Lactobacillus salivarius human isolates in an in vitro model

    Directory of Open Access Journals (Sweden)

    Nicola Lucia

    2010-02-01

    Full Text Available Abstract Background Oral administration of probiotics is known to modulate cytokines profile not only locally, but also systemically. Four strains of Lactobacillus salivarius, LDR0723, BNL1059, RGS1746 and CRL1528, were evaluated for their ability to modulate release of pro- and anti-inflammatory cytokines. Findings Strains were assessed for effects on production of Interleukin-12 (IL-12, Interferon-γ (IFN-γ, Interleukin-4 (IL-4 and Interleukin-5 (IL-5 by incubating bacterial suspensions with THP-1 macrophage like cells. Cytokines were determined by means of specific quantitative enzyme-linked immunosorbent assays. LDR0723 and CRL1528 led to a sustained increment in production of IL-12 and IFN-γ and to a decrease in release of IL-4 and IL-5, while BNL1059 and RGS1746 favoured Th2 response, leading to a decrease in Th1/Th2 ratio with respect to unstimulated cells. Conclusions In conclusion, capability of L. salivarius to modulate immune response was strictly strain dependent and strains of the same species might have opposite effects. Therefore, a careful evaluation of anti-inflammatory properties of lactobacilli should be performed on single strain, before any consideration on potential probiotic use.

  7. Sustained release of melatonin from TiO2 nanotubes for modulating osteogenic differentiation of mesenchymal stem cells in vitro.

    Science.gov (United States)

    Lai, Min; Jin, Ziyang; Tang, Qiang; Lu, Min

    2017-10-01

    To control the sustained release of melatonin and modulate the osteogenic differentiation of mesenchymal stem cells (MSCs), melatonin was firstly loaded onto TiO 2 nanotubes by direct dropping method, and then a multilayered film was coated by a spin-assisted layer-by-layer technique, which was composed of chitosan (Chi) and gelatin (Gel). Successful fabrication was characterized by field emission scanning electron microscopy, atomic force microscope, X-ray photoelectron spectroscopy and contact angle measurement, respectively. The efficient sustained release of melatonin was measured by UV-visible-spectrophotometer. After 2 days of culture, well-spread morphology was observed in MSCs grown on the Chi/Gel multilayer-coated melatonin-loaded TiO 2 nanotube substrates as compared to different groups. After 4, 7, 14 and 21 days of culture, the multilayered-coated melatonin-loaded TiO 2 nanotube substrates increased cell proliferation, increased alkaline phosphatase (ALP) and mineralization, increased expression of mRNA levels for runt-related transcription factor 2 (Runx2), ALP, osteopontin (OPN) and osteocalcin (OC), indicative of osteoblastic differentiation. These results demonstrated that Chi/Gel multilayer-coated melatonin-loaded TiO 2 nanotube substrates promoted cell adhesion, spreading, proliferation and differentiation and could provide an alternative fabrication method for titanium-based implants to enhance the osteointegration between bone tissues and implant surfaces.

  8. Evaluating the Effect of Nuclear Power Plant Buildings on the Atmospheric Dispersion Behavior of Released Radioactive Materials

    International Nuclear Information System (INIS)

    Nassar, N.N.; Tawfik, F.S.; Agamy, S.A.; Nagla, T.F.

    2017-01-01

    One of the most important principles in air pollution is to minimize the release of pollutants to the atmosphere, deposition on the ground and promote sufficient dilution of released pollutants within the atmosphere. Building down wash describes the effect that wind flowing over or around buildings create a cavity of reticulating winds in the are a near the buildings. These cavities cause increased vertical dispersion of plumes emitted from stacks on or near the buildings . Often it leads to elevated concentrations downwind of affected stacks. The aim of this work is to evaluate the effect of the building down wash phenomena on the atmospheric dispersion behavior of released radioactive materials from NPP. In this study, a hypothetical scenario is presented involving a point source with varying stack parameters and rectangular shaped buildings (Mille stone Nuclear Power Plant) using meteorological parameters of a chosen day. The concentrations of assumed released radionuclides, taking into consideration the building down wash effect and without are calculated using the AERMOD Model taking into consideration the effect of the type of atmospheric stability class. Also the analysis includes the model predictions for the highest 1-hour cavity concentration. The results show that the size of the cavity zone is not affected by the type of stability class, but is affected by the stack location and buildings shape. On other hand, the distance at which the plume touches the ground is affected by the type of stability class, the stack location and buildings shape. So, strategies for locating buildings need to be considered to maximize dispersion when planning for constructing several reactors and accessory buildings at a nuclear site

  9. In vitro evaluation of (99m)Tc-EDDA/tricine-HYNIC-Q-Litorin in gastrin-releasing peptide receptor positive tumor cell lines.

    Science.gov (United States)

    Yurt Lambrecht, Fatma; Durkan, Kübra; Ozgür, Aykut; Gündüz, Cumhur; Avcı, Cığır Biray; Susluer, Sunde Yılmaz

    2013-05-01

    Bombesin and its derivatives exhibit a high affinity for gastrin-releasing peptide receptor (GRPr), which is over-expressed in a variety of human cancers (prostate, pancreatic, lung, etc.). The aim of this study was to investigate the in vitro potential of the hydrazinonicotinamide (HYNIC)-Q-Litorin. (99m)Tc labeling was performed by using different co-ligands: tricine and ethylenediamine diacetic acid (EDDA). The radiochemical stability of radiolabeled peptide conjugates was checked at room temperature and in cysteine solution up to 24 h. The in vitro cell uptake of (99m)Tc-EDDA-HYNIC-Q-Litorin and (99m)Tc-tricine-HYNIC-Q-Litorin were evaluated on pancreatic tumor and control cell lines. Optimum specific activity and incubation time were determined for all the cell lines. The results showed that the cell uptake of the radiolabeled peptide conjugates in tumor cell lines were higher than in the control cell line. The findings of this study indicated the need for further development of in vivo study as a radiopharmaceutical for pancreatic tumor imaging.

  10. Bisphenol A Alters β-hCG and MIF Release by Human Placenta: An In Vitro Study to Understand the Role of Endometrial Cells

    Directory of Open Access Journals (Sweden)

    C. Mannelli

    2014-01-01

    Full Text Available A proper fetomaternal immune-endocrine cross-talk in pregnancy is fundamental for reproductive success. This might be unbalanced by exposure to environmental chemicals, such as bisphenol A (BPA. As fetoplacental contamination with BPA originates from the maternal compartment, this study investigated the role of the endometrium in BPA effects on the placenta. To this end, in vitro decidualized stromal cells were exposed to BPA 1 nM, and their conditioned medium (diluted 1 : 2 was used on chorionic villous explants from human placenta. Parallel cultures of placental explants were directly exposed to 0.5 nM BPA while, control cultures were exposed to the vehicle (EtOH 0.1%. After 24–48 h, culture medium from BPA-treated and control cultures was assayed for concentration of hormone human Chorionic Gonadotropin (β-hCG and cytokine Macrophage Migration Inhibitory Factor (MIF. The results showed that direct exposure to BPA stimulated the release of both MIF and β-hCG. These effects were abolished/diminished in placental cultures exposed to endometrial cell-conditioned medium. GM-MS analysis revealed that endometrial cells retain BPA, thus reducing the availability of this chemical for the placenta. The data obtained highlight the importance of in vitro models including the maternal component in reproducing the effects of environmental chemicals on human fetus/placenta.

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

    DEFF Research Database (Denmark)

    Boutrup Stephansen, Karen; García-Díaz, María; Jessen, Flemming

    2016-01-01

    , 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......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...

  12. Drug-induced GABA transporter currents enhance GABA release to induce opioid withdrawal behaviors.

    Science.gov (United States)

    Bagley, Elena E; Hacker, Jennifer; Chefer, Vladimir I; Mallet, Christophe; McNally, Gavan P; Chieng, Billy C H; Perroud, Julie; Shippenberg, Toni S; Christie, MacDonald J

    2011-10-30

    Neurotransmitter transporters can affect neuronal excitability indirectly via modulation of neurotransmitter concentrations or directly via transporter currents. A physiological or pathophysiological role for transporter currents has not been described. We found that GABA transporter 1 (GAT-1) cation currents directly increased GABAergic neuronal excitability and synaptic GABA release in the periaqueductal gray (PAG) during opioid withdrawal in rodents. In contrast, GAT-1 did not indirectly alter GABA receptor responses via modulation of extracellular GABA concentrations. Notably, we found that GAT-1-induced increases in GABAergic activity contributed to many PAG-mediated signs of opioid withdrawal. Together, these data support the hypothesis that GAT-1 activity directly produces opioid withdrawal signs through direct hyperexcitation of GABAergic PAG neurons and nerve terminals, which presumably enhances GABAergic inhibition of PAG output neurons. These data provide, to the best of our knowledge, the first evidence that dysregulation of a neurotransmitter transporter current is important for the maladaptive plasticity that underlies opiate withdrawal.

  13. In Vitro Fertilization Using Luteinizing Hormone-Releasing Hormone Injections Resulted in Healthy Triplets without Increased Attack Rates in a Hereditary Angioedema Case

    Directory of Open Access Journals (Sweden)

    Ceyda Tunakan Dalgıç

    2018-01-01

    Full Text Available Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE is a rare, autosomal dominant disorder. The management of pregnant patients with C1-INH-HAE is a challenge for the physician. Intravenous plasma-derived nanofiltered C1-INH (pdC1INH is the only recommended option throughout pregnancy, postpartum, and breastfeeding period. In order to increase pregnancy rates, physicians use fertilization therapies increasing endogen levels of estrogens. Therefore, these techniques can provoke an increase in the number and severity of edema attacks in C1-INH-HAE. Our patient is a 32-year-old female, diagnosed with C1-INH-HAE type 1 since 2004. She had been taking danazol 50–200 mg/day for 9 years. Due to her pregnancy plans in 2013, danazol was discontinued. PdC1INH was prescribed regularly for prophylactic purpose. Triplet pregnancy occurred by in vitro fertilization using luteinizing hormone-releasing hormone (LHRH injections. In our patient, LHRH injections were done four times without causing any severe attack during in vitro fertilization. Angioedema did not worsen during pregnancy and delivery due to the prophylactic use of intravenous pdC1INH in our patient. According to the attack frequency and severity, there was no difference between the three pregnancy trimesters. To our knowledge, this is the first published case of C1-INH-HAE receiving in vitro fertilization therapies without any angioedema attacks during pregnancy and delivery and eventually having healthy triplets with the prophylactic use of intravenous pdC1INH.

  14. 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.

  15. Assessment of models for steam release from concrete and implications for modeling corium behavior in reactor cavities

    International Nuclear Information System (INIS)

    Washington, K.E.; Carroll, D.E.

    1988-01-01

    Models for concrete outgassing have been developed and incorporated into a developmental version of the CONTAIN code for the assessment of corium behavior in reactor cavities. The resultant code, referred to as CONTAIN/OR in order to distinguish it from the released version of CONTAIN, has the capability to model transient heat conduction and concrete outgassing in core-concrete interaction problems. This study focused on validation and assessment of the outgassing model through comparisons with other concrete response codes. In general, the model is not mechanistic; however, there are certain important processes and feedback effects that are treated rigorously. The CONTAIN outgassing model was compared against two mechanistic concrete response codes (USINT and SLAM). Gas release and temperature profile predictions for several concrete thicknesses and heating rates were performed with acceptable agreement seen in each case. The model was also applied to predict corium behavior in a reactor cavity for a hypothetical severe accident scenario. In this calculation, gases evolving from the concrete during nonablating periods fueled exothermic Zr chemical reactions in the corium. Higher corium temperatures and more concrete ablation were observed when compared with that seen when concrete outgassing was neglected. Even though this result depends somewhat upon the makeup of the corium sources and the concrete type in the cavity, it does show that concrete outgassing can be important in the modeling of corium behavior in reactor cavities. In particular, the need to expand the traditional role of CORCON from steady-state ablation to the consideration of more transient events is clearly evident as a result of this work. 5 refs., 11 figs., 1 tab

  16. Peer pressure on the riverbank: Assessing catch-and-release anglers' willingness to sanction others' (bad) behavior.

    Science.gov (United States)

    Guckian, Meaghan L; Danylchuk, Andy J; Cooke, Steven J; Markowitz, Ezra M

    2018-08-01

    Given the well-documented impacts of angler behavior on the biological fitness of angled and released fish, optimizing the conservation value of catch-and-release angling hinges on the extent to which anglers are willing to adopt recommended best practices and refrain from harmful ones. One potentially powerful mechanism underlying adoption of best practices is the social pressure anglers can apply to one another to enforce community norms and values. Past work in other domains demonstrates that forms of interpersonal communication-including social sanctioning-can foster context-appropriate social norms and increase cooperative behavior; yet to date, little research has examined these dynamics in the context of species conservation. We conducted in-person and online surveys to explore the role of social sanctioning in the context of an internationally renowned wild steelhead (Oncorhynchus mykiss) fishery in British Columbia, Canada. We investigated how diverse social-psychological and demographic factors influence anglers' past and future sanctioning propensity. Results highlight that perceived capacity to influence the angling practices of others and professed concerns about one's own reputation were strongly predictive of both past and future sanctioning. Furthermore, while anglers reported relatively low-levels of past sanctioning behavior, most anglers simultaneously expressed a strong desire to sanction others in the future. Identifying ways to increase the social desirability and visibility of sanctioning actions could assist resource managers in promoting adoption and maintenance of best practices. More broadly, our findings underscore a significant yet underappreciated role for wildlife users and enthusiasts in cultivating a shared conservation ethic to help ensure biological conservation. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Zantac® 150 y ranitidina de producción nacional: liberación in vitro ZantacÒ150 and ranitidine of national production: in vitro release

    Directory of Open Access Journals (Sweden)

    Lisette Martínez Miranda

    2004-08-01

    Full Text Available Dentro del proceso global de la liberación de un fármaco, la disolución constituye el paso más importante pues se encuentra íntimamente relacionada con los procesos de absorción, determinantes en la biodisponibilidad de un medicamento administrado por vía oral. En el presente trabajo se realizaron los perfiles de disolución de 3 lotes de Zantac® (GlaxoWellcome, medicamento líder del principio activo ranitidina (DCI y de 3 lotes de ranitidina 150 mg de producción nacional. Para el estudio de disolución se utilizó el método descrito en la USP 23. Los datos de porcentaje de principio activo liberado contra tiempo fueron sometidos a un estudio de ajuste a 4 modelos comunes a perfiles de disolución mediante el programa CurveExpert. Todos los lotes estudiados cumplen con los criterios de la Food and Drug Administration (FDA para los estudios de bioequivalencia in vitro.Dissolution is the most important step in the global release process of a drug , since it is closely related to the absorption processes, which are determinant in the bioavailability of a drug administered by oral route. The dissolution profiles of 3 batches of Zantac® (Glaxo Wellcome, a leading drug of the ranitidine active principle (DCI, and of 3 batches of ranitidine 150 mg of national production were performed. The method described in the USP 23 was used for the dissolution test. The percentage data of the active principle released against time were subjected to a study of adjustment of 4 models to common disssolution profiles by the CurveExpert program. All the studied batches fulfilled the criteria of the Food and Drug Administration (FDA for the in vitro bioequivalence studies.

  18. Loss of Local Astrocyte Support Disrupts Action Potential Propagation and Glutamate Release Synchrony from Unmyelinated Hippocampal Axon Terminals In Vitro.

    Science.gov (United States)

    Sobieski, Courtney; Jiang, Xiaoping; Crawford, Devon C; Mennerick, Steven

    2015-08-05

    Neuron-astrocyte interactions are critical for proper CNS development and function. Astrocytes secrete factors that are pivotal for synaptic development and function, neuronal metabolism, and neuronal survival. Our understanding of this relationship, however, remains incomplete due to technical hurdles that have prevented the removal of astrocytes from neuronal circuits without changing other important conditions. Here we overcame this obstacle by growing solitary rat hippocampal neurons on microcultures that were comprised of either an astrocyte bed (+astrocyte) or a collagen bed (-astrocyte) within the same culture dish. -Astrocyte autaptic evoked EPSCs, but not IPSCs, displayed an altered temporal profile, which included increased synaptic delay, increased time to peak, and severe glutamate release asynchrony, distinct from previously described quantal asynchrony. Although we observed minimal alteration of the somatically recorded action potential waveform, action potential propagation was altered. We observed a longer latency between somatic initiation and arrival at distal locations, which likely explains asynchronous EPSC peaks, and we observed broadening of the axonal spike, which likely underlies changes to evoked EPSC onset. No apparent changes in axon structure were observed, suggesting altered axonal excitability. In conclusion, we propose that local astrocyte support has an unappreciated role in maintaining glutamate release synchrony by disturbing axonal signal propagation. Certain glial cell types (oligodendrocytes, Schwann cells) facilitate the propagation of neuronal electrical signals, but a role for astrocytes has not been identified despite many other functions of astrocytes in supporting and modulating neuronal signaling. Under identical global conditions, we cultured neurons with or without local astrocyte support. Without local astrocytes, glutamate transmission was desynchronized by an alteration of the waveform and arrival time of axonal

  19. Stimulation of the medial amygdala enhances medial preoptic dopamine release: implications for male rat sexual behavior.

    Science.gov (United States)

    Dominguez, J M; Hull, E M

    2001-11-02

    Increased dopamine (DA) in the medial preoptic area (MPOA) facilitates male sexual behavior. A major source of innervation to the MPOA is the medial amygdala (MeA). We now report that chemical stimulation of the MeA enhanced levels of extracellular MPOA DA in anesthetized male rats. These results suggest that DA activity in the MPOA can be regulated by input from the MeA to the MPOA.

  20. In vitro metal ion release and biocompatibility of amorphous Mg67Zn28Ca5 alloy with/without gelatin coating

    International Nuclear Information System (INIS)

    Chan, W.Y.; Chian, K.S.; Tan, M.J.

    2013-01-01

    Amorphous zinc-rich Mg–Zn–Ca alloys have exhibited good tissue compatibility and low hydrogen evolution in vivo. However, suboptimal cell–surface interaction on magnesium alloy surface observed in vitro could lead to reduced integration with host tissue for regenerative purpose. This study aims to improve cell–surface interaction of amorphous Mg 67 Zn 28 Ca 5 alloy by coating a gelatin layer by electrospinning. Coated/uncoated alloys were immersed and extracted for 3 days under different CO 2 . The immersion results showed that pH and metal ion release in the alloy extracts were affected by gelatin coating and CO 2 , suggesting their roles in alloy biocorrosion and a mechanism has been proposed for the alloy–CO 2 system with/without coating. Cytotoxicity results are evident that gelatin-coated alloy with 2-day crosslinking not only exhibited no indirect cytotoxicity, but also supported attachment of L929 and MG63 cell lines around/on the alloy with high viability. Therefore, amorphous Mg 67 Zn 28 Ca 5 alloy coated with gelatin by electrospinning technique provides a useful method to improve alloy biocompatibility. - Highlights: • Electrospinning is a new method to coat amorphous Mg 67 Zn 28 Ca 5 alloy with gelatin. • Gelatin-coated alloy has differential effect on pH and ion release at various CO 2 . • L929 cell proliferation correlates with Mg 2+ level in alloy extracts. • Biomimetic gelatin coating significantly improves cell–surface interaction

  1. Characteristics of eugenol loaded chitosan-tripolyphosphate particles as affected by initial content of eugenol and their in-vitro release characteristic

    Science.gov (United States)

    Cahyono, B.; A’yun, Qurrotu; Suzery, M.; Hadiyanto

    2018-04-01

    The aim of this research was to determine encapsulation efficiency, loading capacity and controlled release of eugenol loaded chitosan-tpp products which prepared by coaservation method. The characteristic of eugenol-loaded chitosan showed that %EE and % LC increased by increasing the initial eugenol content. The optimum of %EE (72.63%) and %LC (43.96%) were obtained at the ratio of chitosan to eugenol of 1:1.5. The FTIR spectrum showed the characteristic peaks of eugenol appearing on spectrum of eugenol encapsulated and blue-shift in the hydroxyl band from 3425.58 cm-1 in chitosan-tpp to 3417.86 cm-1 and 3394.72 cm-1 in eugenol loaded chitosan-tpp indicating that eugenol was successfully encapsulated. The surface morphologies of freeze-dried particles with the optimum %EE showed that more surface roughness and porosity than plain particles. Furthermore, the in vitro release of particles with minimum and optimum %EE were also investigated in acid (Simulated Gastric Fluid) and base (Simulated Intestinal Fluid) medium at ambient temperature.

  2. Both exogenous 5-HT and endogenous 5-HT, released by fluoxetine, enhance distension evoked propulsion in guinea-pig ileum in vitro

    Directory of Open Access Journals (Sweden)

    Rachel M Gwynne

    2014-09-01

    Full Text Available The roles of 5-HT3 and 5-HT4 receptors in the modulation of intestinal propulsion by luminal application of 5-HT and augmentation of endogenous 5-HT effects were studied in segments of guinea-pig ileum in vitro. Persistent propulsive contractions evoked by saline distension were examined using a modified Trendelenburg method. When 5-HT (30 nM, fluoxetine (selective serotonin reuptake inhibitor; 1 nM, 2-methyl-5-HT (5-HT3 receptor agonist; 1 mM or RS 67506 (5-HT4 receptor agonist, 1 µM was infused into the lumen, the pressure needed to initiate persistent propulsive activity fell significantly. A specific 5-HT4 receptor antagonist, SB 207266 (10 nM in lumen, abolished the effects of 5-HT, fluoxetine, and RS 67506, but not those of 2-methyl-5-HT. Granisetron (5-HT3 receptor antagonist; 1 µM in lumen abolished the effect of 5-HT, fluoxetine, RS 67506 and 2-methyl-5-HT. The NK3 receptor antagonist SR 142801 (100 nM in lumen blocked the effects of 5-HT, fluoxetine and 2-methyl-5-HT. SB 207266, granisetron and SR 142801 had no effect by themselves. Higher concentrations of fluoxetine (100 nM and 300 nM and RS 67506 (3 µM and 10 µM had no effect on the distension threshold for propulsive contractions. These results indicate that luminal application of exogenous 5-HT, or increased release of endogenous mucosal 5-HT above basal levels, acts to lower the threshold for propulsive contractions in the guinea-pig ileum via activation of 5-HT3 and 5-HT4 receptors and the release of tachykinins. The results further indicate that basal release of 5-HT is insufficient to alter the threshold for propulsive motor activity.

  3. Malaria-specific metabolite hemozoin mediates the release of several potent endogenous pyrogens (TNF, MIP-1 alpha, and MIP-1 beta) in vitro, and altered thermoregulation in vivo.

    Science.gov (United States)

    Sherry, B A; Alava, G; Tracey, K J; Martiney, J; Cerami, A; Slater, A F

    1995-01-01

    A characteristic feature of malaria infection is the occurrence of periodic bouts of fever. Experimental and clinical studies have strongly implicated inflammatory cytokines, like tumour necrosis factor (TNF), in the induction of these intermittent fevers [Clark et al., Infect Immunol 32:1058-1066, 1981; Clark et al., Am J Pathol 129:192-199, 1987; Karunaweera et al., Proc Natl Acad Sci USA 89:3200-3203, 1992], but the malaria-specific metabolite(s) which induce the production of such endogenous pyrogens have not yet been fully characterized. It is well known that during the course of malaria infection, a unique schizont component, alternatively referred to as "malaria pigment" or hemozoin, is released along with merozoites as the host erythrocyte bursts [Urquhart, Clin Infect Dis 19:117-131, 1994]. We have recently determined that the core structure of hemozoin comprises a novel insoluble polymer of heme units linked by iron-carboxylate bonds [Slater et al., Proc Natl Acad Sci USA 88:325-329, 1991; Slater et al., Nature 355:167-169, 1992]. We now report that purified native, as well as chemically synthesized, hemozoin crystals potently induce the release of several pyrogenic cytokines, including TNF, MIP-1 alpha, and MIP-1 beta, from murine macrophages and human peripheral blood monocytes in vitro. Also, intravenous administration of chemically synthesized preparations of hemozoin to anaesthetized rats results in a marked drop in body temperature. A similar drop in body temperature is observed following the intravenous injection of other well-characterized pyrogenic cytokines (e.g., TNF) which are known to induce a fever response in awake animals, and is thought to reflect the inability of rats to appropriately regulate their body temperature while anaesthetized. As a consequence of its ability to induce pyrogenic cytokines in vitro, and thermal dysregulation in vivo, we propose that this unique parasite metabolite is an important pyrogen released by malaria

  4. Implantable biodegradable sponges: effect of interpolymer complex formation of chitosan with gelatin on the release behavior of tramadol hydrochloride.

    Science.gov (United States)

    Foda, Nagwa H; El-laithy, Hanan M; Tadros, Mina I

    2007-01-01

    The effect of interpolymer complex formation between positively charged chitosan and negatively charged gelatin (Type B) on the release behavior of tramadol hydrochloride from biodegradable chitosan-gelatin sponges was studied. Mixed sponges were prepared by freeze-drying the cross-linked homogenous stable foams produced from chitosan and gelatin solutions where gelatin acts as a foam builder. Generation of stable foams was optimized where concentration, pH of gelatin solution, temperature, speed and duration of whipping process, and, chitosan-gelatin ratio drastically affect the properties and the stability of the produced foams. The prepared sponges were evaluated for their morphology, drug content, and microstructure using scanning electron microscopy, mechanical properties, uptake capacity, drug release profile, and their pharmacodynamic activity in terms of the analgesic effect after implantation in Wistar rats. It was revealed that whipping 7% (w/w) gelatin solution, of pH 5.5, for 15 min at 25 degrees C with a stirring speed of 1000 rpm was the optimum conditions for stable gelatin foam generation. Moreover, homogenous, uniform chitosan-gelatin foam with small air bubbles were produced by mixing 2.5% w/w chitosan solution with 7% w/w gelatin solution in 1:5 ratio. Indeed, polyionic complexation between chitosan and gelatin overcame the drawbacks of chitosan sponge mechanical properties where, pliable, soft, and compressible sponge with high fluid uptake capacity was produced at 25 degrees C and 65% relative humidity without any added plasticizer. Drug release studies showed a successful retardation of the incorporated drug where the t50% values of the dissolution profiles were 0.55, 3.03, and 4.73 hr for cross-linked gelatin, un-cross-linked chitosan-gelatin, and cross-linked chitosan-gelatin sponges, respectively. All the release experiments followed Higuchi's diffusion mechanism over 12 hr. The achieved drug prolongation was a result of a combined effect

  5. Fluoxetine Alleviates Behavioral Depression while Decreasing Acetylcholine Release in the Nucleus Accumbens Shell

    Science.gov (United States)

    Chau, David T; Rada, Pedro V; Kim, Kay; Kosloff, Rebecca A; Hoebel, Bartley G

    2011-01-01

    Selective serotonin reuptake inhibitors, such as fluoxetine, have demonstrated the ability to alleviate behavioral depression in the forced swim test; however, the sites and mechanisms of their actions remain to be further elucidated. Previous studies have suggested that behavioral depression in the swim test is mediated in part by acetylcholine (ACh) stimulating the cholinergic M1 receptors in the nucleus accumbens (NAc) shell. The current study tested whether acute, local, and chronic, subcutaneous fluoxetine treatments increase escape motivation during the swim test while simultaneously lowering extracellular ACh in the NAc shell. Experiment 1: Fluoxetine (1.0 mM) infused unilaterally in the NAc shell for 40 min reduced extracellular ACh while simultaneously increasing swimming time. Experiment 2: Fluoxetine (0.2, 0.5, and 0.75 mM) infused bilaterally in the NAc shell on day 3 dose-dependently decreased immobility and increased the total escape attempts (swimming and climbing) compared with Ringer given on day 2. Experiment 3: Fluoxetine (0.5 mM) infused bilaterally in the NAc for 40 min did not affect activities in an open field. Experiment 4: Chronic systemic fluoxetine treatment decreased immobility scores and increased total escape attempt scores compared with control saline treatment. In all, 14 days after the initial swim test, basal extracellular ACh in the shell was still elevated in the saline-treated group, but not in the fluoxetine-treated group. In summary, these data suggest that one of the potential mechanisms by which fluoxetine alleviates behavioral depression in the forced swim test may be to suppress cholinergic activities in the NAc shell. PMID:21525864

  6. Lipid nanoparticles for topical and transdermal application for alopecia treatment: development, physicochemical characterization, and in vitro release and penetration studies

    Directory of Open Access Journals (Sweden)

    Gomes MJ

    2014-03-01

    achieved for minoxidil nanoparticles, over 28 days. Controlled release assays in physiological conditions demonstrated that nanoparticles loaded with minoxidil yielded a prolonged release, as desired. Penetration assays through pig ear skin demonstrated that nanoparticles loaded with minoxidil and finasteride had low levels of penetration. These results suggest that the proposed novel formulation presents several good characteristics indicating their suitability for dermal delivery of anti-alopecia active compounds. Keywords: nanostructured lipid carriers (NLC, alopecia, anti-alopecia therapy, minoxidil, finasteride

  7. Creep rupture behavior of polypropylene suture material and its applications as a time-release mechanism

    International Nuclear Information System (INIS)

    Kusy, R.P.; Whitley, J.Q.

    1983-01-01

    The controlled failure of polypropylene (PP) sutures is studied via creep rupture tests. From plots of log time (tB) vs. stress (sigma), linear relationships are generated over the failure times of 1-1000 h. Results show that as a function of stress, the time dependence varies with irradiation dose (15, 20, 25, and 50 Mrad), irradiation atmosphere (air and vacuum), suture diameter (7-0, 6-0, 5-0, and 4-0), and test temperature (26 and 37 degrees C). For a given stress, the time to failure is least for the greatest dose in the presence of air and at the highest temperature. When suture loops are wrapped around a small wire sheave, however, failure occurs in the largest suture as much as two decades sooner than the smallest suture studied. Within the limitations stated herein, they are independent of test method, loop diameter, aging, and humidity. Consequently, after irradiation in vacuum and postirradiation heat treatment, the processed material may be stored at room temperature for at least 1 month. Such materials are advocated when the time release of a dental or medical device is required, for example, in the self-activating cleft palate appliance

  8. Spot the difference: engineered and natural nanoparticles in the environment--release, behavior, and fate.

    Science.gov (United States)

    Wagner, Stephan; Gondikas, Andreas; Neubauer, Elisabeth; Hofmann, Thilo; von der Kammer, Frank

    2014-11-10

    The production and use of nanoparticles leads to the emission of manufactured or engineered nanoparticles into the environment. Those particles undergo many possible reactions and interactions in the environment they are exposed to. These reactions and the resulting behavior and fate of nanoparticles in the environment have been studied for decades through naturally occurring nanoparticulate (1-100 nm) and colloidal (1-1000 nm) substances. The knowledge gained from these investigations is nowhere near sufficiently complete to create a detailed model of the behavior and fate of engineered nanoparticles in the environment, but is a valuable starting point for the risk assessment of these novel materials. It is the aim of this Review to critically compare naturally observed processes with those found for engineered systems to identify the "nanospecific" properties of manufactured particles and describe critical knowledge gaps relevant for the risk assessment of manufactured nanomaterials in the environment. © 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

  9. Growth inhibition of tumor cells in vitro by using monoclonal antibodies against gonadotropin-releasing hormone receptor.

    Science.gov (United States)

    Lee, Gregory; Ge, Bixia

    2010-07-01

    As the continuation of a previous study, synthetic peptides corresponding to the extracellular domains of human gonadotropin-releasing hormone (GnRH) receptor were used to generate additional monoclonal antibodies which were further characterized biochemically and immunologically. Among those identified to recognize GnRH receptor, monoclonal antibodies designated as GHR-103, GHR-106 and GHR-114 were found to exhibit high affinity (Kd L37), when cancer cells were incubated with GnRH or GHR-106. The widespread expressions of GnRH receptor in almost all of the studied human cancer cell lines were also demonstrated by RT-PCR and Western blot assay, as well as indirect immunofluorescence assay with either of these monoclonal antibodies as the primary antibody. In view of the longer half life of antibodies as compared to that of GnRH or its analogs, anti-GnRH receptor monoclonal antibodies in humanized forms could function as GnRH analogs and serve as an ideal candidate of anti-cancer drugs for therapeutic treatments of various cancers in humans as well as for fertility regulations.

  10. Modeling of glucose release from native and modified wheat starch gels during in vitro gastrointestinal digestion using artificial intelligence methods.

    Science.gov (United States)

    Yousefi, A R; Razavi, Seyed M A

    2017-04-01

    Estimation of the amounts of glucose release (AGR) during gastrointestinal digestion can be useful to identify food of potential use in the diet of individuals with diabetes. In this work, adaptive neuro-fuzzy inference system (ANFIS), genetic algorithm-artificial neural network (GA-ANN) and group method of data handling (GMDH) models were applied to estimate the AGR from native (NWS), cross-linked (CLWS) and hydroxypropylated wheat starch (HPWS) gels during digestion under simulated gastrointestinal conditions. The GA-ANN and ANFIS were fed with 3 inputs of digestion time (1-120min), gel volume (7.5 and 15ml) and concentration (8 and 12%, w/w) for prediction of the AGR. The developed ANFIS predictions were close to the experimental data (r=0.977-0.996 and RMSE=0.225-0.619). The optimized GA-ANN, which included 6-7 hidden neurons, predicted the AGR with a good precision (r=0.984-0.993 and RMSE=0.338-0.588). Also, a three layers GMDH model with 3 neurons accurately predicted the AGR (r=0.979-0.986 and RMSE=0.339-0.443). Sensitivity analysis data demonstrated that the gel concentration was the most sensitive factor for prediction of the AGR. The results dedicated that the AGR will be accurately predictable through such soft computing methods providing less computational cost and time. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Uptake and release of 3H-benzo(a)pyrene by arterial cells in vivo and in vitro

    International Nuclear Information System (INIS)

    Pessah-Rasmussen, H.; Stavenow, L.

    1989-01-01

    Cigarette smoking is an established risk factor for the development of clinical manifestations of atherosclerosis. The atherogenicity of the different components of cigarette smoke is still subject to debate. One possible mechanism is that tarderived hydrocarbons might exert toxic and/or mutagenic effects in the arterial wall including a monoclonal proliferation of smooth muscle cells. There is evidence that polycyclic aromatic hydrocarbons (PAH) from cigarette smoke can get access to the blood and that they are transported in plasma lipoproteins. Treatment of chickens with benzo(a)pyrene (BaP) induced or potentiated the development of atherosclerotic lesions. Others have studied the uptake of BaP by fibroblasts in culture. The fate of PAH in the arterial wall and in smooth muscle cells has not been clarified yet. The purpose of the present report was to study the uptake and release of BaP in smooth muscle cells in culture and the uptake of BaP in the arterial wall in vivo. (author)

  12. The effect of an insulin releasing agent, BTS 67582, on advanced glycation end product formation in vitro.

    Science.gov (United States)

    Simpson, A E; Jones, R B

    1999-01-01

    BTS 67582 (1,1-dimeth