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Sample records for succinate sustained-release dvs

  1. Sustained release of radioprotective agents

    International Nuclear Information System (INIS)

    Shani, J.

    1980-11-01

    New pharmaceutical formulations for the sustained release into the G.I. tract of radioprotective agents have been developed by the authors. The experimental method initially consisted in the production of methylcellulose microcapsules. This method failed apparently because of the premature ''explosion'' of the microcapsules and the consequent premature release of massive amounts of the drug. A new method has been developed which consists in drying and pulverising cysteamine and cysteine preparations, mixing them in various proportions with stearic acid and ethylcellulose as carriers. The mixture is then compressed into cylindrical tablets at several pressure values and the leaching rate of the radioprotective agents is then measured by spectrophotometry. The relation between the concentration of the active drug and its rate of release, and the effect on the release rate of the pressure applied to the tablet during its formation were also investigated. Results indicating that the release rate was linearly related to the square root of ''t'' seem to be in agreement with what is predictable, according to Higuchi's equation, save for the very initial and terminal phases. A clear correlation was also established between the stearic acid/ethylcellulose ratios and the release of 20% cysteine, namely a marked decrease in the rate of cysteine release was observed with increasing concentrations of stearic acid. Finally, it was observed that a higher formation pressure results in quicker release of the drug

  2. Formulation and Characterization of Sustained Release Floating ...

    African Journals Online (AJOL)

    Purpose: To formulate sustained release gastroretentive microballoons of metformin hydrochloride with the objective of improving its bioavailability. Methods: Microballoons of metformin hydrochloride were formulated by solvent evaporation and diffusion method using varying mixtures of hydroxypropyl methylcellulose ...

  3. Sustained-release progesterone vaginal suppositories 1--development of sustained-release granule--.

    Science.gov (United States)

    Nakayama, Ayako; Sunada, Hisakazu; Okamoto, Hirokazu; Furuhashi, Kaoru; Ohno, Yukiko; Ito, Mikio

    2009-02-01

    Progesterone (P) is an important hormone for the establishment of pregnancy, and its administration is useful for luteal insufficiency. Considering the problems of commercially available oral and injection drugs, hospital-formulated vaginal suppositories are clinically used. However, since the half-life of P suppositories is short, it is difficult to maintain its constant blood concentration. To sustain drug efficacy and prevent side-effects, we are attempting to develop sustained-release suppositories by examining the degree of sustained-release of active ingredients. In this study, we examined the combinations of granulation methods and release systems for the preparation of sustained-release granules of P, and produced 13 types of sustained-release granules. We also examined the diameter, content, and dissolution of each type of granules, and confirmed that the sustained-release of all types of granules was satisfactory. Among the sustained-release granules, we selected granules with a content and a degree of sustained-release suitable for sustained-release suppositories.

  4. Sustained Release Drug Delivery Applications of Polyurethanes

    Directory of Open Access Journals (Sweden)

    Michael B. Lowinger

    2018-05-01

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

  5. Preparation of venlafaxine hydrochloride sustained-release tablets

    Directory of Open Access Journals (Sweden)

    GUO Lingling

    2013-08-01

    Full Text Available To prepare venlafxine hydrochloride sustained-release tablets.Hydroxypropylmethyl cellulose(HPMC and methyl cellulose(MC were used as main materials to prepare sustained-release tablets of velafaxine hydrochloride and the influence of important factors on in vitro release curves of venlafaxine hydrochloride sustained-release tablets was investigated.Results:The optimal prescription included 100 mg HPMC,25 mg MC,and 2.5% glidant in one tablet prepared with 30kN.The tablets were prepared with the method of wet granulation by NO.16 mesh sieve.The tablets exhibited good sustained-release property in phosphate buffered solution (pH=6.8.The as-prepared venlafxine hydrochloride sustained-release tablets have good sustained-release property.

  6. Formulation of Sustained-Release Diltiazem Matrix Tablets Using ...

    African Journals Online (AJOL)

    Formulation of Sustained-Release Diltiazem Matrix Tablets Using Hydrophilic Gum Blends. A Moin, H.G Shivakumar. Abstract. Purpose: To develop sustained release matrix tablets of diltiazem hydrochloride (DTZ) using karaya gum (K) alone or in combination with locust bean gum (LB) and hydroxypropyl methylcellulose ...

  7. [The enantioselective pharmacokinetic study of desvenlafaxine sustained release tablet in Chinese healthy male volunteers after oral administration].

    Science.gov (United States)

    Chen, Yin-xia; Du, Jiang-bo; Zhang, Yi-fan; Chen, Xiao-yan; Zhong, Da-fang

    2015-04-01

    A chiral LC-MS/MS method for the simultaneous analysis of desvenlafaxine (DVS) enantiomers in human plasma was developed and applied to a pharmacokinetic study on 12 Chinese healthy volunteers. d6-Desvenlafaxine was used as internal standard (IS). Chromatographic separation was performed on the Astec Chirobiotic V chiral column (150 mm x 4.6 mm, 5 μm). The assay was linear over the concentration range of 0.500-150 ng x mL(-1) for both enantiomers (r2 > 0.99). The method was successfully applied to a stereoselective pharmacokinetic study of 100 mg desvenlafaxine sustained release tablets on 12 Chinese healthy volunteers under fasting conditions. The results showed that the pharmacokinetic parameters were similar to both enantiomers in Chinese healthy volunteers. The AUC(0-t), and C(max) of the two enantiomers were about 1.5 times higher than those of blacks and whites reported in the literature.

  8. A Formal Approach for RT-DVS Algorithms Evaluation Based on Statistical Model Checking

    Directory of Open Access Journals (Sweden)

    Shengxin Dai

    2015-01-01

    Full Text Available Energy saving is a crucial concern in embedded real time systems. Many RT-DVS algorithms have been proposed to save energy while preserving deadline guarantees. This paper presents a novel approach to evaluate RT-DVS algorithms using statistical model checking. A scalable framework is proposed for RT-DVS algorithms evaluation, in which the relevant components are modeled as stochastic timed automata, and the evaluation metrics including utilization bound, energy efficiency, battery awareness, and temperature awareness are expressed as statistical queries. Evaluation of these metrics is performed by verifying the corresponding queries using UPPAAL-SMC and analyzing the statistical information provided by the tool. We demonstrate the applicability of our framework via a case study of five classical RT-DVS algorithms.

  9. Development of Sustained-Release Microbeads of Nifedipine and In ...

    African Journals Online (AJOL)

    Methods: Nifedipine microbeads were prepared using sodium alginate and pectin in different ratios by ionic-gelation method. ... Oral sustained release dosage forms provide ... Stability in .... 37oC) in a USP XXII apparatus (Pharma Test,.

  10. DEVELOPMENT OF SUSTAINED RELEASE TABLETS CONTAINING SOLID DISPERSIONS OF BACLOFEN

    Directory of Open Access Journals (Sweden)

    K. H. Janardhana

    2015-07-01

    Full Text Available Sustained release tablets containing solid dispersions granules of a poorly water soluble drug were prepared to investigate the controlled release of the drug. Baclofen was chosen because of its poor water solubility and short elimination half-life. Poloxamer 188 and PEG 6000 were used as solid dispersion carrier. Free flowing solid dispersion granules were prepared by adsorbing the melt of the drug and carriers onto the surface of an adsorbent, Carbopol 934P followed by direct compression with HPMC K4M and HPMC K100 to obtain an solid dispersion loaded sustained release tablets. FTIR studies confirmed that the compatibility of drug and carriers. Differential scanning calorimetry (DSC and X-ray diffraction (XRD revealed partially amorphous structures of the drug in solid dispersion granules. The solid dispersion granules dissolved completely within 30 min, which was much faster than that of pure drug baclofen. The sustained release of baclofen from the solid dispersion containing tablet was achieved for 2 h in gastric fluid (pH 1.2 and for up to 10 h in intestinal fluid (pH 6.8. A combination of solid dispersion techniques using adsorption and sustained release concepts is a promising approach to control the release rate of poorly water-soluble drugs.

  11. DEVELOPMENT OF SUSTAINED RELEASE TABLETS CONTAINING SOLID DISPERSIONS OF BACLOFEN

    Directory of Open Access Journals (Sweden)

    K. H. Janardhana

    2013-12-01

    Full Text Available Sustained release tablets containing solid dispersions granules of a poorly water soluble drug were prepared to investigate the controlled release of the drug. Baclofen was chosen because of its poor water solubility and short elimination half-life. Poloxamer 188 and PEG 6000 were used as solid dispersion carrier. Free flowing solid dispersion granules were prepared by adsorbing the melt of the drug and carriers onto the surface of an adsorbent, Carbopol 934P followed by direct compression with HPMC K4M and HPMC K100 to obtain an solid dispersion loaded sustained release tablets. FTIR studies confirmed that the compatibility of drug and carriers. Differential scanning calorimetry (DSC and X-ray diffraction (XRD revealed partially amorphous structures of the drug in solid dispersion granules. The solid dispersion granules dissolved completely within 30 min, which was much faster than that of pure drug baclofen. The sustained release of baclofen from the solid dispersion containing tablet was achieved for 2 h in gastric fluid (pH 1.2 and for up to 10 h in intestinal fluid (pH 6.8. A combination of solid dispersion techniques using adsorption and sustained release concepts is a promising approach to control the release rate of poorly water-soluble drugs.

  12. Design and development of sustained-release glyburide-loaded

    Indian Academy of Sciences (India)

    The aim of this study was to develop sustained-release glyburide-loaded silica nanoparticles. Silica nanoparticles were synthesized by the sol–gel method using tetra-ethyl ortho-silane as a precursor. Glyburide was successfully entrapped in synthesized silica nanoparticles. To identify the effect of independent variables ...

  13. Sustained Release of a Watermgoluble tiring from Directly ...

    African Journals Online (AJOL)

    Sustained Release of a Watermgoluble tiring from Directly Compressed Okra Gum Matrix. Tablets. Val). Mill, MA. Gilllllbll'ifl'l' AND KT. ... in near noromorder release of aspirin from the matrix tablets. The results indicate that okra gum is .... porous structure including alteration of the shape and size distribution of the pores.

  14. THE SUCCINATED PROTEOME

    OpenAIRE

    Merkley, Eric D.; Metz, Thomas O.; Smith, Richard D.; Baynes, John W.; Frizzell, Norma

    2013-01-01

    The post-translational modifications (PTMs) of cysteine residues include oxidation, S-glutathionylation, S-nitrosylation, and succination, all of which modify protein function or turnover in response to a changing intracellular redox environment. Succination is a chemical modification of cysteine in proteins by the Krebs cycle intermediate, fumarate, yielding S-(2-succino) cysteine (2SC). Intracellular fumarate concentration and succination of proteins are increased by hyperpolarization of th...

  15. GPScheDVS: A New Paradigm of the Autonomous CPU Speed Control for Commodity-OS-based General-Purpose Mobile Computers with a DVS-friendly Task Scheduling

    OpenAIRE

    Kim, Sookyoung

    2008-01-01

    This dissertation studies the problem of increasing battery life-time and reducing CPU heat dissipation without degrading system performance in commodity-OS-based general-purpose (GP) mobile computers using the dynamic voltage scaling (DVS) function of modern CPUs. The dissertation especially focuses on the impact of task scheduling on the effectiveness of DVS in achieving this goal. The task scheduling mechanism used in most contemporary general-purpose operating systems (GPOS) prioritizes t...

  16. The Succinated Proteome

    Energy Technology Data Exchange (ETDEWEB)

    Merkley, Eric D.; Metz, Thomas O.; Smith, Richard D.; Baynes, John; Frizell, Norma

    2014-03-30

    Succination is a chemical modification of cysteine in protein by the Krebs cycle intermediate, fumarate, yielding S-(2-succino)cysteine (2SC). Intracellular fumarate concentration and succination of proteins are increased by hyperpolarization of the inner mitochondrial membrane, in concert with mitochondrial, endoplasmic reticulum (ER) and oxidative stress in adipocytes grown in high glucose medium and in adipose tissue in obesity and diabetes. Increased succination of proteins is also detected in the kidney of a fumarase conditional knock-out mouse which develops renal tumors. Keap1, the gatekeeper of the antioxidant response, was identified as a major succinated protein in renal cancer cells, suggesting that succination may play a role in activation of the antioxidant response. A wide range of proteins is subject to succination, including enzymes, adipokines, cytoskeletal proteins and ER chaperones with functional cysteine residues. There is also significant overlap between succinated and glutathionylated proteins, and with proteins containing cysteine residues that are readily oxidized to the sulfenic (cysteic) acid. Succination of adipocyte proteins is inhibited by uncouplers, which discharge the mitochondrial membrane potential (Δψm) and by ER stress inhibitors. 2SC serves as a biomarker of mitochondrial stress or dysfunction in chronic diseases, such as obesity, diabetes and cancer, and recent studies suggest that succination is a mechanistic link between mitochondrial dysfunction, oxidative and ER stress, and cellular progression toward apoptosis. In this article, we review the history of the succinated proteome and the challenges associated with measuring this non-enzymatic post-translational modification of proteins by proteomics approaches.

  17. Formulation of Dipyridamole Sustained Release Tablet Using Floating System

    Directory of Open Access Journals (Sweden)

    Lenny Mauilida Valentina

    2011-06-01

    Full Text Available Dipyridamole is a drug for prevention of postoperative thromboembolic complication of heart valve replacement and long term therapy of angina pectoris will be well absorbed in stomach. To maintain therapeutic plasma concentration in long time and to increase bioavalaibility is needed a sustained release dosage form having the long residence time in the stomach. The objective of this research was to make floating sustained release tablet of dipyridamole conforming to the requirement that was set up by dipyridamol therapeutic concentration. Tablets were made by wet granulation method using aquadest as a liquid binder, HPMC K4M, Ac-di-sol, Avicel PH 102, talk, and Mg stearat. Dissolution assay was carried out using type 2 release tester at rotation speed of 50 rpm in medium 900 mL HCl 0.1 N at 37 ± 0.5 °C for 8 hours. The formulation containing of 50 mg dipirydamole, HPMC K4M (30%, Ac-di-sol (20%, Avicel PH 102 (37%, talk (2%, and Mg stearat (1% released 59.61 ± 6.73% and 89.34 ± 5.87% of dipyridamole respectively after 4 and 8 hours that conformed to the requirement.

  18. Sustained release of verapamil hydrochloride from sodium alginate microcapsules.

    Science.gov (United States)

    Farhana, S Ayesha; Shantakumar, S M; Shyale, Somashekar; Shalam, Md; Narasu, Laxmi

    2010-04-01

    The objective of the present study was to develop sustained release microcapsules of verapamil hydrochloride (VH) using biodegradable polymers. For this purpose microcapsules embedded verapamil hydrochloride were prepared using sodium alginate alone and also by incorporating some co polymers like methyl cellulose (MC), sodium carboxy methyl cellulose (SCMC) , poly vinyl pyrollidone (PVP) and xanthan gum by employing complex emulsion method of microencapsulation. Microcapsules were prepared in various core: coat ratios to know the effect of polymer and co polymers on drug release. Overall ten formulations were prepared and evaluated for flow behaviour, sieve analysis, drug entrapment efficiency, in vitro dissolution studies, stability studies, including scanning electron microscopy and DSC. The resulting microcapsules were discrete, large, spherical and also free flowing. The drug content in all the batches of microcapsules was found to be uniform. The release was depended on core: coat ratio and nature of the polymers. FTIR analysis revealed chemical integrity between Verapamil hydrochloride (VH), sodium alginate and between the copolymers. Among the four copolymers used methyl cellulose retarded the drug release more than the other three, hence the same formulation was subjected for in vivo studies. The drug release from the microcapsules was found to be following non fickian diffusion. Mechanism of drug release was diffusion controlled first order kinetics. Drug diffusion co efficient and correlation co efficient were also assessed by using various mathematical models. In vivo result analysis of pharmacokinetic parameters revealed that t max of reference and test formulations were almost same. From the study it was concluded that, sustained release Verapamil hydro chloride microcapsules could be achieved with success using sodium alginate alone and also in combination with other biodegradable polymers.

  19. Plant Extract Synthesized PLA Nanoparticles for Controlled and Sustained Release of Quercetin: A Green Approach

    Science.gov (United States)

    Yadav, Sudesh Kumar

    2012-01-01

    Background Green synthesis of metallic nanoparticles (NPs) has been extensively carried out by using plant extracts (PEs) which have property of stabilizers/ emulsifiers. To our knowledge, there is no comprehensive study on applying a green approach using PEs for fabrication of biodegradable PLA NPs. Conventional methods rely on molecules like polyvinyl alcohol, polyethylene glycol, D-alpha-tocopheryl poly(ethylene glycol 1000) succinate as stabilizers/emulsifiers for the synthesis of such biodegradable NPs which are known to be toxic. So, there is urgent need to look for stabilizers which are biogenic and non-toxic. The present study investigated use of PEs as stabilizers/emulsifiers for the fabrication of stable PLA NPs. Synthesized PLA NPs through this green process were explored for controlled release of the well known antioxidant molecule quercetin. Methodology/Principal Findings Stable PLA NPs were synthesized using leaf extracts of medicinally important plants like Syzygium cumini (1), Bauhinia variegata (2), Cedrus deodara (3), Lonicera japonica (4) and Eleaocarpus sphaericus (5). Small and uniformly distributed NPs in the size range 70±30 nm to 143±36 nm were formed with these PEs. To explore such NPs for drugs/ small molecules delivery, we have successfully encapsulated quercetin a lipophilic molecule on a most uniformly distributed PLA-4 NPs synthesized using Lonicera japonica leaf extract. Quercetin loaded PLA-4 NPs were observed for slow and sustained release of quercetin molecule. Conclusions This green approach based on PEs mediated synthesis of stable PLA NPs pave the way for encapsulating drug/small molecules, nutraceuticals and other bioactive ingredients for safer cellular uptake, biodistribution and targeted delivery. Hence, such PEs synthesized PLA NPs would be useful to enhance the therapeutic efficacy of encapsulated small molecules/drugs. Furthermore, different types of plants can be explored for the synthesis of PLA as well as other

  20. Naltrexone sustained-release/bupropion sustained-release for the management of obesity: review of the data to date

    Directory of Open Access Journals (Sweden)

    Caixàs A

    2014-09-01

    Full Text Available Assumpta Caixàs, Lara Albert, Ismael Capel, Mercedes Rigla Endocrinology and Nutrition Department, Parc Tauli Sabadell University Hospital, Autonomous University of Barcelona, Barcelona, Spain Abstract: Obesity is an emerging disease worldwide. Changes in living habits, especially with increased consumption of high-calorie foods and decreased levels of physical activity, lead to an energy imbalance that brings weight gain. Overweight and obesity are major risk factors for several chronic diseases (including cardiovascular diseases, diabetes, and cancer, reduce quality of life, and are associated with higher mortality. For all these reasons, it is of the utmost importance that the trend be reversed and obese people enabled to lose weight. It is known that eating a healthy diet and exercising regularly can help prevent obesity, but data show that in many cases these steps are not enough. This is the reason why, over the last few decades, several antiobesity drugs have been developed. However, the disappointing results demonstrated for the vast majority of them have not discouraged the pharmaceutical industry from continuing to look for an effective drug or combination of drugs. The systematic review presented here focuses on naltrexone sustained-release/bupropion sustained-release combination (Contrave®. We conclude from the current published reports that its effectiveness in the treatment of obesity can be estimated as a placebo-subtracted weight loss of around 4.5%. This weight reduction is moderate but similar to other antiobesity drugs. The safety profile of this combination is acceptable, despite additional data regarding cardiovascular disease being needed. Keywords: Contrave, weight loss, overweight, cardiovascular disease, diabetes, cancer

  1. DVS-SOFTWARE: An Effective Tool for Applying Highly Parallelized Hardware To Computational Geophysics

    Science.gov (United States)

    Herrera, I.; Herrera, G. S.

    2015-12-01

    Most geophysical systems are macroscopic physical systems. The behavior prediction of such systems is carried out by means of computational models whose basic models are partial differential equations (PDEs) [1]. Due to the enormous size of the discretized version of such PDEs it is necessary to apply highly parallelized super-computers. For them, at present, the most efficient software is based on non-overlapping domain decomposition methods (DDM). However, a limiting feature of the present state-of-the-art techniques is due to the kind of discretizations used in them. Recently, I. Herrera and co-workers using 'non-overlapping discretizations' have produced the DVS-Software which overcomes this limitation [2]. The DVS-software can be applied to a great variety of geophysical problems and achieves very high parallel efficiencies (90%, or so [3]). It is therefore very suitable for effectively applying the most advanced parallel supercomputers available at present. In a parallel talk, in this AGU Fall Meeting, Graciela Herrera Z. will present how this software is being applied to advance MOD-FLOW. Key Words: Parallel Software for Geophysics, High Performance Computing, HPC, Parallel Computing, Domain Decomposition Methods (DDM)REFERENCES [1]. Herrera Ismael and George F. Pinder, Mathematical Modelling in Science and Engineering: An axiomatic approach", John Wiley, 243p., 2012. [2]. Herrera, I., de la Cruz L.M. and Rosas-Medina A. "Non Overlapping Discretization Methods for Partial, Differential Equations". NUMER METH PART D E, 30: 1427-1454, 2014, DOI 10.1002/num 21852. (Open source) [3]. Herrera, I., & Contreras Iván "An Innovative Tool for Effectively Applying Highly Parallelized Software To Problems of Elasticity". Geofísica Internacional, 2015 (In press)

  2. Food interactions with sustained-release theophylline preparations. A review.

    Science.gov (United States)

    Jonkman, J H

    1989-03-01

    Currently, theophylline is being used predominantly as sustained-release capsules or tablets. In the mid-seventies the first preparations for use with a dosage interval of 12 hours (twice-daily preparations) were introduced. Since 1983, theophylline preparations that can be given with an interval of 24 hours (once-daily preparations) have become available. The release of theophylline from some of these products can be influenced (either increased or decreased) by concomitant intake of food. With some preparations the composition of the meal (especially the fat content) has an influence on the degree of effect. The consequence may be an effect on the rate of absorption or on the amount absorbed, or both simultaneously. This could result in an unexpected shift of the plasma theophylline concentration. Such a shift is therapeutically undesirable, because theophylline has a fairly narrow therapeutic range. A review is given of those food interactions with the sustained-release theophylline preparations, both twice-daily and once-daily products, that are currently on the world market. Special attention is paid to the specific (bio)pharmaceutical characteristics of the different products, and to the influence of the composition and timing of the meals. For each preparation the effect of food on the following pharmacokinetic parameters is discussed: area under the plasma concentration-time curve, peak plasma drug concentration and time to reach this peak. Where possible, the results for both adults and children are discussed. There are indications that children are more susceptible to food-effects than adults. The regulatory aspects are mentioned briefly. Clinically important effects of food have been observed with the following twice-daily products: 'Theo-Dur Sprinkle', 'Theolair SR' (= 'Nuelin SR') and 'Theograd'. Pronounced effects could have an even greater impact with once-daily preparations, as the total daily dose will be given at a single time. A particularly

  3. Sustained Release of Antibacterial Agents from Doped Halloysite Nanotubes

    Directory of Open Access Journals (Sweden)

    Shraddha Patel

    2015-12-01

    Full Text Available The use of nanomaterials for improving drug delivery methods has been shown to be advantageous technically and viable economically. This study employed the use of halloysite nanotubes (HNTs as nanocontainers, as well as enhancers of structural integrity in electrospun poly-e-caprolactone (PCL scaffolds. HNTs were loaded with amoxicillin, Brilliant Green, chlorhexidine, doxycycline, gentamicin sulfate, iodine, and potassium calvulanate and release profiles assessed. Selected doped halloysite nanotubes (containing either Brilliant Green, amoxicillin and potassium calvulanate were then mixed with poly-e-caprolactone (PLC using the electrospinning method and woven into random and oriented-fibered nanocomposite mats. The rate of drug release from HNTs, HNTs/PCL nanocomposites, and their effect on inhibiting bacterial growth was investigated. Release profiles from nanocomposite mats showed a pattern of sustained release for all bacterial agents. Nanocomposites were able to inhibit bacterial growth for up to one-month with only a slight decrease in bacterial growth inhibition. We propose that halloysite doped nanotubes have the potential for use in a variety of medical applications including sutures and surgical dressings, without compromising material properties.

  4. Sustained Release of Antibacterial Agents from Doped Halloysite Nanotubes

    Science.gov (United States)

    Patel, Shraddha; Jammalamadaka, Uday; Sun, Lin; Tappa, Karthik; Mills, David K.

    2015-01-01

    The use of nanomaterials for improving drug delivery methods has been shown to be advantageous technically and viable economically. This study employed the use of halloysite nanotubes (HNTs) as nanocontainers, as well as enhancers of structural integrity in electrospun poly-e-caprolactone (PCL) scaffolds. HNTs were loaded with amoxicillin, Brilliant Green, chlorhexidine, doxycycline, gentamicin sulfate, iodine, and potassium calvulanate and release profiles assessed. Selected doped halloysite nanotubes (containing either Brilliant Green, amoxicillin and potassium calvulanate) were then mixed with poly-e-caprolactone (PLC) using the electrospinning method and woven into random and oriented-fibered nanocomposite mats. The rate of drug release from HNTs, HNTs/PCL nanocomposites, and their effect on inhibiting bacterial growth was investigated. Release profiles from nanocomposite mats showed a pattern of sustained release for all bacterial agents. Nanocomposites were able to inhibit bacterial growth for up to one-month with only a slight decrease in bacterial growth inhibition. We propose that halloysite doped nanotubes have the potential for use in a variety of medical applications including sutures and surgical dressings, without compromising material properties. PMID:28952563

  5. Sustained release of fungicide metalaxyl by mesoporous silica nanospheres

    Energy Technology Data Exchange (ETDEWEB)

    Wanyika, Harrison, E-mail: hwanyika@gmail.com [Jomo Kenyatta University of Agriculture and Technology, Department of Chemistry (Kenya)

    2013-08-15

    The use of nanomaterials for the controlled delivery of pesticides is nascent technology that has the potential to increase the efficiency of food production and decrease pollution. In this work, the prospect of mesoporous silica nanoparticles (MSN) for storage and controlled release of metalaxyl fungicide has been investigated. Mesoporous silica nanospheres with average particle diameters of 162 nm and average pore sizes of 3.2 nm were prepared by a sol-gel process. Metalaxyl molecules were loaded into MSN pores from an aqueous solution by a rotary evaporation method. The loaded amount of metalaxyl as evaluated by thermogravimetric analysis was about 14 wt%. Release of the fungicide entrapped in the MSN matrix revealed sustained release behavior. About 76 % of the free metalaxyl was released in soil within a period of 30 days while only 11.5 and 47 % of the metalaxyl contained in the MSN carrier was released in soil and water, respectively, within the same period. The study showed that MSN can be used to successfully store metalaxyl molecules in its mesoporous framework and significantly delay their release in soil.

  6. Statistical Optimization of Sustained Release Venlafaxine HCI Wax Matrix Tablet.

    Science.gov (United States)

    Bhalekar, M R; Madgulkar, A R; Sheladiya, D D; Kshirsagar, S J; Wable, N D; Desale, S S

    2008-01-01

    The purpose of this research was to prepare a sustained release drug delivery system of venlafaxine hydrochloride by using a wax matrix system. The effects of bees wax and carnauba wax on drug release profile was investigated. A 3(2) full factorial design was applied to systemically optimize the drug release profile. Amounts of carnauba wax (X(1)) and bees wax (X(2)) were selected as independent variables and release after 12 h and time required for 50% (t(50)) drug release were selected as dependent variables. A mathematical model was generated for each response parameter. Both waxes retarded release after 12 h and increases the t(50) but bees wax showed significant influence. The drug release pattern for all the formulation combinations was found to be approaching Peppas kinetic model. Suitable combination of two waxes provided fairly good regulated release profile. The response surfaces and contour plots for each response parameter are presented for further interpretation of the results. The optimum formulations were chosen and their predicted results found to be in close agreement with experimental findings.

  7. Diclofenac sodium sustained release hot melt extruded lipid matrices.

    Science.gov (United States)

    Vithani, K; Cuppok, Y; Mostafa, S; Slipper, I J; Snowden, M J; Douroumis, D

    2014-08-01

    Sustained release diclofenac sodium (Df-Na) solid lipid matrices with Compritol® 888 ATO were developed in this study. The drug/lipid powders were processed via cold and hot melt extrusion at various drug loadings. The influence of the processing temperatures, drug loading and the addition of excipients on the obtained dissolution rates was investigated. The physicochemical characterization of the extruded batches showed the existence of crystalline drug in the extrudates with a small amount being solubilized in the lipid matrix. The drug content and uniformity on the tablet surface were also investigated by using energy dispersive X-ray microanalysis. The dissolution rates were found to depend on the actual Df-Na loading and the nature of the added excipients, while the effect of the processing temperatures was negligible. The dissolution mechanism of all extruded formulations followed Peppas-Korsemeyer law, based on the estimated determination coefficients and the dissolution constant rates, indicating drug diffusion from the lipid matrices.

  8. Sustained release of fungicide metalaxyl by mesoporous silica nanospheres

    International Nuclear Information System (INIS)

    Wanyika, Harrison

    2013-01-01

    The use of nanomaterials for the controlled delivery of pesticides is nascent technology that has the potential to increase the efficiency of food production and decrease pollution. In this work, the prospect of mesoporous silica nanoparticles (MSN) for storage and controlled release of metalaxyl fungicide has been investigated. Mesoporous silica nanospheres with average particle diameters of 162 nm and average pore sizes of 3.2 nm were prepared by a sol–gel process. Metalaxyl molecules were loaded into MSN pores from an aqueous solution by a rotary evaporation method. The loaded amount of metalaxyl as evaluated by thermogravimetric analysis was about 14 wt%. Release of the fungicide entrapped in the MSN matrix revealed sustained release behavior. About 76 % of the free metalaxyl was released in soil within a period of 30 days while only 11.5 and 47 % of the metalaxyl contained in the MSN carrier was released in soil and water, respectively, within the same period. The study showed that MSN can be used to successfully store metalaxyl molecules in its mesoporous framework and significantly delay their release in soil

  9. [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.

  10. Pharmacokinetics of Sustained-Release Analgesics in Mice

    Science.gov (United States)

    Kendall, Lon V; Hansen, Ryan J; Dorsey, Kathryn; Kang, Sooah; Lunghofer, Paul J; Gustafson, Daniel L

    2014-01-01

    Buprenorphine and carprofen, 2 of the most commonly used analgesics in mice, must be administered every 8 to 12 h to provide sustained analgesia. Sustained-release (SR) formulations of analgesics maintain plasma levels that should be sufficient to provide sustained analgesia yet require less frequent dosing and thus less handling of and stress to the animals. The pharmacokinetics of SR formulations of buprenorphine (Bup-SR), butorphanol (Butp-SR), fentanyl (Fent-SR), carprofen (Carp-SR), and meloxicam (Melox-SR) were evaluated in mice over 72 h and compared with those of traditional, nonSR formulations. Bup-SR provided plasma drug levels greater than the therapeutic level for the first 24 to 48 h after administration, but plasma levels of Bup-HCl fell below the therapeutic level by 4 h. Fent-SR maintained plasma levels greater than reported therapeutic levels for 12 h. Therapeutic levels of the remaining drugs are unknown, but Carp-SR provided plasma drug levels similar to those of Carp for the first 24 h after administration, whereas Melox-SR had greater plasma levels than did Melox for the first 8 h. Butp-SR provided detectable plasma drug levels for the first 24 h, with a dramatic decrease over the first 4 h. These results indicate that Bup-SR provides a stable plasma drug level adequate for analgesia for 24 to 48 h after administration, whereas Carp-SR, Melox-SR, Fent-SR, and Butp-SR would require additional doses to provide analgesic plasma levels beyond 24 h in mice. PMID:25255070

  11. Letter to the editor: naltrexone sustained-release/bupropion sustained-release for the management of obesity: review of the data to date

    Directory of Open Access Journals (Sweden)

    Buehler AM

    2015-01-01

    Full Text Available Anna M Buehler Hospital Alemao Oswaldo Cruz, Institute of Health Education and Sciences, Sao Paulo, BrazilI read with great interest the systematic review by Caixàs et al1 on the effect of naltrexone sustained-release/bupropion sustained-release (NB for the management of obesity. By comprehensively appraising five recent clinical trials, the authors concluded that the naltrexone/bupropion combination might represent an important new therapeutic option for the management of obesity, with a weight reduction effect that is similar to other drugs approved for the treatment of obesity.View original paper by Caixàs and colleagues.

  12. Characterization of unsaturated fatty acid sustained-release microspheres for long-term algal inhibition.

    Science.gov (United States)

    Ni, Lixiao; Jie, Xiaoting; Wang, Peifang; Li, Shiyin; Hu, Shuzhen; Li, Yiping; Li, Yong; Acharya, Kumud

    2015-02-01

    The unsaturated fatty acid (linoleic acid) sustained-release microspheres were prepared with linoleic acid (LA) using alginate-chitosan microcapsule technology. These LA sustained-release microspheres had a high encapsulation efficiency (up to 62%) tested by high performance liquid chromatography with a photo diode array. The dry microspheres were characterized by a scanning electron microscope, X-ray diffraction measurement, dynamic thermogravimetric analysis and Fourier transform infrared spectral analysis. The results of characterization showed that the microspheres had good thermal stability (decomposition temperature of 236°C), stable and temperature independent release properties (release time of more than 40 d). Compared to direct dosing of LA, LA sustained-released microspheres could inhibit Microcystis aeruginosa growth to the non-growth state. The results of this study suggested that the LA sustained-release microspheres may be a potential candidate for algal inhibition. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. [Sustained-release progesterone vaginal suppositories 3-development and clinical feasibility testing].

    Science.gov (United States)

    Nakayama, Ayako; Yamaguchi, Naho; Ohno, Yukiko; Miyata, Chihiro; Kondo, Haruomi; Sunada, Hisakazu; Okamoto, Hirokazu

    2013-01-01

      Although progesterone vaginal suppositories (hospital-formulated) are used for the treatment of infertility, their half-life is so short that multiple doses are required. In this study, we aimed to develop sustained-release vaginal suppositories suitable for clinical use which maintain an effective blood concentration by once-a-day treatment, and prepared 7 types of suppository containing the sustained-release progesterone tablets to characterize their sustained-release performance. We selected one candidate suppository among them, taking recovery rate, reproducibility, and hardness, as well as the sustained-release performance into consideration. The shell of the selected suppository is composed of VOSCO S-55 and progesterone for rapid release. The molded progesterone tablets for sustained release were embedded inside. The distribution of the weight and content of the suppository was limited, and the release rate of progesterone was significantly slower than that of a conventional progesterone suppository prepared in our hospital. The single-dose administration of the selected suppository to five healthy volunteers led to significant extension of the blood concentration. We also confirmed the rise of the basic value by multiple administration. The simulation comparison suggested that the blood progesterone concentration is controlled by once-a-day administration of the selected suppository better than twice-a-day administration of the conventional suppository. In conclusion, the sustained-release vaginal suppository prepared in this study was considered to be useful for clinical treatment.

  14. 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.

  15. The preparation and the sustained release of titanium dioxide hollow particles encapsulating L-ascorbic acid

    Science.gov (United States)

    Tominaga, Yoko; Kadota, Kazunori; Shimosaka, Atsuko; Yoshida, Mikio; Oshima, Kotaro; Shirakawa, Yoshiyuki

    2018-05-01

    The preparation of the titanium dioxide hollow particles encapsulating L-ascorbic acid via sol-gel process using inkjet nozzle has been performed, and the sustained release and the effect protecting against degradation of L-ascorbic acid in the particles were investigated. The morphology of titanium dioxide particles was evaluated by scanning electron microscopy (SEM) and energy dispersive X-ray spectrometry (EDS). The sustained release and the effect protecting against degradation of L-ascorbic acid were estimated by dialysis bag method in phosphate buffer saline (PBS) (pH = 7.4) as release media. The prepared titanium dioxide particles exhibited spherical porous structures. The particle size distribution of the titanium dioxide particles was uniform. The hollow titanium dioxide particles encapsulating L-ascorbic acid showed the sustained release. It was also found that the degradation of L-ascorbic acid could be inhibited by encapsulating L-ascorbic acid in the titanium dioxide hollow particles.

  16. Evaluation of the coat quality of sustained release pellets by individual pellet dissolution methodology.

    Science.gov (United States)

    Xu, Min; Liew, Celine Valeria; Heng, Paul Wan Sia

    2015-01-15

    This study explored the application of 400-DS dissolution apparatus 7 for individual pellet dissolution methodology by a design of experiment approach and compared its capability with that of the USP dissolution apparatus 1 and 2 for differentiating the coat quality of sustained release pellets. Drug loaded pellets were prepared by extrusion-spheronization from powder blends comprising 50%, w/w metformin, 25%, w/w microcrystalline cellulose and 25%, w/w lactose, and then coated with ethyl cellulose to produce sustained release pellets with 8% and 10%, w/w coat weight gains. Various pellet properties were investigated, including cumulative drug release behaviours of ensemble and individual pellets. When USP dissolution apparatus 1 and 2 were used for drug release study of the sustained release pellets prepared, floating and clumping of pellets were observed and confounded the release profiles of the ensemble pellets. Hence, the release profiles obtained did not characterize the actual drug release from individual pellet and the applicability of USP dissolution apparatus 1 and 2 to evaluate the coat quality of sustained release pellets was limited. The cumulative release profile of individual pellet using the 400-DS dissolution apparatus 7 was found to be more precise at distinguishing differences in the applied coat quality. The dip speed and dip interval of the reciprocating holder were critical operational parameters of 400-DS dissolution apparatus 7 that affected the drug release rate of a sustained release pellet during the individual dissolution study. The individual dissolution methodology using the 400-DS dissolution apparatus 7 is a promising technique to evaluate the individual pellet coat quality without the influence of confounding factors such as pellet floating and clumping observed during drug release test with dissolution apparatus 1 and 2, as well as to facilitate the elucidation of the actual drug release mechanism conferred by the applied sustained

  17. Preparation and Application of Sustained-Release Potassium Ferrate(VI

    Directory of Open Access Journals (Sweden)

    Xuan Xu

    2014-01-01

    Full Text Available In this study, a composite system for the sustained release of potassium ferrate(VI (sustained-release K2FeO4 was prepared and applied for water treatment. The objective of this research was to maximize the effectiveness of K2FeO4 for water treatment by enhancing its stability using diatomite. The sustained-release K2FeO4 was characterized using X-ray diffraction, scanning electron microscopy, and Fourier transform infrared spectroscopy. The results indicated that no new crystal phase was formed during the preparation and some K2FeO4 crystals entered the pores of the diatomite. From K2FeO4 release experiments, we found that the decomposition rate of K2FeO4 was obviously decreased, which greatly improved the contact rate between released K2FeO4 and pollutants. Via degradation of methyl orange, which was used as a model pollutant, the influential factor of K2FeO4 content within the complete sustained-release K2FeO4 system was studied. The optimal K2FeO4 content within the sustained-release K2FeO4 system was approximately 70%. In natural water samples, sustained-release K2FeO4 at a dosage of 0.06 g/L and with a reaction time of 20 minutes removed 36.84% of soluble microbial products and 17.03% of simple aromatic proteins, and these removal rates were better than those observed after traditional chlorine disinfection.

  18. 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 ...

  19. Physical-chemical aspects of a coaxial sustained release device based on Poly-Eva

    NARCIS (Netherlands)

    Laarhoven, Johannes Antonius Hendrikus van

    2005-01-01

    Sustained release of dugs offers several advantages like increased efficacy, safety, compliance and convenience. As a consequence sustained drug delivery is often preferred above daily administration of drugs. Furthermore, drug delivery systems can be designed to deliver one or more drugs at a

  20. Pharmacokinetics of propafenone hydrochloride sustained-release capsules in male beagle dogs.

    Science.gov (United States)

    Pan, Liping; Qian, Yafang; Cheng, Minlu; Gu, Pan; He, Yanna; Xu, Xiaowen; Ding, Li

    2015-01-01

    This paper describes the development and validation of a liquid chromatography-mass spectrometric assay for propafenone and its application to a pharmacokinetic study of propafenone administered as a new propafenone hydrochloride sustained-release capsule (SR-test), as an instant-release tablet (IR-reference) and as the market leader sustained-release capsule (Rythmol, SR-reference) in male beagle dogs (n=8). In Study A comparing SR-test with IR-reference in a crossover design T max and t 1/2 of propafenone for SR-test were significantly higher than those for IR-reference while C max and AUC were lower demonstrating the sustained release properties of the new formulation. In Study B comparing SR-test with SR-reference the observed C max and AUC of propafenone for SR-test (124.5±140.0 ng/mL and 612.0±699.2 ng·h/mL, respectively) were higher than for SR-reference (78.52±72.92 ng/mL and 423.6±431.6 ng·h/mL, respectively) although the differences were not significant. Overall, the new formulation has as good if not better sustained release characteristics to the market leader formulation.

  1. Pharmacokinetics of propafenone hydrochloride sustained-release capsules in male beagle dogs

    Directory of Open Access Journals (Sweden)

    Liping Pan

    2015-01-01

    Full Text Available This paper describes the development and validation of a liquid chromatography–mass spectrometric assay for propafenone and its application to a pharmacokinetic study of propafenone administered as a new propafenone hydrochloride sustained-release capsule (SR-test, as an instant-release tablet (IR-reference and as the market leader sustained-release capsule (Rythmol, SR-reference in male beagle dogs (n=8. In Study A comparing SR-test with IR-reference in a crossover design Tmax and t1/2 of propafenone for SR-test were significantly higher than those for IR-reference while Cmax and AUC were lower demonstrating the sustained release properties of the new formulation. In Study B comparing SR-test with SR-reference the observed Cmax and AUC of propafenone for SR-test (124.5±140.0 ng/mL and 612.0±699.2 ng·h/mL, respectively were higher than for SR-reference (78.52±72.92 ng/mL and 423.6±431.6 ng·h/mL, respectively although the differences were not significant. Overall, the new formulation has as good if not better sustained release characteristics to the market leader formulation.

  2. Nanosized sustained-release pyridostigmine bromide microcapsules: process optimization and evaluation of characteristics

    Science.gov (United States)

    Tan, Qunyou; Jiang, Rong; Xu, Meiling; Liu, Guodong; Li, Songlin; Zhang, Jingqing

    2013-01-01

    Background Pyridostigmine bromide (3-[[(dimethylamino)-carbonyl]oxy]-1-methylpyridinium bromide), a reversible inhibitor of cholinesterase, is given orally in tablet form, and a treatment schedule of multiple daily doses is recommended for adult patients. Nanotechnology was used in this study to develop an alternative sustained-release delivery system for pyridostigmine, a synthetic drug with high solubility and poor oral bioavailability, hence a Class III drug according to the Biopharmaceutics Classification System. Novel nanosized pyridostigmine-poly(lactic acid) microcapsules (PPNMCs) were expected to have a longer duration of action than free pyridostigmine and previously reported sustained-release formulations of pyridostigmine. Methods The PPNMCs were prepared using a double emulsion-solvent evaporation method to achieve sustained-release characteristics for pyridostigmine. The preparation process for the PPNMCs was optimized by single-factor experiments. The size distribution, zeta potential, and sustained-release behavior were evaluated in different types of release medium. Results The optimal volume ratio of inner phase to external phase, poly(lactic acid) concentration, polyvinyl alcohol concentration, and amount of pyridostigmine were 1:10, 6%, 3% and 40 mg, respectively. The negatively charged PPNMCs had an average particle size of 937.9 nm. Compared with free pyridostigmine, PPNMCs showed an initial burst release and a subsequent very slow release in vitro. The release profiles for the PPNMCs in four different types of dissolution medium were fitted to the Ritger-Peppas and Weibull models. The similarity between pairs of dissolution profiles for the PPNMCs in different types of medium was statistically significant, and the difference between the release curves for PPNMCs and free pyridostigmine was also statistically significant. Conclusion PPNMCs prepared by the optimized protocol described here were in the nanometer range and had good uniformity

  3. Postoperative Analgesia Due to Sustained-Release Buprenorphine, Sustained-Release Meloxicam, and Carprofen Gel in a Model of Incisional Pain in Rats (Rattus norvegicus).

    Science.gov (United States)

    Seymour, Travis L; Adams, Sean C; Felt, Stephen A; Jampachaisri, Katechan; Yeomans, David C; Pacharinsak, Cholawat

    2016-01-01

    Postoperative analgesia in laboratory rats is complicated by the frequent handling associated with common analgesic dosing requirements. Here, we evaluated sustained-release buprenorphine (Bup-SR), sustained-release meloxicam (Melox-SR), and carprofen gel (CG) as refinements for postoperative analgesia. The aim of this study was to investigate whether postoperative administration of Bup-SR, Melox-SR, or CG effectively controls behavioral mechanical and thermal hypersensitivity in a rat model of incisional pain. Rats were randomly assigned to 1 of 5 treatment groups: saline, 1 mL/kg SC BID; buprenorphine HCl (Bup HCl), 0.05 mg/kg SC BID; Bup-SR, 1.2 mg/kg SC once; Melox-SR, 4 mg/kg SC once; and CG, 2 oz PO daily. Mechanical and thermal hypersensitivity were tested daily from day-1 through 4. Bup HCl and Bup-SR attenuated mechanical and thermal hypersensitivity on days 1 through 4. Melox-SR and CG attenuated mechanical hypersensitivity-but not thermal hypersensitivity-on days 1 through 4. Plasma concentrations, measured by using UPLC with mass spectrometry, were consistent between both buprenorphine formulations. Gross pathologic examination revealed no signs of toxicity in any group. These findings suggest that postoperative administration of Bup HCl and Bup-SR-but not Melox-SR or CG-effectively attenuates mechanical and thermal hypersensitivity in a rat model of incisional pain.

  4. Succinic acid production from Jerusalem artichoke

    DEFF Research Database (Denmark)

    Gunnarsson, Ingólfur Bragi; Karakashev, Dimitar Borisov; Angelidaki, Irini

    In this work, A. succinogenes 130Z was used to produce succinic acid from Jerusalem artichoke tuber hydrolysate. Results showed that both fructose and glucose in the tuber hydrolysate were utilized for succinic acid production. The sugar utilization was found to be dependent on process control...... that Jerusalem artichoke tubers could be utilized for production of bio-succinic acid....

  5. 21 CFR 582.1091 - Succinic acid.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Succinic acid. 582.1091 Section 582.1091 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS....1091 Succinic acid. (a) Product. Succinic acid. (b) Conditions of use. This substance is generally...

  6. Thermal and Isothermal Methods in Development of Sustained Release Dosage Forms of Ketorolac Tromethamine

    Directory of Open Access Journals (Sweden)

    Dimple Chopra

    2008-01-01

    Full Text Available Differential scanning calorimetry (DSC is a rapid and convenient and conclusive method of screening drug-polymer blend during preformulation studies as it allows polymer incompatibility to be established instantaneously. Various batches of matrix tablets of ketorolac tromethamine (KTM with a series of compatible polymers were prepared. Batches of tablets which gave desired sustained release profile were subjected to stability testing according to ICH guidelines. The analysis for drug content was done using high performance liquid chromatography (HPLC method. The results revealed that there was no statistically significant change in drug content after storage of matrix tablets at elevated temperature of 40°C and 75% relative humidity. From our study we conclude that with careful selection of different polymers and their combinations, a stable sustained release oral dosage form of ketorolac tromethamine can be achieved.

  7. The physical and chemical stability of suspensions of sustained-release diclofenac microspheres.

    Science.gov (United States)

    Lewis, L; Boni, R L; Adeyeye, C M

    1998-01-01

    The major challenge in liquid sustained-release oral suspensions is to minimize drug diffusion into the suspending medium and to retain the original properties of the microparticles during storage. Diclofenac wax microspheres prepared by the hydrophobic congealable disperse phase method were formulated as a sustained release suspension and stored at three different temperatures (25, 37 and 45 degrees C) for 3 months, to evaluate the physical and chemical stability of the suspended microspheres. Suspensions of microspheres stored at ambient temperatures were both physically and chemically stable, but at higher temperatures, up to 45 degrees C, there was a decrease in drug release due to scaling and melting on the microsphere surface as observed by scanning electron microscopy. However, on prolonged storage, up to 90 days, especially at 45 degrees C, temperature became a dominant factor causing an increase in drug release. The suspension of diclofenac microspheres was chemically stable for 3 months, while the plain drug suspension exhibited slight degradation.

  8. [Establishment of modern multi-component sustained-release preparations of oral traditional Chinese medicines].

    Science.gov (United States)

    Xia, Hai-Jian; Zhang, Zhen-Hai; Liu, Dan; Yu, Dan-Hong; Jia, Xiao-Bin

    2013-10-01

    Traditional Chinese medicines have a long history, with a large quantity of efficient traditional Chinese medicines and prescriptions. However, the vast majority of pharmaceutical dose forms remain common preparations, with very few efficient, long-lasting and low-dose preparations. The sustain-release preparation allows sustained drug release in a longer period of time, maintains blood drug concentration, reduces the toxic effect and medication frequency, and improves medication compliance. Unlike monomer drugs, the material base of traditional Chinese medicine and compounds is multi-component, instead of single or several active monomers. Therefore, under the guidance of the Chinese medicine theories, modern multi-component sustained-release preparations were developed for oral traditional Chinese medicines, with the aim of finally improving the clinical efficacy of traditional Chinese medicines.

  9. Sustained-release progesterone nanosuspension following intramuscular injection in ovariectomized rats

    OpenAIRE

    Kharshoum, rasha

    2010-01-01

    Heba F SalemFaculty of Pharmacy, Beni-Suef University, Beni-Suef, EgyptAbstract: The production of an intramuscular (IM) injection of natural progesterone would provide a safer solution than using semi synthetic progesterone. However, disadvantages such as low solubility and a short half life prevent the use of natural progesterone. In this study, we formulated a sustained release form of natural progesterone to be given as IM injection. A progesterone nanosuspension (PNS) was first developed...

  10. Progesterone PLGA/mPEG-PLGA Hybrid Nanoparticle Sustained-Release System by Intramuscular Injection.

    Science.gov (United States)

    Xie, Bin; Liu, Yang; Guo, Yuting; Zhang, Enbo; Pu, Chenguang; He, Haibing; Yin, Tian; Tang, Xing

    2018-02-14

    To prepare sustained-release PLGA/mPEG-PLGA hybrid nanoparticles of progesterone (PRG), and evaluate the descending required administration dosage in vivo. PRG hybrid nanoparticles (PRG H-NPs) based on PLGA/mPEG-PLGA were compared with PRG nanoparticles (PRG-NPs) of pure PLGA as the matrix and PRG-oil solutions. Nanoparticles (NPs) were formed by the method of nanoemulsion, and the pharmacokinetics of the sustained-release PRG H-NPs in male Sprague dawley (SD) rats were investigated. The rats were randomly divided into four groups, each group received: single dose of PRG H-NPs (14.58 mg/kg, i.m.) and PRG-NPs (14.58 mg/kg, i.m.), repeated dosing for 7 days of PRG-oil (2.08 mg/kg, i.m.) solution (Oil-L) and a higher dosage of PRG-oil (6.24 mg/kg, i.m.) solution (Oil-H), respectively. In the pharmacokinetic test, the PRG H-NPs exhibited a comparatively good sustained-release effect against the PRG-NPs without mPEG-PLGA and PRG-oil solution. The pharmacokinetic parameters of the PRG H-NPs, PRG-NPs, Oil-L and Oil-H were AUC 0-t (ng·h·mL -1 ) 8762.1, 1546.1, 1914.5, and 12,138.9, t 1/2 (h)52.7, 44.1, 8.4 and 44.6 respectively. Owing to the modification of PEG, PRG H-NPs can act as safe delivery platforms for sustained-release of drugs with a lower dosage required.

  11. Sustained release of estrogens from PEGylated nanoparticles for treatment of secondary spinal cord injury

    Science.gov (United States)

    Barry, John

    Spinal Cord Injury (SCI) is a debilitating condition which causes neurological damage and can result in paralysis. SCI results in immediate mechanical damage to the spinal cord, but secondary injuries due to inflammation, oxidative damage, and activated biochemical pathways leading to apoptosis exacerbate the injury. The only currently available treatment, methylprednisolone, is controversial because there is no convincing data to support its therapeutic efficacy for SCI treatment. In the absence of an effective SCI treatment option, 17beta-estradiol has gained significant attention for its anti-oxidant, anti-inflammatory, and anti-apoptotic abilities, all events associated with secondary. Sadly, 17beta-estradiol is associated with systemic adverse effects preclude the use of free estrogen even for local administration due to short drug half-life in the body. Biodegradable nanoparticles can be used to increase half-life after local administration and to bestow sustained release. Sustained release using PEGylated biodegradable polymeric nanoparticles constructed from poly(lactic-co-glycolic acid) (PLGA) will endow a consistent, low, but effective dose to be delivered locally. This will limit systemic effects due to local administration and low dose, sustained release. PLGA was chosen because it has been used extensively for sustained release, and has a record of safety in humans. Here, we show the in vitro efficacy of PEGylated nanoparticles loaded with 17beta-estradiol for treatment of secondary SCI. We achieved a high loading efficiency and controlled release from the particles over a several day therapeutic window. The particles also show neuroprotection in two in vitro cell culture models. Both the dose and pretreatment time with nanoparticles was evaluated in an effort to translate the treatment into an animal model for further study.

  12. Preparation and evaluation of tolmetin sodium conventional and sustained-release suppositories

    OpenAIRE

    B., Baloǧlu; O., Kirkaǧaçhoǧlu

    2002-01-01

    Conventional suppositories of tolmetin sodium were prepared by using two different types of Witepsol as an oily base and two different ratios of polyethylene glycol 400: polyethylene glycol 4000 as an water-soluble base. In addition, sustained- release suppositories were prepared by adding Eudragit L-100 ta the suppositories. The effects of the suppository base and the ratios of the polyethylene glycol 400: polyethylene glycols 4000 on the in vitro release characteristics were investigated. T...

  13. Development of Sustained Release Capsules Containing “Coated Matrix Granules of Metoprolol Tartrate”

    OpenAIRE

    Siddique, Sabahuddin; Khanam, Jasmina; Bigoniya, Papiya

    2010-01-01

    The objective of this investigation was to prepare sustained release capsule containing coated matrix granules of metoprolol tartrate and to study its in vitro release and in vivo absorption. The design of dosage form was performed by choosing hydrophilic hydroxypropyl methyl cellulose (HPMC K100M) and hydrophobic ethyl cellulose (EC) polymers as matrix builders and Eudragit® RL/RS as coating polymers. Granules were prepared by composing drug with HPMC K100M, EC, dicalcium phosphate by wet gr...

  14. Influence of Natural, Synthetic Polymers and Fillers on sustained release matrix tablets of Pregabalin

    OpenAIRE

    Vijaya Durga. K; Ashok Kumar. P; Suresh V Kulkarni

    2013-01-01

    The objective of the present study was to develop sustained release matrix tablets of Pregabalin for the treatment of neuropathic pain and epilepsy. The tablets were prepared by wet granulation and formulated using drug with Hydrophilic, hydrophobic, synthetic, natural polymers and 4 different fillers were used. The effect of Polymer concentration, combination and fillers on drug release rate was analyzed for the formulations F-1 to F-17. The tablets were subjected to physicochemical studies,...

  15. 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.

  16. Experience with sustained-release melatonin for the treatment of sleep disorders in depression

    Directory of Open Access Journals (Sweden)

    Svetlana Vladimirovna Prokhorova

    2015-01-01

    Full Text Available The data available in the literature on the role of melatonin in the regulation of circadian rhythms and sleep disorders in the population and in patients with mental diseases are analyzed. The cause of insomnia may be circadian rhythm disorders due to the age-related decline in the elaboration of the endogenous hormones that are responsible for the quality and duration of sleep, one of which is melatonin.Sustained-release melatonin is a synthetic analogue of the endogenous human pineal hormone melatonin. According to clinical findings, the main proven clinical effects of sustained-release melatonin 2 mg are a reduction in the latency of sleep, improvement of its quality, and lack of daytime sleepiness. The drug causes no dependence on its long use and rebound symptoms (increased insomnia symptoms, positively affects cognitive functions, and lowers nocturnal blood pressure in hypertensive patients.The paper describes a clinical case of a female patient with recurrent depressive disorder, in whom sustained-release melatonin 2 mg has demonstrated high efficacy and good tolerability in the combination therapy of sleep disorders in the pattern of depression.

  17. Sustained release of sphingosine 1-phosphate for therapeutic arteriogenesis and bone tissue engineering.

    Science.gov (United States)

    Sefcik, Lauren S; Petrie Aronin, Caren E; Wieghaus, Kristen A; Botchwey, Edward A

    2008-07-01

    Sphingosine 1-phosphate (S1P) is a bioactive phospholipid that impacts migration, proliferation, and survival in diverse cell types, including endothelial cells, smooth muscle cells, and osteoblast-like cells. In this study, we investigated the effects of sustained release of S1P on microvascular remodeling and associated bone defect healing in vivo. The murine dorsal skinfold window chamber model was used to evaluate the structural remodeling response of the microvasculature. Our results demonstrated that 1:400 (w/w) loading and subsequent sustained release of S1P from poly(lactic-co-glycolic acid) (PLAGA) significantly enhanced lumenal diameter expansion of arterioles and venules after 3 and 7 days. Incorporation of 5-bromo-2-deoxyuridine (BrdU) at day 7 revealed significant increases in mural cell proliferation in response to S1P delivery. Additionally, three-dimensional (3D) scaffolds loaded with S1P (1:400) were implanted into critical-size rat calvarial defects, and healing of bony defects was assessed by radiograph X-ray, microcomputed tomography (muCT), and histology. Sustained release of S1P significantly increased the formation of new bone after 2 and 6 weeks of healing and histological results suggest increased numbers of blood vessels in the defect site. Taken together, these experiments support the use of S1P delivery for promoting microvessel diameter expansion and improving the healing outcomes of tissue-engineered therapies.

  18. Therapeutic effects of 5-fluorouracil sustained-release particles in 81 malignant pericardial effusion patients

    Directory of Open Access Journals (Sweden)

    Yong-Li Ji

    2015-02-01

    Full Text Available This study aimed to investigate the clinical application value of the 5-fluorouracil (5-FU sustained-release particles implanted along the cardiac tangent direction into malignant pericardial effusion (MPCE. A total of 81 MPCE patients underwent pericardiocentesis, and were implanted with 5-FU sustained-release particles into the pericardial cavity under ultrasound guidance. The puncturing path was along the cardiac tangent direction. Ultrasound examinations were performed every week, and the efficacy was evaluated 4 weeks after treatment. The 45 patients who were treated with pericardial catheter drainage and simultaneous intracavitary chemotherapy were used as the control group. The success rate of pericardiocentesis was 100%. Ultrasound reviews performed 4 weeks after treatment showed that 71 cases achieved complete remission and eight cases achieved partial remission, while treatment was completely ineffective in two cases. The total remission rate was 97.53%, which was significantly higher than that of the control group (77.78%, p < 0.01. The implantation of 5-FU sustained-release particles along the cardiac tangent direction was safe, and demonstrated good efficacy and fewer adverse reactions. Thus, this method could be ideal for the treatment of MPCE.

  19. Spray drying of silica microparticles for sustained release application with a new sol-gel precursor.

    Science.gov (United States)

    Wang, Bifeng; Friess, Wolfgang

    2017-10-30

    A new precursor, tetrakis(2-methoxyethyl) orthosilicate (TMEOS) was used to fabricate microparticles for sustained release application, specifically for biopharmaceuticals, by spray drying. The advantages of TMEOS over the currently applied precursors are its water solubility and hydrolysis at moderate pH without the need of organic solvents or catalyzers. Thus a detrimental effect on biomolecular drug is avoided. By generating spray-dried silica particles encapsulating the high molecular weight model compound FITC-dextran 150 via the nano spray dryer Büchi-90, we demonstrated how formulation parameters affect and enable control of drug release properties. The implemented strategies to regulate release included incorporating different quantities of dextrans with varying molecular weight as well as adjusting the pH of the precursor solution to modify the internal microstructures. The addition of dextran significantly altered the released amount, while the release became faster with increasing dextran molecular weight. A sustained release over 35days could be achieved with addition of 60 kD dextran. The rate of FITC-Dextran 150 release from the dextran 60 containing particles decreased with higher precursor solution pH. In conclusion, the new precursor TMEOS presents a promising alternative sol-gel technology based carrier material for sustained release application of high molecular weight biopharmaceutical drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Escherichia coli yjjPB genes encode a succinate transporter important for succinate production.

    Science.gov (United States)

    Fukui, Keita; Nanatani, Kei; Hara, Yoshihiko; Yamakami, Suguru; Yahagi, Daiki; Chinen, Akito; Tokura, Mitsunori; Abe, Keietsu

    2017-09-01

    Under anaerobic conditions, Escherichia coli produces succinate from glucose via the reductive tricarboxylic acid cycle. To date, however, no genes encoding succinate exporters have been established in E. coli. Therefore, we attempted to identify genes encoding succinate exporters by screening an E. coli MG1655 genome library. We identified the yjjPB genes as candidates encoding a succinate transporter, which enhanced succinate production in Pantoea ananatis under aerobic conditions. A complementation assay conducted in Corynebacterium glutamicum strain AJ110655ΔsucE1 demonstrated that both YjjP and YjjB are required for the restoration of succinate production. Furthermore, deletion of yjjPB decreased succinate production in E. coli by 70% under anaerobic conditions. Taken together, these results suggest that YjjPB constitutes a succinate transporter in E. coli and that the products of both genes are required for succinate export.

  1. Preparation of deuterated succinic acids

    Energy Technology Data Exchange (ETDEWEB)

    Tashiro, Masashi; Tsuzuki, Hirohisa; Goto, Hideyuki; Ogasahara, Shoji; Mataka, Shuntaro (Kyushu Univ., Fukuoka (Japan)); Isobe, Shin-ichiro; Yonemitsu, Tadashi (Kyushu Sangyo Univ., Fukuoka (Japan). Dept. of Industrial Chemistry)

    1991-04-01

    Succinic (2,3-{sup 2}H{sub 2})- and (2,2,3,3-{sup 2}H{sub 4})-acids were prepared from maleic anhydride and dimethyl fumarate, and acetylene dicarboxylic acid and its dimethyl ester by treatment with Cu-Al and Ni-Al alloys in 10% NaOD-D{sub 2}0 in 95% to 100% isotopic purity. The succinic {sup 2}H{sub 4} acid having high isotopic purity was also obtained on the hydrolysis of 1,2-ethanedinitrile with alkaline deuterium oxide. Based on the {sup 1}H({sup 2}H) spectra analysis of N-(o-biphenyl)(2,3-{sup 2}H{sub 2})succinimide, it was elucidated that the Raney alloy reduction with alkaline deuterium oxide proceeds stepwise. (author).

  2. Formulation and Evaluation of a Sustained-Release Tablets of Metformin Hydrochloride Using Hydrophilic Synthetic and Hydrophobic Natural Polymers

    OpenAIRE

    Wadher, K. J.; Kakde, R. B.; Umekar, M. J.

    2011-01-01

    Metformin hydrochloride has relatively short plasma half-life, low absolute bioavailability. The need for the administration two to three times a day when larger doses are required can decrease patient compliance. Sustained release formulation that would maintain plasma level for 8-12 h might be sufficient for daily dosing of metformin. Sustained release products are needed for metformin to prolong its duration of action and to improve patient compliances. The overall objective of this study ...

  3. Taste masking of ofloxacin and formation of interpenetrating polymer network beads for sustained release

    Directory of Open Access Journals (Sweden)

    A. Michael Rajesh

    2017-08-01

    Full Text Available The objective of this study was to carry out taste masking of ofloxacin (Ofl by ion exchange resins (IERs followed by sustained release of Ofl by forming interpenetrating polymer network (IPN beads. Drug-resin complexes (DRCs with three different ratios of Ofl to IERs (1:1, 1:2, 1:4 were prepared by batch method and investigated for in vivo and in vitro taste masking. DRC of methacrylic acid-divinyl benzene (MD resin and Ofl prepared at a ratio of 1:4 was used to form IPN beads. IPN beads of MD 1:4 were prepared by following the ionic cross-linking method using sodium carboxymethyl xanthan gum (SCMXG and SCMXG-sodium carboxymethyl cellulose (SCMXG-SCMC. IPN beads were characterized with FT-IR and further studied on sustained release of Ofl at different pH. In vivo taste masking carried out by human volunteers showed that MD 1:4 significantly reduced the bitterness of Ofl. Characterization studies such as FT-IR, DSC, P-XRD and taste masking showed that complex formation took place between drug and resin. In vitro study at gastric pH showed complete release of drug from MD 1:4 within 30 min whereas IPN beads took 5 h at gastric pH and 10 h at salivary pH for the complete release of drug. As the crosslinking increased the release kinetics changed into non-Fickian diffusion to zero-order release mechanism. MD 1:4 showed better performance for the taste masking of Ofl and IPNs beads prepared from it were found useful for the sustained release of Ofl at both the pH, indicating a versatile drug delivery system.

  4. Layer-by-layer films assembled from natural polymers for sustained release of neurotrophin

    International Nuclear Information System (INIS)

    Zhang, Zhiling; Li, Qianqi; Han, Lin; Zhong, Yinghui

    2015-01-01

    Cortical neural prostheses (CNPs) hold great promise for paralyzed patients by recording neural signals from the brain and translating them into movement commands. However, these electrodes normally fail to record neural signals weeks to months after implantation due to inflammation and neuronal loss around the implanted neural electrodes. Sustained local delivery of neurotrophins from biocompatible coatings on CNPs can potentially promote neuron survival and attract the nearby neurons to migrate toward the electrodes to increase neuron density at the electrode/brain interface, which is important for maintaining the recording quality and long-term performance of the implanted CNPs. However, sustained release of neurotrophins from biocompatible ultrathin coatings is very difficult to achieve. In this study, we investigated the potential of several biocompatible natural polyanions including heparin, dextran sulfate, and gelatin to form layer-by-layer (LbL) assembly with positively charged neurotrophin nerve growth factor (NGF) and its model protein lysozyme, and whether sustained release of NGF and lysozyme can be achieved from the nanoscale thin LbL coatings. We found that gelatin, which is less negatively charged than heparin and dextran sulfate, showed the highest efficacy in loading proteins into the LbL films because other interactions in addition to electrostatic interactions were involved in LbL assembly. Sustained release of NGF and lysozymes for approximately 2 weeks was achieved from the gelatin-based LbL coatings. Released NGF maintained the bioactivity to stimulate neurite outgrowth from PC12 cells. Gelatin is generally recognized as safe by the FDA. Thus, the biocompatible LbL coating developed in this study is highly promising to be used for implanted CNPs to improve their long-term performance in human patients. (paper)

  5. Formulation and In Vitro, In Vivo Evaluation of Effervescent Floating Sustained-Release Imatinib Mesylate Tablet

    Science.gov (United States)

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

    2015-01-01

    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

  6. 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

  7. Evaluation of rate of swelling and erosion of verapamil (VRP) sustained-release matrix tablets.

    Science.gov (United States)

    Khamanga, Sandile M; Walker, Roderick B

    2006-01-01

    Tablets manufactured in-house were compared to a marketed sustained-release product of verapamil to investigate the rate of hydration, erosion, and drug-release mechanism by measuring the wet and subsequent dry weights of the products. Swelling and erosion rates depended on the polymer and granulating fluid used, which ultimately pointed to their permeability characteristics. Erosion rate of the marketed product was highest, which suggests that the gel layer that formed around these tablets was weak as opposed to the robust and resistant layers of test products. Anomalous and near zero-order transport mechanisms were dominant in tests and commercial product, respectively.

  8. LC for analysis of two sustained-release mixtures containing cough cold suppressant drugs.

    Science.gov (United States)

    El-Gindy, Alaa; Sallam, Shehab; Abdel-Salam, Randa A

    2010-07-01

    A liquid chromatographic method was applied for the analysis of two sustained-release mixtures containing dextromethorphane hydrobromide, carbinoxamine maleate with either phenylephrine hydrochloride in pharmaceutical capsules (Mix 1) or phenyl-propanolamine, methylparaben, and propylparaben, which bonds as a drug base to ion exchange resin in pharmaceutical syrup (Mix 2). The method was used for their simultaneous determination using a CN column with a mobile phase consisting of acetonitrile-12 mM ammonium acetate in the ratio of 60:40 (v/v, pH 6.0) for Mix 1 and 45:55 (v/v, pH 6.0) for Mix 2.

  9. Natural gums and modified natural gums as sustained-release carriers.

    Science.gov (United States)

    Bhardwaj, T R; Kanwar, M; Lal, R; Gupta, A

    2000-10-01

    Although natural gums and their derivatives are used widely in pharmaceutical dosage forms, their use as biodegradable polymeric materials to deliver bioactive agents has been hampered by the synthetic materials. These natural polysaccharides do hold advantages over the synthetic polymers, generally because they are nontoxic, less expensive, and freely available. Natural gums can also be modified to have tailor-made materials for drug delivery systems and thus can compete with the synthetic biodegradable excipients available in the market. In this review, recent developments in the area of natural gums and their derivatives as carriers in the sustained release of drugs are explored.

  10. 21 CFR 184.1091 - Succinic acid.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Succinic acid. 184.1091 Section 184.1091 Food and... Substances Affirmed as GRAS § 184.1091 Succinic acid. (a) Succinic acid (C4H6O4, CAS Reg. No. 110-15-6), also referred to as amber acid and ethylenesuccinic acid, is the chemical 1,4-butanedioic acid. It is...

  11. Design and characterization of sustained release ketoprofen entrapped carnauba wax microparticles.

    Science.gov (United States)

    Oliveira, Rodinelli B; Nascimento, Thais L; Lima, Eliana M

    2012-01-01

    Ketoprofen is a non-steroid anti-inflammatory drug (NSAID) used in the treatment of rheumatic diseases and in mild to moderate pain. Ketoprofen has a short biological half-life and the commercially available conventional release formulations require dosages to be administered at least 2-3 times a day. Due to these characteristics, ketoprofen is a good candidate for the preparation of controlled release formulations. In this work, a multiparticulate-sustained release dosage form containing ketoprofen in a carnauba wax matrix was developed. Particles were prepared by an emulsion congealing technique. System variables were optimized using fractional factorial and response surface experimental design. Characterization of the particles included size and morphology, flow rate, drug loading and in vitro drug release. Spherical particles were obtained with high drug load and sustained drug release profile. The optimized particles had an average diameter of approximately 200 µm, 50% (w/w) drug load, good flow properties and prolonged ketoprofen release for more than 24 h. Carnauba wax microspheres prepared in this work represent a new multiparticulate-sustained release system for the NSAID ketoprofen, exhibiting good potential for application in further pharmaceutical processes.

  12. Preparation and characterization of bee venom-loaded PLGA particles for sustained release.

    Science.gov (United States)

    Park, Min-Ho; Jun, Hye-Suk; Jeon, Jong-Woon; Park, Jin-Kyu; Lee, Bong-Joo; Suh, Guk-Hyun; Park, Jeong-Sook; Cho, Cheong-Weon

    2016-12-14

    Bee venom-loaded poly(lactic-co-glycolic acid) (PLGA) particles were prepared by double emulsion-solvent evaporation, and characterized for a sustained-release system. Factors such as the type of organic solvent, the amount of bee venom and PLGA, the type of PLGA, the type of polyvinyl alcohol, and the emulsification method were considered. Physicochemical properties, including the encapsulation efficiency, drug loading, particle size, zeta-potential and surface morphology were examined by Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD). The size of the bee venom-loaded PLGA particles was 500 nm (measured using sonication). Zeta-potentials of the bee venom-loaded PLGA particles were negative owing to the PLGA. FT-IR results demonstrated that the bee venom was completely encapsulated in the PLGA particles, indicated by the disappearance of the amine and amide peaks. In addition, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis indicated that the bee venom in the bee venom-loaded PLGA particles was intact. In vitro release of the bee venom from the bee venom-loaded PLGA particles showed a sustained-release profile over 1 month. Bee venom-loaded PLGA particles can help improve patients' quality of life by reducing the number of injections required.

  13. Sustained release of a novel anti-quorum-sensing agent against oral fungal biofilms.

    Science.gov (United States)

    Feldman, Mark; Shenderovich, Julia; Al-Quntar, Abed Al Aziz; Friedman, Michael; Steinberg, Doron

    2015-04-01

    Thiazolidinedione-8 (S-8) has recently been identified as a potential anti-quorum-sensing/antibiofilm agent against bacteria and fungi. Based on these results, we investigated the possibility of incorporating S-8 in a sustained-release membrane (SRM) to increase its pharmaceutical potential against Candida albicans biofilm. We demonstrated that SRM containing S-8 inhibits fungal biofilm formation in a time-dependent manner for 72 h, due to prolonged release of S-8. Moreover, the SRM effectively delivered the agent in its active form to locations outside the membrane reservoir. In addition, eradication of mature biofilm by the SRM containing S-8 was also significant. Of note, S-8-containing SRM affected the characteristics of mature C. albicans biofilm, such as thickness, exopolysaccharide (EPS) production, and morphogenesis of fungal cells. The concept of using an antibiofilm agent with no antifungal activity incorporated into a sustained-release delivery system is new in medicine and dentistry. This concept of an SRM containing a quorum-sensing quencher with an antibiofilm effect could pave the way for combating oral fungal infectious diseases. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  14. An Injectable System for Local and Sustained Release of Antimicrobial Agents in the Periodontal Pocket.

    Science.gov (United States)

    Morelli, Laura; Cappelluti, Martino Alfredo; Ricotti, Leonardo; Lenardi, Cristina; Gerges, Irini

    2017-08-01

    Periodontitis treatments usually require local administration of antimicrobial drugs with the aim to reduce the bacterial load inside the periodontal pocket. Effective pharmaceutical treatments may require sustained local drug release for several days in the site of interest. Currently available solutions are still not able to fulfill the clinical need for high-quality treatments, mainly in terms of release profiles and patients' comfort. This work aims to fill this gap through the development of an in situ gelling system, capable to achieve controlled and sustained release of antimicrobial agents for medium-to-long-term treatments. The system is composed of micrometer-sized β-cyclodextrin-based hydrogel (bCD-Jef-MPs), featured by a strong hydrophilic character, suspended in a synthetic block-co-polymer solution (Poloxamer 407), which is capable to undergo rapid thermally induced sol-gel phase transition at body temperature. The chemical structure of bCD-Jef-MPs was confirmed by cross-correlating data from Fourier transform infrared (FTIR) spectroscopy, swelling test, and degradation kinetics. The thermally induced sol-gel phase transition is demonstrated by rheometric tests. The effectiveness of the described system to achieve sustained release of antimicrobial agents is demonstrated in vitro, using chlorhexidine digluconate as a drug model. The results achieved in this work disclose the potential of the mentioned system in effectively treating periodontitis lesions. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Sustained release of BMP-2 in bioprinted alginate for osteogenicity in mice and rats.

    Directory of Open Access Journals (Sweden)

    Michelle T Poldervaart

    Full Text Available The design of bioactive three-dimensional (3D scaffolds is a major focus in bone tissue engineering. Incorporation of growth factors into bioprinted scaffolds offers many new possibilities regarding both biological and architectural properties of the scaffolds. This study investigates whether the sustained release of bone morphogenetic protein 2 (BMP-2 influences osteogenicity of tissue engineered bioprinted constructs. BMP-2 loaded on gelatin microparticles (GMPs was used as a sustained release system, which was dispersed in hydrogel-based constructs and compared to direct inclusion of BMP-2 in alginate or control GMPs. The constructs were supplemented with goat multipotent stromal cells (gMSCs and biphasic calcium phosphate to study osteogenic differentiation and bone formation respectively. BMP-2 release kinetics and bioactivity showed continuous release for three weeks coinciding with osteogenicity. Osteogenic differentiation and bone formation of bioprinted GMP containing constructs were investigated after subcutaneous implantation in mice or rats. BMP-2 significantly increased bone formation, which was not influenced by the release timing. We showed that 3D printing of controlled release particles is feasible and that the released BMP-2 directs osteogenic differentiation in vitro and in vivo.

  16. Storage and sustained release of volatile substances from a hollow silica matrix

    Energy Technology Data Exchange (ETDEWEB)

    Wang Jiexin [Key Lab for Nanomaterials, Ministry of Education, Beijing 100029 (China); Ding Haomin [Research Center of the Ministry of Education for High Gravity Engineering and Technology, Beijing University of Chemical Technology, Beijing 100029 (China); Tao Xia [Key Lab for Nanomaterials, Ministry of Education, Beijing 100029 (China); Chen Jianfeng [Key Lab for Nanomaterials, Ministry of Education, Beijing 100029 (China)

    2007-06-20

    Porous hollow silica nanospheres (PHSNSs) prepared by adopting a nanosized CaCO{sub 3} template were utilized for the first time as a novel carrier for the storage and sustained release of volatile substances. Two types of volatile substances, Indian pipal from perfumes and peroxyacetic acid from disinfectants, were selected and then tested by one simple adsorption process with two separate comparative carriers, i.e. activated carbon and solid porous silica. It was demonstrated that a high storage capacity (9.6 ml{sub perfume}/mg{sub carrier}) of perfume could be achieved in a PHSNS matrix, which was almost 14 times as much as that of activated carbon. The perfume release profiles showed that PHSNSs exhibited sustained multi-stage release behaviour, while the constant release of activated carbon at a low level was discerned. Further, a Higuchi model study proved that the release process of perfume in both carriers followed a Fickian diffusion mechanism. For peroxyacetic acid as a disinfectant model, PHSNSs also displayed a much better delayed-delivery process than a solid porous silica system owing to the existence of unique hollow frameworks. Therefore, the aforementioned excellent sustained-release behaviours would make PHSNSs a promising carrier for storage and sustained delivery applications of volatile substances.

  17. Sustained release of antibiotics from injectable and thermally responsive polypeptide depots.

    Science.gov (United States)

    Adams, Samuel B; Shamji, Mohammed F; Nettles, Dana L; Hwang, Priscilla; Setton, Lori A

    2009-07-01

    Biodegradable polymeric scaffolds are of interest for delivering antibiotics to local sites of infection in orthopaedic applications, such as bone and diarthrodial joints. The objective of this study was to develop a biodegradable scaffold with ease of drug loading in aqueous solution, while providing for drug depot delivery via syringe injection. Elastin-like polypeptides (ELPs) were used for this application, biopolymers of repeating pentapeptide sequences that were thermally triggered to undergo in situ depot formation at body temperature. ELPs were modified to enable loading with the antibiotics, cefazolin, and vancomycin, followed by induction of the phase transition in vitro. Cefazolin and vancomycin concentrations were monitored, as well as bioactivity of the released antibiotics, to test an ability of the ELP depot to provide for prolonged release of bioactive drugs. Further tests of formulation viscosity were conducted to test suitability as an injectable drug carrier. Results demonstrate sustained release of therapeutic concentrations of bioactive antibiotics by the ELP, with first-order time constants for drug release of approximately 25 h for cefazolin and approximately 500 h for vancomycin. These findings illustrate that an injectable, in situ forming ELP depot can provide for sustained release of antibiotics with an effect that varies across antibiotic formulation. ELPs have important advantages for drug delivery, as they are known to be biocompatible, biodegradable, and elicit no known immune response. These benefits suggest distinct advantages over currently used carriers for antibiotic drug delivery in orthopedic applications. (c) 2008 Wiley Periodicals, Inc.

  18. Formulation and evaluation of sustained release matrix tablet of rabeprazole using wet granulation technique

    Directory of Open Access Journals (Sweden)

    Ruqaiyah Khan

    2014-01-01

    Full Text Available Introduction: Rabeprazole, a member of substituted benzimidazoles, inhibits the final step in gastric acid secretions. This drug claims to cause fastest acid separation (due to higher pKa, and more rapidly converts to the active species to aid gastric mucin synthesis. The most significant pharmacological action of Rabeprazole is dose dependent suppression of gastric acid secretion; without anticholinergic or H2-blocking action. It completely abolishes the hydrochloric acid secretion as it is powerful inhibitor of gastric acid. Rabeprazole is acid labile and hence commonly formulated as an enteric coated tablet. The absorption of rabeprazole occurs rapidly as soon as tablet leaves the stomach. Aim: In the present study an attempt was made to formulate and evaluate Rabeprazole sustained release matrix tablet using wet granulation technique incorporating various polymers like HPMC-E15, Carbopol934, and sodium carboxymethyl cellulose (CMC. Materials and Methods: The Formulated tablets were evaluated for different physicochemical properties like rheological properties, weight variation, thickness, hardness, % friability, in vitro release studies and drug content. Results: Studies revealed that all the physicochemical parameters comply with the official standards. The in vitro release studies exhibits the release up to 90%, over a prolonged period of time which confirms the extended release profile of formulation, having better bioavailability as well as decreased dosing frequency with reduced doses. Conclusion: The sustained release matrix tablets of rabiprazole shown better bioavailability, efficacy and potency, when compared with official standards.

  19. Clinical applications of the sustained-release dexamethasone implant for treatment of macular edema

    Directory of Open Access Journals (Sweden)

    Rocío Herrero-Vanrell, Jose Augusto Cardillo

    2011-02-01

    Full Text Available Rocío Herrero-Vanrell1, Jose Augusto Cardillo2, Baruch D Kuppermann31Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, Complutense University, Madrid, Spain; 2Hospital de Olhos de Araraquara, Araraquara, São Paulo, Brazil; 3Gavin Herbert Eye Institute, University of California, Irvine, CA, USAAbstract: Macular edema is one of the leading causes of vision loss among patients with retinal vein occlusion, diabetic retinopathy, and posterior chamber inflammatory disease. However, the treatment of macular edema is considerably limited by the difficulty in delivering effective doses of therapeutic agents into the vitreous cavity. In recent years, the development of a sustained-release dexamethasone intravitreal implant (Ozurdex® has enabled more controlled drug release at a stable rate over a long period of time, with a potentially lower rate of adverse events. Clinical studies indicate that this dexamethasone implant is a promising new treatment option for patients with persistent macular edema resulting from retinal vein occlusion, diabetic retinopathy, and uveitis or Irvine-Gass syndrome.Keywords: diabetic retinopathy, macular edema, Ozurdex®, posterior-segment inflammatory disease, retinal vein occlusion, sustained-release dexamethasone implant

  20. [Construction and evaluation of the tissue engineered nerve of bFGF-PLGA sustained release microspheres].

    Science.gov (United States)

    Wang, Guanglin; Lin, Wei; Gao, Weiqiang; Xiao, Yuhua; Dong, Changchao

    2008-12-01

    To study the outcomes of nerve defect repair with the tissue engineered nerve, which is composed of the complex of SCs, 30% ECM gel, bFGF-PLGA sustained release microspheres, PLGA microfilaments and permeable poly (D, L-lactic acid) (PDLLA) catheters. SCs were cultured and purified from the sciatic nerves of 1-day-old neonatal SD rats. The 1st passage cells were compounded with bFGF-PLGA sustained release microspheres and ECM gel, and then were injected into permeable PDLLA catheters with PLGA microfilaments inside. In this way, the tissue engineered nerve was constructed. Sixty SD rats were included. The model of 15-mm sciatic nerve defects was made, and then the rats were randomly divided into 5 groups, with 12 rats in each. In group A, autograft was adopted. In group B, the blank PDLLA catheters with PBS inside were used. In group C, PDLLA catheters, with PLGA microfilaments and 30% ECM gel inside, were used. In group D, PDLLA catheters, with PLGA microfilaments, SCs and 30% ECM gel inside, were used. In group E, the tissue engineered nerve was applied. After the operation, observation was made for general conditions of the rats. The sciatic function index (SFI) analysis was performed at 12, 16, 20 and 24 weeks after the operation, respectively. Electrophysiological detection and histological observation were performed at 12 and 24 weeks after the operation, respectively. All rats survived to the end of the experiment. At 12 and 16 weeks after the operation, group E was significantly different from group B in SFI (P fibers in group E were significantly differents from those in groups A, B and C (P fibers in group E were smaller than those in group A (P fibers in group E was significantly different from those in groups A, B, C (P fibers in group E were bigger than those in groups B and C (P < 0.05). The tissue engineered nerve with the complex of SCs, ECM gel, bFGF-PLGA sustained release microspheres, PLGA microfilaments and permeable PDLLA catheters promote

  1. 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.

  2. Succinic Acid: Technology Development and Commercialization

    Directory of Open Access Journals (Sweden)

    Nhuan P. Nghiem

    2017-06-01

    Full Text Available Succinic acid is a precursor of many important, large-volume industrial chemicals and consumer products. It was once common knowledge that many ruminant microorganisms accumulated succinic acid under anaerobic conditions. However, it was not until the discovery of Anaerobiospirillum succiniciproducens at the Michigan Biotechnology Institute (MBI, which was capable of producing succinic acid up to about 50 g/L under optimum conditions, that the commercial feasibility of producing the compound by biological processes was realized. Other microbial strains capable of producing succinic acid to high final concentrations subsequently were isolated and engineered, followed by development of fermentation processes for their uses. Processes for recovery and purification of succinic acid from fermentation broths were simultaneously established along with new applications of succinic acid, e.g., production of biodegradable deicing compounds and solvents. Several technologies for the fermentation-based production of succinic acid and the subsequent conversion to useful products are currently commercialized. This review gives a summary of the development of microbial strains, their fermentation, and the importance of the down-stream recovery and purification efforts to suit various applications in the context of their current commercialization status for biologically derived succinic acid.

  3. Sustained-release microsphere formulation containing an agrochemical by polyurethane polymerization during an agitation granulation process.

    Science.gov (United States)

    Terada, Takatoshi; Tagami, Manabu; Ohtsubo, Toshiro; Iwao, Yasunori; Noguchi, Shuji; Itai, Shigeru

    2016-07-25

    In this report, a new solventless microencapsulation method by synthesizing polyurethane (PU) from polyol and isocyanate during an agglomeration process in a high-speed mixing apparatus was developed. Clothianidin (CTD), which is a neonicotinoid insecticide and highly effective against a wide variety of insect pests, was used as the model compound. The microencapsulated samples covered with PU (CTD microspheres) had a median diameter of <75μm and sustained-release properties. The CTD microspheres were analyzed by synchrotron X-ray computed tomography measurements. Multiple cores of CTD and other solid excipient were dispersed in PU. Although voids appeared in the CTD microspheres after CTD release, the spherical shape of the microspheres remained stable and no change in its framework was observed. The experimental release data were highly consistent with the Baker-Lonsdale model derived from drug release of spherical monolithic dispersions and consistent with the computed tomography measurements. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. The Stability, Sustained Release and Cellular Antioxidant Activity of Curcumin Nanoliposomes

    Directory of Open Access Journals (Sweden)

    Xing Chen

    2015-08-01

    Full Text Available Curcumin is a multifunctional and natural agent considered to be pharmacologically safe. However, its application in the food and medical industry is greatly limited by its poor water solubility, physicochemical instability and inadequate bioavailability. Nanoliposome encapsulation could significantly enhance the solubility and stability of curcumin. Curcumin nanoliposomes exhibited good physicochemical properties (entrapment efficiency = 57.1, particle size = 68.1 nm, polydispersity index = 0.246, and zeta potential = −3.16 mV. Compared with free curcumin, curcumin nanoliposomes exhibited good stability against alkaline pH and metal ions as well as good storage stability at 4 °C. Curcumin nanoliposomes also showed good sustained release properties. Compared with free curcumin, curcumin nanoliposomes presented an equal cellular antioxidant activity, which is mainly attributed to its lower cellular uptake as detected by fluorescence microscopy and flow cytometry. This study provide theoretical and practical guides for the further application of curcumin nanoliposomes.

  5. Floating solid cellulose nanofibre nanofoams for sustained release of the poorly soluble model drug furosemide

    DEFF Research Database (Denmark)

    Svagan, Anna Justina; Müllertz, Anette; Löbmann, Korbinian

    2017-01-01

    OBJECTIVES: This study aimed to prepare a furosemide-loaded sustained release cellulose nanofibre (CNF)-based nanofoams with buoyancy. METHODS: Dry foams consisting of CNF and the model drug furosemide at concentrations of 21% and 50% (w/w) have been prepared by simply foaming a CNF-drug suspension...... followed by drying. The resulting foams were characterized towards their morphology, solid state properties and dissolution kinetics. KEY FINDINGS: Solid state analysis of the resulting drug-loaded foams revealed that the drug was present as an amorphous sodium furosemide salt and in form of furosemide...... form I crystals embedded in the CNF foam cell walls. The foams could easily be shaped and were flexible, and during the drug release study, the foam pieces remained intact and were floating on the surface due to their positive buoyancy. Both foams showed a sustained furosemide release compared...

  6. Sustained Release Talazoparib Implants for Localized Treatment of BRCA1-deficient Breast Cancer.

    Science.gov (United States)

    Belz, Jodi E; Kumar, Rajiv; Baldwin, Paige; Ojo, Noelle Castilla; Leal, Ana S; Royce, Darlene B; Zhang, Di; van de Ven, Anne L; Liby, Karen T; Sridhar, Srinivas

    2017-01-01

    Talazoparib, a potent PARP inhibitor, has shown promising clinical and pre-clinical activity by inducing synthetic lethality in cancers with germline Brca1/2 mutations. Conventional oral delivery of Talazoparib is associated with significant off-target effects, therefore we sought to develop new delivery systems in the form of an implant loaded with Talazoparib for localized, slow and sustained release of the drug at the tumor site in Brca1 -deficient breast cancer. Poly(lactic-co-glycolic acid) (PLGA) implants (0.8 mm diameter) loaded with subclinical dose (25 or 50 µg) Talazoparib were fabricated and characterized. In vitro studies with Brca1 -deficient W780 and W0069 breast cancer cells were conducted to test sensitivity to PARP inhibition. The in vivo therapeutic efficacy of Talazoparib implants was assessed following a one-time intratumoral injection in Brca1 Co/Co ;MMTV-Cre;p53 +/- mice and compared to drug-free implants and oral gavage. Immunohistochemistry studies were performed on tumor sections using PCNA and γ-H2AX staining. Sustained release of Talazoparib was observed over 28 days in vitro . Mice treated with Talazoparib implants showed statistically significant tumor growth inhibition compared to those receiving drug-free implants or free Talazoparib orally. Talazoparib implants were well-tolerated at both drug doses and resulted in less weight loss than oral gavage. PARP inhibition in mice treated with Talazoparib implants significantly increased double-stranded DNA damage and decreased tumor cell proliferation as shown by PCNA and γ-H2AX staining as compared to controls. These results demonstrate that localized and sustained delivery of Talazoparib via implants has potential to provide superior treatment outcomes at sub-clinical doses with minimal toxicity in patients with BRCA1 deficient tumors.

  7. Phytantriol based liquid crystal provide sustained release of anticancer drug as a novel embolic agent.

    Science.gov (United States)

    Qin, Lingzhen; Mei, Liling; Shan, Ziyun; Huang, Ying; Pan, Xin; Li, Ge; Gu, Yukun; Wu, Chuanbin

    2016-01-01

    Phytantriol has received increasing amount of attention in drug delivery system, however, the ability of the phytantriol based liquid crystal as a novel embolic agent to provide a sustained release delivery system is yet to be comprehensively demonstrated. The purpose of this study was to prepare a phytantriol-based cubic phase precursor solution loaded with anticancer drug hydroxycamptothecine (HCPT) and evaluate its embolization properties, in vitro drug release and cytotoxicity. Phase behavior of the phytantriol-solvent-water system was investigated by visual inspection and polarized light microscopy, and no phase transition was observed in the presence of HCPT within the studied dose range. Water uptake by the phytantriol matrices was determined gravimetrically, suggesting that the swelling complied with the second order kinetics. In vitro evaluation of embolic efficacy indicated that the isotropic solution displayed a satisfactory embolization effect. In vitro drug release results showed a sustained-release up to 30 days and the release behavior was affected by the initial composition and drug loading. Moreover, the in vitro cytotoxicity and anticancer activity were evaluated by MTT assay. No appreciable mortality was observed for NIH 3T3 cells after 48 h exposure to blank formulations, and the anticancer activity of HCPT-loaded formulations to HepG2 and SMMC7721 cells was strongly dependent on the drug loading and treatment time. Taken together, these results indicate that phytantriol-based cubic phase embolic gelling solution is a promising potential carrier for HCPT delivery to achieve a sustained drug release by vascular embolization, and this technology may be potential for clinical applications.

  8. Development of sustained release capsules containing "coated matrix granules of metoprolol tartrate".

    Science.gov (United States)

    Siddique, Sabahuddin; Khanam, Jasmina; Bigoniya, Papiya

    2010-09-01

    The objective of this investigation was to prepare sustained release capsule containing coated matrix granules of metoprolol tartrate and to study its in vitro release and in vivo absorption. The design of dosage form was performed by choosing hydrophilic hydroxypropyl methyl cellulose (HPMC K100M) and hydrophobic ethyl cellulose (EC) polymers as matrix builders and Eudragit® RL/RS as coating polymers. Granules were prepared by composing drug with HPMC K100M, EC, dicalcium phosphate by wet granulation method with subsequent coating. Optimized formulation of metoprolol tartrate was formed by using 30% HPMC K100M, 20% EC, and ratio of Eudragit® RS/RL as 97.5:2.5 at 25% coating level. Capsules were filled with free flowing optimized granules of uniform drug content. This extended the release period upto 12 h in vitro study. Similarity factor and mean dissolution time were also reported to compare various dissolution profiles. The network formed by HPMC and EC had been coupled satisfactorily with the controlled resistance offered by Eudragit® RS. The release mechanism of capsules followed Korsemeyer-Peppas model that indicated significant contribution of erosion effect of hydrophilic polymer. Biopharmaceutical study of this optimized dosage form in rabbit model showed 10 h prolonged drug release in vivo. A close correlation (R(2) = 0.9434) was established between the in vitro release and the in vivo absorption of drug. The results suggested that wet granulation with subsequent coating by fluidized bed technique, is a suitable method to formulate sustained release capsules of metoprolol tartrate and it can perform therapeutically better than conventional immediate release dosage form.

  9. 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

  10. Effect of sustained-release isosorbide dinitrate on post-prandial gastric emptying and gastroduodenal motility in healthy humans

    DEFF Research Database (Denmark)

    Madsen, Jan Lysgård; Rasmussen, S L; Linnet, J

    2004-01-01

    and gastroduodenal motility after a meal. Eleven healthy volunteers participated in a double-blind, placebo-controlled, cross-over study. Each subject ingested 40 mg isosorbide dinitrate orally as a sustained-release formulation or oral placebo, in random order. Gastric emptying and gastroduodenal motility were...... consecutive 15-min periods. A 40 mg single dose of sustained-released isosorbide dinitrate does not seem to alter gastric emptying or gastroduodenal motility after a meal.......Nitric oxide (NO) is an inhibitory neurotransmitter released by non-adrenergic and non-cholinergic neurons that innervate the smooth muscles of the gastrointestinal tract. We examined whether NO, derived from a sustained-release preparation of isosorbide dinitrate, influenced gastric emptying...

  11. Preparation and characterization of genipin-cross-linked silk fibroin/chitosan sustained-release microspheres

    Directory of Open Access Journals (Sweden)

    Zeng SG

    2015-05-01

    Full Text Available Shuguang Zeng,1,* Manwen Ye,1,2,* Junqi Qiu,1 Wei Fang,1 Mingdeng Rong,1 Zehong Guo,1 Wenfen Gao11Department of Oral and Maxillofacial Surgery, Guangdong Provincial Stomatological Hospital, Southern Medical University, 2Department of Stomatology, Guangdong Women and Children Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workAbstract: We report the effects of distinct concentrations of genipin and silk fibroin (SF:chitosan (CS ratios on the formation of SF–CS composite microspheres. We selected microspheres featuring an SF:CS ratio of 1:1, encapsulated various concentrations of bovine serum albumin (BSA, and then compared their encapsulation efficiency and sustained-release rate with those of pure CS microspheres. We determined that the following five groups of microspheres were highly spherical and featured particle sizes ranging from 70 µm to 147 µm: mass ratio of CS:SF =1:0.5, 0.1 g or 0.5 g genipin; CS:SF =1:1, 0.05 g or 1 g genipin; and CS:SF =1:2, 0.5 g genipin. The microspheres prepared using 1:1 CS:SF ratio and 0.05 g genipin in the presence of 10 mg, 20 mg, and 50 mg of BSA exhibited encapsulation efficiencies of 50.16%±4.32%, 56.58%±3.58%, and 42.19%±7.47%, respectively. Fourier-transform infrared spectroscopy (FTIR results showed that SF and CS were cross-linked and that the α-helices and random coils of SF were converted into β-sheets. BSA did not chemically react with CS or SF. Moreover, thermal gravimetric analysis (TGA results showed that the melting point of BSA did not change, which confirmed the FTIR results, and X-ray diffraction results showed that BSA was entrapped in microspheres in a noncrystalline form, which further verified the TGA and FTIR data. The sustained-release microspheres prepared in the presence of 10 mg, 20 mg, and 50 mg of BSA burst release 30.79%±3.43%, 34.41%±4.46%, and 41.75%±0.96% of the

  12. Nanomedicine for glaucoma: liposomes provide sustained release of latanoprost in the eye

    Directory of Open Access Journals (Sweden)

    Natarajan JV

    2012-01-01

    Full Text Available Jayaganesh V Natarajan1*, Marcus Ang2*, Anastasia Darwitan1, Sujay Chattopadhyay3, Tina T Wong2, Subbu S Venkatraman1 1Materials Science and Engineering, Nanyang Technological University, Singapore; 2Singapore Eye Research Institute, Singapore; 3Polymer Division, Indian Institute of Technology Roorkee, India*These authors contributed equally to this workPurpose: To report the development and therapeutic evaluation of a liposomal nanocarrier for sustained release of latanoprost, in the rabbit eye.Methods: We fabricated latanoprost-loaded egg-phosphatidylcholine (EggPC liposomes using the film hydration technique. The delivery vehicles were nano-sized (Z avg = 109 ± 18 nm, had a narrow poly dispersity index (PDI = 0.19 ± 0.04, and a very high loading efficiency (94% ± 5%. Based on in vitro data, we evaluated this formulation for lowering intraocular pressure (IOP in rabbit eyes. Following a single subconjunctival injection of the latanoprost loaded formulation, the eyes were clinically monitored and the IOP recorded.Results: Latanoprost-loaded EggPC liposomes demonstrated a high drug/lipid mole ratio of 0.181, remained stable for at least 6 months on storage (4°C, and at least 1 month at 25°C. A slow and sustained release of 60% of latanoprost was achieved by 14 days in the in vitro release study. The same formulation demonstrated a greater sustained IOP lowering effect compared with daily administration of topical latanoprost beyond 90 days (4.8 ± 1.5 vs 2.5 ± 0.9 mmHg; P < 0.001. No signs of inflammation were evident in the eyes from slit-lamp examination analysis.Conclusion: The loading required for a long-term sustained delivery of latanoprost for up to 90 days in the rabbit eyes was achieved with EggPC liposomes. A single injection of latanoprost-loaded EggPC liposomes can lower the IOP for up to 90 days, with a greater IOP lowering effect than daily topical administration of latanoprost.Keywords: nanomedicine, nanoliposomes, Egg

  13. Diclofenac sodium ion exchange resin complex loaded melt cast films for sustained release ocular delivery.

    Science.gov (United States)

    Adelli, Goutham R; Balguri, Sai Prachetan; Bhagav, Prakash; Raman, Vijayasankar; Majumdar, Soumyajit

    2017-11-01

    The goal of the present study is to develop polymeric matrix films loaded with a combination of free diclofenac sodium (DFS free ) and DFS:Ion exchange resin complexes (DFS:IR) for immediate and sustained release profiles, respectively. Effect of ratio of DFS and IR on the DFS:IR complexation efficiency was studied using batch processing. DFS:IR complex, DFS free , or a combination of DFS free  +   DFS:IR loaded matrix films were prepared by melt-cast technology. DFS content was 20% w/w in these matrix films. In vitro transcorneal permeability from the film formulations were compared against DFS solution, using a side-by-side diffusion apparatus, over a 6 h period. Ocular disposition of DFS from the solution, films and corresponding suspensions were evaluated in conscious New Zealand albino rabbits, 4 h and 8 h post-topical administration. All in vivo studies were carried out as per the University of Mississippi IACUC approved protocol. Complexation efficiency of DFS:IR was found to be 99% with a 1:1 ratio of DFS:IR. DFS release from DFS:IR suspension and the film were best-fit to a Higuchi model. In vitro transcorneal flux with the DFS free  +   DFS:IR (1:1) (1 + 1) was twice that of only DFS:IR (1:1) film. In vivo, DFS solution and DFS:IR (1:1) suspension formulations were not able to maintain therapeutic DFS levels in the aqueous humor (AH). Both DFS free and DFS free  +   DFS:IR (1:1) (3 + 1) loaded matrix films were able to achieve and maintain high DFS concentrations in the AH, but elimination of DFS from the ocular tissues was much faster with the DFS free formulation. DFS free  +   DFS:IR combination loaded matrix films were able to deliver and maintain therapeutic DFS concentrations in the anterior ocular chamber for up to 8 h. Thus, free drug/IR complex loaded matrix films could be a potential topical ocular delivery platform for achieving immediate and sustained release characteristics.

  14. Preparation of rifampicin/poly(d,l-lactice) nanoparticles for sustained release by supercritical assisted atomization technique

    CSIR Research Space (South Africa)

    Labuschagne, Philip W

    2014-11-01

    Full Text Available In this work supercritical assisted atomization (SAA) process was used for the co-precipitation of poly(d,l-lactide) (PDLLA) and rifampicin (RIF) as nanoparticles for sustained release applications. The effect of the variation of PDLLA/RIF ratio...

  15. Managing cancer pain and symptoms of outpatients by rotation to sustained-release hydromorphone: a prospective clinical trial

    NARCIS (Netherlands)

    Wirz, Stefan; Wartenberg, Hans Christian; Elsen, Christian; Wittmann, Maria; Diederichs, Marta; Nadstawek, Joachim

    2006-01-01

    PURPOSE: In this prospective clinical trial we examined the technique of opioid rotation to oral sustained-release hydromorphone for controlling pain and symptoms in outpatients with cancer pain. METHODS: Before and after rotation, 50 patients were assessed by Numerical Analog Scales [Numerical

  16. Effect of sustained-release isosorbide dinitrate on post-prandial gastric emptying and gastroduodenal motility in healthy humans

    DEFF Research Database (Denmark)

    Madsen, J L; Rasmussen, S L; Linnet, J

    2004-01-01

    Nitric oxide (NO) is an inhibitory neurotransmitter released by non-adrenergic and non-cholinergic neurons that innervate the smooth muscles of the gastrointestinal tract. We examined whether NO, derived from a sustained-release preparation of isosorbide dinitrate, influenced gastric emptying and...

  17. Genetics Home Reference: succinic semialdehyde dehydrogenase deficiency

    Science.gov (United States)

    ... Additional NIH Resources (1 link) National Institute of Neurological Disorders and Stroke: Epilepsy Information Page Educational Resources (5 links) Boston Children's Hospital: Seizures and Epilepsy Disease InfoSearch: Succinic semialdehyde ...

  18. 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

  19. A bioequivalence study of two tamsulosin sustained-release tablets in Indonesian healthy volunteers.

    Science.gov (United States)

    Prasaja, Budi; Harahap, Yahdiana; Lusthom, Windy; Setiawan, Evy C; Ginting, Mena B; Hardiyanti; Lipin

    2011-06-01

    The bioavailability of two 0.4 mg tamsulosin sustained-release film-coated tablet formulations was compared; using generic tablets (Prostam(®)) as test formulation and the originator product as reference formulation. Twenty-four subjects were included in this single-dose, open-label, randomized two-way crossover design following an overnight fasting. A one-week wash-out period was applied. Blood samples were drawn up to 72 h following drug administration. Plasma concentration of tamsulosin was determined by liquid chromatography-tandem mass spectrometry method with TurboIonSpray mode. Pharmacokinetic parameters AUC(0-t,) AUC(0-∞), C (max) and t (½) were determined and used for bioequivalence evaluation after log-transformation, whereas t (max) ratios were evaluated non-parametrically. The estimated point and 90% confidence intervals (CI) for AUC(0-t,) AUC(0-∞), C (max) and t (½) were 109.55% (96.41-124.49%), 109.94% (96.85-124.81%), 105.87% (92.88-120.67%) and 100.00% (90.56-110.43%), respectively. These results indicated that the two formulations of tamsulosin were bioequivalent; therefore they may be prescribed interchangeably.

  20. 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.

  1. Halloysite Clay Nanotubes for Loading and Sustained Release of Functional Compounds.

    Science.gov (United States)

    Lvov, Yuri; Wang, Wencai; Zhang, Liqun; Fakhrullin, Rawil

    2016-02-10

    Halloysite is an alumosilicate tubular clay with a diameter of 50 nm, an inner lumen of 15 nm and a length of 600-900 nm. It is a natural biocompatible nanomaterial available in thousands of tons at low price, which makes it a good candidate for nanoarchitectural composites. The inner lumen of halloysite may be adjusted by etching to 20-30% of the tube volume and loading with functional agents (antioxidants, anticorrosion agents, flame-retardant agents, drugs, or proteins) allowing for formulations with sustained release tuned by the tube end-stoppers for hours and days. Clogging the tube ends in polymeric composites allows further extension of the release time. Thus, antioxidant-loaded halloysite doped into rubber enhances anti-aging properties for at least 12 months. The addition of 3-5 wt% of halloysite increases the strength of polymeric materials, and the possibility of the tube's orientation promises a gradient of properties. Halloysite nanotubes are a promising mesoporous media for catalytic nanoparticles that may be seeded on the tube surface or synthesized exclusively in the lumens, providing enhanced catalytic properties, especially at high temperatures. In vitro and in vivo studies on biological cells and worms indicate the safety of halloysite, and tests for efficient adsorption of mycotoxins in animals' stomachs are also carried out. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Chlorogenic acid loaded chitosan nanoparticles with sustained release property, retained antioxidant activity and enhanced bioavailability

    Directory of Open Access Journals (Sweden)

    Ilaiyaraja Nallamuthu

    2015-06-01

    Full Text Available In this study, chlorogenic acid (CGA, a phenolic compound widely distributed in fruits and vegetables, was encapsulated into chitosan nanoparticles by ionic gelation method. The particles exhibited the size and zeta potential of 210 nm and 33 mV respectively. A regular, spherical shaped distribution of nanoparticles was observed through scanning electron microscopy (SEM and the success of entrapment was confirmed by FTIR analysis. The encapsulation efficiency of CGA was at about 59% with the loading efficiency of 5.2%. In vitro ABTS assay indicated that the radical scavenging activity of CAG was retained in the nanostructure and further, the release kinetics study revealed the burst release of 69% CGA from nanoparticles at the end of 100th hours. Pharmacokinetic analysis in rats showed a lower level of Cmax, longer Tmax, longer MRT, larger AUC0–t and AUC0–∞ for the CGA nanoparticles compared to free CGA. Collectively, these results suggest that the synthesised nanoparticle with sustained release property can therefore ease the fortification of food-matrices targeted for health benefits through effective delivery of CGA in body.

  3. Treatment of Gastrin-Secreting Tumor With Sustained-Release Octreotide Acetate in a Dog.

    Science.gov (United States)

    Kim, Sangho; Hosoya, Kenji; Takagi, Satoshi; Okumura, Masahiro

    2015-01-01

    An 8 yr old, intact male Shiba Inu was presented with loose stool, polydipsia, hematuria, vomiting, and anorexia. On abdominal ultrasonography, numerous nodules were detected in the hepatic parenchyma distributed diffusely throughout all lobes. Excisional biopsy of one of the nodules was performed via exploratory laparotomy. A histopathological diagnosis of the lesion was carcinoid, and the tumor cells stained positive to chromogranin A and gastrin. The serum gastrin level of the dog was 45,613 pg/mL (reference range: 160-284). In addition to medical treatment with omeprazole(c) and famotidine(e), suppression of gastrin secretion was attempted with octreotide acetate. A test dose of octreotide acetate significantly decreased the serum gastrin level to approximately one third of the baseline in 2 hr and the effect lasted approximately for 6 hr. On day 21, treatment with sustained-release formulation of octreotide acetate(a) (5 mg intramuscular, q 4 wk) was initiated. The serum gastrin concentration gradually decreased over 32 days and then progressively increased in parallel with the progression of the hepatic nodules. The dog gradually developed recurrence of initial clinical signs, and was lost to follow-up on day 510.

  4. Reduction of radiocesium transfer to animal products using sustained release boli with ammoniumiron(3)-Hexacyanoferrate(2)

    International Nuclear Information System (INIS)

    Hove, K.; Hansen, H.S.

    1993-01-01

    A sustained release boulus with the cesium binder ammoniumiron(III) - hexacyanoferrate (AFCF) has been developed as a countermeasure for small ruminants grazing pastures contaminated by radiocesium ( 134 Cs+ 137 Cs). The boli (40-50 g) are produced by compression of a mixture of AFCF, barite and wax. The release of AFCF from boli labelled with 137Cs-iron-hexacyanoferrate complex was studied in laboratory sheep. The release rate followed first order kinetics during the 108 d of observation and decreased from 40 to 22, 110 to 35 and 280 to 25 mg d -1 in sheep treated with 1, 2 or 3 boli respectively. The efficiency of boli in reducing radiocesium transfer to meat and milk was tested in laboratory studies with goats fed 134 Cs tracer. Until 40 d after treatment the transfer of radiocesium to milk was reduced by 35%, 60% and 85% in goats given 1, 2 og 3 boli, respectively. The reduction in radiocaesium transfer persisted for 90 d but with a lower efficiency. A similar relationship was found between number of boli and the reduction in radiocesium transfer to meat with an observed maximal reduction of 60%. (au) (20 refs.)

  5. Preparation of sustained release capsules by electrostatic dry powder coating, using traditional dip coating as reference.

    Science.gov (United States)

    Yang, Yan; Shen, Lian; Yuan, Feng; Fu, Hui; Shan, Weiguang

    2018-05-30

    Lately, a great deal of attention is being paid to capsule coating, since the coat protects active pharmaceutical ingredients (APIs) from damage, as is in the case of tablet and pellet. However, moisture and heat sensitivity of gelatin shells make it challenging to coat capsules using the conventional aqueous coating techniques. In an effort to overcome this challenge, the present study aims to coat capsules using two different coating techniques: electrostatic dry powder coating (EDPC) and dip coating (DC). Both capsule coatings and free films were prepared by these two coating techniques, and the effects of coating formulations and processing conditions on the film quality were investigated. The corresponding drug in vitro release and mechanisms were characterized and compared. The results of dissolution tests demonstrated that the drug release behavior of both EDPC and DC coated capsules could be optimized to a sustained release of 24 h, following the Fick's diffusion law. The results of this study suggest that EDPC method is better than DC method for coating capsules, with respect to the higher production efficiency and better stability, indicating that this dry coating technology has promised in gelatin capsule coating applications. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. WATER HYACINTH: A POSSIBLE ALTERNATIVE RATE RETARDING NATURAL POLYMER USED IN SUSTAINED RELEASE TABLET DESIGN

    Directory of Open Access Journals (Sweden)

    Sabera eKhatun

    2014-06-01

    Full Text Available In recent years natural polymers have been widely used, because of their effectiveness and availability over synthetic polymers. In this present investigation matrix tablets of Metformin hydrochloride were formulated using Water hyacinth powder and its rate retardant activity was studied. Tablets were prepared using wet granulation method with 8% starch as granulating agent and 5%, 10%, 15%, 20%, 25% and 30% of Water hyacinth powder to the drug. In preformulation study, angle of repose, Carr’s Index and Hausner ratio were calculated. Fourier Transform Infrared Spectroscopy (FTIR, Differential Scanning Calorimetry (DSC and Scanning Electron Microscopy (SEM studies were performed and no interactions were found between drug and excipients. Weight variation, friability, hardness, thickness, diameter, and in vitro release study were performed with the prepared matrix tablets. Dissolution studies were conducted using USP type II apparatus at a speed of 100 rpm at 37oC ± 0.5 temperature, for 8 hours. All the formulations comply with both BP and USP requirements, but among all the formulations F-1 (5% of Water hyacinth was the best fitted formula. The drug release patterns were explained in different kinetic models such as Zero order, First order, Higuchi, Hixson Crowell and Korsmeyer-Peppas equations. The current investigation implies that Water hyacinth has the potential to be used as a rate-retarding agent in sustained release drug formulations.

  7. Effect of cross-linked biodegradable polymers on sustained release of sodium diclofenac-loaded microspheres

    Directory of Open Access Journals (Sweden)

    Avik Kumar Saha

    2013-12-01

    Full Text Available The objective of this study was to formulate an oral sustained release delivery system of sodium diclofenac(DS based on sodium alginate (SA as a hydrophilic carrier in combination with chitosan (CH and sodium carboxymethyl cellulose (SCMC as drug release modifiers to overcome the drug-related adverse effects and to improve bioavailability. Microspheres of DS were prepared using an easy method of ionotropic gelation. The prepared beads were evaluated for mean particle size, entrapment efficiency, swelling capacity, erosion and in-vitro drug release. They were also subjected to various studies such as Fourier Transform Infra-Red Spectroscopy (FTIR for drug polymer compatibility, Scanning Electron Microscopy for surface morphology, X-ray Powder Diffraction Analysis (XRD and Differential Scanning Calorimetric Analysis (DSC to determine the physical state of the drug in the beads. The addition of SCMC during the preparation of polymeric beads resulted in lower drug loading and prolonged release of the DS. The release profile of batches F5 and F6 showed a maximum drug release of 96.97 ± 0.356% after 8 h, in which drug polymer ratio was decreased. The microspheres of sodium diclofenac with the polymers were formulated successfully. Analysis of the release profiles showed that the data corresponds to the diffusion-controlled mechanism as suggested by Higuchi.

  8. Surface modified zeolite-based granulates for the sustained release of diclofenac sodium.

    Science.gov (United States)

    Serri, Carla; de Gennaro, Bruno; Quagliariello, Vincenzo; Iaffaioli, Rosario Vincenzo; De Rosa, Giuseppe; Catalanotti, Lilia; Biondi, Marco; Mayol, Laura

    2017-03-01

    In this study, a granulate for the oral controlled delivery of diclofenac sodium (DS), an anionic sparingly soluble nonsteroidal anti-inflammatory drug, has been realized by wet granulation, using a surface modified natural zeolite (SMNZ) as an excipient. The surface modification of the zeolite has been achieved by means of a cationic surfactant, so as to allow the loading of DS through ionic interaction and bestow a control over the drug release mechanism. The granules possessed a satisfactory dosage uniformity, a flowability suitable for an oral dosage form manufacturing, along with a sustained drug release up to 9h, driven by both ion exchange and transport kinetics. Furthermore, the obtained granulate did not elicit a significant cytotoxicity and could also induce a prolonged anti-inflammatory effect on RAW264.7 cells. Taking also into account that natural zeolites are generally abundant and economic, SMNZ can be considered as an attracting alternative excipient for the production of granules with sustained release features. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. 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.

  10. Direct encapsulation of water-soluble drug into silica microcapsules for sustained release applications

    International Nuclear Information System (INIS)

    Wang Jiexin; Wang Zhihui; Chen Jianfeng; Yun, Jimmy

    2008-01-01

    Direct encapsulation of water-soluble drug into silica microcapsules was facilely achieved by a sol-gel process of tetraethoxysilane (TEOS) in W/O emulsion with hydrochloric acid (HCl) aqueous solution containing Tween 80 and drug as well as cyclohexane solution containing Span 80. Two water-soluble drugs of gentamicin sulphate (GS) and salbutamol sulphate (SS) were chosen as model drugs. The characterization of drug encapsulated silica microcapsules by scanning electronic microscopy (SEM), FTIR, thermogravimetry (TG) and N 2 adsorption-desorption analyses indicated that drug was successfully entrapped into silica microcapsules. The as-prepared silica microcapsules were uniform spherical particles with hollow structure, good dispersion and a size of 5-10 μm, and had a specific surface area of about 306 m 2 /g. UV-vis and thermogravimetry (TG) analyses were performed to determine the amount of drug encapsulated in the microcapsules. The BJH pore size distribution (PSD) of silica microcapsules before and after removing drug was examined. In vitro release behavior of drug in simulated body fluid (SBF) revealed that such system exhibited excellent sustained release properties

  11. Development and evaluation of new multiple-unit levodopa sustained-release floating dosage forms.

    Science.gov (United States)

    Goole, J; Vanderbist, F; Amighi, K

    2007-04-04

    This work relates to the development and the in vitro evaluation of sustained-release minitablets (MT), prepared by melt granulation and subsequent compression, which are designed to float over an extended period of time. Levodopa was used as a model drug. The importance of the composition and manufacturing parameters of the MT on their floating and dissolution properties was then examined. The investigation showed that MT composition and MT diameter had the greatest influence on drug release, which was sustained for more than 8h. By using the same formulation, the best floating properties were obtained with 3mm MT prepared at low compression forces ranging between 50 and 100N. Their resultant-weight (RW) values were always higher than those obtained with a marketed HBS dosage form within 13h. When they were filled into gelatin capsules, no sticking was observed. By evaluating the dissolution profiles of levodopa at different pH values, it was found that dissolution profiles depend more on the prolonged-release ability of Methocel K15M than on the pH-dependent solubility of levodopa. Finally, the robustness of the floating MT was assessed by testing the drug release variability in function of the stirring conditions during dissolution tests.

  12. Electrospun Blank Nanocoating for Improved Sustained Release Profiles from Medicated Gliadin Nanofibers

    Directory of Open Access Journals (Sweden)

    Xinkuan Liu

    2018-03-01

    Full Text Available Nanomaterials providing sustained release profiles are highly desired for efficacious drug delivery. Advanced nanotechnologies are useful tools for creating elaborate nanostructure-based nanomaterials to achieve the designed functional performances. In this research, a modified coaxial electrospinning was explored to fabricate a novel core-sheath nanostructure (nanofibers F2, in which a sheath drug-free gliadin layer was successfully coated on the core ketoprofen (KET-gliadin nanocomposite. A monolithic nanocomposite (nanofibers F1 that was generated through traditional blending electrospinning of core fluid was utilized as a control. Scanning electron microscopy demonstrated that both nanofibers F1 and F2 were linear. Transmission electron microscopy verified that nanofibers F2 featured a clear core-sheath nanostructure with a thin sheath layer about 25 nm, whereas their cores and nanofibers F1 were homogeneous KET-gliadin nanocomposites. X-ray diffraction patterns verified that, as a result of fine compatibility, KET was dispersed in gliadin in an amorphous state. In vitro dissolution tests demonstrated that the thin blank nanocoating in nanofibers F2 significantly modified drug release kinetics from a traditional exponential equation of nanofibers F1 to a zero-order controlled release model, linearly freeing 95.7 ± 4.7% of the loaded cargoes over a time period of 16 h.

  13. Electrospun Blank Nanocoating for Improved Sustained Release Profiles from Medicated Gliadin Nanofibers.

    Science.gov (United States)

    Liu, Xinkuan; Shao, Wenyi; Luo, Mingyi; Bian, Jiayin; Yu, Deng-Guang

    2018-03-22

    Nanomaterials providing sustained release profiles are highly desired for efficacious drug delivery. Advanced nanotechnologies are useful tools for creating elaborate nanostructure-based nanomaterials to achieve the designed functional performances. In this research, a modified coaxial electrospinning was explored to fabricate a novel core-sheath nanostructure (nanofibers F2), in which a sheath drug-free gliadin layer was successfully coated on the core ketoprofen (KET)-gliadin nanocomposite. A monolithic nanocomposite (nanofibers F1) that was generated through traditional blending electrospinning of core fluid was utilized as a control. Scanning electron microscopy demonstrated that both nanofibers F1 and F2 were linear. Transmission electron microscopy verified that nanofibers F2 featured a clear core-sheath nanostructure with a thin sheath layer about 25 nm, whereas their cores and nanofibers F1 were homogeneous KET-gliadin nanocomposites. X-ray diffraction patterns verified that, as a result of fine compatibility, KET was dispersed in gliadin in an amorphous state. In vitro dissolution tests demonstrated that the thin blank nanocoating in nanofibers F2 significantly modified drug release kinetics from a traditional exponential equation of nanofibers F1 to a zero-order controlled release model, linearly freeing 95.7 ± 4.7% of the loaded cargoes over a time period of 16 h.

  14. Novel bio-active lipid nanocarriers for the stabilization and sustained release of sitosterol

    International Nuclear Information System (INIS)

    Lacatusu, I; Badea, N; Stan, R; Meghea, A

    2012-01-01

    In this work, new stable and efficiently bio-active lipid nanocarriers (NLCs) with antioxidant properties have been developed for the transport of active ingredients in food. The novel NLCs loaded with β-sitosterol/β-sitosterol and green tea extract (GTE) and prepared by a combination of natural oils (grape seed oil, fish oil and squalene) and biological lipids with food grade surfactants, were physico-chemically examined by DLS, TEM, electrokinetic potential, DSC and HPLC and found to have main diameters less than 200 nm, a spherical morphology, excellent physical stability, an imperfect crystalline lattice and high entrapment efficiency. The novel loaded-NLCs have demonstrated the potential to develop a high blocking action of chain reactions, trapping up to 92% of the free-oxygen radicals, as compared to the native β-sitosterol (AA%=36.5). Another advantage of this study is associated with the quality of bio-active NLCs based on grape seed oil and squalene to manifest a better sitosterol—sustained release behaviour as compared to their related nanoemulsions. By coupling both in vitro results, i.e. the enhanced antioxidant activity and superior release properties, this study emphasizes the sustainability of novel bio-active nanocarriers to gain specific bio-food features for development of functional foods with a high applicability spectrum. (paper)

  15. Sustained Release of Protein Therapeutics from Subcutaneous Thermosensitive Biocompatible and Biodegradable Pentablock Copolymers (PTSgels

    Directory of Open Access Journals (Sweden)

    Elizabeth Schaefer

    2016-01-01

    Full Text Available Objective. To evaluate thermosensitive, biodegradable pentablock copolymers (PTSgel for sustained release and integrity of a therapeutic protein when injected subcutaneously. Materials and Methods. Five PTSgels with PEG-PCL-PLA-PCL-PEG block arrangements were synthesized. In vitro release of IgG from PTSgels and concentrations was evaluated at 37°C. Released IgG integrity was characterized by SDS-PAGE. In vitro disintegration for 10GH PTSgel in PBS was monitored at 37°C over 72 days using gravimetric loss and GPC analysis. Near-infrared IgG in PTSgel was injected subcutaneously and examined by in vivo imaging and histopathology for up to 42 days. Results. IgG release was modulated from approximately 7 days to more than 63 days in both in vitro and in vivo testing by varying polymer composition, concentration of PTSgel aqueous solution, and concentration of IgG. Released IgG in vitro maintained structural integrity by SDS-PAGE. Subcutaneous PTSgels were highly biocompatible and in vitro IgG release occurred in parallel with the disappearance of subcutaneous gel in vivo. Conclusions. Modulation of release of biologics to fit the therapeutic need can be achieved by varying the biocompatible and biodegradable PTSgel composition. Release of IgG parallels disappearance of the polymeric gel; hence, little or no PTSgel remains after drug release is complete.

  16. Laboratory and Field Evaluation of Biodegradable Polyesters for Sustained Release of Isometamidium and Ethidium

    Directory of Open Access Journals (Sweden)

    S Geerts

    1999-03-01

    Full Text Available An overview is presented of the results obtained with biodegradable sustained release devices (SRDs containing a mixture of polymers and either isometamidium (ISMM or ethidium. Under controlled laboratory conditions (monthly challenge with tsetse flies infected with Trypanosoma congolense the protection period in SRD treated cattle could be extended by a factor 2.8 (for ethidium up to 4.2 (for ISMM as compared to animals treated intramuscularly with the same drugs. Using a competitive drug ELISA ISMM concentrations were detected up to 330 days after the implantation of the SRDs, whereas after i.m. injection the drug was no longer present three to four months post treatment. Two field trials carried out in Mali under heavy tsetse challenge showed that the cumulative infection rate was significantly lower in the ISMM-SRD implanted cattle than in those which received ISMM intramuscularly. Using ethidium SRD, however, contradictory results were obtained in field trials in Zambia and in Mali. The potential advantages and inconvenients of the use of SRDs are discussed and suggestions are made in order to further improve the currently available devices.

  17. 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.

  18. Reduction of radiocesium transfer to animal products using sustained release boli with ammoniumiron(3)-Hexacyanoferrate(2)

    Energy Technology Data Exchange (ETDEWEB)

    Hove, K; Hansen, H S [Department of Animal Science, Agricultural University of Norway, Aas (Norway)

    1993-01-01

    A sustained release boulus with the cesium binder ammoniumiron(III) - hexacyanoferrate (AFCF) has been developed as a countermeasure for small ruminants grazing pastures contaminated by radiocesium ([sup 134]Cs+[sup 137]Cs). The boli (40-50 g) are produced by compression of a mixture of AFCF, barite and wax. The release of AFCF from boli labelled with 137Cs-iron-hexacyanoferrate complex was studied in laboratory sheep. The release rate followed first order kinetics during the 108 d of observation and decreased from 40 to 22, 110 to 35 and 280 to 25 mg d[sup -1] in sheep treated with 1, 2 or 3 boli respectively. The efficiency of boli in reducing radiocesium transfer to meat and milk was tested in laboratory studies with goats fed [sup 134]Cs tracer. Until 40 d after treatment the transfer of radiocesium to milk was reduced by 35%, 60% and 85% in goats given 1, 2 og 3 boli, respectively. The reduction in radiocaesium transfer persisted for 90 d but with a lower efficiency. A similar relationship was found between number of boli and the reduction in radiocesium transfer to meat with an observed maximal reduction of 60%. (au) (20 refs.).

  19. A sustained release system using porous cellulose spheres modified by grafting as matrices

    International Nuclear Information System (INIS)

    Hosoi, Fumio; Makuuchi, Keizo; Saito, Kenji; Koishi, Masumi.

    1987-01-01

    Polymer-coated spheres, obtained by the graft polymerization of methyl methacrylate (MMA) onto porous spheres based on cellulose by the pre-irradiation method, were used as matrices for the drug sustained release system for salicylic acid. The adsorption of salicylic acid was carried out by dipping the grafted spheres in a 50% aqueous ethanol solution containing salicylic acid. The amount of salicylic acid adsorbed (Q) increased proportionately with the percent graft of MMA (G) to the power of 2.9. Adsorption mechanism of salicylic acid could be expressed in term of Langmuir's adsorption isotherm. The ratio of constants for adsorption and desorption (k) and the saturated amount of salicylic acid adsorbed (Q 0 ) were expressed as k = k 1 G and Q 0 = k 2 G 2.4 , respectively. These results indicate that the number of adsorption sites increased proportionately with the nth power of G as a results of the interaction of grafted poly (methyl methacrylate)(PMMA) and cellulose. Similar results were obtained with grafting of MMA, MMA-styrene (St), and MMA-methacrylic acid (MAc) in the presence of salicylic acid. (author)

  20. Development and validation of dissolution study of sustained release dextromethorphan hydrobromide tablets.

    Science.gov (United States)

    Rajan, Sekar; Colaco, Socorrina; Ramesh, N; Meyyanathan, Subramania Nainar; Elango, K

    2014-02-01

    This study describes the development and validation of dissolution tests for sustained release Dextromethorphan hydrobromide tablets using an HPLC method. Chromatographic separation was achieved on a C18 column utilizing 0.5% triethylamine (pH 7.5) and acetonitrile in the ratio of 50:50. The detection wavelength was 280 nm. The method was validated and response was found to be linear in the drug concentration range of 10-80 microg mL(-1). The suitable conditions were clearly decided after testing sink conditions, dissolution medium and agitation intensity. The most excellent dissolution conditions tested, for the Dextromethorphan hydrobromide was applied to appraise the dissolution profiles. The method was validated and response was found to be linear in the drug concentration range of 10-80 microg mL(-1). The method was established to have sufficient intermediate precision as similar separation was achieved on another instrument handled by different operators. Mean Recovery was 101.82%. Intra precisions for three different concentrations were 1.23, 1.10 0.72 and 1.57, 1.69, 0.95 and inter run precisions were % RSD 0.83, 1.36 and 1.57%, respectively. The method was successfully applied for dissolution study of the developed Dextromethorphan hydrobromide tablets.

  1. Novel Injectable Pentablock Copolymer Based Thermoresponsive Hydrogels for Sustained Release Vaccines.

    Science.gov (United States)

    Bobbala, Sharan; Tamboli, Viral; McDowell, Arlene; Mitra, Ashim K; Hook, Sarah

    2016-01-01

    The need for multiple vaccinations to enhance the immunogenicity of subunit vaccines may be reduced by delivering the vaccine over an extended period of time. Here, we report two novel injectable pentablock copolymer based thermoresponsive hydrogels made of polyethyleneglycol-polycaprolactone-polylactide-polycaprolactone-polyethyleneglycol (PEG-PCL-PLA-PCL-PEG) with varying ratios of polycaprolactone (PCL) and polylactide (PLA), as single shot sustained release vaccines. Pentablock copolymer hydrogels were loaded with vaccine-encapsulated poly lactic-co-glycolic acid nanoparticles (PLGA-NP) or with the soluble vaccine components. Incorporation of PLGA-NP into the thermoresponsive hydrogels increased the complex viscosity of the gels, lowered the gelation temperature, and minimized the burst release of antigen and adjuvants. The two pentablock hydrogels stimulated both cellular and humoral responses. The addition of PLGA-NP to the hydrogels sustained immune responses for up to 49 days. The polymer with a higher ratio of PCL to PLA formed a more rigid gel, induced stronger immune responses, and stimulated effective anti-tumor responses in a prophylactic melanoma tumor model.

  2. Protein instability and immunogenicity: roadblocks to clinical application of injectable protein delivery systems for sustained release.

    Science.gov (United States)

    Jiskoot, Wim; Randolph, Theodore W; Volkin, David B; Middaugh, C Russell; Schöneich, Christian; Winter, Gerhard; Friess, Wolfgang; Crommelin, Daan J A; Carpenter, John F

    2012-03-01

    Protein instability and immunogenicity are two main roadblocks to the clinical success of novel protein drug delivery systems. In this commentary, we discuss the need for more extensive analytical characterization in relation to concerns about protein instability in injectable drug delivery systems for sustained release. We then will briefly address immunogenicity concerns and outline current best practices for using state-of-the-art analytical assays to monitor protein stability for both conventional and novel therapeutic protein dosage forms. Next, we provide a summary of the stresses on proteins arising during preparation of drug delivery systems and subsequent in vivo release. We note the challenges and difficulties in achieving the absolute requirement of quantitatively assessing the degradation of protein molecules in a drug delivery system. We describe the potential roles for academic research in further improving protein stability and developing new analytical technologies to detect protein degradation byproducts in novel drug delivery systems. Finally, we provide recommendations for the appropriate approaches to formulation design and assay development to ensure that stable, minimally immunogenic formulations of therapeutic proteins are created. These approaches should help to increase the probability that novel drug delivery systems for sustained protein release will become more readily available as effective therapeutic agents to treat and benefit patients. Copyright © 2011 Wiley Periodicals, Inc.

  3. Water hyacinth: a possible alternative rate retarding natural polymer used in sustained release tablet design.

    Science.gov (United States)

    Khatun, Sabera; Sutradhar, Kumar B

    2014-01-01

    In recent years natural polymers have been widely used because of their effectiveness and availability over synthetic polymers. In this present investigation matrix tablets of Metformin hydrochloride were formulated using Water hyacinth powder and its rate retardant activity was studied. Tablets were prepared using wet granulation method with 8% starch as granulating agent and 5, 10, 15, 20, 25 and 30% of Water hyacinth powder to the drug. In preformulation study, angle of repose, Carr's Index and Hausner ratio were calculated. Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and Scanning Electron Microscopy (SEM) studies were performed and no interactions were found between drug and excipients. Weight variation, friability, hardness, thickness, diameter, and in vitro release study were performed with the prepared matrix tablets. Dissolution studies were conducted using USP type II apparatus at a speed of 100 rpm at 37°C ± 0.5 temperature for 8 h. Though all the formulations comply with both BP and USP requirements, formulation F-1 (5% of Water hyacinth) was the best fitted formula. The drug release patterns were explained in different kinetic models such as Zero order, First order, Higuchi, Hixson Crowell, and Korsmeyer-Peppas equations. The current investigation implies that Water hyacinth has the potential to be used as a rate-retarding agent in sustained release drug formulations.

  4. Preparation and properties of a drug sustained-release hydrogel film

    International Nuclear Information System (INIS)

    Yue Ling; Yang Zhanshan; Yang Shuqin; Li Qinghua

    2009-01-01

    A hydrogel film of drug sustained-release was prepared to accelerate wound healing. The hydrogel films containing drug or not were prepared by the freezing and thawing process. Their properties such as the physicochemical property and the drug release behavior in vitro were studied. Effect of the freezing and thawing process on antimicrobial efficacy of the gentamicin was evaluated by diffusion method. The results indicate that swelling ratio of the hydrogel films freezed for 4h is 841.21% and their gel fraction, tensile strength and elongation at break is 96.10%, 0.222 MPa and 673.50% respectively. The antimicrobial efficacy of the gentamicin has no change. The hydrogel film contained gentamicin releases the antibiotic to peak during 6 h with the cumulative drug release rate of 59.57%. The drug releases continually up to the 5th day. The drug delivery conforms to Higuchi kinetic equation, and mechanism of the drug release is matrix diffusion. The results show that the hydrogel film prepared by the freezing and thawing process display satisfactory physicochemical properties and can be used as a drug delivery system. (authors)

  5. A dual strategy to improve psychotic patients’ compliance using sustained release quetiapine oral disintegrating tablets

    Directory of Open Access Journals (Sweden)

    Refaat Ahmed

    2016-12-01

    Full Text Available Quetiapine (QT is a short acting atypical antipsychotic drug effective in schizophrenia and bipolar disorder. This study aims at designing a novel dosage form of sustained release taste-masked QT orally disintegrating tablets (ODTs based on solid lipid micro-pellets (SLMPs. QT SLMPs were prepared using the hot melt extrusion technique and utilizing three lipid carriers: Compritol, Precirol and white beeswax either alone or in mixtures. They showed sustained QT release and a taste masking effect. The selected QT SLMP was further blended with an aqueous solution containing polyvinylpyrollidone (2.5 %, croscarmellose sodium (2 % and mannitol (50 %; it was then lyophilized into ODT in a mass ratio of 1:2, respectively. ODTs containing QT SLMPs showed: average wetting time (40.92 s, average oral disintegration time (21.49 s, average hardness (16.85 N and also imparted suitable viscosity to suspend pellets during the lyophilization process. In conclusion, lyophilization is a promising technique for the formulation of multiparticulate systems into ODTs.

  6. Synthesis of thiolated arabinoxylan and its application as sustained release mucoadhesive film former.

    Science.gov (United States)

    Zaman, Muhammad; Hanif, Muhammad; Sultana, Kishwar; Atta-Ur-Rehman

    2018-02-08

    The present work aimed to synthesize thiolated arabinoxylan (TAX), and to evaluate its mucoadhesive potential. Synthesis of TAX was accomplished by esterification of arabinoxylan (AX) with thioglycolic acid (TGA). The appearance of a characteristic peak at 2516 cm -1 in the FTIR spectrum of TAX, and presence of 6.01 ± 1.03 m moles of thiol per gram of the polymer confirmed successful thiolation of AX. The incorporation of the thiol group considerably promoted mucoadhesive strength of the polymer-viz. 3.99-fold. Moreover, in vivo safety analysis in albino rats revealed TAX to be safe in the concentration range of 750-1000 mg kg -1 body weight. Synthesized TAX was utilized to prepare Tizanidine HCl (TZN HCl) loaded sustained release (SR) mucoadhesive buccal films using a solvent casting technique. Results proved that the prepared films were of uniform thickness, good mechanical strength (with folding endurance >300), acceptable moisture contents (5%-7%) and surface pH (6.23 ± 0.81 to 6.43 ± 0.49) compatible to that of the buccal cavity. Presence of greater that 90% of drug contents indicated the excellent drug loading ability of the prepared films. Results of in vitro dissolution studies and ex vivo permeation studies conducted respectively by USP dissolution apparatus II and Franz diffusion cell indicated that sustained effect of TAX was achieved for 8 h. These results have conclusively proven that TAX has the potential to improve the bioavailability of TZN HCl due to enhanced mucoadhesion in buccal cavity, hence signifying its suitability as a mucoadhesive buccal film former.

  7. Decreased absorption as a possible cause for the lower bioavailability of a sustained-release propranolol.

    Science.gov (United States)

    Takahashi, H; Ogata, H; Warabioka, R; Kashiwada, K; Ohira, M; Someya, K

    1990-03-01

    The influence of sustained absorption on the oral availability of propranolol (P) and the metabolic disposition of P were investigated by obtaining the partial metabolic clearances (CLm) following long-acting P (LA) dosing in comparison with the conventional propranolol tablet (CP). Ten healthy volunteers were given a single oral dose of an LA capsule (60 mg) and CP (20 mg x 3) using a crossover design. Blood and urine samples were collected over 24- and 48-h postdose periods, respectively. Concentrations of P, propranolol glucuronide (PG), 4-hydroxypropranolol (4P), 4-hydroxypropranolol glucuronide (4PG), 4-hydroxypropranolol sulfate (4PS), and naphthoxylactic acid (NLA) were determined by HPLC with fluorescence and UV detection. Significant differences were observed between LA and CP in the area under the plasma concentration-time curves (AUCs) for P, PG, and NLA and in the amounts excreted into urine (Ae) for all measured metabolites (i.e., PG, 4P, 4PG, 4PS, and NLA). The parallel decrease of the AUC for P and the excreted amounts of all measured metabolites following LA dosing resulted in partial metabolic clearances (CLm) and renal clearances (CL) for P and its metabolites that were similar to those observed for CP. Therefore, the hepatic metabolism of P would not be affected by the slower absorption at a single oral dose of 60 mg. These results indicate that the poor absorption of P from the gastrointestinal tract might be one of the factors causing the low bioavailability of P observed after administration of the sustained-release formulation.

  8. Development and evaluation of Ketoprofen sustained release matrix tablet using Hibiscus rosa-sinensis leaves mucilage

    Directory of Open Access Journals (Sweden)

    M. Kaleemullah

    2017-07-01

    Full Text Available Currently, the use of natural gums and mucilage is of increasing importance in pharmaceutical formulations as valuable drug excipient. Natural plant-based materials are economic, free of side effects, biocompatible and biodegradable. Therefore, Ketoprofen matrix tablets were formulated by employing Hibiscus rosa-sinensis leaves mucilage as natural polymer and HPMC (K100M as a synthetic polymer to sustain the drug release from matrix system. Direct compression method was used to develop sustained released matrix tablets. The formulated matrix tablets were evaluated in terms of physical appearance, weight variation, thickness, diameter, hardness, friability and in vitro drug release. The difference between the natural and synthetic polymers was investigated concurrently. Matrix tablets developed from each formulation passed all standard physical evaluation tests. The dissolution studies of formulated tablets revealed sustained drug release up to 24 h compared to the reference drug Apo Keto® SR tablets. The dissolution data later were fitted into kinetic models such as zero order equation, first order equation, Higuchi equation, Hixson Crowell equation and Korsmeyer-Peppas equation to study the release of drugs from each formulation. The best formulations were selected based on the similarity factor (f2 value of 50% and more. Through the research, it is found that by increasing the polymers concentration, the rate of drug release decreased for both natural and synthetic polymers. The best formulation was found to be F3 which contained 40% Hibiscus rosa-sinensis mucilage polymer and showed comparable dissolution profile to the reference drug with f2 value of 78.03%. The release kinetics of this formulation has shown to follow non-Fickian type which involved both diffusion and erosion mechanism. Additionally, the statistical results indicated that there was no significant difference (p > 0.05 between the F3 and reference drug in terms of MDT and

  9. Sustained release of intravitreal flurbiprofen from a novel drug-in-liposome-in-hydrogel formulation.

    Science.gov (United States)

    Pachis, K; Blazaki, S; Tzatzarakis, M; Klepetsanis, P; Naoumidi, E; Tsilimbaris, M; Antimisiaris, S G

    2017-11-15

    A novel Flurbiprofen (FLB)-in-liposome-in-hydrogel formulation was developed, as a method to sustain the release and increase the ocular bioavailability of FLB following intravitreal injection. For this, FLB loading into liposomes was optimized and liposomes were entrapped in thermosensitive hydrogels consisted of Pluronic F-127 (P). FLB solution, liposomes, and FLB dissolved in hydrogel were also used as control formulations. Actively loaded liposomes were found to be optimal for high FLB loading and small size, while in vitro studies revealed that P concentration of 18% (w/v) was best to retain the integrity of the hydrogel-dispersed liposome, compared to a 20% concentration. The in vitro release of FLB was significantly sustained when FLB-liposomes were dispersed in the hydrogel compared to hydrogel dissolved FLB, as well as the other control formulations. In vivo studies were carried out in pigmented rabbits which were injected through a 27G needle with 1mg/mL FLB in the different formulation-types. Ophthalmic examinations after intravitreal injection of all FLB formulations, revealed no evidence of inflammation, hemorrhage, uveitis or endophthalmitis. Pharmacokinetic analysis results confirm that the hybrid drug delivery system increases the bioavailability (by 1.9 times compared to solution), and extends the presence of the drug in the vitreous cavity, while liposome and hydrogel formulations demonstrate intermediate performance. Furthermore the hybrid system increases MRT of FLB in aqueous humor and retina/choroid tissues, compared to all the control formulations. Currently the potential therapeutic advances of FLB sustained release formulations for IVT administration are being evaluated. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Development of Sustained Release "NanoFDC (Fixed Dose Combination" for Hypertension - An Experimental Study.

    Directory of Open Access Journals (Sweden)

    Anjuman Arora

    Full Text Available The present study was planned to formulate, characterize and evaluate the pharmacokinetics of a novel "NanoFDC" comprising three commonly prescribed anti-hypertensive drugs, hydrochlorothiazide (a diuretic, candesartan (ARB and amlodipine (a calcium channel blocker.The candidate drugs were loaded in Poly (DL-lactide-co-gycolide (PLGA by emulsion- diffusion-evaporation method. The formulations were evaluated for their size, morphology, drug loading and in vitro release individually. Single dose pharmacokinetic profiles of the nanoformulations alone and in combination, as a NanoFDC, were evaluated in Wistar rats.The candidate drugs encapsulated inside PLGA showed entrapment efficiencies ranging from 30%, 33.5% and 32% for hydrochlorothiazide, candesartan and amlodipine respectively. The nanoparticles ranged in size from 110 to 180 nm. In vitro release profile of the nanoformulation showed 100% release by day 6 in the physiological pH 7.4 set up with PBS (phosphate buffer saline and by day 4-5 in the intestinal pH 1.2 and 8.0 set up SGF (simulated gastric fluid and SIF (simulated intestinal fluid respectively. In pharmacokinetic analysis a sustained-release for 6 days and significant increase in the mean residence time (MRT, as compared to the respective free drugs was noted [MRT of amlodipine, hydrochlorothiazide and candesartan changed from 8.9 to 80.59 hours, 11 to 69.20 hours and 9 to 101.49 hours respectively].We have shown for the first time that encapsulating amlodipine, hydrochlorothiazide and candesartan into a single nanoformulation, to get the "NanoFDC (Fixed Dose Combination" is a feasible strategy which aims to decrease pill burden.

  11. Development of theophylline sustained release dosage form based on Kollidon SR.

    Science.gov (United States)

    Reza, Md Selim; Quadir, Mohiuddin Abdul; Haider, Syed Shabbir

    2002-01-01

    Sustained release theophylline matrix tablets constituting Kollidon SR (Polyvinyl acetate and povidone based matrix retarding polymer) were developed in this study in an attempt to design a dosage form that manifests desirable release profile and thorough adherence to official monographs. Four matrix tablet formulations were prepared by dry blending and direct compression of Kollidon SR and HPMC-15cps (hydroxypropylmethylcellulose) in varying proportion with fixed percentage of theophylline. Tablets containing only Kollidon SR with the active ingredient demonstrated a rapid rate of drug release with an initial burst effect. Incorporation of HPMC-15cps in the matrix tablet prolonged the release of drug with subsequent minimization of burst effect as confirmed by mean dissolution time, T50 and Higuchi release rate data. Among the batches containing HPMC-15 cps, a direct relationship was obtained between release rate and the percentage of HPMC used. A suitable controlled release profile was obtained with the matrix tablets containing 20% Kollidon SR and 30% HPMC-15cps. The formulation showed close resemblance to commercial products and compliance with USP specification. The results were explored and explained by the difference of physico-chemical property and hydration characteristics of the polymers. In addition to this result, the exponential model was applied to characterize the drug release behaviour from polymeric systems. It was found that, Fickian release is predominant in tablets containing Kollidon SR alone and non-Fickian mechanism plays an important role in the release of drug from HPMC containing tablets with a trend towards zero-order or case II release. In vitro release profile of two commercial brands were also undertaken for comparison and modulation of the experimental batches.

  12. 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.

  13. Adverse Events With Sustained-Release Donepezil in Alzheimer Disease: Relation to Body Mass Index.

    Science.gov (United States)

    Lee, Chunsoo; Lee, Kyungsang; Yu, Hyewon; Ryu, Seung-Ho; Moon, Seok Woo; Han, Changsu; Lee, Jun-Young; Lee, Young Min; Kim, Shin-Gyeom; Kim, Ki Woong; Lee, Dong Woo; Kim, Seong Yoon; Lee, Sang-Yeol; Bae, Jae Nam; Jung, Young-Eun; Kim, Jeong Lan; Kim, Byung-Soo; Shin, Il-Seon; Kim, Young Hoon; Kim, Bong Jo; Kang, Hyo Shin; Myung, Woojae; Carroll, Bernard J; Kim, Doh Kwan

    2017-08-01

    Sustained-release, high-dose (23 mg/d) donepezil has been approved for treatment of moderate to severe Alzheimer disease (AD). Based on a previous clinical trial, body weight of less than 55 kg is a risk factor for adverse events with donepezil 23 mg/d treatment in global population. To clarify whether this finding is consistent across ethnic groups that vary in absolute body mass, we recruited Korean patients aged 45 to 90 years with moderate to severe AD who had been receiving standard donepezil immediate release 10 mg/d for at least 3 months. After screening, we analyzed a final cohort of 166 patients who received donepezil 23 mg/d for 24 weeks to compare the occurrence of treatment-emergent adverse events (TEAEs) between patients with high versus low body mass index (BMI) based on the World Health Organization overweight criteria for Asian populations (23 kg/m). Treatment-emergent adverse events were reported by 79.45% of patients in the lower BMI group and 58.06% of patients in the higher BMI group (odds ratio, 2.79; 95% confidence interval, 1.39-5.63; χ = 7.58, P = 0.006). In a multivariable survival analysis, the group with lower BMI showed a higher occurrence of TEAEs (hazard ratio, 1.83; 95% confidence interval, 1.25-2.68; P = 0.002). In Korean patients with moderate to severe AD receiving high-dose donepezil over 24 weeks, TEAEs were significantly more common in those with lower BMI (not clinically overweight), especially nausea. This finding may inform clinical practice for Asian patients.

  14. Oral sustained release tablets of zidovudine using binary blends of natural and synthetic polymers.

    Science.gov (United States)

    Emeje, Martins; Olaleye, Olajide; Isimi, Christiana; Fortunak, Joseph; Byrn, Stephen; Kunle, Olobayo; Ofoefule, Sabinus

    2010-01-01

    Oral sustained release matrix tablets of zidovudine (ZDV) were prepared using different types, proportions and blends of carbopol 71G (C71) and a plant gum obtained from Abelmoschus esculentus (AEG). The effect of various formulation factors like polymer proportion, polymer type and pH of the dissolution medium on the in vitro release of the drug was studied, using the half change technique, in 900 ml of dissolution medium, at 100 rpm. Release kinetics were analyzed using Zero-order, Higuchi's square-root and Ritger-Peppas' empirical equations. In vitro release performance as revealed by the time taken for 70% of the drug to be released (t70%), showed that the release rate decreased with increase in polymer proportion. Matrix tablets containing 10 and 20% AEG were found to exhibit immediate-release characteristics. Matrix tablets containing 30% AEG showed t70% value of 204 min and extended the release up to 5 h, while matrix tablets containing 30% carbopol showed t70% value of 234 min and extended the release up to 6 h. Three blends of AEG and C71 at the ratio of 1:2, 2:1 and 1:3 showed t70% values of 132, 312 and 102 min respectively and extended the release up to 8 h. Mathematical analysis of the release kinetics indicated that the nature of drug release from the matrix tablets followed Fickian and anomalous release. Drug release from matrix tablets of zidovudine containing blends of AEG and C71 demonstrates the advantage of blending a natural and synthetic polymer over single polymer use.

  15. Development and evaluation of Ketoprofen sustained release matrix tablet using Hibiscus rosa-sinensis leaves mucilage.

    Science.gov (United States)

    Kaleemullah, M; Jiyauddin, K; Thiban, E; Rasha, S; Al-Dhalli, S; Budiasih, S; Gamal, O E; Fadli, A; Eddy, Y

    2017-07-01

    Currently, the use of natural gums and mucilage is of increasing importance in pharmaceutical formulations as valuable drug excipient. Natural plant-based materials are economic, free of side effects, biocompatible and biodegradable. Therefore, Ketoprofen matrix tablets were formulated by employing Hibiscus rosa-sinensis leaves mucilage as natural polymer and HPMC (K100M) as a synthetic polymer to sustain the drug release from matrix system. Direct compression method was used to develop sustained released matrix tablets. The formulated matrix tablets were evaluated in terms of physical appearance, weight variation, thickness, diameter, hardness, friability and in vitro drug release. The difference between the natural and synthetic polymers was investigated concurrently. Matrix tablets developed from each formulation passed all standard physical evaluation tests. The dissolution studies of formulated tablets revealed sustained drug release up to 24 h compared to the reference drug Apo Keto® SR tablets. The dissolution data later were fitted into kinetic models such as zero order equation, first order equation, Higuchi equation, Hixson Crowell equation and Korsmeyer-Peppas equation to study the release of drugs from each formulation. The best formulations were selected based on the similarity factor ( f 2 ) value of 50% and more. Through the research, it is found that by increasing the polymers concentration, the rate of drug release decreased for both natural and synthetic polymers. The best formulation was found to be F3 which contained 40% Hibiscus rosa-sinensis mucilage polymer and showed comparable dissolution profile to the reference drug with f 2 value of 78.03%. The release kinetics of this formulation has shown to follow non-Fickian type which involved both diffusion and erosion mechanism. Additionally, the statistical results indicated that there was no significant difference (p > 0.05) between the F3 and reference drug in terms of MDT and T50% with p

  16. 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

  17. Sustained-release indomethacin in the management of the acute painful shoulder from bursitis and/or tendinitis.

    Science.gov (United States)

    Calabro, J J; Londino, A V; Eyvazzadeh, C

    1985-10-25

    Of all the forms of nonarticular rheumatism, by far the most common are bursitis and tendinitis. Yet, the bursae and neighboring tendon sheaths are the most neglected anatomic structures of the body. Moreover, like the joints, they are lined by synovial membrane, secrete synovial fluid, and are common sites of rheumatic problems. The vast majority of painful shoulder problems are caused by acute subacromial (subdeltoid) bursitis and bicipital tendinitis. In the management of these periarticular disorders, the ultimate goal is to preserve shoulder motion. Although this is accomplished by daily range-of-motion exercises, it is clearly facilitated by suppression of periarticular inflammation and discomfort through the use of nonsteroidal anti-inflammatory drugs. Of these, sustained-release indomethacin provides the anti-inflammatory efficacy of indomethacin and by virtue of its sustained-release formulation, may promote patient compliance since it need be given only once or twice daily.

  18. Sustained release of simvastatin from hollow carbonated hydroxyapatite microspheres prepared by aspartic acid and sodium dodecyl sulfate.

    Science.gov (United States)

    Wang, Ke; Wang, Yinjing; Zhao, Xu; Li, Yi; Yang, Tao; Zhang, Xue; Wu, Xiaoguang

    2017-06-01

    Hollow carbonated hydroxyapatite (HCHAp) microspheres as simvastatin (SV) sustained-release vehicles were fabricated through a novel and simple one-step biomimetic strategy. Firstly, hollow CaCO 3 microspheres were precipitated through the reaction of CaCl 2 with Na 2 CO 3 in the presence of aspartic acid and sodium dodecyl sulfate. Then, the as-prepared hollow CaCO 3 microspheres were transformed into HCHAp microspheres with a controlled anion-exchange method. The HCHAp microspheres were 3-5μm with a shell thickness of 0.5-1μm and were constructed of short needle nanoparticles. The HCHAp microspheres were then loaded with SV, exhibiting excellent drug-loading capacity and sustained release properties. These results present a new material synthesis strategy for HCHAp microspheres and suggest that the as-prepared HCHAp microspheres are promising for applications in drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Formulation and evaluation of rifampicin sustained release tablets using juice of Citrus limetta as bio-retardant.

    Science.gov (United States)

    Gaur, K Pawan; Soam, Kulwant; Gupta, S K; Dabral, Prashant

    2012-03-01

    The advantages of biopolymers over synthetic polymers are low cost, natural origin, free from side effects, biocompatible, bio-acceptable, environmental friendly processing, local availability, better patient tolerance as well as public acceptance. Sustained release tablets containing rifampicin was prepared by adding 100 mg polymer and 50 mg Drug and Granules. Same procedure was followed with 3% and 5% of polymer for preparation of sustained release tablets. Additional Tablets of 100 mg, 200 mg and 400 mg were prepared using 5% of the polymer. The results indicated that the selected biopolymer had a good release retardant property thus it can be concluded that the selected biopolymer can be utilized as low cost natural biocompatible and biodegradable agent.

  20. Formulation and evaluation of rifampicin sustained release tablets using juice of Citrus limetta as bio-retardant

    Directory of Open Access Journals (Sweden)

    K Pawan Gaur

    2012-01-01

    Full Text Available The advantages of biopolymers over synthetic polymers are low cost, natural origin, free from side effects, biocompatible, bio-acceptable, environmental friendly processing, local availability, better patient tolerance as well as public acceptance. Sustained release tablets containing rifampicin was prepared by adding 100 mg polymer and 50 mg Drug and Granules. Same procedure was followed with 3% and 5% of polymer for preparation of sustained release tablets. Additional Tablets of 100 mg, 200 mg and 400 mg were prepared using 5% of the polymer. The results indicated that the selected biopolymer had a good release retardant property thus it can be concluded that the selected biopolymer can be utilized as low cost natural biocompatible and biodegradable agent.

  1. The effect of food on gastrointestinal (GI) transit of sustained-release ibuprofen tablets as evaluated by gamma scintigraphy

    International Nuclear Information System (INIS)

    Borin, M.T.; Khare, S.; Beihn, R.M.; Jay, M.

    1990-01-01

    The GI transit of radiolabeled sustained-release ibuprofen 800-mg tablets in eight healthy, fed volunteers was monitored using external gamma scintigraphy. Ibuprofen serum concentrations were determined from blood samples drawn over 36 hr following dosing. Sustained-release ibuprofen tablets containing 0.18% of 170Er2O3 (greater than 96% 170Er) in the bulk formulation were manufactured under pilot-scale conditions and were radiolabeled utilizing a neutron activation procedure which converted stable 170Er to radioactive 171Er (t1/2 = 7.5 hr). At the time of dosing, each tablet contained 50 mu Ci of 171Er. Dosage form position were reported at various time intervals. In five subjects the sustained-release tablet remained in the stomach and eroded slowly over 7-12 hr, resulting in gradual increases in small bowel radioactivity. In the remaining three subjects, the intact tablet was ejected from the stomach and a gastric residence time of approximately 4 hr was measured. This is in marked contrast to a previous study conducted in fasted volunteers in which gastric retention time ranged from 10 to 60 min. Differences in GI transit between fed and fasted volunteers had little effect on ibuprofen bioavailability. AUC and Tmax were unaltered and Cmax was increased by 24%, which is in agreement with results from a previous, crossover-design food effect study

  2. Formulation and evaluation of a sustained-release tablets of metformin hydrochloride using hydrophilic synthetic and hydrophobic natural polymers.

    Science.gov (United States)

    Wadher, K J; Kakde, R B; Umekar, M J

    2011-03-01

    Metformin hydrochloride has relatively short plasma half-life, low absolute bioavailability. The need for the administration two to three times a day when larger doses are required can decrease patient compliance. Sustained release formulation that would maintain plasma level for 8-12 h might be sufficient for daily dosing of metformin. Sustained release products are needed for metformin to prolong its duration of action and to improve patient compliances. The overall objective of this study was to develop an oral sustained release metformin hydrochloride tablet by using hydrophilic Eudragit RSPO alone or its combination with hydrophobic natural polymers Gum copal and gum damar as rate controlling factor. The tablets were prepared by wet granulation method. The in vitro dissolution study was carried out using USP 22 apparatus I, paddle method and the data was analysed using zero order, first order, Higuchi, Korsmeyer and Hixson-Crowell equations. The drug release study revealed that Eudragit RSPO alone was unable to sustain the drug release. Combining Eudragit with gum Copal and gum Damar sustained the drug release for more than 12 h. Kinetic modeling of in vitro dissolution profiles revealed the drug release mechanism ranges from diffusion controlled or Fickian transport to anomalous type or non-Fickian transport. Fitting the in vitro drug release data to Korsmeyer equation indicated that diffusion along with erosion could be the mechanism of drug release.

  3. Sustained-release progesterone nanosuspension following intramuscular injection in ovariectomized rats

    Directory of Open Access Journals (Sweden)

    Heba F Salem

    2010-11-01

    Full Text Available Heba F SalemFaculty of Pharmacy, Beni-Suef University, Beni-Suef, EgyptAbstract: The production of an intramuscular (IM injection of natural progesterone would provide a safer solution than using semi synthetic progesterone. However, disadvantages such as low solubility and a short half life prevent the use of natural progesterone. In this study, we formulated a sustained release form of natural progesterone to be given as IM injection. A progesterone nanosuspension (PNS was first developed and then dispersed in a thermosensitive gel matrix. The selected nanoparticles showed an average particle size of 267 nm and a zeta potential approaching-41 mV. The in vitro release profile of PNS from the F127 plus methyl cellulose gel followed zero order kinetics and correlated linearly with the weight percentage of gel dissolved, demonstrating that the overall rate of release of PNS is controlled by dissolution of the pluronic F127/methyl cellulose (MC gel (r2 > 0.99. The pharmacokinetic parameters of the PNS (6 mg/mL in pluronic F127/MC gel were evaluated in comparison with the control progesterone suspension. After the administration of PNS in F127/MC gel into the rats, a maximum serum concentration of 22.1 ± 1.9 ng/mL was reached at a Tmax of 4.05 ± 0.1 h. The terminal half life was 12.7 ± 0.8 h. The area under the curve AUC0-∞ of the injected formula was 452.75 ± 42.8 ng•h/mL and the total mean residence time was 18.57 ± 1.44 h. The PNS in gel was significantly different from the control in rate and extent at P < 0.001. The natural progesterone which was nanosized and formulated in a thermosensitive gel significantly sustained the action of natural progesterone so that it could be injected every 36 h instead of every day. Moreover, this formula is expected to provide a much safer choice than the use of semi-synthetic progesterone.Keywords: progesterone, nanosuspension, thermosensitive gel, ovariectomized female rats

  4. Sustained-release progesterone nanosuspension following intramuscular injection in ovariectomized rats.

    Science.gov (United States)

    Salem, Heba F

    2010-11-10

    The production of an intramuscular (IM) injection of natural progesterone would provide a safer solution than using semi synthetic progesterone. However, disadvantages such as low solubility and a short half life prevent the use of natural progesterone. In this study, we formulated a sustained release form of natural progesterone to be given as IM injection. A progesterone nanosuspension (PNS) was first developed and then dispersed in a thermosensitive gel matrix. The selected nanoparticles showed an average particle size of 267 nm and a zeta potential approaching-41 mV. The in vitro release profile of PNS from the F127 plus methyl cellulose gel followed zero order kinetics and correlated linearly with the weight percentage of gel dissolved, demonstrating that the overall rate of release of PNS is controlled by dissolution of the pluronic F127/methyl cellulose (MC) gel (r² > 0.99). The pharmacokinetic parameters of the PNS (6 mg/mL) in pluronic F127/MC gel were evaluated in comparison with the control progesterone suspension. After the administration of PNS in F127/MC gel into the rats, a maximum serum concentration of 22.1 ± 1.9 ng/mL was reached at a T(max) of 4.05 ± 0.1 h. The terminal half life was 12.7 ± 0.8 h. The area under the curve AUC₀₋∞ of the injected formula was 452.75 ± 42.8 ng·h/mL and the total mean residence time was 18.57 ± 1.44 h. The PNS in gel was significantly different from the control in rate and extent at P < 0.001. The natural progesterone which was nanosized and formulated in a thermosensitive gel significantly sustained the action of natural progesterone so that it could be injected every 36 h instead of every day. Moreover, this formula is expected to provide a much safer choice than the use of semi-synthetic progesterone.

  5. Tannate complexes of antihistaminic drug: sustained release and taste masking approaches.

    Science.gov (United States)

    Rahman, Ziyaur; Zidan, Ahmed S; Berendt, Robert T; Khan, Mansoor A

    2012-01-17

    The aim of this investigation was to evaluate the complexation potential of brompheniramine maleate (BPM) and tannic acid (TA) for sustained release and taste masking effects. The complexes (1:1-1:7 TA to BPM ratio) were prepared by the solvent evaporation method using methanol, phosphate buffer pH 6.8 or 0.1N HCl as common solvents. The complexes were characterized microscopically by scanning electron microscopy (SEM), chemically by Fourier transform infrared (FTIR) and solid-state NMR (SSNMR), thermally by differential scanning calorimetry (DSC), for crystallinity by powder X-ray powder diffraction (PXRD), for organoleptic evaluation by electronic tongue (e-tongue), and for solubility in 0.1N HCl and phosphate buffer pH 6.8. The dissolution studies were carried out using the USP II method at 50 rpm in 500 ml of dissolution media (0.1N HCl or phosphate buffer pH 6.8). SEM images revealed that the morphology of complexes were completely different from the individual components, and all complexes had the same morphological characteristics, irrespective of the solvent used for their preparation, pH or ratio of BPM and TA. The FTIR spectra showed the presence of chemical interactions between the TA and BPM. DSC, PXRD and SSNMR indicated that the drug lost its crystalline nature by formation of the complex. Complexation has significantly reduced the solubility of BPM and sustained the drug release up to 24h in phosphate buffer pH 6.8 media. The bitter taste of the BPM was completely masked which was indicated by Euclidean distance values which was far from the drug but near to its placebo in the complexes in all ratios studied. The taste masked complexes can be potentially developed as suitable dosage forms for pediatric use. In summary, complexation of BPM and TA effectively sustained the dissolution and masked the bitter taste of drug for the development of suitable dosage forms for pediatric use. Published by Elsevier B.V.

  6. Effect of Misoprostol on the Pharmacokinetics of Sustained Release Diclofenac in Myanmar Healthy Male Volunteers

    Directory of Open Access Journals (Sweden)

    Htet Htet Aung

    2017-03-01

    Full Text Available Background: Sustained release diclofenac (diclofenac SR is the commonly used non-steroidal anti-inflammatory drug for chronic inflammatory conditions such as rheumatoid arthritis. Misoprostol, prostaglandin analogue, is the agent that enhances gastrointestinal mucosal defense. Concomitant administration of misoprostol with diclofenac SR can prevent the gastrointestinal side effects of diclofenac SR. Objective: The purpose of the study was to explore the effect of misoprostol on the pharmacokinetics of diclofenac SR in healthy volunteers. Methods: Crossover study was evaluated in 14 male volunteers. Single oral dose of 100 mg diclofenac SR was concomitantly administered with 200 μg misoprostol with one-week wash out period. Plasma concentrations at 0, 0.5, 1, 1.5, 2, 3, 6 and 10 hrs were determined by high performance liquid chromatography (HPLC. Pharmacokinetic parameters such as area under concentration-time curve (AUC0-α, peak plasma concentration (Cmax, time to achieve peak plasma concentration (Tmax, absorption half-life (T½(ab, elimination half-life (T1/2(el, absorption rate constant (Kab, and elimination rate constant (Kel were determined. Results: With misoprostol, the mean AUC0-α of diclofenac SR was significantly reduced from 12.11±5.25μg/ mL×hr to 4.17±2.72μg/mL×hr (p0.05. The mean T½(ab was decreased from 0.56±0.23hr to 0.54±0.19hr (p>0.05. The mean Kab were almost the same 1.43±0.54hr-1 and 1.43±0.48hr-1. The mean T1/2(el was decreased from 3.68±1.64hr to 3.03±1.08hr (p>0.05. The mean Kel was increased from 0.21±0.09hr-1 to 0.25±0.09hr-1 (p>0.05. Conclusion: There was a significant reduction in the extent of absorption of diclofenac SR when concomitantly administered with misoprostol. Therefore, the dose of diclofenac SR may need to be increased to avoid therapeutic failure of diclofenac SR or concurrent use with misoprostol may need to be changed to other gastroprotective agents.

  7. 2-Amino-5-bromopyridinium hydrogen succinate

    Directory of Open Access Journals (Sweden)

    Hoong-Kun Fun

    2010-03-01

    Full Text Available In the title compound, C5H6BrN2+·C4H5O4−, the pyridine N atom of the 2-amino-5-bromopyridine molecule is protonated. The protonated N atom and the amino group are linked via N—H...O hydrogen bonds to the carboxylate O atoms of the singly deprotonated succinate anion. The hydrogen succinate anions are linked via O—H...O hydrogen bonds. A weak intermolecular C—H...O hydrogen bond is also observed.

  8. 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

  9. Sustained-release bupropion versus naltrexone in the treatment of pathological gambling: a preliminary blind-rater study.

    Science.gov (United States)

    Dannon, Pinhas N; Lowengrub, Katherine; Musin, Ernest; Gonopolski, Yehudit; Kotler, Moshe

    2005-12-01

    Pathological gambling (PG) is a relatively common and highly disabling impulse control disorder. A range of psychotherapeutic agents, including selective serotonin reuptake inhibitors, mood stabilizers, and opioid antagonists, has been shown to be effective in the treatment of PG. The use of selective serotonin reuptake inhibitors and opioid antagonists for PG is consistent with the observation that PG shares features of both the obsessive-compulsive spectrum disorders and addictive disorders. The aim of the study is to compare the effectiveness of sustained-release bupropion versus naltrexone in the treatment of PG. Thirty-six male pathological gamblers were enrolled in our study. A comprehensive psychiatric diagnostic evaluation was performed at baseline on all patients, and patients were screened for symptoms of gambling, depression, and anxiety using the South Oaks Gambling Screen, the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, and the Clinical Global Impression-Severity Scale. In addition, the patients completed self-report questionnaires about their demographic status. Patients were randomized in 2 groups and received either naltrexone (n = 19) or sustained-release bupropion (n = 17) for 12 weeks in a parallel fashion. Treatment response was monitored using the Clinical Global Impression-Improvement Scale which was performed at weeks 2, 4, 8, and 12. Patients were also assessed for the presence of gambling behavior via an unstructured interview, which was also performed at weeks 2, 4, 6, 8, and 12. Raters were blind to the study treatment. The majority of patients responded well to the drug treatment. Twelve of 17 patients in the sustained-release bupropion group completed the 12-week study, and 13 of 19 naltrexone patients completed the study. Nine (75%) of the 12 completers were rated as full responders in the sustained-release bupropion group versus 10 (76%) of 12 in the naltrexone group. Three (25%) of 12 completers in the

  10. Prospects for a bio-based succinate industry.

    Science.gov (United States)

    McKinlay, James B; Vieille, C; Zeikus, J Gregory

    2007-09-01

    Bio-based succinate is receiving increasing attention as a potential intermediary feedstock for replacing a large petrochemical-based bulk chemical market. The prospective economical and environmental benefits of a bio-based succinate industry have motivated research and development of succinate-producing organisms. Bio-based succinate is still faced with the challenge of becoming cost competitive against petrochemical-based alternatives. High succinate concentrations must be produced at high rates, with little or no by-products to most efficiently use substrates and to simplify purification procedures. Herein are described the current prospects for a bio-based succinate industry, with emphasis on specific bacteria that show the greatest promise for industrial succinate production. The succinate-producing characteristics and the metabolic pathway used by each bacterial species are described, and the advantages and disadvantages of each bacterial system are discussed.

  11. Effect of succinic acid concentration in poly(glycerol citrate/succinate) properties

    International Nuclear Information System (INIS)

    Brioude, Michel M.; Guimaraes, Danilo H.; Fiuza, Raigenis P.; Jose, Nadia M.

    2011-01-01

    In this work were prepared and characterized polymer based on glycerol, citric and succinic acid, in three different ratios to evaluate the effect of succinic acid concentration in materials properties. The polymers were obtained by polycondensation reaction between polyol and poly acids, and were characterized by X-ray diffraction (XRD), infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), scanning differential calorimetry (DSC), scanning electron microscopy (SEM). The materials are amorphous polyesters and its thermal and morphological properties change depending on the succinic acid concentration. (author)

  12. 21 CFR 172.275 - Synthetic paraffin and succinic derivatives.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Synthetic paraffin and succinic derivatives. 172... FOOD FOR HUMAN CONSUMPTION Coatings, Films and Related Substances § 172.275 Synthetic paraffin and succinic derivatives. Synthetic paraffin and succinic derivatives identified in this section may be safely...

  13. The effect of alpha-tocopheryl succinate on succinate respiration in rat liver mitochondria

    Czech Academy of Sciences Publication Activity Database

    Sobotka, O.; Drahota, Zdeněk; Kučera, O.; Endlicher, R.; Rauchová, Hana; Červinková, Z.

    2015-01-01

    Roč. 64, Suppl.5 (2015), S609-S615 ISSN 0862-8408 Institutional support: RVO:67985823 Keywords : tocopheryl succinate * Complex II * liver * mitochondria * homogenate * hepatocytes Subject RIV: ED - Physiology Impact factor: 1.643, year: 2015

  14. Formulation and evaluation of a bilayer tablet comprising of diclofenac potassium as orodispersible layer and diclofenac sodium as sustained release core

    OpenAIRE

    Abbas, Jabbar; Bashir, Sajid; Samie, Muhammad; Laghari, Sadaf

    2017-01-01

    Diclofenac a phenylacetic acid derivative has long been used as an anti-inflammatory and analgesic drug to treat certain conditions however its sustained release formulation with immediate release loading dose is desirable. The rationale of the current work was to develop and evaluate bilayer tablets with diclofenac potassium as orodispersible layer and diclofenac sodium as sustained release core. The diclofenac sodium core was prepared by wet granulation method while the...

  15. 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

  16. Pharmacokinetics of a Sustained-release Formulation of Meloxicam After Subcutaneous Administration to Hispaniolan Amazon Parrots (Amazona ventralis).

    Science.gov (United States)

    Guzman, David Sanchez-Migallon; Court, Michael H; Zhu, Zhaohui; Summa, Noémie; Paul-Murphy, Joanne R

    2017-09-01

    Meloxicam has been shown to have a safe and favorable pharmacodynamic profile with individual variability in Hispaniolan Amazon parrots (Amazona ventralis). In the current study, we determined the pharmacokinetics of a sustained-release formulation of meloxicam after subcutaneous administration to Hispaniolan Amazon parrots. Twelve healthy adult parrots, 6 males and 6 females, were used in the study. Blood samples were collected before (time 0) and at 0.5, 1, 2, 6, 12, 24, 48, 72, 96, and 120 hours after a single dose of the sustained-release meloxicam formulation (3 mg/kg SC). Plasma meloxicam concentrations were measured by high-pressure liquid chromatography. Pharmacokinetic parameters were determined by noncompartmental analysis. Plasma concentrations reached a mean C max of 23.4 μg/mL (range, 14.7-46.0 μg/mL) at 1.8 hours (range, 0.5-6 hours), with a terminal half-life of 7.4 hours (range, 1.4-40.9 hours). Individual variation was noticeable, such that some parrots (4 of 12 birds) had very low plasma meloxicam concentrations, similar to the high variability reported in a previous pharmacokinetic study of the standard meloxicam formulation in the same group of birds. Two birds developed small self-resolving scabs at the injection site. On the basis of these results, the sustained-release meloxicam formulation could be administered every 12 to 96 hours in Hispaniolan Amazon parrots to manage pain. Because of these highly variable results, the use of this formulation in this species cannot be recommended until further pharmacokinetic, safety, and pharmacogenomic evaluations are performed to establish accurate dosing recommendations and to understand the high pharmacokinetic variability.

  17. Improvement in autologous human fat transplant survival with SVF plus VEGF-PLA nano-sustained release microspheres.

    Science.gov (United States)

    Li, Liqun; Pan, Shengsheng; Ni, Binting; Lin, Yuanshao

    2014-08-01

    Early neovascularization is important for autologous fat transplant survival. SVF cells are ideal seed cells. Both vascular endothelial growth factor (VEGF) and SVF cells can promote neovascularization. However, the half-life (about 50 min) of VEGF is too short to sustain an adequate local concentration. We have investigated whether VEGF-polylactic acid (PLA) nano-sustained release microspheres plus SVF cells can improve neovascularization and survival of transplanted fat tissues. SVF cells were harvested and constructed VEGF-PLA nano-sustained release microspheres in vitro. Human fat tissues was mixed with SVF cells plus VEGF-PLA, SVF cells alone or Dulbecco's modified Eagle's medium as the control. These three mixtures were injected into random sites in 18 nude mice. Two months later, the transplants were weighed and examined histologically; and capillaries were counted to quantify neovascularization. Hematoxylin-eosin (HE) and anti-VEGF stains were applied to reveal cell infiltration. The mean wet weight of fat in the SVF plus VEGF-PLA, SVF alone, and control transplants were 0.18 ± 0.013 g, 0.16 ± 0.015 g, and 0.071 ± 0.12 g, respectively; the differences between groups were statistically significant. More vessels were present in the SVF plus VEGF-PLA transplants than in the other two types. Transplants mixed with SVF cells also had an acceptable density of capillaries. Histological analysis revealed that both the SVF plus VEGF-PLA and SVF alone transplants, but not the control transplants, were composed of adipose tissue, and had less fat necrosis and less fibrosis than control specimens. SVF plus VEGF-PLA transplants had significantly greater capillary density and VEGF expression than the other two transplant groups. Thus transplanted fat tissue survival and quality can be enhanced by the addition of VEGF-PLA nano-sustained release microspheres plus SVF cells. © 2014 International Federation for Cell Biology.

  18. Absorption kinetics and steady-state plasma concentrations of theophylline following therapeutic doses of two sustained-release preparations

    DEFF Research Database (Denmark)

    Andersen, O; Nielsen, M K; Eriksen, P B

    1983-01-01

    Ten healthy volunteers received two sustained-release preparations as a single and multiple dose regimen in an open crossover study. Plasma theophylline concentrations were measured by an enzyme immunoassay. The limited fluctuation of the theophylline levels at steady state, with twice daily...... formulation, whereas this was not the case for the other (r = 0.27 and 0.49). The daily dose necessary to keep the plasma concentration within the therapeutic range of 55-110 mumole/liter varied from 7.9 to 22.9 mg/kg. Only mild side effects were recorded, but they were not correlated to the plasma...... theophylline concentration....

  19. Development and evaluation of sustained release losartan potassium matrix tablet using kollidon SR as release retardant

    Directory of Open Access Journals (Sweden)

    Shahid Sarwar

    2012-12-01

    Full Text Available The present study was undertaken to develop sustained release (SR matrix tablets of losartan potassium, an angiotensin-II antagonist for the treatment of hypertension. The tablets were prepared by direct compression method, along with Kollidon SR as release retardant polymer. The amount of losartan potassium remains fixed (100 mg for all the three formulations whereas the amounts of Kollidon SR were 250 mg, 225 mg, and 200 mg for F-1, F-2, and F-3 respectively. The evaluation involves three stages: the micromeritic properties evaluation of granules, physical property studies of tablets, and in-vitro release kinetics studies. The USP apparatus type II was selected to perform the dissolution test, and the dissolution medium was 900 mL phosphate buffer pH 6.8. The test was carried out at 75 rpm, and the temperature was maintained at 37 ºC ± 0.5 ºC. The release kinetics was analyzed using several kinetics models. Higher polymeric content in the matrix decreased the release rate of drug. At lower polymeric level, the rate and extent of drug release were enhanced. All the formulations followed Higuchi release kinetics where the Regression co-efficient (R² values are 0.958, 0.944, and 0.920 for F-1, F-2, and F-3 respectively, and they exhibited diffusion dominated drug release. Statistically significant (PO presente estudo foi realizado para desenvolver (SR matriz de comprimidos de liberação sustentada de losartana, um antagonista da angiotensina II, para o tratamento da hipertensão arterial. Os comprimidos foram preparados pelo método de compressão direta com Kollidon SR como polímero de liberação lenta. A quantidade de losartana potássica permanece fixa (100 mg para todas as três formulações enquanto que as quantidades de Kollidon SR foram de 250 mg, 225 mg e 200 mg para F-1, F-2 e F-3, respectivamente. A avaliação envolve três etapas- propriedades micromeríticas dos grânulos, estudo das propriedades físicas dos comprimidos e

  20. 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.

  1. A Meta-Analysis of the Efficacy of Bupropion Sustained-Release for Smoking Cessation in Heavy Smokers

    Directory of Open Access Journals (Sweden)

    Adrian Paszek

    2017-09-01

    Full Text Available Cigarette smoking damages just about every organ in the body and reduces overall health. Even with the prevalence of accessible nicotine replacement therapies and behavioral counseling, there remains a need for alternative therapies to improve the odds of successfully abstaining from smoking in the long term. Bupropion sustained-release (SR is a pharmacological, prescription-only intervention that is approved as a first-line treatment for smoking cessation. This meta-analysis examines the effectiveness of bupropion sustained-release for smoking cessation amongst heavy smokers, defined as those who consistently smoke at least fifteen or more cigarettes per day. Across five qualifying studies, bupropion SR increased odds of cessation over placebo treatment at six and twelve months. Bupropion SR is a well-tolerated, non-nicotinic therapy for smoking cessation. Treatment with bupropion SR reduces initial cravings and withdrawal effects but does not appear to address the multi-faceted problem of cigarette addiction, resulting in decreased abstinence rates over time. An integrated approach incorporating bupropion SR with other interventions, such as nicotine replacement therapies and psychotherapy, may provide the necessary means to achieve lasting cessation and promote well-being.

  2. Taste masking of ciprofloxacin by ion-exchange resin and sustain release at gastric-intestinal through interpenetrating polymer network

    Directory of Open Access Journals (Sweden)

    A. Michael Rajesh

    2015-07-01

    Full Text Available The aim of the study was to taste mask ciprofloxacin (CP by using ion-exchange resins (IERs followed by sustain release of CP by forming interpenetrating polymer network (IPN. IERs based on the copolymerization of acrylic acid with different cross linking agents were synthesised. Drug-resin complexes (DRCs with three different ratios of drug to IERs (1:1, 1:2, 1:4 were prepared & evaluated for taste masking by following in vivo and in vitro methods. Human volunteers graded ADC 1:4, acrylic acid-divinyl benzene (ADC-3 resin as tasteless. Characterization studies such as FTIR, SEM, DSC, P-XRD differentiated ADC 1:4, from physical mixture (PM 1:4 and confirmed the formation of complex. In vitro drug release of ADC 1:4 showed complete release of CP within 60 min at simulated gastric fluid (SGF i.e. pH 1.2. IPN beads were prepared with ADC 1:4 by using sodium alginate (AL and sodium alginate-chitosan (AL-CS for sustain release of CP at SGF pH and followed by simulated intestinal fluid (SIF i.e. pH 7.4. FTIR spectra confirmed the formation of IPN beads. The release of CP was sustain at SGF pH (75%. The kinetic model of IPN beads showed the release of CP was non-Fickian diffusion type.

  3. The effect of sustained release boli with ammoniumiron(III)-hexacyanoferrate(II) on radiocesium accumulation in sheep grazing contaminated pasture

    International Nuclear Information System (INIS)

    Hansen, H.S.; Hove, K.; Barvik, K.

    1996-01-01

    Sustained release boli with the cesium binder ammoniumiron(III)-hexacyanoferrate(II) (AFCF) were tested under practical conditions for sheep grazing on pastures contaminated with radiocesium ( 134 Cs+ 137 Cs) from the Chernobyl fallout. Two types of AFCF boli were developed: boli without a protective surface coating intended to last 4-8 wk; and boli coated by a wax-mixture with an extended duration of 10-12 wk. From 1989 to 1993 we measured the effect of wax-coated and uncoated boli administered at various times during the grazing season to a total of 3,248 animals. Reductions in radiocesium levels in meat of sheep were measured by in vivo monitoring. Administration of AFCF boli without a wax-coating reduced the mean radiocesium levels in lambs by 42-75% over a 408 wk period, and administration of the wax-coated AFCF boli reduced the mean radiocesium levels by 48-65% over a 9-11 wk period. The coefficients of variation in meat radiocesium levels were similar in treated and control groups at the end of the observation period, showing that the reduction of meat radiocesium values was homogeneous throughout the treated groups. The boli giving sustained release of AFCF is a labor-saving and cost effective counter-measure for sheep grazing radiocesium contaminated pastures. 16 refs., 4 figs., 4 tabs

  4. Preparation and stability investigation of tamsulosin hydrochloride sustained release pellets containing acrylic resin polymers with two different techniques

    Directory of Open Access Journals (Sweden)

    Rui Fan

    2017-03-01

    Full Text Available The objective of this study was to prepare tamsulosin hydrochloride-sustained release (TSH-SR pellets which showed good release stability with frame-controlled method. TSH was added to Eudragit®NE30D and Eudragit®L30D-55 polymers to form drug-loaded inner core. Afterwards, enteric Eudragit®L30D-55 polymer was modified on the surface of it to the final product. Dissolution studies showed that TSH-SR pellets were more stable during the coating process, different curing temperatures and storage conditions compared with TSH pellets produced by film-controlled technique. Appearances and glass transition temperatures (Tgs of free films and surface morphologies observed by scanning electron microscopy (SEM of blank sustained release pellets prepared by different ratios of Eudragit®NE30D and Eudragit®L30D-55 further indicated that temperature and relative humidity (RH were the key factors when Eudragit®NE30D blended with Eudragit®L30D-55 were applied to sustained/controlled release preparations. In addition, SEM identified the surface morphologies of TSH-SR pellets before and after dissolution, which showed intact surface structure and great correlation with release curve respectively.

  5. 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.

  6. Sorption/Desorption Behavior and Mechanism of NH4(+) by Biochar as a Nitrogen Fertilizer Sustained-Release Material.

    Science.gov (United States)

    Cai, Yanxue; Qi, Hejinyan; Liu, Yujia; He, Xiaowei

    2016-06-22

    Biochar, the pyrolysis product of biomass material with limited oxygen, has the potential to increase crop production and sustained-release fertilizer, but the understanding of the reason for improving soil fertility is insufficient, especially the behavior and mechanism of ammonium sulfate. In this study, the sorption/desorption effect of NH4(+) by biochar deriving from common agricultural wastes under different preparation temperatures from 200 to 500 °C was studied and its mechanism was discussed. The results showed that biochar displayed excellent retention ability in holding NH4(+) above 90% after 21 days under 200 °C preparation temperature, and it can be deduced that the oxygen functional groups, such as carboxyl and keto group, played the primary role in adsorbing NH4(+) due to hydrogen bonding and electrostatic interaction. The sorption/desorption effect and mechanism were studied for providing an optional way to dispose of agricultural residues into biochar as a nitrogen fertilizer sustained-release material under suitable preparation temperature.

  7. Preparation of sustained-release coated particles by novel microencapsulation method using three-fluid nozzle spray drying technique.

    Science.gov (United States)

    Kondo, Keita; Niwa, Toshiyuki; Danjo, Kazumi

    2014-01-23

    We prepared sustained-release microcapsules using a three-fluid nozzle (3N) spray drying technique. The 3N has a unique, three-layered concentric structure composed of inner and outer liquid nozzles, and an outermost gas nozzle. Composite particles were prepared by spraying a drug suspension and an ethylcellulose solution via the inner and outer nozzles, respectively, and mixed at the nozzle tip (3N-PostMix). 3N-PostMix particles exhibited a corrugated surface and similar contact angles as ethylcellulose bulk, thus suggesting encapsulation with ethylcellulose, resulting in the achievement of sustained release. To investigate the microencapsulation process via this approach and its usability, methods through which the suspension and solution were sprayed separately via two of the four-fluid nozzle (4N) (4N-PostMix) and a mixture of the suspension and solution was sprayed via 3N (3N-PreMix) were used as references. It was found that 3N can obtain smaller particles than 4N. The results for contact angle and drug release corresponded, thus suggesting that 3N-PostMix particles are more effectively coated by ethylcellulose, and can achieve higher-level controlled release than 4N-PostMix particles, while 3N-PreMix particles are not encapsulated with pure ethylcellulose, leading to rapid release. This study demonstrated that the 3N spray drying technique is useful as a novel microencapsulation method. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Correlation of ibuprofen bioavailability with gastrointestinal transit by scintigraphic monitoring of 171Er-labeled sustained-release tablets

    International Nuclear Information System (INIS)

    Parr, A.F.; Beihn, R.M.; Franz, R.M.; Szpunar, G.J.; Jay, M.

    1987-01-01

    External gamma scintigraphy was used to monitor the gastrointestinal (GI) transit of radiolabeled sustained-release tablets containing 800 mg ibuprofen in eight fasted healthy volunteers. Ibuprofen serum concentrations were determined from blood samples drawn sequentially over a 24-hr period. Serum concentrations and related parameters were correlated to the position of the dosage form in the GI tract from the scintiphotos. The sustained-release tablets were radiolabeled intact utilizing a neutron activation procedure, by incorporating 0.18% of 170 Er2O3 (enriched to greater than 96% 170 Er) into the bulk formulation. After manufacture of the final dosage forms, the tablets were irradiated in a neutron flux (4.4 x 10(13) n/cm2.sec) for 2 min, converting the stable 170 Er to radioactive 171 Er (t1/2 = 7.5 hr). Each tablet contained 50 microCi of 171 Er at the time of administration. The scintigraphy studies suggested that the greatest proportion of ibuprofen was absorbed from this dosage form while the tablet was in the large bowel. The dosage forms eroded slowly in the small bowel and appeared to lose their integrity in the large bowel. In vitro studies showed only minimal effects of the neutron irradiation procedure on the dosage form performance

  9. BER-Myriant Succinic Acid Biorefinery

    Energy Technology Data Exchange (ETDEWEB)

    Shmorhun, Mark [Myriant Lake Providence, Inc., Lake Providence, LA (United States)

    2015-12-31

    Myriant Corporation (Myriant) has successfully produced the bioproduct succinic acid by the fermentation of glucose at a commercial scale operation in Lake Providence, Louisiana. The MySAB facility (Myriant Succinic Acid Biorefinery) came on stream in May 2013 and has been producing product since then. The MySAB facility is a demonstration-scale plant, capable of utilizing sorghum grits and commercially available dextrose, to ferment glucose into succinic acid. A downstream processing train has demonstrated the ability to produce an industrial, a standard and a polymer grade product. It consists of cell separation, membrane filtration, continuous chromatography, polishing to remove ionic and color bodies impurities, and final evaporation and crystallization. A by-product of the process is ammonium sulfate which is sold as a liquid fertilizer product. Since 2007 when development work began in the Woburn, Massachusetts R&D laboratories, the succinic acid bio-process has evolved through: Process development (microbiology, fermentation, and downstream) – R&D development laboratories; Piloting efforts at Fermic S.A. de C.V., Mexico City, Mexico – upstream and downstream processes; Design, construction, commissioning, and commercial production operations at the MySAB facility Additionally, Myriant became a wholly-owned subsidiary of the PTT Global Chemical Plc., Thailand, in late 2015, their investment into and support of Myriant goes back to 2011. The support of PTT Global Chemical Plc. helped to improve the upstream and downstream processes, and produce significant metric ton quantities of high quality bio-based succinic acid. The product has gone into a number of commercial markets worldwide for customer applications, development and production. The experience base gained via operations at the MySAB facility since May 2013, along with continued R&D development efforts involving Microbiology, Fermentation, and Downstream processes, at both the Woburn, Massachusetts

  10. Therapeutic effect of an injectable sustained-release sinomenine hydrochloride and sodium hyaluronate compound in a rabbit model of osteoarthritis.

    Science.gov (United States)

    Liu, Wen-Guang; Ling, Pei-Xue; Lin, Xiu-Kun; Chen, Jian-Ying; Wang, Shao-Jin; Li, Peng; Wu, Xiao-Juan; Zhao, Dong-Mei; Liu, Sheng-Hou

    2012-07-01

    While intra-articular injection of sinomenine hydrochloride has a therapeutic effect on osteoarthritis, it has a short half-life, and is thermolabile and photolabile. The aim of this research was to evaluate the sustained-release of sinomenine hydrochloride from an injectable sinomenine hydrochloride and sodium hyaluronate compound (CSSSI) and its therapeutic effect in a rabbit model of osteoarthritis following intra-articular injection. An injectable compound consisting of 1% sodium hyaluronate and 2.5% sinomenine hydrochloride was prepared and kept as the experiment group, and 2.5% sinomenine hydrochloride was prepared and kept as the control group. The cumulative mass release was measured at different time points in each group in vitro. Sixty-five male Zelanian rabbits were randomly divided into five groups: 15 (30 knees) each for the control, sodium hyaluronate, sinomenine hydrochloride, and CSSSI groups respectively, and five (10 knees) for the modeling group. Papain was injected into both knees of each rabbit for model establishment. Subsequently, 0.2 ml of the corresponding drugs was injected into the articular cavities of the remaining experiment groups, while the control group was treated with 0.2 ml normal saline. All groups were treated once a week for 4 weeks. Seven days after the last treatment, knees were anatomized to perform pathological observations and Mankin's evaluation of the synovium. Four groups were compared using the SPSS 13.0 software package. In the in vitro sustained-release experiments, 90% of the drug was released in the experiment group 360 minutes following the injection. Comparison of the Mankin's evaluations of the four groups illustrated statistical discrepancies (P sodium hyaluronate/sinomenine hydrochloride groups, statistical significance was uniformly obtained. Moreover, sodium hyaluronate and sinomenine hydrochloride treatments showed significant improvement over the modeling control (P sodium hyaluronate vs. sinomenine

  11. Microbiota-Produced Succinate Improves Glucose Homeostasis via Intestinal Gluconeogenesis

    DEFF Research Database (Denmark)

    De Vadder, Filipe; Kovatcheva-Datchary, Petia; Zitoun, Carine

    2016-01-01

    Beneficial effects of dietary fiber on glucose and energy homeostasis have long been described, focusing mostly on the production of short-chain fatty acids by the gut commensal bacteria. However, bacterial fermentation of dietary fiber also produces large amounts of succinate and, to date......, no study has focused on the role of succinate on host metabolism. Here, we fed mice a fiber-rich diet and found that succinate was the most abundant carboxylic acid in the cecum. Dietary succinate was identified as a substrate for intestinal gluconeogenesis (IGN), a process that improves glucose...

  12. Modified thermoresponsive Poloxamer 407 and chitosan sol-gels as potential sustained-release vaccine delivery systems

    DEFF Research Database (Denmark)

    Kojarunchitt, Thunjiradasiree; Baldursdottir, Stefania; Dong, Yao-Da

    2015-01-01

    Thermoresponsive, particle-loaded, Poloxamer 407 (P407)-Pluronic-R® (25R4) or chitosan-methyl cellulose (MC) formulations were developed as single-dose, sustained release vaccines. The sol-gels, loaded either with a particulate vaccine (cubosomes) or soluble antigen (ovalbumin) and adjuvants (Quil...... the chitosan-MC sol-gels sustained the release of antigen up to at least 14 days after administration. The chitosan-MC sol-gels stimulated both cellular and humoral responses. The inclusion of cubosomes in the sol-gels did not provide a definitive beneficial effect. Further analysis of the formulations...... with small-angle X-ray scattering (SAXS) revealed that while cubosomes were stable in chitosan-MC gels they were not stable in P407-25R4 formulations. The reason for the mixed response to cubosome-loaded vehicles requires more investigation, however it appears that the cubosomes did not facilitate...

  13. The effects of sustained release metofluthrin on the biting, movement, and mortality of Aedes aegypti in a domestic setting.

    Science.gov (United States)

    Rapley, Luke P; Russell, Richard C; Montgomery, Brian L; Ritchie, Scott A

    2009-07-01

    The impact of a sustained release metofluthrin emanator and an allethrin-based mosquito coil on biting, movement and mortality of female Aedes aegypti was assessed in an apartment. In the room in which the metofluthrin emanator was activated, mosquito biting counts were reduced to zero. Metofluthrin also had a spillover effect, significantly (P metofluthrin. Indeed, a significantly (P = 0.023) greater proportion of mosquitoes were found in the treated room after exposure to metofluthrin when compared with either the coil or control treatment. Furthermore, in the room treated with metofluthrin the majority of mosquitoes died and a spillover effect into the neighboring room caused greater than one-third mortality of the mosquitoes. Metofluthrin could be used to prevent dengue transmission within a household.

  14. Modified thermoresponsive Poloxamer 407 and chitosan sol-gels as potential sustained-release vaccine delivery systems.

    Science.gov (United States)

    Kojarunchitt, Thunjiradasiree; Baldursdottir, Stefania; Dong, Yao-Da; Boyd, Ben J; Rades, Thomas; Hook, Sarah

    2015-01-01

    Thermoresponsive, particle-loaded, Poloxamer 407 (P407)-Pluronic-R® (25R4) or chitosan-methyl cellulose (MC) formulations were developed as single-dose, sustained release vaccines. The sol-gels, loaded either with a particulate vaccine (cubosomes) or soluble antigen (ovalbumin) and adjuvants (Quil A and monophosphoryl lipid A), were free-flowing liquids at room temperature and formed stable gels at physiological temperatures. Rheological results showed that both systems meet the criteria of being thermoresponsive gels. The P407-25R4 sol-gels did not significantly sustain the release of antigen in vivo while the chitosan-MC sol-gels sustained the release of antigen up to at least 14 days after administration. The chitosan-MC sol-gels stimulated both cellular and humoral responses. The inclusion of cubosomes in the sol-gels did not provide a definitive beneficial effect. Further analysis of the formulations with small-angle X-ray scattering (SAXS) revealed that while cubosomes were stable in chitosan-MC gels they were not stable in P407-25R4 formulations. The reason for the mixed response to cubosome-loaded vehicles requires more investigation, however it appears that the cubosomes did not facilitate synchronous vaccine release and may in fact retard release, reducing efficacy in some cases. From these results, chitosan-MC sol-gels show potential as sustained release vaccine delivery systems, as compared to the P407-25R4 system that had a limited ability to sustain antigen release. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. High loading efficiency and sustained release of siRNA encapsulated in PLGA nanoparticles: quality by design optimization and characterization.

    Science.gov (United States)

    Cun, Dongmei; Jensen, Ditte Krohn; Maltesen, Morten Jonas; Bunker, Matthew; Whiteside, Paul; Scurr, David; Foged, Camilla; Nielsen, Hanne Mørck

    2011-01-01

    Poly(DL-lactide-co-glycolide acid) (PLGA) is an attractive polymer for delivery of biopharmaceuticals owing to its biocompatibility, biodegradability and outstanding controlled release characteristics. The purpose of this study was to understand and define optimal parameters for preparation of small interfering RNA (siRNA)-loaded PLGA nanoparticles by the double emulsion solvent evaporation method and characterize their properties. The experiments were performed according to a 2(5-1) fractional factorial design based on five independent variables: The volume ratio between the inner water phase and the oil phase, the PLGA concentration, the sonication time, the siRNA load and the amount of acetylated bovine serum albumin (Ac-BSA) in the inner water phase added to stabilize the primary emulsion. The effects on the siRNA encapsulation efficiency and the particle size were investigated. The most important factors for obtaining an encapsulation efficiency as high as 70% were the PLGA concentration and the volume ratio whereas the size was mainly affected by the PLGA concentration. The viscosity of the oil phase was increased at high PLGA concentration, which explains the improved encapsulation by stabilization of the primary emulsion and reduction of siRNA leakage to the outer water phase. Addition of Ac-BSA increased the encapsulation efficiency at low PLGA concentrations. The PLGA matrix protected siRNA against nuclease degradation, provided a burst release of surface-localized siRNA followed by a triphasic sustained release for two months. These results enable careful understanding and definition of optimal process parameters for preparation of PLGA nanoparticles encapsulating high amounts of siRNA with immediate and long-term sustained release properties. Copyright © 2010 Elsevier B.V. All rights reserved.

  16. Sustained release of piroxicam from solid lipid nanoparticle as an effective anti-inflammatory therapeutics in vivo.

    Science.gov (United States)

    Peng, Li-Hua; Wei, Wei; Shan, Ying-Hui; Chong, Yee-Song; Yu, Lian; Gao, Jian-Qing

    2017-01-01

    This study aims to investigate the solid lipid nanoparticle (SLN) as a novel vehicle for the sustained release and transdermal delivery of piroxicam, as well as to determine the anti-inflammation effect of piroxicam-loaded SLN. SLN formulation was optimized and the particle size, polydispersity index, zeta potential (ZP), encapsulation efficiency, drug release, and morphological properties were characterized. The transdermal efficiency and mechanism of the piroxicam-loaded SLNs were investigated in vitro. With the inflammation induced edema model in rat, the anti-inflammatory efficiency of piroxicam-enriched SLNs (Pir-SLNs) was evaluated. The SLN formulation was optimized as: lecithin 100 mg, glycerin monostearate 200 mg, and Tween (1%, w/w). The particle size is around 102 ± 5.2 nm with a PDI of 0.262. The ZP is 30.21 ± 2.05 mV. The prepared SLNs showed high entrapment efficiency of 87.5% for piroxicam. There is no interaction between piroxicam and the vehicle components. The presence of polymorphic form of lipid with higher drug content in the optimized Pir-SLNs enables the Pir-SLNs to release the drug with a sustained manner. Pir-SLNs with oleic acid as enhancer can radically diffuse into both the stratum corneum and dermal layer, as well as penetrate through the hair follicles and sebaceous glands with significantly higher density than the other control groups. Pir-SLNs promptly inhibited the inflammation since the 3rd hour after the treatment by decreasing the PGE 2 level. SLN was demonstrated to be a promising carrier for encapsulation and sustained release of piroxicam. Pir-SLN is a novel topical preparation with great potential for anti-inflammation application.

  17. Development and Evaluation of High Bioavailable Sustained-Release Nimodipine Tablets Prepared with Monolithic Osmotic Pump Technology.

    Science.gov (United States)

    Kong, Hua; Yu, Fanglin; Liu, Yan; Yang, Yang; Li, Mingyuan; Cheng, Xiaohui; Hu, Xiaoqin; Tang, Xuemei; Li, Zhiping; Mei, Xingguo

    2018-01-01

    Frequent administration caused by short half-life and low bioavailability due to poor solubility and low dissolution rate limit the further application of poorly water-soluble nimodipine, although several new indications have been developed. To overcome these shortcomings, sophisticated technologies had to be used since the dose of nimodipine was not too low and the addition of solubilizers could not resolve the problem of poor release. The purpose of this study was to obtain sustained and complete release of nimodipine with a simple and easily industrialized technology. The expandable monolithic osmotic pump tablets containing nimodipine combined with poloxamer 188 and carboxymethylcellulose sodium were prepared. The factors affecting drug release including the amount of solubilizing agent, expanding agent, retarding agent in core tablet and porogenic agent in semipermeable film were optimized. The release behavior was investigated both in vitro and in beagle dogs. It was proved that the anticipant release of nimodipine could be realized in vitro. The sustained and complete release of nimodipine was also realized in beagles because the mean residence time of nimodipine from the osmotic pump system was longer and Cmax was lower than those from the sustained-release tablets in market while there was no difference in AUC(0-t) of the monolithic osmotic pump tablets and the sustained release tablets in market. It was reasonable to believe that the sustained and complete release of poorly watersoluble nimodipine could be realized by using simple expandable monolithic osmotic pump technology combined with surfactant. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Local sustained-release delivery systems of the antibiofilm agent thiazolidinedione-8 for prevention of catheter-associated urinary tract infections.

    Science.gov (United States)

    Shenderovich, Julia; Feldman, Mark; Kirmayer, David; Al-Quntar, Abed; Steinberg, Doron; Lavy, Eran; Friedman, Michael

    2015-05-15

    Thiazolidinedione-8 (TZD-8) is an anti-quorum-sensing molecule that has the potential to effectively prevent catheter-associated urinary tract infections, a major healthcare challenge. Sustained-release drug-delivery systems can enhance drugs' therapeutic potential, by maintaining their therapeutic level and reducing their side effects. Varnishes for sustained release of TZD-8 based on ethylcellulose or ammonio methacrylate copolymer type A (Eudragit(®) RL) were developed. The main factors affecting release rate were found to be film thickness and presence of a hydrophilic or swellable polymer in the matrix. The release mechanism of ethylcellulose-based systems matched the Higuchi model. Selected varnishes were retained on catheters for at least 8 days. Sustained-release delivery systems of TZD-8 were active against Candida albicans biofilms. The present study demonstrates promising results en route to developing applications for the prevention of catheter-associated infections. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Citrate and succinate uptake by potato mitochondria

    International Nuclear Information System (INIS)

    Jung, D.W.; Laties, G.G.

    1979-01-01

    Potato mitochondria, in the absence of respiration, have a very low capacity for uptake by exchange with endogenous anions, taking up only 2.4 nanomoles citrate and 2.0 nanomoles succinate per milligram protein. Maximum citrate uptake of over 17 nanomoles per milligram protein occurs in the presence of inorganic phosphate, a dicarboxylic acid, and an external energy source (NADH), conditions where net anion accumulation proceeds, mediated by the interlinking of the inorganic phosphate, dicarboxylate, and tricarboxylate carriers. Maximum succinate uptake in the absence of respiratory inhibitors requires only added inorganic phosphate. Compounds which inhibit respiration (antimycin), the exchange carriers (mersalyl and benzylmalonate), or the establishment of the membrane proton motive force (uncouplers) reduce substrate accumulation. A potent inhibitor of the citrate carrier in animal mitochondria, 1,2,3-benzenetricarboxylic acid, does not inhibit citrate uptake in potato mitochondria. Citrate uptake is reduced by concurrent ADP phosphorylation and this reduction is sensitive to oligomycin. The initiation of state 3 after a 3-minute substrate state results in a reduction of the steady-state of citrate uptake by approximately 50%. Accumulation of succinate initially is inhibited by increasing sucrose concentration in the reaction medium from 50 to 400 millimolar. Limited substrate uptake is one of the factors responsible for the often observed depressed initial state 3 respiration rates in many mitochondrial preparations. Since nonlimiting levels of substrate in the matrix cannot be attained by energy-independent exchange, a dependence on respiration for adequate uptake results. Substrate limitation therefore occurs in the matrix for the period of time needed for energy-dependent accumulation of nonlimiting levels

  20. INFLUENCE OF METOPROLOL SUCCINATE ON REGULATORY AND ADAPTIVE STATUS OF PATIENTS WITH CHRONIC HEART FAILURE FUNCTIONAL CLASS I. RESULTS OF NOT COMPARATIVE STUDY

    Directory of Open Access Journals (Sweden)

    V. G. Tregubov

    2011-01-01

    Full Text Available Aim. To estimate metoprolol succinate effect on regulatory and adaptive status (RAS of patients with сhronic heart failure (CHF functional class (FC I and arterial hypertension (HT I-II stages. Material and methods. 51 patients with CHF FC I and HT I-II stage, (30 men and 21 women aged 52.6±1.4 yeas. Cardio-respiratory synchronism (CRS test, 6-minute walking test, tread-mill burden test with registration of maximal oxygen consumption, 24-hour blood pressure monitoring, echocardiography and determination of N-terminal pro-brain natriuretic peptide (NT-proBNP blood level were performed initially and after 6 months of therapy with metoprolol succinate (dose 78.1±5.7 mg/day in sustained-release presentation. Results. Metoprolol succinate therapy had no significant effect on RAS (there was no unidirectional dynamics of the basic CRS test parameters: a range of synchronization decreased significantly from 8.8±0.4 to 7.2±0.6 сardio-respiratory cycles per minute (in 18%; р<0.05, and duration of CRS development on the minimal boundary from 18.8±2.2 to 14.3±1.2 сardiocycles (in 24%; р<0,05; RAS index considerably did not change, myocardium structure, exercise tolerance and neuro-humoral activity. Metoprolol therapy only moderately improved left ventricle diastolic function. Conclusion. Metoprolol succinate therapy has no significant effect on RAS of patients with CHF FC I and HT I-II stages.

  1. Spurious cooperativity in alkylated succinic acids

    Science.gov (United States)

    Ben-Naim, A.

    1998-03-01

    The proton-proton correlation, as measured by the ratio between the second and the first dissociation constants of dibasic acid, is sometimes very large and far beyond what could be explained by electrostatic theories. We propose a novel interpretation of this phenomenon based on the idea of spurious cooperativity. The general theoretical framework underlying the onset of spurious cooperativity is developed first. The basic result is that whenever a binding (or dissociating) two-site (or more) system splits into a mixture of noninterconverting isomers the binding isotherm (or the titration curve) behaves as if it is more negatively cooperative compared with the genuine cooperativities of the individual isomer. The theory is applied to a specific system of α-α' dialkyl succinic acid. It is known that the Meso form of these alkylated derivatives show a normal correlation of the same order of magnitude as in succinic acid. On the other hand, the Racemic form of these alkylated derivatives shows anomalous strong negative correlations when the alkyl groups become large (e.g., isopropyl and tert butyl). It is shown that the theory of spurious cooperativity can explain the different behavior of the Racemic and the Meso forms, as well as the onset of anomalous strong negative correlations when the alkyl groups become large.

  2. TREATMENT OF CHRONIC HEART FAILURE: FOCUS ON METOPROLOL SUCCINATE

    Directory of Open Access Journals (Sweden)

    O. D. Ostroumova

    2012-01-01

    Full Text Available Advantages of metoprolol succinate in patients with chronic heart failure (CHF are covered. Results of MERIT-HF study are taken as the main evidences. Patterns of the metoprolol succinate use in the treatment of different categories of patients with CHF (women, the elderly , severe CHF forms, CHF with concomitant hypertension or diabetes are considered.

  3. TREATMENT OF CHRONIC HEART FAILURE: FOCUS ON METOPROLOL SUCCINATE

    Directory of Open Access Journals (Sweden)

    O. D. Ostroumova

    2015-12-01

    Full Text Available Advantages of metoprolol succinate in patients with chronic heart failure (CHF are covered. Results of MERIT-HF study are taken as the main evidences. Patterns of the metoprolol succinate use in the treatment of different categories of patients with CHF (women, the elderly , severe CHF forms, CHF with concomitant hypertension or diabetes are considered.

  4. A multicenter, randomized, double-blind, placebo-controlled, 6-month trial of bupropion hydrochloride sustained-release tablets as an aid to smoking cessation in hospital employees

    DEFF Research Database (Denmark)

    Dalsgareth, Oli Jacob; Hansen, Niels-Christian Gerner; Søes-Petersen, Ulrik

    2004-01-01

    Despite changes in smoking behavior, one-third of the Danish population continues to smoke. Many of these smokers are hospital employees. This 6-month, multicenter, parallel group, randomized, double-blind, placebo-controlled study evaluated treatment with bupropion hydrochloride sustained release...

  5. 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.

  6. 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

  7. [Sustained release of recombinant human bone morphogenetic protein-2 combined with stromal vascular fraction cells in promoting posterolateral spinal fusion in rat model].

    Science.gov (United States)

    Yuan, Wei; Zheng, Jun; Qian, Jinyu; Zhou, Xiaoxiao; Wang, Minghui; Wang, Xiuhui

    2017-07-01

    To observe the effect of stromal vascular fraction cells (SVFs) from rat fat tissue combined with sustained release of recombinant human bone morphogenetic protein-2 (rhBMP-2) in promoting the lumbar fusion in rat model. SVFs were harvested from subcutaneous fat of bilateral inguinal region of 4-month-old rat through the collagenase I digestion. The sustained release carrier was prepared via covalent bond of the rhBMP-2 and β-tricalcium phosphate (β-TCP) by the biominetic apatite coating process. The sustained release effect was measured by BCA method. Thirty-two rats were selected to establish the posterolateral lumbar fusion model and were divided into 4 groups, 8 rats each group. The decalcified bone matrix (DBX) scaffold+PBS, DBX scaffold+rhBMP-2/β-TCP sustained release carrier, DBX scaffold+SVFs, and DBX scaffold+rhBMP-2/β-TCP sustained release carrier+SVFs were implanted in groups A, B, C, and D respectively. X-ray films, manual spine palpation, and high-resolution micro-CT were used to evaluate spinal fusion at 8 weeks after operation; bone mineral density (BMD) and bone volume fraction were analyzed; the new bone formation was evaluated by HE staining and Masson's trichrome staining, osteocalcin (OCN) was detected by immunohistochemical staining. The cumulative release amount of rhBMP-2 was about 40% at 2 weeks, indicating sustained release effect of rhBMP-2; while the control group was almost released within 2 weeks. At 8 weeks, the combination of manual spine palpation, X-ray, and micro-CT evaluation showed that group D had the strongest bone formation (100%, 8/8), followed by group B (75%, 6/8), group C (37.5%, 3/8), and group A (12.5%, 1/8). Micro-CT analysis showed BMD and bone volume fraction were significantly higher in group D than groups A, B, and C ( P cells with bone matrix deposition, and an active osteogenic process similar to the mineralization of long bones in group D. The bone formation of group B was weaker than that of group D, and

  8. Single-Dose pharmacokinetics of sustained-release fampridine (Fampridine-SR) in healthy volunteers and adults with renal impairment.

    Science.gov (United States)

    Smith, William; Swan, Suzanne; Marbury, Thomas; Henney, Herbert

    2010-02-01

    Fampridine-SR is a sustained-release formulation of fampridine (4-aminopyridine), a potassium channel blocker demonstrated to improve walking ability in patients with multiple sclerosis. This study evaluated the pharmacokinetics of fampridine and its metabolites after administration of fampridine-SR 10 mg in healthy volunteers and in subjects with mild, moderate, or severe renal impairment (5 per group). Analysis of variance was used to calculate 90% confidence intervals (CIs) for the ratios (impaired/healthy) of least squares mean in maximum plasma concentration (C(max)) and area under the plasma concentration-time curve (AUC). Clearance was primarily through urinary excretion. In renally impaired subjects, fampridine plasma concentrations were consistently higher than in healthy individuals: ratios for C(max) ranged from 166.5% to 199.9% for mild and severe renal impairment, respectively. AUC(0-infinity) ratios ranged from 175.3% to 398.7%, respectively, for mild and severe renal impairment. Mean terminal disposition half-life was 6.4 hours in healthy individuals, compared with 7.4, 8.1, and 14.3 hours in patients with mild, moderate, and severe renal impairment, respectively. Regression analysis confirmed the significant relationship between creatinine clearance and extent of exposure as quantified by AUC for fampridine and its metabolites, suggesting cautious use in patients with mild renal impairment and avoidance in cases of moderate or severe renal impairment.

  9. 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.

  10. Preparation and evaluation of tamsulosin hydrochloride sustained-release pellets modified by two-layered membrane techniques

    Directory of Open Access Journals (Sweden)

    Jingmin Wang

    2015-02-01

    Full Text Available The aim of the present study was to develop tamsulosin hydrochloride sustained-release pellets using two-layered membrane techniques. Centrifugal granulator and fluidized-bed coater were employed to prepare drug-loaded pellets and to employ two-layered membrane coating respectively. The prepared pellets were evaluated for physicochemical characterization, subjected to differential scanning calorimetry (DSC and in vitro release of different pH. Different release models and scanning electron microscopy (SEM were utilized to analyze the release mechanism of Harnual® and home-made pellets. By comparing the dissolution profiles, the ratio and coating weight gain of Eudragit® NE30D and Eudragit® L30D55 which constitute the inside membrane were identified as 18:1 and 10%–11%. The coating amount of outside membrane containing Eudragit® L30D55 was determined to be 0.8%. The similarity factors (f2 of home-made capsule and commercially available product (Harnual® were above 50 in different dissolution media. DSC studies confirmed that drug and excipients had good compatibility and SEM photographs showed the similarities and differences of coating surface between Harnual® and self-made pellets before and after dissolution. According to Ritger-Peppas model, the two dosage form had different release mechanism.

  11. Design of sustained release pellets of ferrous fumarate using cow ghee as hot-melt coating agent.

    Science.gov (United States)

    Sakarkar, Dinesh M; Dorle, Avinash K; Mahajan, Nilesh Manoharrao; Sudke, Suresh Gendappa

    2013-07-01

    The objective of the present study was to design ferrous fumarate (FF) sustained release (SR) pellets using of cow ghee (CG) as an important hot-melt coating (HMC) agent. The pellets were coated by HMC technique using CG and ethyl cellulose composition by conventional coating pan without the use of spray system. FF formulated as pellets and characterized with regard to the drug content and physico-chemical properties. Stability studies were carried out on the optimized formulation for a period of 6 months at 40 ± 2°C and 75 ± 5% relative humidity. Pellets with good surface morphology and smooth texture confirmed by stereo micrographs. HMC is easy, efficient, rapid and simple method since virtually no agglomeration seen during coating. In-vitro release from pellets at a given level of coating and for present pellet size was dependent upon the physico-chemical property of the drug and mostly aqueous solubility of the drug. The selection of optimized FF formulation was confirmed by comparing percent cumulative drug release with theoretical release profile. Formulation F2 had difference factor (f 1) and similarity factor (f 2) values was found to be 5 and 66 respectively. F2 showed SR of drug for 8 h with cumulative per cent release of 98.03 ± 4.49%. Release kinetics indicates approximately zero order release pattern. HMC pellets were stable during the course of stability study. By means of HMC using CG and ethyl cellulose, SR pellets containing FF were successfully prepared.

  12. High-amylose sodium carboxymethyl starch matrices: development and characterization of tramadol hydrochloride sustained-release tablets for oral administration.

    Science.gov (United States)

    Nabais, Teresa; Leclair, Grégoire

    2014-01-01

    Substituted amylose (SA) polymers were produced from high-amylose corn starch by etherification of its hydroxyl groups with chloroacetate. Amorphous high-amylose sodium carboxymethyl starch (HASCA), the resulting SA polymer, was spray-dried to obtain an excipient (SD HASCA) with optimal binding and sustained-release (SR) properties. Tablets containing different percentages of SD HASCA and tramadol hydrochloride were produced by direct compression and evaluated for dissolution. Once-daily and twice-daily SD HASCA tablets containing two common dosages of tramadol hydrochloride (100 mg and 200 mg), a freely water-soluble drug, were successfully developed. These SR formulations presented high crushing forces, which facilitate further tablet processing and handling. When exposed to both a pH gradient simulating the pH variations through the gastrointestinal tract and a 40% ethanol medium, a very rigid gel formed progressively at the surface of the tablets providing controlled drug-release properties. These properties indicated that SD HASCA was a promising and robust excipient for oral, sustained drug-release, which may possibly minimize the likelihood of dose dumping and consequent adverse effects, even in the case of coadministration with alcohol.

  13. Co-extrusion as a processing technique to manufacture a dual sustained release fixed-dose combination product.

    Science.gov (United States)

    Vynckier, An-Katrien; Voorspoels, Jody; Remon, Jean Paul; Vervaet, Chris

    2016-05-01

    This study aimed to design a fixed-dose combination dosage form which provides a sustained release profile for both the freely water-soluble metformin HCl and the poorly soluble gliclazide, two antidiabetic compounds used to treat diabetes mellitus. Hot-melt co-extrusion was used as an innovative manufacturing technique for a pharmaceutical fixed-dose combination product. In this way, a matrix formulation that sustained metformin release could be developed, despite the high drug load in the formulation and the freely soluble nature of the drug. It was clear that co-extrusion was perfectly suited to produce a fixed-dose combination product with adequate properties for each of the incorporated APIs. A coat layer, containing at least 30% CAPA(®) 6506 as a hydrophobic polymer, was necessary to adequately sustain the release of the highly dosed freely soluble drug from the 70% metformin HCl-loaded CAPA(®) 6506 core of the co-extrudate. To obtain a complete gliclazide release over 24-h solubilization in Kollidon(®) VA, added as a second polymer to the CAPA(®) 6506 in the coat, was needed. Both active pharmaceutical ingredients (APIs), which have different physicochemical characteristics, were formulated in a single dosage form, using co-extrusion. © 2016 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology.

  14. Metal ion-assisted self-assembly of complexes for controlled and sustained release of minocycline for biomedical applications

    International Nuclear Information System (INIS)

    Zhang, Zhiling; Wang, Zhicheng; Nong, Jia; Nix, Camilla A; Zhong, Yinghui; Ji, Hai-Feng

    2015-01-01

    This study reports the development of novel drug delivery complexes self-assembled by divalent metal ion-assisted coacervation for controlled and sustained release of a hydrophilic small drug molecule minocycline hydrochloride (MH). MH is a multifaceted agent that has demonstrated therapeutic effects in infection, inflammation, tumor, as well as cardiovascular, renal, and neurological disorders due to its anti-microbial, anti-inflammatory, and cytoprotective properties. However, the inability to translate the high doses used in experimental animals to tolerable doses in human patients limits its clinical application. Localized delivery can potentially expose the diseased tissue to high concentrations of MH that systemic delivery cannot achieve, while minimizing the side effects from systemic exposure. The strong metal ion binding-assisted interaction enabled high drug entrapment and loading efficiency, and stable long term release for more than 71 d. Released MH demonstrated potent anti-biofilm, anti-inflammatory, and neuroprotective activities. Furthermore, MH release from the complexes is pH-sensitive as the chelation between minocycline and metal ions decreases with pH, allowing ‘smart’ drug release in response to the severity of pathology-induced tissue acidosis. This novel metal ion binding-mediated drug delivery mechanism can potentially be applied to other drugs that have high binding affinity for metal ions and may lead to the development of new delivery systems for a variety of drugs. (paper)

  15. Developments in human growth hormone preparations: sustained-release, prolonged half-life, novel injection devices, and alternative delivery routes

    Directory of Open Access Journals (Sweden)

    Cai Y

    2014-07-01

    Full Text Available Yunpeng Cai,1,2 Mingxin Xu,2 Minglu Yuan,2 Zhenguo Liu,1 Weien Yuan2 1Department of Neurology, Xinhua Hospital, School of Medicine, 2School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People’s Republic of China Abstract: Since the availability of recombinant human growth hormone (rhGH enabled the application of human growth hormone both in clinical and research use in the 1980s, millions of patients were prescribed a daily injection of rhGH, but noncompliance rates were high. To address the problem of noncompliance, numerous studies have been carried out, involving: sustained-release preparations, prolonged half-life derivatives, new injectors that cause less pain, and other noninvasive delivery methods such as intranasal, pulmonary and transdermal deliveries. Some accomplishments have been made and launched already, such as the Nutropin Depot® microsphere and injectors (Zomajet®, Serojet®, and NordiFlex®. Here, we provide a review of the different technologies and illustrate the key points of these studies to achieve an improved rhGH product. Keywords: intranasal, pulmonary, transdermal, microsphere, microneedle, hydrogel

  16. Preparation and Optimization of Immediate Release/Sustained Release Bilayered Tablets of Loxoprofen Using Box-Behnken Design.

    Science.gov (United States)

    Tak, Jin Wook; Gupta, Biki; Thapa, Raj Kumar; Woo, Kyu Bong; Kim, Sung Yub; Go, Toe Gyeong; Choi, Yongjoo; Choi, Ju Yeon; Jeong, Jee-Heon; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

    2017-05-01

    The aim of our current study was to characterize and optimize loxoprofen immediate release (IR)/sustained release (SR) tablet utilizing a three-factor, three-level Box-Behnken design (BBD) combined with a desirability function. The independent factors included ratio of drug in the IR layer to total drug (X 1 ), ratio of HPMC to drug in the SR layer (X 2 ), and ratio of Eudragit RL PO to drug in the SR layer (X 3 ). The dependent variables assessed were % drug released in distilled water at 30 min (Y 1 ), % drug released in pH 1.2 at 2 h (Y 2 ), and % drug released in pH 6.8 at 12 h (Y 3 ). The responses were fitted to suitable models and statistical validation was performed using analysis of variance. In addition, response surface graphs and contour plots were constructed to determine the effects of different factor level combinations on the responses. The optimized loxoprofen IR/SR tablets were successfully prepared with the determined amounts of ingredients that showed close agreement in the predicted and experimental values of tablet characterization and drug dissolution profile. Therefore, BBD can be utilized for successful optimization of loxoprofen IR/SR tablet, which can be regarded as a suitable substitute for the current marketed formulations.

  17. Application of Metal-Organic Framework Nano-MIL-100(Fe) for Sustainable Release of Doxycycline and Tetracycline.

    Science.gov (United States)

    Taherzade, Seyed Dariush; Soleimannejad, Janet; Tarlani, Aliakbar

    2017-08-06

    Nanostructures of MIL-100 were synthesized and used as a drug delivery platform for two members of the Tetracycline family. Doxycycline monohydrate (DOX) and Tetracycline hydrochloride (TC) were loaded separately on nano-MIL-100 (nanoparticles of drug@carrier were abbreviated as DOX@MIL-100 and TC@MIL-100). Characterizations were carried out using FT-IR, XRD, BET, DLS, and SEM. The FT-IR spectra revealed that the drugs were loaded into the framework of the carrier. The XRD patterns of DOX@MIL-100 and TC@MIL-100 indicated that no free DOX or TC were present. It could be concluded that the drugs are well dispersed into the pores of nano-MIL-100. The microporosity of the carrier was confirmed by BJH data. BET analysis showed a reduction in the free surface for both DOX@MIL-100 and TC@MIL-100. The release of TC and DOX was investigated, and it was revealed that MIL-100 mediated the drug solubility in water, which in turn resulted in a decrease in the release rate of TC (accelerating in DOX case) without lowering the total amount of released drug. After 48 h, 96 percent of the TC was sustain released, which is an unprecedented amount in comparison with other methods.

  18. Induction of fertile estrus in bitches using a sustained-release formulation of a GnRH agonist (leuprolide acetate).

    Science.gov (United States)

    Inaba, T; Tani, H; Gonda, M; Nakagawa, A; Ohmura, M; Mori, J; Torii, R; Tamada, H; Sawada, T

    1998-04-01

    A single subcutaneous injection of a sustained-release formulation of a potent GnRH agonist, leuprolide acetate (LA; [D-Leu6, Pro9NEt]-GnRH), was evaluated as a method of inducing fertile estrus in 12 mature anestrous and 6 prepubertal beagle bitches. The bitches were treated with microencapsulated LA (100 micrograms/kg, s.c.) at 120 or 150 d post partum, or at 1 yr of age, followed by a GnRH-analogue (fertirelin; [Pro9NEt]-GnRH, 3 micrograms/kg, i.m.) on the first day of induced estrus. Signs of estrus were seen within 10.3 +/- 0.9 d after LA administration in all bitches. The interestrous interval in 120- and 150-d post-partum bitches was shortened (P bitches. All LA treated dogs demonstrated behavioral estrus and mated. Three of 6 (50%) at 120 d post partum, 6 of 6 (100%) at 150 d post partum and 5 of 6 (83%) of prepubertal (1-yr old) bitches then became pregnant and produced a mean litter size of 4.1 +/- 0.8 pups. A normal circulating estrogen and progesterone response pattern was observed in mature anestrous bitches. A prepubertal bitch that failed to become pregnant had a similar estrogen response pattern but an insufficient progesterone profile. The results suggest that microencapsulated LA can be useful in inducing fertile estrus in the domestic dogs.

  19. Pharmacokinetics and Paw Withdrawal Pressure in Female Guinea Pigs (Cavia porcellus) Treated with Sustained-Release Buprenorphine and Buprenorphine Hydrochloride.

    Science.gov (United States)

    Smith, Brian J; Wegenast, Daniel J; Hansen, Ryan J; Hess, Ann M; Kendall, Lon V

    2016-11-01

    Providing appropriate analgesia is essential in minimizing pain and maintaining optimal animal care and welfare in laboratory animals. Guinea pigs are common animal models in biomedical research, often requiring analgesic support. Here we evaluated the pharmacokinetics and efficacy of a sustained-release formulation of buprenorphine (Bup-SR) in this species. Guinea pigs (n = 7 each group) received either Bup-HCl (0.05 mg/kg BID for 3 d) or Bup-SR (0.3 mg/kg once). Plasma collection and measurement of paw-withdrawal pressure (PWP) was conducted at 0, 1, 3, 6, 12, 26, 48, and 72 h after treatment. Plasma levels of Bup-HCl peaked at 2331 pg/mL at 1 h after administration and declined to 165 pg/mL by 12 h. Plasma concentrations of Bup-SR peaked at 1344 pg/mL at 26 h after administration and declined to 429 pg/mL by 48 h. The PWP of the Bup-HCltreated guinea pigs peaked at 674 g at 1 h and declined to 402 g at 6 h, whereas that of Bup-SRtreated guinea pigs at 1 h was 361 g, 555 g at 6 h (significantly higher than that after Bup-HCl), and peaked at 680 g at 12 h. The PWP of both treatments was similar from 24 to 72 h and ranged from 348 to 450 g. The plasma concentration and PWP showed good correlation. These results suggest that Bup-SR provides consistent analgesia equivalent to that of Bup-HCl for a prolonged period of time and that Bup-SR is an alternative method of analgesia in guinea pigs.

  20. 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

  1. Sustained release of neurotrophin-3 via calcium phosphate-coated sutures promotes axonal regeneration after spinal cord injury.

    Science.gov (United States)

    Hanna, Amgad; Thompson, Daniel L; Hellenbrand, Daniel J; Lee, Jae-Sung; Madura, Casey J; Wesley, Meredith G; Dillon, Natalie J; Sharma, Tapan; Enright, Connor J; Murphy, William L

    2016-07-01

    Because of the dynamics of spinal cord injury (SCI), the optimal treatment will almost certainly be a combination approach to control the environment and promote axonal growth. This study uses peripheral nerve grafts (PNGs) as scaffolds for axonal growth while delivering neurotrophin-3 (NT-3) via calcium phosphate (CaP) coatings on surgical sutures. CaP coating was grown on sutures, and NT-3 binding and release were characterized in vitro. Then, the NT-3-loaded sutures were tested in a complete SCI model. Rats were analyzed for functional improvement and axonal growth into the grafts. The CaP-coated sutures exhibited a burst release of NT-3, followed by a sustained release for at least 20 days. Functionally, the rats with PNGs + NT-3-loaded sutures and the rats treated with PNGs scored significantly higher than controls on day 56 postoperatively. However, functional scores in rats treated with PNGs + NT-3-loaded suture were not significantly different from those of rats treated with PNGs alone. Cholera toxin subunit B (CTB) labeling rostral to the graft was not observed in any controls, but CTB labeling rostral to the graft was observed in almost all rats that had had a PNG. Neurofilament labeling on transverse sections of the graft revealed that the rats treated with the NT-3-loaded sutures had significantly more axons per graft than rats treated with an NT-3 injection and rats without NT-3. These data demonstrate that PNGs serve as scaffolds for axonal growth after SCI and that CaP-coated sutures can efficiently release NT-3 to increase axonal regeneration. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. Attitude and perception of patients and health care practitioners toward oral sustained release dosage forms in Palestine.

    Science.gov (United States)

    Zaid, Abdel Naser

    2010-10-01

    To evaluate the knowledge of health professionals in Palestine regarding the advantages of sustained release dosage forms (SRDFs) over conventional therapy. Data were gathered from a questionnaire that was handed out to community pharmacists, physicians and patients. Pharmaceutical industry decision makers were enrolled in this study. Data were analyzed using the SPSS. Pharmacists (92.9%) and 89.2% of physicians thought that SRDFs improve patient compliance. 81.5% of pharmacists and 77% of physicians were in agreement regarding the capacity of SRDFs to maintain therapeutic activity during night. In this study, 81.5% of pharmacists and 81% of physicians believed that SRDFs provide further advantage with psychiatric patients who forget to take their medications. Pharmacists (63.1%) and only 63.5% of physicians believed that SRDFs yield a time saving for nurses who use SRDFs in hospital. Only 45.3% of physicians and 43.4% of pharmacists thought that SRDFs result in cost saving due to better disease management. Pharmacists (95.2%) and 95.9% of physicians agreed that SRDFs could be the right choice for faith patient's who must take their medication during the month of Ramadan. Pharmacists (66.7%) and 50.7% of physicians recognize that SRDFs may be unsafe if they are improperly formulated. Bad swallowing was also recognized as inconveniences of SRDFs by 67.9% of pharmacists and 57.3% of physicians. Given the above advantages, 75% of patients showed economical problems regarding the cost of the single course therapy of SRDFs and 100% of interviewed patients were enthusiastic about the advantage of SRDFs during Ramadan. The advantages of SRDFs are not completely understood by Palestinian health professionals. Pharmaceutical industries should pay more attention to the development and advertising of SRDFs due to the valuable advantages of these dosage forms.

  3. Bypassing the EPR effect with a nanomedicine harboring a sustained-release function allows better tumor control.

    Science.gov (United States)

    Shen, Yao An; Shyu, Ing Luen; Lu, Maggie; He, Chun Lin; Hsu, Yen Mei; Liang, Hsiang Fa; Liu, Chih Peng; Liu, Ren Shyan; Shen, Biing Jiun; Wei, Yau Huei; Chuang, Chi Mu

    2015-01-01

    The current enhanced permeability and retention (EPR)-based approved nanomedicines have had little impact in terms of prolongation of overall survival in patients with cancer. For example, the two Phase III trials comparing Doxil(®), the first nanomedicine approved by the US Food and Drug Administration, with free doxorubicin did not find an actual translation of the EPR effect into a statistically significant increase in overall survival but did show less cardiotoxicity. In the current work, we used a two-factor factorial experimental design with intraperitoneal versus intravenous delivery and nanomedicine versus free drug as factors to test our hypothesis that regional (intraperitoneal) delivery of nanomedicine may better increase survival when compared with systemic delivery. In this study, we demonstrate that bypassing, rather than exploiting, the EPR effect via intraperitoneal delivery of nanomedicine harboring a sustained-release function demonstrates dual pharmacokinetic advantages, producing more efficient tumor control and suppressing the expression of stemness markers, epithelial-mesenchymal transition, angiogenesis signals, and multidrug resistance in the tumor microenvironment. Metastases to vital organs (eg, lung, liver, and lymphatic system) are also better controlled by intraperitoneal delivery of nanomedicine than by standard systemic delivery of the corresponding free drug. Moreover, the intraperitoneal delivery of nanomedicine has the potential to replace hyperthermic intraperitoneal chemotherapy because it shows equal efficacy and lower toxicity. In terms of efficacy, exploiting the EPR effect may not be the best approach for developing a nanomedicine. Because intraperitoneal chemotherapy is a type of regional chemotherapy, the pharmaceutical industry might consider the regional delivery of nanomedicine as a valid alternative pathway to develop their nanomedicine(s) with the goal of better tumor control in the future.

  4. Use of ibuprofen sustained release for treating osteoarthritic pain: findings from 15 general medical practices in Egypt

    Directory of Open Access Journals (Sweden)

    Khalifa N

    2014-05-01

    Full Text Available Nabil Khalifa,1 Timour El-Husseini,1 Ahmed Morrah,2 Elshenawy Mostafa,3 Hesham Hamoud41Department of Orthopedic Surgery, Ain Shams University, Cairo, Egypt; 2Department of Orthopedic Surgery, Cairo University, Cairo, Egypt; 3Department of Orthopedic Surgery, Mansoura University, Mansoura, Egypt; 4Department of Rheumatology, Azhar University, Cairo, EgyptPurpose: Ibuprofen sustained release (SR has been shown to provide effective symptomatic pain relief in chronic arthritic conditions such as osteoarthritis in European and US patient populations. Few studies have been conducted in other patient populations. A 4-week prospective multicenter open-label observational study was designed to explore and describe the combined effect of ibuprofen SR and standard medical care in patients suffering from osteoarthritis in 15 general medical practices in Egypt.Patients and methods: In total, 519 patients were prescribed ibuprofen SR 2 ×800 mg once daily for 4 weeks.Results: Ibuprofen SR combined with standard medical care significantly improved day and night pain, with 99.4% of the patients reporting improvement. The treatment reduced the symptom severity of joint tenderness/stiffness and the duration of morning stiffness, and allowed more patients to carry out normal activities. Overall compliance with the prescribed ibuprofen SR regimen was 98.6%. Ibuprofen SR was generally well tolerated with no serious adverse events reported during the study. There was no increase in blood pressure or heart rate.Conclusion: The combined treatment provided effective relief of pain in patients with osteoarthritis in a large real-life general medical practice setting in Egypt. Owing to its convenient once-daily dosing regimen, ibuprofen SR may enhance patient compliance.Keywords: chronic arthritis, compliance, pain score, real-life

  5. Structural and magnetic studies on copper succinate dihydrate ...

    Indian Academy of Sciences (India)

    M P BINITHA

    2017-08-21

    Aug 21, 2017 ... rials chemistry, heterogeneous catalysis, gas storage, polymer magnets, etc. ... super exchange interactions among copper atoms through bridging .... Thus, these two water molecules in the structure of copper succinate are.

  6. Succinic acid production by escherichia coli under anaerobic fermentation

    International Nuclear Information System (INIS)

    El Shafey, H.M.; Meleigy, S.A.

    2009-01-01

    The effect of alteration of growth conditions, addition of different sodium salts, and irradiation by gamma rays on succinic acid production by E. coli was studied. Twenty one isolates were obtained from buffalo's rumen, and anaerobic screening of the isolated bacterial strains showed the abilities of seventeen strains to produce succinic acid. The two bacterial strains having highest succinic acid production were identified as escherichia coli SP9 and SP16, and were selected for further studies. Results showed that growth conditions yielded highest succinic acid production for the two isolates were: 72 hours incubation, 37 degree c incubation temperature, initial ph of the fermentation medium 6.0,and 3% (v/v)inoculum size. Addition of 5 mm of nine different sodium salts to the fermentation medium showed stimulating effect on succinic acid production of the nine tried sodium salts, sodium carbonate was found to have the highest enhancing effect, especially if used at 15 mm concentration. Gamma irradiation doses tried were in the range of (0.25-1.50 kGy). An enhancing effect on succinic acid production was shown in the range of 0.25-0.75 kGy with a maximal production at 0.75 kGy (giving 8.36% increase) for e.coli SP9, and in the range of 0.25-1.00 kGy with a maximal production at 1.0 kGy (7.60% increase) for e.coli SP16. higher gamma doses led to a decrease in the enhancing effect. An overall increase in the succinic acid yield of 79.45% and 94.26% for e. coli SP9 and SP16, respectively, was achieved in implicating all optimized factors for succinic acid production in one time

  7. The Succinated Proteome of FH-Mutant Tumours

    Directory of Open Access Journals (Sweden)

    Ming Yang

    2014-08-01

    Full Text Available Inherited mutations in the Krebs cycle enzyme fumarate hydratase (FH predispose to hereditary leiomyomatosis and renal cell cancer (HLRCC. Loss of FH activity in HLRCC tumours causes accumulation of the Krebs cycle intermediate fumarate to high levels, which may act as an oncometabolite through various, but not necessarily mutually exclusive, mechanisms. One such mechanism, succination, is an irreversible non-enzymatic modification of cysteine residues by fumarate, to form S-(2-succinocysteine (2SC. Previous studies have demonstrated that succination of proteins including glyceraldehyde 3-phosphate dehydrogenase (GAPDH, kelch-like ECH-associated protein 1 (KEAP1 and mitochondrial aconitase (ACO2 can have profound effects on cellular metabolism. Furthermore, immunostaining for 2SC is a sensitive and specific biomarker for HLRCC tumours. Here, we performed a proteomic screen on an FH-mutant tumour and two HLRCC-derived cancer cell lines and identified 60 proteins where one or more cysteine residues were succinated; 10 of which were succinated at cysteine residues either predicted, or experimentally proven, to be functionally significant. Bioinformatic enrichment analyses identified most succinated targets to be involved in redox signaling. To our knowledge, this is the first proteomic-based succination screen performed in human tumours and cancer-derived cells and has identified novel 2SC targets that may be relevant to the pathogenesis of HLRCC.

  8. [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.

  9. Novel Fabrication of Biodegradable Superabsorbent Microspheres with Diffusion Barrier through Thermo-Chemical Modification and Their Potential Agriculture Applications for Water Holding and Sustained Release of Fertilizer.

    Science.gov (United States)

    Feng, Diejing; Bai, Bo; Wang, Honglun; Suo, Yourui

    2017-07-26

    Synergistic utilization of water and fertilizer has vital contribution to the modern production of agriculture. This work reports on a simple and facile strategy to prepare biodegradable yeast/sodium alginate/poly(vinyl alcohol) superabsorbent microspheres with a diffusion barrier merit by thermo-chemical modification route. The integrated performances, including water absorbency, water retention, water evaporation ratio, leaching loss control, sustained-release behaviors, and degradation in soil, were systematically investigated. The results revealed that the modified microspheres were a triumphant water and fertilizer manager to effectively hold water and control the unexpected leakage of fertilizer for sustained release. Therefore, this work provides a promising approach to ameliorate the utilization efficiency of water and fertilizer in potential agriculture applications.

  10. Application of 5-Fluorouracil-Polycaprolactone Sustained-Release Film in Ahmed Glaucoma Valve Implantation Inhibits Postoperative Bleb Scarring in Rabbit Eyes.

    Science.gov (United States)

    Bi, Xiu-Zeng; Pan, Wei-Hua; Yu, Xin-Ping; Song, Zong-Ming; Ren, Zeng-Jin; Sun, Min; Li, Cong-Hui; Nan, Kai-Hui

    2015-01-01

    This study was designed to investigate whether 5-fluorouracil (5-Fu)-polycaprolactone sustained-release film in Ahmed glaucoma valve implantation inhibits postoperative bleb scarring in rabbit eyes. Eighteen New Zealand white rabbits were randomly divided into three groups (A, B and C; n = 6 per group). Group A received combined 5-Fu-polycaprolactone sustained-release film application and Ahmed glaucoma valve implantation, group B received local infiltration of 5-Fu and Ahmed glaucoma valve implantation, and group C received Ahmed glaucoma valve implantation. Postoperative observations were made of the anterior segment, intraocular pressure, central anterior chamber depth, blebs, drainage tube, and accompanying ciliary body detachment. The pathology of the blebs and surrounding tissues were observed at month 3 postoperatively. We revealed that the 5-Fu-polycaprolactone sustained-release film maintained a release concentration range of 13.7 ± 0.12 to 37.41 ± 0.47 μg/ml over three months in vitro. Postoperatively, diffuse blebs with ridges were found in all eyes in group A, two blebs were observed in group B, and no bleb formation was present in group C. The postoperative central anterior chamber depth in group A was significantly less than that of the other two groups. The postoperative intraocular pressure of group A stabilized at 6.33-8.67 mmHg, whereas that of group C gradually remained at 7.55-10.02 mmHg. The histopathology showed that the fibrous tissue thickness of the blebs in group A was significantly thinner than that of the other groups. We conclude that the 5-Fu-polycaprolactone sustained-release film had a sustained drug release effect, which promoted the inhibition of bleb scarring after Ahmed glaucoma valve implantation.

  11. Development of a Sustainable Release System for a Ranibizumab Biosimilar Using Poly(lactic-co-glycolic acid) Biodegradable Polymer-Based Microparticles as a Platform.

    Science.gov (United States)

    Tanetsugu, Yusuke; Tagami, Tatsuaki; Terukina, Takayuki; Ogawa, Takaya; Ohta, Masato; Ozeki, Tetsuya

    2017-01-01

    Ranibizumab is a humanized monoclonal antibody fragment against vascular endothelial growth factor (VEGF)-A and is widely used to treat age-related macular degeneration (AMD) caused by angiogenesis. Ranibizumab has a short half-life in the eye due to its low molecular weight and susceptibility to proteolysis. Monthly intravitreal injection of a large amount of ranibizumab formulation is a burden for both patients and medical staff. We therefore sought to develop a sustainable release system for treating the eye with ranibizumab using a drug carrier. A ranibizumab biosimilar (RB) was incorporated into microparticles of poly(lactic-co-glycolic acid) (PLGA) biodegradable polymer. Ranibizumab was sustainably released from PLGA microparticles (80+% after 3 weeks). Assay of tube formation by endothelial cells indicated that RB released from PLGA microparticles inhibited VEGF-induced tube formation and this tendency was confirmed by a cell proliferation assay. These results indicate that RB-loaded PLGA microparticles are useful for sustainable RB release and suggest the utility of intraocular sustainable release systems for delivering RB site-specifically to AMD patients.

  12. In situ depot comprising phase-change materials that can sustainably release a gasotransmitter H2S to treat diabetic wounds.

    Science.gov (United States)

    Lin, Wei-Chih; Huang, Chieh-Cheng; Lin, Shu-Jyuan; Li, Meng-Ju; Chang, Yen; Lin, Yu-Jung; Wan, Wei-Lin; Shih, Po-Chien; Sung, Hsing-Wen

    2017-11-01

    Patients with diabetes mellitus are prone to develop refractory wounds. They exhibit reduced synthesis and levels of circulating hydrogen sulfide (H 2 S), which is an ephemeral gaseous molecule. Physiologically, H 2 S is an endogenous gasotransmitter with multiple biological functions. An emulsion method is utilized to prepare a microparticle system that comprises phase-change materials with a nearly constant temperature of phase transitions to encapsulate sodium hydrosulfide (NaHS), a highly water-labile H 2 S donor. An emulsion technique that can minimize the loss of water-labile active compounds during emulsification must be developed. The as-prepared microparticles (NaHS@MPs) provide an in situ depot for the sustained release of exogenous H 2 S under physiological conditions. The sustained release of H 2 S promotes several cell behaviors, including epidermal/endothelial cell proliferation and migration, as well as angiogenesis, by extending the activation of cellular ERK1/2 and p38, accelerating the healing of full-thickness wounds in diabetic mice. These experimental results reveal the strong potential of NaHS@MPs for the sustained release of H 2 S for the treatment of diabetic wounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Formulation development and optimization of sustained release matrix tablet of Itopride HCl by response surface methodology and its evaluation of release kinetics.

    Science.gov (United States)

    Bose, Anirbandeep; Wong, Tin Wui; Singh, Navjot

    2013-04-01

    The objective of this present investigation was to develop and formulate sustained release (SR) matrix tablets of Itopride HCl, by using different polymer combinations and fillers, to optimize by Central Composite Design response surface methodology for different drug release variables and to evaluate drug release pattern of the optimized product. Sustained release matrix tablets of various combinations were prepared with cellulose-based polymers: hydroxy propyl methyl cellulose (HPMC) and polyvinyl pyrolidine (pvp) and lactose as fillers. Study of pre-compression and post-compression parameters facilitated the screening of a formulation with best characteristics that underwent here optimization study by response surface methodology (Central Composite Design). The optimized tablet was further subjected to scanning electron microscopy to reveal its release pattern. The in vitro study revealed that combining of HPMC K100M (24.65 MG) with pvp(20 mg)and use of LACTOSE as filler sustained the action more than 12 h. The developed sustained release matrix tablet of improved efficacy can perform therapeutically better than a conventional tablet.

  14. Pharmacokinetics and Adverse Effects of 3 Sustained-release Buprenorphine Dosages in Healthy Guinea Pigs (Cavia porcellus).

    Science.gov (United States)

    Zanetti, Andrea S; Putta, Sumanth K; Casebolt, Donald B; Louie, Stan G

    2017-11-01

    In guinea pigs, studies addressing the efficacy, safety, and pharmacokinetic profiles of different sustained-release buprenorphine (SRB) formulations are still in their infancy. Here we assessed the pharmacokinetic profiles of 3 SRB dosages (SR-LAB, ZooPharm; SRBLow, 0.15 mg/kg; SRBMedium, 0.3 mg/kg; and SRBHigh, 0.6 mg/kg) for 72 h after a single subcutaneous administration to 8 (4 male and 4 female) healthy guinea pigs. Body weight, fecal output, and cortisol levels were also monitored and the results compared with those of the sham group. Within the first h after administration, the maximal plasma concentration (Cmax) of the drug was 64.3 ± 9.2 ng/mL (males) and 71.3 ± 3.7 ng/mL (females) in the SRBHigh group; 11.5 ± 3.2 ng/mL (males) and 6.9 ± 0.9 ng/mL (females) in the SRBMedium group; and 2.3 ± 0.8 ng/mL (males) and 2.0 ± 0.5 ng/mL (females) in the SRBLow group. After 72 h, therapeutic levels of the drug (>1 ng/mL) were observed only in guinea pigs treated with SRBHigh (both sexes) and males treated with SRBMediu cm. Fecal output (quantity and distribution) and body weight were significantly lower in the SRB groups as compared with the sham group, and with the SRBHigh group showing larger reductions. Baseline levels of serum cortisol in healthy females (1440 ± 106 ng/mL) were significantly greater than in males (550 ± 66 ng/mL). But, independent of the sex, SRB administration significantly reduced those levels. In conclusion, the data indicate that all 3 SRB dosages can be safely used in guinea pigs. However, therapeutic levels of the drug were observed for at least 48 h only guinea pigs treated with SRBHigh and SRBMedium. Further investigation is needed to determine if these dosages can alleviate pain in guinea pigs.

  15. Sustained release of growth hormone and sodium nitrite from biomimetic collagen coating immobilized on silicone tubes improves endothelialization.

    Science.gov (United States)

    Salehi-Nik, Nasim; Malaie-Balasi, Zahra; Amoabediny, Ghassem; Banikarimi, Seyedeh Parnian; Zandieh-Doulabi, Behrouz; Klein-Nulend, Jenneke

    2017-08-01

    Biocompatibility of biomedical devices can be improved by endothelialization of blood-contacting parts mimicking the vascular endothelium's function. Improved endothelialization might be obtained by using biomimetic coatings that allow local sustained release of biologically active molecules, e.g. anti-thrombotic and growth-inducing agents, from nanoliposomes. We aimed to test whether incorporation of growth-inducing nanoliposomal growth hormone (nGH) and anti-thrombotic nanoliposomal sodium nitrite (nNitrite) into collagen coating of silicone tubes enhances endothelialization by stimulating endothelial cell proliferation and inhibiting platelet adhesion. Collagen coating stably immobilized on acrylic acid-grafted silicone tubes decreased the water contact angle from 102° to 56°. Incorporation of 50 or 500nmol/ml nNitrite and 100 or 1000ng/ml nGH into collagen coating decreased the water contact angle further to 48°. After 120h incubation, 58% nitrite and 22% GH of the initial amount of sodium nitrite and GH in nanoliposomes were gradually released from the nNitrite-nGH-collagen coating. Endothelial cell number was increased after surface coating of silicone tubes with collagen by 1.6-fold, and with nNitrite-nGH-collagen conjugate by 1.8-3.9-fold after 2days. After 6days, endothelial cell confluency in the absence of surface coating was 22%, with collagen coating 74%, and with nNitrite-nGH-collagen conjugate coating 83-119%. In the absence of endothelial cells, platelet adhesion was stimulated after collagen coating by 1.3-fold, but inhibited after nNitrite-nGH-collagen conjugate coating by 1.6-3.7-fold. The release of anti-thrombotic prostaglandin I 2 from endothelial cells was stimulated after nNitrite-nGH-collagen conjugate coating by 1.7-2.2-fold compared with collagen coating. Our data shows improved endothelialization and blood compatibility using nNitrite-nGH-collagen conjugate coating on silicone tubes suggesting that these coatings are highly suitable

  16. Preparation and characterization of cross-linked excipient of coprocessed xanthan gum-acacia gum as matrix for sustained release tablets

    Science.gov (United States)

    Surini, Silvia; Wati, Dina Risma; Syahdi, Rezi Riadhi

    2018-02-01

    Sustained release tablet is solid dosage form which is designed to release drugs slowly in the body. This research was intended to prepare and characterize the cross-linked excipients of co-processed xanthan gum-acacia gum (CL-Co-XGGA) as matrices for sustained release tablets with gliclazide as a model drug. CL-Co-XGGA excipients were cross-linked materials of co-processed excipients of xanthan gum-acacia gum (Co-XGGA) using sodium trimetaphosphate. Co-processed excipients of xanthan gum-acacia gum were prepared in the ratio of each excipient 1:2, 1:1 and 2:1. Co-XGGA and CL-Co-XGGA excipients were characterized physically, chemically and functionally. Then, the sustained release (SR) tablets were formulated by wet granulation method using CL-Co-XGGA excipients as matrices. Also, the dissolution study of the gliclazide SR tablets was carried out in phosphate buffer medium pH 7,4 containing sodium lauryl sulphate 0.2% for 12 hours. The results showed that the degree of substitution (DS) of CL-Co-XGGA 1:2, 1:1, 2:1 excipients were respectively 0.067, 0.082 and 0.08. Besides that, the excipients gel strengths were 14.03, 17.27 and 20,70 gF, respectively. The cross-linked excipients had improved flow properties and swelling capability compared to the Co-XGGA excipients. The results of the gliclazide SR tablets evaluations showed that all tablets were passed all tablet requirements. Moreover, the gliclazide release from SR tablets F1 - F6 revealed the sustained release profile, which was following zero order kinetics (F1, F2, F3, F6) and Higuchi kinetics (F4 and F5). It could be concluded that the obtained CL-Co-XGGA excipients might be used as matrices for sustained release tablets and could retard drug release up to 8 until 32 hours.

  17. Effect of Hydroxyl Monomers on the Enzymatic Degradation of Poly(ethylene succinate, Poly(butylene succinate, and Poly(hexylene succinate

    Directory of Open Access Journals (Sweden)

    Zhenhui Bai

    2018-01-01

    Full Text Available Poly(ethylene succinate (PES, poly(butylene succinate (PBS, and poly(hexylene succinate (PHS, were synthesized using succinic acid and different dihydric alcohols as materials. Enzymatic degradability by cutinase of the three kinds of polyesters was studied, as well as their solid-state properties. The biodegradation behavior relied heavily on the distance between ester groups, crystallinity, and the hydrophilicity-hydrophobicity balance of polyester surfaces. The weight loss through degradation of the three kinds of polyesters with different hydroxyl monomers took place in the order PHS > PBS > PES. The degradation behavior of the polyesters before and after degradation was analyzed by scanning electron microscopy, differential scanning calorimetry, powder X-ray diffraction, Fourier transform infrared spectroscopy, gel permeation chromatography, and thermogravimetric analysis. The decrease in relative intensity at 1800–1650 estedpolyesters were degraded simultaneously. The frequencies of the crystalline and amorphous bands were almost identical before and after degradation. Thus, enzymatic degradation did not change the crystalline structure but destroyed it, and the degree of crystallinity markedly decreased. The molecular weight and polydispersity index only changed slightly. The thermal stability of the three kinds of polyesters decreased during enzymatic degradation.

  18. MODIFIKASI ASAM SUKSINAT - GELOMBANG PENDEK UNTUK\tPRODUKSI TAPIOKA SUKSINAT Succinic Acid-Microwave Modification to Produce Succinic Tapioca

    Directory of Open Access Journals (Sweden)

    Heny Herawati

    2012-05-01

    Full Text Available Indonesia as tropical country has great cassava potency. The great chance of cassava product development could be increased its added value through modified tapioca processing. One of modified starch that could be implemented as a food additive is succinic starch. The tapioca succinilation processed through combination process of reacting tapioca with succinic acid and microwave treatment. The research method was conducted by factorial design with 3 factors: substrate concentration (30 %, 40 %, succinic acid concentration (1 %, 3 %, 5 %, and drying method (oven and microwave. Succinic tapioca was analyzed both physical and chemical characteristics, while optimal product was fur- ther analyzed for nutrition contents and surface microstructure using SEM. Succinic acid and microwave modification influenced to the physical and chemical succinic tapioca, except ash content. The highest substitution degree value was 0.929 which was obtained by combination of substrate concentration 40 %, succinic acid added 5 % and microwave processed. The change of granule size was not significant, just the distribution among granule correlated with the tapi- oca modification. The succinic tapioca granule size ranged 5.35 µm until 17.20 µm with average 11.15 µm. Succinic tapioca characteristic hopefully could be advanced food implementation. ABSTRAK Indonesia merupakan negara tropis yang memiliki potensi produksi ubi kayu yang cukup besar. Peluang pengem- bangan produk berbasis ubi kayu di Indonesia masih cukup besar diantaranya yaitu peningkatan nilai tambah ubi kayu melalui proses modifikasi tapioka. Salah satu potensi pati termodifikasi yang dapat dipergunakan untuk bahan tambahan makanan yaitu pati suksinat. Pada penelitian ini proses suksinilasi tapioka dilakukan dengan cara mereak- sikan asam suksinat yang dikombinasikan dengan mempergunakan microwave. Metodologi penelitian yang dilakukan menggunakan rancangan faktorial dengan 3 faktor, yaitu konsentrasi

  19. Crystallization behavior of partially miscible biodegradable poly(butylene succinate)/poly(ethylene succinate) blends

    International Nuclear Information System (INIS)

    He, Yi-Song; Zeng, Jian-Bing; Li, Shao-Long; Wang, Yu-Zhong

    2012-01-01

    Graphical abstract: Crystallization rate of PBS in the blends decreased first and then increased with increase in PES content, and that of PES increased steadily with increase in PBS content. The rich component formed a continuous phase and the other formed a dispersed phase of the blend. Crystal structures of PBS and PES were almost unchanged after blending with each other. Highlights: ► PBS/PES blend systems are partially miscible. ► Blending did not change the crystallization mechanisms of PBS and PES not affects the crystallization rates. ► The rich component formed the continuous phase while the poor component formed the dispersed phase of the blends. ► Crystal structures of PBS and PES were almost unchanged after blending with each other. - Abstract: Biodegradable blend of poly(butylene succinate) (PBS) and poly(ethylene succinate) (PES) was prepared by solution blending and casting method with chloroform as a mutual solvent. Miscibility of the blends was investigated by differential scanning calorimetry (DSC). The results indicated that PBS and PES were partially miscible. Crystallization kinetics, crystalline morphology and crystal structure of the blends were studied by DSC, polarized optical microscope (POM), and wide-angle X-ray diffraction (WAXD), respectively. Nonisothermal and isothermal crystallization kinetics suggested that the crystallizability of PBS in the blends decreased first and then increased with increase in PES content, and that of PES increased steadily with increase in PBS content. POM observation illustrated that the rich component formed a continuous phase and the other formed a dispersed phase. The results of WAXD indicated that the crystal structures of PBS and PES were almost unchanged before and after blending, since the positions of characteristic diffraction peaks of both components remain almost unchanged.

  20. Mutant E. coli strain with increased succinic acid production

    Science.gov (United States)

    Donnelly, Mark; Millard, Cynthia S.; Stols, Lucy

    2001-09-25

    A method for isolating succinic acid producing bacteria is provided comprising increasing the biomass of an organism which lacks the ability to catabolize pyruvate, and then subjecting the biomass to glucose-rich medium in an anaerobic environment to enable pyruvate-catabolizing mutants to grow. The invention also provides for a mutant that produces high amounts of succinic acid, which has been derived from a parent which lacked the genes for pyruvate formate lyase and lactate dehydrogenase, and which belongs to the E.coli Group of Bacteria.

  1. Mutant E. coli strain with increased succinic acid production

    Science.gov (United States)

    Donnelly, Mark; Millard, Cynthia S.; Stols, Lucy

    1998-01-01

    A method for isolating succinic acid producing bacteria is provided comprising increasing the biomass of an organism which lacks the ability to catabolize pyruvate, and then subjecting the biomass to glucose-rich medium in an anaerobic environment to enable pyruvate-catabolizing mutants to grow. The invention also provides for a mutant that produces high amounts of succinic acid, which as been derived from a parent which lacked the genes for pyruvate formate lyase and lactate dehydrogenase, and which belongs to the E.coli Group of Bacteria.

  2. Biophysical properties of phenyl succinic acid derivatised hyaluronic acid

    DEFF Research Database (Denmark)

    Neves-Petersen, Maria Teresa; Klitgaard, Søren; Skovsen, Esben

    2010-01-01

    Modification of hyaluronic acid (HA) with aryl succinic anhydrides results in new biomedical properties of HA as compared to non-modified HA, such as more efficient skin penetration, stronger binding to the skin, and the ability to blend with hydrophobic materials. In the present study, hyaluronic...... acid has been derivatised with the anhydride form of phenyl succinic acid (PheSA). The fluorescence of PheSA was efficiently quenched by the HA matrix. HA also acted as a singlet oxygen scavenger. Fluorescence lifetime(s) of PheSA in solution and when attached to the HA matrix has been monitored...

  3. An efficient method for synthesis of succinate-based MMP inhibitors.

    Science.gov (United States)

    Sibi, Mukund P; Hasegawa, Hikaru

    2002-10-03

    A differentially protected fumarate undergoes radical addition followed by allylstannane trapping to provide disubstituted succinates in good yields and high anti diastereoselectivity. The conversion of the succinate to a known MMP inhibitor has been accomplished. [reaction: see text

  4. SMALL SCALE PREPARATION OF C14 LABELED SUCCINIC, MALIC, FUMARICAND TARTARIC ACIDS

    Energy Technology Data Exchange (ETDEWEB)

    Jorgensen, E.C.; Bassham, J.A.; Calvin, M.; Tolbert, B.M.

    1951-06-12

    The directions for preparing the following acids from labeled acetic acid on a 1 to 20 millimole scale is presented: Succinic acid, malic acid, fumaric acid and tartaric acid. Two methods for preparing the succinic acid are detailed.

  5. 78 FR 76567 - Tall Oil, Polymer With Polyethylene Glycol and Succinic Anhydride Monopolyisobutylene Derivs...

    Science.gov (United States)

    2013-12-18

    ..., Polymer With Polyethylene Glycol and Succinic Anhydride Monopolyisobutylene Derivs.; Tolerance Exemption... an exemption from the requirement of a tolerance for residues of tall oil, polymer with polyethylene..., polymer with polyethylene glycol and succinic anhydride monopolyisobutylene derivs. on food or feed...

  6. Depressive symptoms as a side effect of the sustained release form of methylphenidate in a 7-year-old boy with attention-deficit hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Lakić Aneta

    2012-01-01

    Full Text Available Introduction. Hyperkinetic disorder or attention-deficit hyperactivity disorder (ADHD is a clinical entity consisting of a cluster of symptoms including hyperactivity, attention disorder and impulse control disorder group. In the context of ADHD etiology we may say that genetic, clinical and imaging studies point out a disruption of the brain dopamine system, which is corroborated by the clinical effectiveness of stimulant drugs, which increase extracellular dopamine in the brain. Basically, it is a biological and not psychological disorder, which is important both for the comprehension and therapeutical approach to this problem. Today, the best recommended approach regarding children with ADHD is a combination of two therapeutic modalities: pharmacotherapy and behavioral treatment. The first-choice drugs for this disorder belong to the group of sympathomimetics - psychostimulants and atomoxetine (more recently. As the firstchoice therapy, methylphenydate in sustained release form has numerous advantages. Like all drugs, methylphenidate has its unwanted side effects. Most common are: loss of appetite, weight loss, sleeping disorders, irritability, headache. These side effects are well-known and documented in the literature. By analysing the available literature we have found cases of psychiatric side effects such as: psychosis, mania, visual hallucinations, agitation, suicidal ideas. We have not found examples of ADHD in children who use increased dosage of sustained release of methylphenidate leading to depressive symptomatology. On the other side, methylphenidate may be prescribed for off-label use in treatmentresistant cases of depression. Case report. The case of a 7- year-old boy diagnosed with ADHD was on a minimal dose of sustained release form of methylphenidate. After initial titration of the drug, i.e. after raising the dose to the next level the boy developed clinical signs of depression. The treatment was ceased and depressive

  7. Structural and magnetic studies on copper succinate dihydrate

    Indian Academy of Sciences (India)

    The four bis-bidendate succinate anions form syn–syn bridges among two copper atomsto form a polymeric two-dimensional chain. From room temperature vibrating sample magnetometer (VSM) studies themagnetic moment of the material is calculated as 1.35 Bohr magneton (BM), indicating antiferromagnetic interaction ...

  8. Natural history of succinic semialdehyde dehydrogenase deficiency through adulthood

    NARCIS (Netherlands)

    Lapalme-Remis, S.; Lewis, E.C.; De Meulemeester, C.; Chakraborty, P.; Gibson, K.M.; Torres, C.; Guberman, A.; Salomons, G.; Jakobs, C.; Ali-Ridha, A.; Parviz, M.; Pearl, P.L.

    2015-01-01

    Objective: The natural history of succinic semialdehyde dehydrogenase (SSADH) deficiency in adulthood is unknown; we elucidate the clinical manifestations of the disease later in life. Methods: A 63-year-old man with long-standing intellectual disability was diagnosed with SSADH deficiency following

  9. Sustained release vancomycin-coated titanium alloy using a novel electrostatic dry powder coating technique may be a potential strategy to reduce implant-related infection.

    Science.gov (United States)

    Han, Jing; Yang, Yi; Lu, Junren; Wang, Chenzhong; Xie, Youtao; Zheng, Xuebin; Yao, Zhenjun; Zhang, Chi

    2017-07-24

    In order to tackle the implant-related infection, a novel way was developed in this study to coat vancomycin particles mixed with controlled release coating materials onto the surface of titanium alloy by using an electrostatic dry powder coating technique. To characterize this sustained release antibacterial coating, surface morphology, in vitro and in vivo drug release were sequentially evaluated. In vitro cytotoxicity was tested by Cell Counting Kit-8 (CCK-8) assay and cytological changes were observed by inverted microscope. The antibacterial properties against MRSA, including a bacterial growth inhibition assay and a colony-counting test by spread plate method were performed. Results indicated that the vancomycin-coated sample was biocompatible for Human osteoblast cell line MG-63 and displayed effective antibacterial ability against MRSA. The coating film was revealed uniform by scanning electron microscopy. Both the in vitro and in vivo drug release kinetics showed an initially high release rate, followed by an extended period of sustained drug release over 7 days. These results suggest that with good biocompatibility and antibacterial ability, the sustained release antibacterial coating of titanium alloy using our novel electrostatic dry powder coating process may provide a promising candidate for the treatment of orthopedic implant-related infection.

  10. Development and Characterization of Chitosan Cross-Linked With Tripolyphosphate as a Sustained Release Agent in Tablets, Part I: Design of Experiments and Optimization.

    Science.gov (United States)

    Pinto, Colin A; Saripella, Kalyan K; Loka, Nikhil C; Neau, Steven H

    2018-04-01

    Certain issues with the use of particles of chitosan (Ch) cross-linked with tripolyphosphate (TPP) in sustained release formulations include inefficient drug loading, burst drug release, and incomplete drug release. Acetaminophen was added to Ch:TPP particles to test for advantages of drug addition extragranularly over drug addition made during cross-linking. The influences of Ch concentration, Ch:TPP ratio, temperature, ionic strength, and pH were assessed. Design of experiments allowed identification of factors and 2-factor interactions that have significant effects on average particle size and size distribution, yield, zeta potential, and true density of the particles, as well as drug release from the directly compressed tablets. Statistical model equations directed production of a control batch that minimized span, maximized yield, and targeted a t 50 of 90 min (sample A); sample B that differed by targeting a t 50 of 240-300 min to provide sustained release; and sample C that differed from sample B by maximizing span. Sample B maximized yield and provided its targeted t 50 and the smallest average particle size, with the higher zeta potential and the lower span of samples B and C. Extragranular addition of a drug to Ch:TPP particles achieved 100% drug loading, eliminated a burst drug release, and can accomplish complete drug release. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  11. Extracellular Matrix (ECM) Multilayer Membrane as a Sustained Releasing Growth Factor Delivery System for rhTGF-β3 in Articular Cartilage Repair

    Science.gov (United States)

    Park, Sang-Hyug; Kim, Moon Suk; Kim, Young Jick; Choi, Byung Hyune; Lee, Chun Tek; Park, So Ra; Min, Byoung-Hyun

    2016-01-01

    Recombinant human transforming growth factor beta-3 (rhTGF-β3) is a key regulator of chondrogenesis in stem cells and cartilage formation. We have developed a novel drug delivery system that continuously releases rhTGF-β3 using a multilayered extracellular matrix (ECM) membrane. We hypothesize that the sustained release of rhTGF-β3 could activate stem cells and result in enhanced repair of cartilage defects. The properties and efficacy of the ECM multilayer-based delivery system (EMLDS) are investigated using rhTGF-β3 as a candidate drug. The bioactivity of the released rhTGF-ß3 was evaluated through chondrogenic differentiation of mesenchymal stem cells (MSCs) using western blot and circular dichroism (CD) analyses in vitro. The cartilage reparability was evaluated through implanting EMLDS with endogenous and exogenous MSC in both in vivo and ex vivo models, respectively. In the results, the sustained release of rhTGF-ß3 was clearly observed over a prolonged period of time in vitro and the released rhTGF-β3 maintained its structural stability and biological activity. Successful cartilage repair was also demonstrated when rabbit MSCs were treated with rhTGF-β3-loaded EMLDS ((+) rhTGF-β3 EMLDS) in an in vivo model and when rabbit chondrocytes and MSCs were treated in ex vivo models. Therefore, the multilayer ECM membrane could be a useful drug delivery system for cartilage repair. PMID:27258120

  12. Design of sustained release fine particles using two-step mechanical powder processing: particle shape modification of drug crystals and dry particle coating with polymer nanoparticle agglomerate.

    Science.gov (United States)

    Kondo, Keita; Ito, Natsuki; Niwa, Toshiyuki; Danjo, Kazumi

    2013-09-10

    We attempted to prepare sustained release fine particles using a two-step mechanical powder processing method; particle-shape modification and dry particle coating. First, particle shape of bulk drug was modified by mechanical treatment to yield drug crystals suitable for the coating process. Drug crystals became more rounded with increasing rotation speed, which demonstrates that powerful mechanical stress yields spherical drug crystals with narrow size distribution. This process is the result of destruction, granulation and refinement of drug crystals. Second, the modified drug particles and polymer coating powder were mechanically treated to prepare composite particles. Polymer nanoparticle agglomerate obtained by drying poly(meth)acrylate aqueous dispersion was used as a coating powder. The porous nanoparticle agglomerate has superior coating performance, because it is completely deagglomerated under mechanical stress to form fine fragments that act as guest particles. As a result, spherical drug crystals treated with porous agglomerate were effectively coated by poly(meth)acrylate powder, showing sustained release after curing. From these findings, particle-shape modification of drug crystals and dry particle coating with nanoparticle agglomerate using a mechanical powder processor is expected as an innovative technique for preparing controlled-release coated particles having high drug content and size smaller than 100 μm. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Extracellular Matrix (ECM Multilayer Membrane as a Sustained Releasing Growth Factor Delivery System for rhTGF-β3 in Articular Cartilage Repair.

    Directory of Open Access Journals (Sweden)

    Soon Sim Yang

    Full Text Available Recombinant human transforming growth factor beta-3 (rhTGF-β3 is a key regulator of chondrogenesis in stem cells and cartilage formation. We have developed a novel drug delivery system that continuously releases rhTGF-β3 using a multilayered extracellular matrix (ECM membrane. We hypothesize that the sustained release of rhTGF-β3 could activate stem cells and result in enhanced repair of cartilage defects. The properties and efficacy of the ECM multilayer-based delivery system (EMLDS are investigated using rhTGF-β3 as a candidate drug. The bioactivity of the released rhTGF-ß3 was evaluated through chondrogenic differentiation of mesenchymal stem cells (MSCs using western blot and circular dichroism (CD analyses in vitro. The cartilage reparability was evaluated through implanting EMLDS with endogenous and exogenous MSC in both in vivo and ex vivo models, respectively. In the results, the sustained release of rhTGF-ß3 was clearly observed over a prolonged period of time in vitro and the released rhTGF-β3 maintained its structural stability and biological activity. Successful cartilage repair was also demonstrated when rabbit MSCs were treated with rhTGF-β3-loaded EMLDS ((+ rhTGF-β3 EMLDS in an in vivo model and when rabbit chondrocytes and MSCs were treated in ex vivo models. Therefore, the multilayer ECM membrane could be a useful drug delivery system for cartilage repair.

  14. 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.

  15. 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.

  16. Studies on the toxic effects of periodontal sustained release drug containing ornidazole and pefloxacin mesylate on early embryonic development of SD rat

    Directory of Open Access Journals (Sweden)

    Zheng-mou DONG

    2011-01-01

    Full Text Available Objective To evaluate the toxic effects of periodontal sustained release drug containing ornidazole and pefloxacin mesylate on early embryonic development of SD rats.Methods A total of 100female SD rats were randomly divided into negative control,low-,medium-,high-dose group and intervention group(20each.Rats in low-,medium-and high-dose group were fed daily with the sustained release drug at 1,4,and 8g/kg respectively;those in negative control group were fed daily with distilled water from the 14th day before mating to the 7th day of pregnancy continuously,and those in intervention group received cyclophosphamide(40mg/kgby intraperitoneal injection for 5successive days.During this period,the general status,mating,pregnancy,coefficient of ovary and uterus,the numbers of corpus luteum,nidation,live births,stillbirths,absorbed embryo,prenidatory and postnidatory mortality,serum testosterone(Tand estradiol(E2were determined respectively.Histopathologic examination of the ovary and uterus,immunohistochemical observation of ovaries for proliferating cell nuclear antigen(PCNAand Bcl-2associated X protein(Baxwere also performed respectively.Results The general status of those rats was good except one in the low-dose group and one in the intervention group died on the 14th day of administration,and one in negative control and one in high dose group died on the 5th day of pregnancy,respectively.The body weight of animals decreased significantly(P 0.05.The serum T level in medium-and high-dose group and the E2level in high-dose group declined compared to that in negative control group(P < 0.05.Conclusions Although the periodontal sustained release drug containing ornidazole and pefloxacin mesylate shows no toxicity to the early embryonic development of SD rats,the high dose drug has certain toxicity to ovary.Declined serum concentrations of T and E2,reduced expression of PCNA,and increased Bax may be the causes of the toxicity.

  17. Evaluating the patient experience after implantation of a 0.4 mg sustained release dexamethasone intracanalicular insert (DextenzaTM: results of a qualitative survey

    Directory of Open Access Journals (Sweden)

    Gira JP

    2017-03-01

    Full Text Available Joseph P Gira,1 Reginald Sampson,2 Steven M Silverstein,3 Thomas R Walters,4 Jamie Lynne Metzinger,5 Jonathan H Talamo5 1Ophthalmology Consultants, St Louis, MO, 2Montebello Medical Center, Inc., Montebello, CA, 3Silverstein Eye Centers, Kansas City, MO, 4Texan Eye, Austin, TX, 5Ocular Therapeutix, Inc., Bedford, MA, USA Purpose: The purpose of this study is to evaluate the patient experience of sustained release dexamethasone intracanalicular insert (Dextenza™ following cataract surgery as part of a Phase III clinical trial program. Methods: This cross-sectional, qualitative evaluation involved individual interviews lasting approximately 45 minutes. Patients from four US investigational study sites who had previously received an insert were enrolled. There were no predesignated end points; this was a qualitative survey seeking a deeper understanding of patient experience. Results: Twenty-five patients were interviewed. Most patients (92% reported the highest level of satisfaction grade with regard to overall product satisfaction. All patients described the insert as comfortable. Most patients (96% described their overall experience with the insert as very convenient or extremely convenient. Twenty-two of 23 (96% participants rated their experience with the insert as “very” or “extremely convenient”, compared to previous topical therapy, and 88% of patients stated that if they were to undergo cataract surgery again, they would request the insert. When asked if they would recommend the insert to family members or friends, 92% stated they would. The survey found that 84% of participants would be willing to pay more for the insert than for eye drop therapy. Conclusion: The dexamethasone insert was found by patients to be highly favorable with regard to overall satisfaction, convenience, and comfort. The insert was well received and largely preferred over topical therapy alternatives following surgery. More extensive evaluation of the

  18. A multicenter, randomized, double-blind, placebo-controlled, 6-month trial of bupropion hydrochloride sustained-release tablets as an aid to smoking cessation in hospital employees

    DEFF Research Database (Denmark)

    Dalsgareth, O.J.; Gerner Hansen, Niels-Christian; Soes-Petersen, U.

    2004-01-01

    (Zyban) compared with placebo as an aid to smoking cessation in health care workers. A total of 336 hospital employees who smoked at least 10 cigarettes daily were randomized (2:1) to 7 weeks of treatment with bupropion (n=222) or placebo (n=114). All participants were motivated to quit smoking......Despite changes in smoking behavior, one-third of the Danish population continues to smoke. Many of these smokers are hospital employees. This 6-month, multicenter, parallel group, randomized, double-blind, placebo-controlled study evaluated treatment with bupropion hydrochloride sustained release...... more frequently in the bupropion group than in the placebo group. Bupropion was effective as an aid to smoking cessation in a broad group of hospital employees in Denmark....

  19. 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

  20. A novel organic nonlinear optical crystal: Creatininium succinate

    Energy Technology Data Exchange (ETDEWEB)

    Thirumurugan, R.; Anitha, K., E-mail: singlecerystalxrd@gmail.ciom [School of Physics, Madurai Kamraj University, Madurai 625021 (India)

    2015-06-24

    A novel organic material complex of creatininium succinate (CS) has been synthesized and single crystals were grown by the reaction of creatinine and succinic acid from aqueous solution by employing the technique of slow evaporation at room temperature. The structure of the grown crystal has been elucidated using single crystal X-ray diffraction analysis and the structure was refined by least-squares method to R = 0.027 for 1840 reflections. FT-IR spectral investigation has been carried out to identify the various functional groups in the title compound. UV–Vis transmission was carried out which shows the crystal has a good optical transmittance in the visible region with lower cutoff wavelength around 220 nm. Nonlinear optical property of the crystal was confirmed by Kurtz-Perry powder technique.

  1. Formulation of a poorly water-soluble drug in sustained-release hollow granules with a high viscosity water-soluble polymer using a fluidized bed rotor granulator.

    Science.gov (United States)

    Asada, Takumi; Yoshihara, Naoki; Ochiai, Yasushi; Kimura, Shin-Ichiro; Iwao, Yasunori; Itai, Shigeru

    2018-04-25

    Water-soluble polymers with high viscosity are frequently used in the design of sustained-release formulations of poorly water-soluble drugs to enable complete release of the drug in the gastrointestinal tract. Tablets containing matrix granules with a water-soluble polymer are preferred because tablets are easier to handle and the multiple drug-release units of the matrix granules decreases the influences of the physiological environment on the drug. However, matrix granules with a particle size of over 800 μm sometimes cause a content uniformity problem in the tableting process because of the large particle size. An effective method of manufacturing controlled-release matrix granules with a smaller particle size is desired. The aim of this study was to develop tablets containing matrix granules with a smaller size and good controlled-release properties, using phenytoin as a model poorly water-soluble drug. We adapted the recently developed hollow spherical granule granulation technology, using water-soluble polymers with different viscosities. The prepared granules had an average particle size of 300 μm and sharp particle size distribution (relative width: 0.52-0.64). The values for the particle strength of the granules were 1.86-1.97 N/mm 2 , and the dissolution profiles of the granules were not affected by the tableting process. The dissolution profiles and the blood concentration levels of drug released from the granules depended on the viscosity of the polymer contained in the granules. We succeeded in developing the desired controlled-release granules, and this study should be valuable in the development of sustained-release formulations of poorly water-soluble drugs. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Formulation of polylactide-co-glycolic acid nanospheres for encapsulation and sustained release of poly(ethylene imine-poly(ethylene glycol copolymers complexed to oligonucleotides

    Directory of Open Access Journals (Sweden)

    Wheatley Margaret A

    2009-04-01

    Full Text Available Abstract Antisense oligonucleotides (AOs have been shown to induce dystrophin expression in muscles cells of patients with Duchenne Muscular Dystrophy (DMD and in the mdx mouse, the murine model of DMD. However, ineffective delivery of AOs limits their therapeutic potential. Copolymers of cationic poly(ethylene imine (PEI and non-ionic poly(ethylene glycol (PEG form stable nanoparticles when complexed with AOs, but the positive surface charge on the resultant PEG-PEI-AO nanoparticles limits their biodistribution. We adapted a modified double emulsion procedure for encapsulating PEG-PEI-AO polyplexes into degradable polylactide-co-glycolic acid (PLGA nanospheres. Formulation parameters were varied including PLGA molecular weight, ester end-capping, and sonication energy/volume. Our results showed successful encapsulation of PEG-PEI-AO within PLGA nanospheres with average diameters ranging from 215 to 240 nm. Encapsulation efficiency ranged from 60 to 100%, and zeta potential measurements confirmed shielding of the PEG-PEI-AO cationic charge. Kinetic measurements of 17 kDa PLGA showed a rapid burst release of about 20% of the PEG-PEI-AO, followed by sustained release of up to 65% over three weeks. To evaluate functionality, PEG-PEI-AO polyplexes were loaded into PLGA nanospheres using an AO that is known to induce dystrophin expression in dystrophic mdx mice. Intramuscular injections of this compound into mdx mice resulted in over 300 dystrophin-positive muscle fibers distributed throughout the muscle cross-sections, approximately 3.4 times greater than for injections of AO alone. We conclude that PLGA nanospheres are effective compounds for the sustained release of PEG-PEI-AO polyplexes in skeletal muscle and concomitant expression of dystrophin, and may have translational potential in treating DMD.

  3. Carnauba wax as a promising excipient in melt granulation targeting the preparation of mini-tablets for sustained release of highly soluble drugs.

    Science.gov (United States)

    Nart, Viviane; Beringhs, André O'Reilly; França, Maria Terezinha; de Espíndola, Brenda; Pezzini, Bianca Ramos; Stulzer, Hellen Karine

    2017-01-01

    Mini-tablets are a new tendency in solid dosage form design for overcoming therapeutic obstacles such as impaired swallowing and polypharmacy therapy. Among their advantages, these systems offer therapeutic benefits such as dose flexibility and combined drug release patterns. The use of lipids in the formulation has also drawn considerable interest as means to modify the drug release from the dosage form. Therefore, this paper aimed at developing sustained release mini-tablets containing the highly soluble drugs captopril and metformin hydrochloride. Carnauba wax was used as a lipid component in melt granulation, targeting the improvement of the drugs poor flowability and tabletability, as well as to sustain the drug release profiles in association with other excipients. To assist sustaining the drug release, Ethocel™ (EC) and Kollicoat® SR 30D associated with Opadry® II were employed as matrix-forming and reservoir-forming materials, respectively. The neat drugs, granules and the bulk formulations were evaluated for their angle of repose, compressibility index, Hausner ratio and tabletability. Mini-tablets were evaluated for their weight variation, hardness, friability, drug content and in-vitro drug release. The results indicated that melt granulation with carnauba wax improved the flow and the tabletability of the drugs, allowing the preparation of mini-tablets with adequate tensile strength under reduced compaction pressures. All mini-tablet formulations showed acceptable hardness (within the range of 1.16 to 3.93Kp) and friability (carnauba wax proved to be a promising excipient in melt granulation targeting the preparation of mini-tablets for sustained release of soluble drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Evaluating the patient experience after implantation of a 0.4 mg sustained release dexamethasone intracanalicular insert (Dextenza™): results of a qualitative survey.

    Science.gov (United States)

    Gira, Joseph P; Sampson, Reginald; Silverstein, Steven M; Walters, Thomas R; Metzinger, Jamie Lynne; Talamo, Jonathan H

    2017-01-01

    The purpose of this study is to evaluate the patient experience of sustained release dexamethasone intracanalicular insert (Dextenza™) following cataract surgery as part of a Phase III clinical trial program. This cross-sectional, qualitative evaluation involved individual interviews lasting approximately 45 minutes. Patients from four US investigational study sites who had previously received an insert were enrolled. There were no predesignated end points; this was a qualitative survey seeking a deeper understanding of patient experience. Twenty-five patients were interviewed. Most patients (92%) reported the highest level of satisfaction grade with regard to overall product satisfaction. All patients described the insert as comfortable. Most patients (96%) described their overall experience with the insert as very convenient or extremely convenient. Twenty-two of 23 (96%) participants rated their experience with the insert as "very" or "extremely convenient", compared to previous topical therapy, and 88% of patients stated that if they were to undergo cataract surgery again, they would request the insert. When asked if they would recommend the insert to family members or friends, 92% stated they would. The survey found that 84% of participants would be willing to pay more for the insert than for eye drop therapy. The dexamethasone insert was found by patients to be highly favorable with regard to overall satisfaction, convenience, and comfort. The insert was well received and largely preferred over topical therapy alternatives following surgery. More extensive evaluation of the patient experience is warranted, and future studies should help inform design of the next generation of sustained release drug delivery systems.

  5. Investigation of in situ gelling alginate formulations as a sustained release vehicle for co-precipitates of dextromethrophan and Eudragit S 100

    Directory of Open Access Journals (Sweden)

    Maghraby Gamal Mohamed El

    2014-03-01

    Full Text Available Alginate vehicles are capable of forming a gel matrix in situ when they come into contact with gastric medium in the presence of calcium ions. However, the gel structure is pH dependent and can break after gastric emptying, leading to dose dumping. The aim of this work was to develop modified in situ gelling alginate formulations capable of sustaining dextromethorphan release throughout the gastrointestinal tract. Alginate solution (2 %, m/m was used as a vehicle for the tested formulations. Solid matrix of the drug and Eudragit S 100 was prepared by dissolving the drug and polymer in acetone. The organic solvent was then evaporated and the deposited solid matrix was micronized, sieved and dispersed in alginate solution to obtain candidate formulations. The release behavior of dextromethorphan was monitored and evaluated in a medium simulating the gastric and intestinal pH. Drug-polymer compatibility and possible solid-state interactions suggested physical interaction through hydrogen bonding between the drug and the polymer. A significant decrease in the rate and extent of dextromethorphan release was observed with increasing Eudragit S 100 concentration in the prepared particles. Most formulations showed sustained release profiles similar to that of a commercial sustained-release liquid based on ion exchange resin. The release pattern indicated strict control of drug release both under gastric and intestinal conditions, suggesting the potential advantage of using a solid dispersion of drug-Eudragit S 100 to overcome the problem of dose dumping after the rupture of the pH dependent alginate gels

  6. 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.

  7. Molecular and Supramolecular Changes in Polybutylene Succinate (PBS and Polybutylene Succinate Adipate (PBSA Copolymer during Degradation in Various Environmental Conditions

    Directory of Open Access Journals (Sweden)

    Michał Puchalski

    2018-03-01

    Full Text Available In this paper, the influence of the various degradation conditions, on the molecular and supramolecular structure of polybutylene succinate (PBS and polybutylene succinate adipate (PBSA copolymer during degradation is described. The experiment was carried out by the use of injection molded samples and normalized conditions of biodegradation in soil, composting and artificial weathering. Materials were studied by size-exclusion chromatography (SEC coupled with multiangle laser light scattering (MALLS detection and wide-angle X-ray diffraction (WAXD. Additionally, the physical and mechanical properties of the samples were determined. The performed experiments clearly show difference impacts of the selected degradation conditions on the macroscopic, supramolecular and molecular parameters of the studied aliphatic polyesters. The structural changes in PBS and PBSA explain the observed changes in the physical and mechanical properties of the obtained injection molded samples.

  8. Recovery of succinic acid produced by fermentation of a metabolically engineered Mannheimia succiniciproducens strain.

    Science.gov (United States)

    Song, Hyohak; Huh, Yun Suk; Lee, Sang Yup; Hong, Won Hi; Hong, Yeon Ki

    2007-12-01

    There have recently been much advances in the production of succinic acid, an important four-carbon dicarboxylic acid for many industrial applications, by fermentation of several natural and engineered bacterial strains. Mannheimia succiniciproducens MBEL55E isolated from bovine rumen is able to produce succinic acid with high efficiency, but also produces acetic, formic and lactic acids just like other anaerobic succinic acid producers. We recently reported the development of an engineered M. succiniciproducens LPK7 strain which produces succinic acid as a major fermentation product while producing much reduced by-products. Having an improved succinic acid producer developed, it is equally important to develop a cost-effective downstream process for the recovery of succinic acid. In this paper, we report the development of a simpler and more efficient method for the recovery of succinic acid. For the recovery of succinic acid from the fermentation broth of LPK7 strain, a simple process composed of a single reactive extraction, vacuum distillation, and crystallization yielded highly purified succinic acid (greater than 99.5% purity, wt%) with a high yield of 67.05wt%. When the same recovery process or even multiple reactive extraction steps were applied to the fermentation broth of MBEL55E, lower purity and yield of succinic acid were obtained. These results suggest that succinic acid can be purified in a cost-effective manner by using the fermentation broth of engineered LPK7 strain, showing the importance of integrating the strain development, fermentation and downstream process for optimizing the whole processes for succinic acid production.

  9. Progress of succinic acid production from renewable resources: Metabolic and fermentative strategies.

    Science.gov (United States)

    Jiang, Min; Ma, Jiangfeng; Wu, Mingke; Liu, Rongming; Liang, Liya; Xin, Fengxue; Zhang, Wenming; Jia, Honghua; Dong, Weiliang

    2017-12-01

    Succinic acid is a four-carbon dicarboxylic acid, which has attracted much interest due to its abroad usage as a precursor of many industrially important chemicals in the food, chemicals, and pharmaceutical industries. Facing the shortage of crude oil supply and demand of sustainable development, biological production of succinic acid from renewable resources has become a topic of worldwide interest. In recent decades, robust producing strain selection, metabolic engineering of model strains, and process optimization for succinic acid production have been developed. This review provides an overview of succinic acid producers and cultivation technology, highlight some of the successful metabolic engineering approaches. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Fermentative Succinate Production: An Emerging Technology to Replace the Traditional Petrochemical Processes

    Directory of Open Access Journals (Sweden)

    Yujin Cao

    2013-01-01

    Full Text Available Succinate is a valuable platform chemical for multiple applications. Confronted with the exhaustion of fossil energy resources, fermentative succinate production from renewable biomass to replace the traditional petrochemical process is receiving an increasing amount of attention. During the past few years, the succinate-producing process using microbial fermentation has been made commercially available by the joint efforts of researchers in different fields. In this review, recent attempts and experiences devoted to reduce the production cost of biobased succinate are summarized, including strain improvement, fermentation engineering, and downstream processing. The key limitations and challenges faced in current microbial production systems are also proposed.

  11. Improvement of succinate production by release of end-product inhibition in Corynebacterium glutamicum.

    Science.gov (United States)

    Chung, Soon-Chun; Park, Joon-Song; Yun, Jiae; Park, Jin Hwan

    2017-03-01

    Succinate is a renewable-based platform chemical that may be used to produce a wide range of chemicals including 1,4-butanediol, tetrahydrofurane, and γ-butyrolactone. However, industrial fermentation of organic acids is often subject to end-product inhibition, which significantly retards cell growth and limits metabolic activities and final productivity. In this study, we report the development of metabolically engineered Corynebacterium glutamicum for high production of succinate by release of end-product inhibition coupled with an increase of key metabolic flux. It was found that the rates of glucose consumption and succinate production were significantly reduced by extracellular succinate in an engineered strain, S003. To understand the mechanism underlying the inhibition by succinate, comparative transcriptome analysis was performed. Among the downregulated genes, overexpression of the NCgl0275 gene was found to suppress the inhibition of glucose consumption and succinate production, resulting in a 37.7% increase in succinate production up to 55.4g/L in fed-batch fermentation. Further improvement was achieved by increasing the metabolic flux from PEP to OAA. The final engineered strain was able to produce 152.2g/L succinate, the highest production reported to date, with a yield of 1.1g/g glucose under anaerobic condition. These results suggest that the release of end-product inhibition coupled with an increase in key metabolic flux is a promising strategy for enhancing production of succinate. Copyright © 2017. Published by Elsevier Inc.

  12. Sustained-release of FGF-2 from a hybrid hydrogel of heparin-poloxamer and decellular matrix promotes the neuroprotective effects of proteins after spinal injury

    Directory of Open Access Journals (Sweden)

    Xu HL

    2018-02-01

    Full Text Available  He-Lin Xu,1,* Fu-Rong Tian,1,* Jian Xiao,1,* Pian-Pian Chen,1 Jie Xu,1 Zi-Liang Fan,1 Jing-Jing Yang,1 Cui-Tao Lu,1 Ying-Zheng Zhao1,2 1Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 2Hainan Medical College, Haikou, China *These authors contributed equally to this work Introduction: The short lifetime of protein-based therapies has largely limited their therapeutic efficacy in injured nervous post-spinal cord injury (post-SCI. Methods: In this study, an affinity-based hydrogel delivery system provided sustained-release of proteins, thereby extending the efficacy of such therapies. The affinity-based hydrogel was constructed using a novel polymer, heparin-poloxamer (HP, as a temperature-sensitive bulk matrix and decellular spinal cord extracellular matrix (dscECM as an affinity depot of drug. By tuning the concentration of HP in formulation, the cold ternary fibroblast growth factor-2 (FGF2-dscECM-HP solution could rapidly gelatinize into a hydrogel at body temperature. Due to the strong affinity for FGF2, hybrid FGF2-dscECM-HP hydrogel enabled sustained-release of encapsulated FGF2 over an extended period in vitro. Results: Compared to free FGF2, it was observed that both neuron functions and tissue morphology after SCI were clearly recovered in rats treated with FGF2-dscECM-HP hydrogel. Moreover, the expression of neurofilament protein and the density of axons were increased after treatment with hybrid FGF2-dscECM-HP. In addition, the neuroprotective effects of FGF2-dscECM-HP were related to inhibition of chronic endoplasmic reticulum stress-induced apoptosis.Conclusion: The results revealed that a hybrid hydrogel system may be a potential carrier to deliver macromolecular proteins to the injured site and enhance the therapeutic effects of proteins.Keywords: spinal cord injury, decellularized extracellular matrix, thermosensitive hydrogel, adsorption, basic fibroblast growth factor

  13. Dose proportionality and pharmacokinetics of carvedilol sustained-release formulation: a single dose-ascending 10-sequence incomplete block study

    Directory of Open Access Journals (Sweden)

    Kim YH

    2015-06-01

    Full Text Available Yo Han Kim,1 Hee Youn Choi,1 Yook-Hwan Noh,1 Shi Hyang Lee,1 Hyeong-Seok Lim,1 Chin Kim,2 Kyun-Seop Bae11Department of Clinical Pharmacology and Therapeutics, College of Medicine, University of Ulsan, Asan Medical Center, 2Chong Kun Dang Clinical Research and Clinical Epidemiology and Medical Information, CKD Pharmaceuticals, Seoul, Republic of KoreaBackground: Carvedilol is a third-generation β-blocker indicated for congestive heart failure and high blood pressure. The aim of this study was to investigate the dose proportionality of the carvedilol sustained-release (SR formulation in healthy male subjects.Methods: An open-label, single dose-ascending, 10-sequence, 3-period balanced incomplete block study was performed using healthy male subjects. In varying sequences, each subject received three of five carvedilol SR formulations (8, 16, 32, 64, or 128 mg once. The treatment periods were separated by a washout period of 7 days. Serial blood samples were collected up to 48 h after dosing. The plasma concentrations of carvedilol were determined by using validated liquid chromatography–tandem mass spectrometry. Pharmacokinetic parameters including the area under the plasma concentration–time curve (AUC from time 0 to the last measurable time (AUClast, AUC extrapolated to infinity (AUCinf, and the measured peak plasma concentration (Cmax were obtained by noncompartmental analysis. Dose proportionality was evaluated if the ln–ln plots of AUClast, AUCinf, and Cmax versus dose were linear and the 90% confidence intervals (CIs of the slopes were within 0.9195 and 1.0805. Tolerability was assessed by vital signs, electrocardiogram, clinical laboratory tests, and monitoring of adverse events (AEs throughout the study.Results: A total of 31 subjects were enrolled, and 30 completed the study. The assessment of dose proportionality meets the statistical criteria; the point estimates of slope were 1.0104 (90% CI: 0.9849–1.0359 for AUClast, 1

  14. 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

  15. Lipid-coated hollow mesoporous silica nanospheres for co-delivery of doxorubicin and paclitaxel: Preparation, sustained release, cellular uptake and pharmacokinetics

    International Nuclear Information System (INIS)

    Qiu, Yang; Wu, Chao; Jiang, Jie; Hao, Yanna; Zhao, Ying; Xu, Jie; Yu, Tong; Ji, Peng

    2017-01-01

    A carrier consisting of lipid-coated hollow mesoporous silica nanospheres (L-HMSN) was produced for the combination of the water-insoluble drug (paclitaxel, PTX) and the water-soluble drug (doxorubicin, DOX). DOX was adsorbed into the nanoscale hollow structure of the hollow mesoporous silica nanospheres (HMSN) by adsorption and PTX was wrapped in the phospholipid layer of the HMSN surface by lipid film hydration method. The characterization results showed that DOX and PTX were present in the nanopheres in an amorphous state. The loaded L-HMSN (DOX/PTX@L-HMSN) in vitro drug release showed a sustained release in phosphate buffered solution (PBS) at pH 6.8 and 0.001%SDS. The cellular uptake experiment indicated that L-HMSN was successfully taken up by A549 cells. In addition, the combination of DOX and PTX in L-HMSN exhibited a marked synergistic effect in inhibiting the proliferation of A549 cells. The pharmacokinetic study demonstrated that L-HMSN could significantly improve the relative bioavailability of DOX and PTX. These results confirm that L-HMSN is a promising carrier for successful drug combination. - Highlights: • L-HMSN as a platform is used for combination of DOX and PTX • The drug delivery system demonstrates synergy effect in inhibiting A549 cell proliferation • The drug delivery system slowly releases the drugs and improves drug absorption

  16. Lipid-coated hollow mesoporous silica nanospheres for co-delivery of doxorubicin and paclitaxel: Preparation, sustained release, cellular uptake and pharmacokinetics

    Energy Technology Data Exchange (ETDEWEB)

    Qiu, Yang; Wu, Chao, E-mail: wuchao27@126.com; Jiang, Jie; Hao, Yanna; Zhao, Ying; Xu, Jie; Yu, Tong; Ji, Peng

    2017-02-01

    A carrier consisting of lipid-coated hollow mesoporous silica nanospheres (L-HMSN) was produced for the combination of the water-insoluble drug (paclitaxel, PTX) and the water-soluble drug (doxorubicin, DOX). DOX was adsorbed into the nanoscale hollow structure of the hollow mesoporous silica nanospheres (HMSN) by adsorption and PTX was wrapped in the phospholipid layer of the HMSN surface by lipid film hydration method. The characterization results showed that DOX and PTX were present in the nanopheres in an amorphous state. The loaded L-HMSN (DOX/PTX@L-HMSN) in vitro drug release showed a sustained release in phosphate buffered solution (PBS) at pH 6.8 and 0.001%SDS. The cellular uptake experiment indicated that L-HMSN was successfully taken up by A549 cells. In addition, the combination of DOX and PTX in L-HMSN exhibited a marked synergistic effect in inhibiting the proliferation of A549 cells. The pharmacokinetic study demonstrated that L-HMSN could significantly improve the relative bioavailability of DOX and PTX. These results confirm that L-HMSN is a promising carrier for successful drug combination. - Highlights: • L-HMSN as a platform is used for combination of DOX and PTX • The drug delivery system demonstrates synergy effect in inhibiting A549 cell proliferation • The drug delivery system slowly releases the drugs and improves drug absorption.

  17. Recovery of oxidative stress-induced damage in Cisd2-deficient cardiomyocytes by sustained release of ferulic acid from injectable hydrogel.

    Science.gov (United States)

    Cheng, Yung-Hsin; Lin, Feng-Huei; Wang, Chien-Ying; Hsiao, Chen-Yuan; Chen, Hung-Ching; Kuo, Hsin-Yu; Tsai, Ting-Fen; Chiou, Shih-Hwa

    2016-10-01

    Aging-related oxidative stress is considered a major risk factor of cardiovascular diseases (CVD) and could be associated with mitochondrial dysfunction and reactive oxygen species (ROS) overproduction. Cisd2 is an outer mitochondrial membrane protein and plays an important role in controlling the lifespan of mammals. Ferulic acid (FA), a natural antioxidant, is able to improve cardiovascular functions and inhibit the pathogenetic CVD process. However, directly administering therapeutics with antioxidant molecules is challenging because of stability and bioavailability issues. In the present study, thermosensitive chitosan-gelatin-based hydrogel containing FA was used to treat Cisd2-deficient (Cisd2(-/-)) cardiomyocytes (CM) derived from induced pluripotent stem cells of Cisd2(-/-) murine under oxidative stress. The results revealed that the developed hydrogel could provide a sustained release of FA and increase the cell viability. Post-treatment of FA-loaded hydrogel effectively decreased the oxidative stress-induced damage in Cisd2(-/-) CM via increasing catalase activity and decreasing endogenous reactive oxygen species (ROS) production. The in vivo biocompatibility of FA-loaded hydrogel was confirmed in subcutaneously injected rabbits and intramyocardially injected Cisd2(-/-) mice. These results suggest that the thermosensitive FA-loaded hydrogel could rescue Cisd2(-/-) CM from oxidative stress-induced damage and may have potential applications in the future treatment of CVD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. 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.

  19. Bupropion sustained release treatment decreases craving for video games and cue-induced brain activity in patients with Internet video game addiction.

    Science.gov (United States)

    Han, Doug Hyun; Hwang, Jun Won; Renshaw, Perry F

    2010-08-01

    Bupropion has been used in the treatment of patients with substance dependence based on its weak inhibition of dopamine and norepinephrine reuptake. We hypothesized that 6 weeks of bupropion sustained release (SR) treatment would decrease craving for Internet game play as well as video game cue-induced brain activity in patients with Internet video game addiction (IAG). Eleven subjects who met criteria for IAG, playing StarCraft (>30 hr/week), and eight healthy comparison subjects (HC) who had experience playing StarCraft (game, and the severity of Internet addiction were evaluated by Beck Depression Inventory, self-report of craving on a 7-point visual analogue scale, and Young's Internet Addiction Scale, respectively. In response to game cues, IAG showed higher brain activation in left occipital lobe cuneus, left dorsolateral prefrontal cortex, and left parahippocampal gyrus than HC. After a 6 week period of bupropion SR, craving for Internet video game play, total game play time, and cue-induced brain activity in dorsolateral prefrontal cortex were decreased in the IAG. We suggest that bupropion SR may change craving and brain activity in ways that are similar to those observed in individuals with substance abuse or dependence. PsycINFO Database Record 2010 APA, all rights reserved.

  20. 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.

  1. Sustained release of stem cell factor in a double network hydrogel for ex vivo culture of cord blood-derived CD34+ cells.

    Science.gov (United States)

    Zhang, Yuanhao; Pan, Xiuwei; Shi, Zhen; Cai, Haibo; Gao, Yun; Zhang, Weian

    2018-04-01

    Stem cell factor (SCF) is considered as a commonly indispensable cytokine for proliferation of haematopoietic stem cells (HSCs), which is used in large dosages during ex vivo culture. The work presented here aimed to reduce the consumption of SCF by sustained release but still support cells proliferation and maintain the multipotency of HSCs. Stem cell factor was physically encapsulated within a hyaluronic acid/gelatin double network (HGDN) hydrogel to achieve a slow release rate. CD34 + cells were cultured within the SCF-loaded HGDN hydrogel for 14 days. The cell number, phenotype and functional capacity were investigated after culture. The HGDN hydrogels had desirable properties and encapsulated SCF kept being released for more than 6 days. SCF remained the native bioactivity, and the proliferation of HSCs within the SCF-loaded HGDN hydrogel was not affected, although the consumption of SCF was only a quarter in comparison with the conventional culture. Moreover, CD34 + cells harvested from the SCF-loaded HGDN hydrogels generated more multipotent colony-forming units (CFU-GEMM). The data suggested that the SCF-loaded HGDN hydrogel could support ex vivo culture of HSCs, thus providing a cost-effective culture protocol for HSCs. © 2017 John Wiley & Sons Ltd.

  2. Non-isothermal crystallization kinetics and characterization of biodegradable poly(butylene succinate-co-neopentyl glycol succinate) copolyesters.

    Science.gov (United States)

    Xie, Wen-Jie; Zhou, Xiao-Ming

    2015-01-01

    Both biodegradable aliphatic neat poly(butylene succinate) (PBS) and poly(butylene succinate-co-neopentyl glycol succinate) (P(BS-co-NPGS)) copolyesters with different 1,4-butanediol/neopentyl glycol ratios were synthesized through a two-step process of transesterification and polycondensation using stannous chloride and 4-Methylbenzenesulfonic acid as the co-catalysts. The structure, non-isothermal crystallization behavior, crystalline morphology and crystal structure of neat PBS and P(BS-co-NPGS) copolyesters were characterized by (1)H NMR, differential scanning calorimetry (DSC), polarized optical microscope (POM) and wide angle X-ray diffraction (WAXD), respectively. The Avrami equation modified by Jeziorny and Mo's method was employed to describe the non-isothermal crystallization kinetics of the neat PBS and its copolyesters. The modified Avrami equation could adequately describe the primary stage of non-isothermal crystallization kinetics of the neat PBS and its copolyesters. Mo's method provided a fairly satisfactory description of the non-isothermal crystallization of neat PBS and its copolyesters. Interestingly, the values of 1/t1/2, Zc and F(T) obtained by the modified Avrami equation and Mo's method analysis indicated that the crystallization rate increased first and then decreased with an increase of NPGS content compared that of neat PBS, whereas the crystallization mechanism almost kept unchanged. The results of tensile testing showed that the ductility of PBS was largely improved by incorporating NPGS units. The elongation at break increased remarkably with increasing NPGS content. In particular, the sample with 20% NPGS content showed around 548% elongation at break. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Non-isothermal crystallization kinetics and characterization of biodegradable poly(butylene succinate-co-neopentyl glycol succinate) copolyesters

    International Nuclear Information System (INIS)

    Xie, Wen-Jie; Zhou, Xiao-Ming

    2015-01-01

    Both biodegradable aliphatic neat poly(butylene succinate) (PBS) and poly(butylene succinate-co-neopentyl glycol succinate) (P(BS-co-NPGS)) copolyesters with different 1,4-butanediol/neopentyl glycol ratios were synthesized through a two-step process of transesterification and polycondensation using stannous chloride and 4-Methylbenzenesulfonic acid as the co-catalysts. The structure, non-isothermal crystallization behavior, crystalline morphology and crystal structure of neat PBS and P(BS-co-NPGS) copolyesters were characterized by 1 H NMR, differential scanning calorimetry (DSC), polarized optical microscope (POM) and wide angle X-ray diffraction (WAXD), respectively. The Avrami equation modified by Jeziorny and Mo's method was employed to describe the non-isothermal crystallization kinetics of the neat PBS and its copolyesters. The modified Avrami equation could adequately describe the primary stage of non-isothermal crystallization kinetics of the neat PBS and its copolyesters. Mo's method provided a fairly satisfactory description of the non-isothermal crystallization of neat PBS and its copolyesters. Interestingly, the values of 1/t 1/2 , Z c and F(T) obtained by the modified Avrami equation and Mo's method analysis indicated that the crystallization rate increased first and then decreased with an increase of NPGS content compared that of neat PBS, whereas the crystallization mechanism almost kept unchanged. The results of tensile testing showed that the ductility of PBS was largely improved by incorporating NPGS units. The elongation at break increased remarkably with increasing NPGS content. In particular, the sample with 20% NPGS content showed around 548% elongation at break. - Highlights: • The incorporation of NPGS units reduced the spherulite size of BS unit. • The existence of NPGS units did not change the crystal structure of BS unit. • The NPGS units incorporated in PBS could significantly improve the ductility of PBS. • The

  4. Synthesis, stability and bioavailability of astaxanthin succinate diester.

    Science.gov (United States)

    Qiao, Xing; Yang, Lu; Zhang, Ting; Zhou, Qingxin; Wang, Yuming; Xu, Jie; Xue, Changhu

    2018-06-01

    We synthesized astaxanthin succinate diester (ASD), a novel astaxanthin (AST) derivate, with succinic anhydride and free AST. ASD was purified and characterized using silica gel column chromatography and spectrometry, respectively. The ASD final synthesis rate was 82.63%. A stability test revealed a high AST and ASD retention rate at pH 5.0-7.0. ASD showed better stability than did AST under acidic conditions. Both sample ions showed lower retention rates under Fe 2+ and Fe 3+ states. The ASD metabolic curve showed serum and liver area under the curve from 0 h to time t (AUC 0-t ) values of 45.05 ± 4.58 and 120.38 ± 23.66 µg h -1  mL -1 , respectively. The long-term accumulation was significantly higher in the ASD group than in the AST group, which showed higher accumulation in the heart, muscle and spleen than in other tissues in vivo. The thermal stability and bioavailability of ASD were higher than that of the non-esterified free AST and common free AST, respectively. Additionally, AST accumulation in different tissues of the ASD group was multifold higher than that of free AST. These results prove that ASD may serve as a better source of AST for human nutrition than does free AST. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  5. Vitamin E Succinate as an Adjuvant for Dendritic Cell Based Vaccines

    National Research Council Canada - National Science Library

    Ramanathapuram, Lalitha V

    2006-01-01

    .... Vitamin E succinate or alpha tocopheryl succinate ( -TOS) is a non-toxic, esterified analogue of Vitamin E that has been shown to be selectively toxic to tumor cell lines in vitro as well as inhibit the growth of tumors in animal models in vivo...

  6. Vitamin E Succinate as an Adjuvant for Dendritic Cell-Based Vaccines

    National Research Council Canada - National Science Library

    Ramanathapuram, Lalitha V; Akporiaye, Emmanuel T

    2005-01-01

    .... Vitamin E succinate or alpha tocopheryl succinate (a-TOS) is a non-toxic, esterified analogue of Vitamin E that has been shown to be selectively toxic to tumor cell lines in vitro as well as inhibit the growth of tumors in animal models in vivo...

  7. Vitamin E Succinate as an Adjuvant for Dendritic Cell Based Vaccines

    National Research Council Canada - National Science Library

    Ramanathapuram, Lalitha

    2004-01-01

    .... In this study we have employed Vitamin E succinate also known as alpha-tocopheryl succinate (alpha-TOS), a non-toxic esterified analogue of Vitamin E, as an adjuvant to enhance the effectiveness of DC vaccines in treating established murine mammary...

  8. Receptor structure-based discovery of non-metabolite agonists for the succinate receptor GPR91

    DEFF Research Database (Denmark)

    Trauelsen, Mette; Rexen Ulven, Elisabeth; Hjorth, Siv A

    2017-01-01

    OBJECTIVE: Besides functioning as an intracellular metabolite, succinate acts as a stress-induced extracellular signal through activation of GPR91 (SUCNR1) for which we lack suitable pharmacological tools. METHODS AND RESULTS: Here we first determined that the cis conformation of the succinate...

  9. Krebs cycle metabolite profiling for identification and stratification of pheochromocytomas/paragangliomas due to succinate dehydrogenase deficiency

    NARCIS (Netherlands)

    Richter, S; Peitzsch, M.; Rapizzi, E.; Lenders, J.W.M.; Qin, N.; Cubas, A.A. de; Schiavi, F.; Rao, J.U.; Beuschlein, F.; Quinkler, M.; Timmers, H.J.L.M.; Opocher, G.; Mannelli, M.; Pacak, K.; Robledo, M.; Eisenhofer, G.

    2014-01-01

    CONTEXT: Mutations of succinate dehydrogenase A/B/C/D genes (SDHx) increase susceptibility to development of pheochromocytomas and paragangliomas (PPGLs), with particularly high rates of malignancy associated with SDHB mutations. OBJECTIVE: We assessed whether altered succinate dehydrogenase

  10. Evaporation of methyl- and dimethyl-substituted malonic, succinic, glutaric and adipic acid particles at ambient temperatures

    DEFF Research Database (Denmark)

    Mønster, Jacob Garbrecht; Rosenørn, Thomas; Svenningsson, Birgitta

    2004-01-01

    Evaporation; organic aerosols; vapor pressure; dicarboxylic acid; maonic acid; succinic acid; glutaric acid; adipic acid......Evaporation; organic aerosols; vapor pressure; dicarboxylic acid; maonic acid; succinic acid; glutaric acid; adipic acid...

  11. DEVELOPMENT OF SUSTAINED RELEASE TABLETS ...

    African Journals Online (AJOL)

    2013-12-31

    Dec 31, 2013 ... The SR dosage forms that release drugs pH independently in .... were determined; Post compression parameters such as weight variation test, hardness, ... Based on the ICH guidelines 12, the stability studies were carried out ...

  12. Supramolecular micellar nanoaggregates based on a novel chitosan/vitamin E succinate copolymer for paclitaxel selective delivery

    Directory of Open Access Journals (Sweden)

    Lian H

    2011-12-01

    Full Text Available He Lian1, Jin Sun1, Yan Ping Yu1, Yan Hua Liu2, Wen Cao1, Yong Jun Wang1, Ying Hua Sun1, Si Ling Wang1, Zhong Gui He11School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 2Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University, Ningxia, People's Republic of ChinaBackground: Nowadays, many cytotoxic anticancer drugs exhibit low solubility and poor tumor selectivity, which means that the drug formulation is very important. For example, in the case of paclitaxel (PTX, Cremophor EL® (BASF, Ludwigshafen, Germany needs to be used as a solubilizer in its clinical formulation (Taxol®, Bristol-Myers Squibb, New York, NY, although it can cause serious side effects. Nanomicellar systems are promising carriers to resolve the above problems, and the polymer chosen is the key element.Methods: In this study, a novel amphiphilic chitosan/vitamin E succinate (CS-VES copolymer was successfully synthesized for self-assembling polymeric micelles. Proton nuclear magnetic resonance spectroscopy and infrared were used to characterize the molecular structure of the copolymer. The PTX-loaded CS-VES polymeric micelles (PTX-micelles were characterized by dynamic light scattering, transmission electron microscopy, X-ray diffraction, and differential scanning calorimetry.Results: The critical micelle concentration of CS-VES was about 12.6 µg/mL, with the degree of amino group substitution being 20.4%. PTX-micelles were prepared by a nanoprecipitation/dispersion technique without any surfactant being involved. PTX-micelles exhibited a drug loading as high as 21.37% and an encapsulation efficiency of 81.12%, with a particle size ranging from 326.3 to 380.8 nm and a zeta potential of +20 mV. In vitro release study showed a near zero-order sustained release, with 51.06%, 50.88%, and 44.35% of the PTX in the micelles being released up to 168 hours at three drug loadings of 7.52%, 14.09%, and 21.37%, respectively. The cellular uptake

  13. Bio-succinic acid production: Escherichia coli strains design from genome-scale perspectives

    Directory of Open Access Journals (Sweden)

    Bashir Sajo Mienda

    2017-10-01

    Full Text Available Escherichia coli (E. coli has been established to be a native producer of succinic acid (a platform chemical with different applications via mixed acid fermentation reactions. Genome-scale metabolic models (GEMs of E. coli have been published with capabilities of predicting strain design strategies for the production of bio-based succinic acid. Proof-of-principle strains are fundamentally constructed as a starting point for systems strategies for industrial strains development. Here, we review for the first time, the use of E. coli GEMs for construction of proof-of-principles strains for increasing succinic acid production. Specific case studies, where E. coli proof-of-principle strains were constructed for increasing bio-based succinic acid production from glucose and glycerol carbon sources have been highlighted. In addition, a propose systems strategies for industrial strain development that could be applicable for future microbial succinic acid production guided by GEMs have been presented.

  14. Genetic manipulation of a metabolic enzyme and a transcriptional regulator increasing succinate excretion from unicellular cyanobacterium

    Directory of Open Access Journals (Sweden)

    Takashi eOsanai

    2015-10-01

    Full Text Available Succinate is a building block compound that the U.S. Department of Energy has declared as important in biorefineries, and it is widely used as a commodity chemical. Here, we identified the two genes increasing succinate production of the unicellular cyanobacterium Synechocystis sp. PCC 6803. Succinate was excreted under dark, anaerobic conditions, and its production level increased by knocking out ackA, which encodes an acetate kinase, and by overexpressing sigE, which encodes an RNA polymerase sigma factor. Glycogen catabolism and organic acid biosynthesis were enhanced in the mutant lacking ackA and overexpressing sigE, leading to an increase in succinate production reaching 5 times of the wild-type levels. Our genetic and metabolomic analyses thus demonstrated the effect of genetic manipulation of a metabolic enzyme and a transcriptional regulator on succinate excretion from this cyanobacterium with the data based on metabolomic technique.

  15. Thermochemical pretreatments for enhancing succinic acid production from industrial hemp (Cannabis sativa L.).

    Science.gov (United States)

    Gunnarsson, Ingólfur B; Kuglarz, Mariusz; Karakashev, Dimitar; Angelidaki, Irini

    2015-04-01

    The aim of this study was to develop an efficient thermochemical method for treatment of industrial hemp biomass, in order to increase its bioconversion to succinic acid. Industrial hemp was subjected to various thermochemical pretreatments using 0-3% H2SO4, NaOH or H2O2 at 121-180°C prior to enzymatic hydrolysis. The influence of the different pretreatments on hydrolysis and succinic acid production by Actinobacillus succinogenes 130Z was investigated in batch mode, using anaerobic bottles and bioreactors. Enzymatic hydrolysis and fermentation of hemp material pretreated with 3% H2O2 resulted in the highest overall sugar yield (73.5%), maximum succinic acid titer (21.9 g L(-1)), as well as the highest succinic acid yield (83%). Results obtained clearly demonstrated the impact of different pretreatments on the bioconversion efficiency of industrial hemp into succinic acid. Copyright © 2015. Published by Elsevier Ltd.

  16. Thermochemical pretreatments for enhancing succinic acid production from industrial hemp (Cannabis sativa L.)

    DEFF Research Database (Denmark)

    Gunnarsson, Ingólfur Bragi; Kuglarz, Mariusz; Karakashev, Dimitar Borisov

    2015-01-01

    The aim of this study was to develop an efficient thermochemical method for treatment of industrial hemp biomass, in order to increase its bioconversion to succinic acid. Industrial hemp was subjected to various thermochemical pretreatments using 0-3% H2SO4, NaOH or H2O2 at 121-180°C prior...... to enzymatic hydrolysis. The influence of the different pretreatments on hydrolysis and succinic acid production by Actinobacillus succinogenes 130Z was investigated in batch mode, using anaerobic bottles and bioreactors. Enzymatic hydrolysis and fermentation of hemp material pretreated with 3% H2O2 resulted...... in the highest overall sugar yield (73.5%), maximum succinic acid titer (21.9gL-1), as well as the highest succinic acid yield (83%). Results obtained clearly demonstrated the impact of different pretreatments on the bioconversion efficiency of industrial hemp into succinic acid....

  17. 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

  18. Reduction of exit-site infections of tunnelled intravascular catheters among neutropenic patients by sustained-release chlorhexidine dressings: results from a prospective randomized controlled trial.

    Science.gov (United States)

    Chambers, S T; Sanders, J; Patton, W N; Ganly, P; Birch, M; Crump, J A; Spearing, R L

    2005-09-01

    Exit-site and tunnel infections of tunnelled central intravascular catheters are a frequent source of morbidity among neutropenic patients and may necessitate catheter removal. They require antimicrobial therapy that increases healthcare costs and is associated with adverse drug reactions. A prospective randomized clinical trial was conducted among adult patients undergoing chemotherapy in a haematology unit. Tunnelled intravascular catheters were randomized to receive the control of a standard dressing regimen as recommended by the British Committee for Standards in Haematology, or to receive the intervention of a sustained-release chlorhexidine dressing. Follow-up data were available in 112 of 114 tunnelled intravascular catheters which were randomized. Exit-site or combined exit-site/tunnel infections occurred in 23 (43%) of 54 catheters in the control group, and five (9%) of 58 catheters in the intervention group [odds ratio (OR) for intervention group compared with control group =0.13, 95% confidence intervals (CI) 0.04-0.37, P<0.001]. More tunnelled intravascular catheters were prematurely removed from the control group than the intervention group for documented infections [20/54 (37%) vs 6/58 (10%), OR=0.20, 95%CI 0.53-0.07]. However, there was no difference in the numbers of tunnelled intravascular catheters removed for all proven and suspected intravascular catheter-related infections [21/54 (39%) vs 19/58 (33%)], or in the time to removal of catheters for any reason other than death or end of treatment for underlying disease. Thus chlorhexidine dressings reduced the incidence of exit-site/tunnel infections of indwelling tunnelled intravascular catheters without prolonging catheter survival in neutropenic patients, and could be considered as part of the routine management of indwelling tunnelled intravascular catheters among neutropenic patients.

  19. Effect of Metformin-sustained Release Therapy on Low-density Lipoprotein Size and Adiponectin in the South Indian Women with Polycystic Ovary Syndrome.

    Science.gov (United States)

    Kumar, D Rama Nagendra; Seshadri, Krishna G; Pandurangi, Monna

    2017-01-01

    The aim of the study is to compare surrogate markers of cardiovascular disease (CVD) risk, such as adiponectin (APN) levels and low-density lipoprotein (LDL) size, before and after sustained release metformin (Met-SR) therapy in women with polycystic ovarian syndrome (PCOS). Sixty women with PCOS and sixty age-matched controls in the age group 18-45 years were recruited after obtaining informed consent. Women with PCOS were initiated on Met-SR 1 g orally, which was increased to 1.5 g after 2 weeks and continued up to 24 weeks. Demographic data along with family history of type 2 diabetes mellitus, PCOS, and CVD were collected. Lipid profile plasma APN levels and LDL size were measured before and after therapy in the PCOS group. Data analysis was performed using the GraphPad Prism-5 software. Women with PCOS had greater dyslipidemia, lower APN level and LDL size, and increased lipid accumulating product index as compared to controls. After 6 months of Met-SR therapy, women with PCOS demonstrated significant increase in plasma APN levels and LDL size and significant decrease in weight, waist-hip ratio (WHR), waist circumference (WC), and blood pressure (BP). A significant decrease was observed in body mass index (BMI) in the overweight and obese PCOS subgroups. Met-SR increases LDL size, APN concentration and decreases weight, WC, WHR, and BP in patients with PCOS. Met-SR may have salutary effects on LDL particle size through effects on APN levels in women with PCOS.

  20. 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

  1. Evaluation of a 12-Hour Sustained-Release Acetaminophen (Paracetamol) Formulation: A Randomized, 3-Way Crossover Pharmacokinetic and Safety Study in Healthy Volunteers.

    Science.gov (United States)

    Yue, Yong; Collaku, Agron; Liu, Dongzhou J

    2018-01-01

    Acetaminophen (paracetamol) is a first-line treatment for mild and moderate pain. A twice-daily sustained-release (SR) formulation may be more convenient for chronic users than standard immediate-release (IR) acetaminophen. This randomized, 3-way crossover study evaluated pharmacokinetics and safety of single-dose 1500- and 2000-mg SR acetaminophen formulations and 2 doses of IR acetaminophen 1000 mg given 6 hours apart in healthy adults (n = 14). Primary outcome was time that plasma acetaminophen concentration was ≥4 μg/mL (T C≥4μg/mL ). Key secondary outcomes were area under the plasma concentration-time curve (AUC) from time 0 to time t, when plasma acetaminophen was detectable (AUC 0-t ), AUC from 0 to infinity (AUC 0-inf ), and maximum plasma acetaminophen concentration (C max ). T C≥4μg/mL from 2000-mg SR acetaminophen was similar to that from 2 doses of IR acetaminophen, whereas T C≥4μg/mL for 1500-mg SR acetaminophen was significantly shorter than that for IR acetaminophen (P = .004). The extent of acetaminophen absorption from 2000-mg SR and 2 doses of the IR formulation was similar and within bioequivalence limits with regard to AUC 0-12 , AUC 0-t , and AUC 0-inf . The extent of acetaminophen absorption from 1500-mg SR was significantly lower than that from IR acetaminophen. The 2000-mg SR represents a potential candidate formulation for 12-hour dosing with acetaminophen. © 2017, The American College of Clinical Pharmacology.

  2. Vincristine sulfate loaded dextran microspheres amalgamated with thermosensitive gel offered sustained release and enhanced cytotoxicity in THP-1, human leukemia cells: In vitro and in vivo study.

    Science.gov (United States)

    Thakur, Vivek; Kush, Preeti; Pandey, Ravi Shankar; Jain, Upendra Kumar; Chandra, Ramesh; Madan, Jitender

    2016-04-01

    Vincristine sulfate (VCS) is a drug of choice for the treatment of childhood and adult acute lymphocytic leukemia, Hodgkin's, non-Hodgkin's lymphoma as well as solid tumors including sarcomas. However, poor biopharmaceutical and pharmacokinetic traits of VCS like short serum half-life (12 min), high dosing frequency (1.4 mg/m(2) per week for 4 weeks) and extensive protein binding (75%) limit the clinical potential of VCS in cancer therapy. In present investigation, injectable vincristine sulfate loaded dextran microspheres (VCS-Dextran-MSs) were prepared and amalgamated with chitosan-β-glycerophosphate gel (VCS-Dextran-MSs-Gel) to surmount the biopharmaceutical and pharmacokinetic limitations of VCS that consequently induced synergistic sustained release pattern of the drug. Particle size and zeta-potential of VCS-Dextran-MSs were measured to be 6.8 ± 2.4 μm and -18.3 ± 0.11 mV along with the encapsulation efficiency of about 60.4 ± 4.5%. Furthermore, VCS-Dextran-MSs and VCS-Dextran-MSs-Gel exhibited slow release pattern and 94.7% and 95.8% of the drug was released in 72 h and 720 h, respectively. Results from cell viability assay and pharmacokinetic as well as histopathological analysis in mice indicated that VCS-Dextran-MSs-Gel offers superior therapeutic potential and higher AUClast than VCS-Dextran-MSs and drug solution. In conclusion, VCS-Dextran-MSs-Gel warrants further preclinical tumor growth study to scale up the technology. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Development and Characterization of Sodium Hyaluronate Microparticle-Based Sustained Release Formulation of Recombinant Human Growth Hormone Prepared by Spray-Drying.

    Science.gov (United States)

    Kim, Sun J; Kim, Chan W

    2016-02-01

    The purpose of this study was to develop and characterize a sodium hyaluronate microparticle-based sustained release formulation of recombinant human growth hormone (SR-rhGH) prepared by spray-drying. Compared to freeze-drying, spray-dried SR-rhGH showed not only prolonged release profiles but also better particle property and injectability. The results of size-exclusion high-performance liquid chromatography showed that no aggregate was detected, and dimer was just about 2% and also did not increase with increase of inlet temperature up to 150 °C. Meanwhile, the results of reversed-phase high-performance liquid chromatography revealed that related proteins increased slightly from 4.6% at 100 °C to 6.3% at 150 °C. Thermal mapping test proved that product temperature did not become high to cause protein degradation during spray-drying because thermal energy was used for the evaporation of surface moisture of droplets. The structural characterization by peptide mapping, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and circular dichroism revealed that the primary, secondary, and tertiary structures of rhGH in SR-rhGH were highly comparable to those of reference somatropin materials. The biological characterization by rat weight gain and cell proliferation assays provided that bioactivity of SR-rhGH was equivalent to that of native hGH. These data establish that spray-dried SR-rhGH is highly stable by preserving intact rhGH and hyaluronate microparticle-based formulation by spray-drying can be an alternative delivery system for proteins. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  4. Incorporation of 14C-succinate in Synechococcus

    International Nuclear Information System (INIS)

    Doehler, G.

    1983-01-01

    The cyanobacterium Synechococcus (= Anacystis nidulans) was grown under normal air conditions (0.03 vol.% CO 2 ) and in low white light (0.5 x 10 3 μW/cm 2 ) at 37 0 C. Kinetics of 14 C incorporation into several soluble products and pigments were studied after adding 14 C-succinate during photosynthesis and in the dark using the autoradiographic method. Radioactivity was found mainly in glutamate and aspartate during the photosynthetic period independent on 3-(3',4'-dichlorphenyl)-1,1-dimethylurea preincubation. In the dark period 14 C label could also be detected in malate. Short-term kinetics experiments showed a decrease in 14 C label of glutamate and a parallel increase of aspartate. Results were discussed in respect to the interrupted tricarboxylic acid cycle. (author)

  5. The succinate receptor as a novel therapeutic target for oxidative and metabolic stress-related conditions.

    Directory of Open Access Journals (Sweden)

    Ana Carolina eAriza

    2012-02-01

    Full Text Available The succinate receptor (also known as GPR91 is a G protein-coupled receptor that is closely related to the family of P2Y purinoreceptors. It is expressed in a variety of tissues, including blood cells, adipose tissue, the liver, retina and kidney. In these tissues, this receptor and its ligand succinate have recently emerged as novel mediators in local stress situations, including ischemia, hypoxia, toxicity and hyperglycemia. Amongst others, the succinate receptor is involved in recruitment of immune cells to transplanted tissues. Moreover, it was shown to play a key role in the development of diabetic retinopathy. However, most prominently, the role of locally increased succinate levels and succinate receptor activation in the kidney, stimulating the systemic and local renin-angiotensin system, starts to unfold: The succinate receptor is a key mediator in the development of hypertension and possibly fibrosis in diabetes mellitus and metabolic syndrome. This makes the succinate receptor a promising drug target to counteract or prevent cardiovascular and fibrotic defects in these expanding disorders. Recent development of SUCNR1-specific antagonists opens novel possibilities for research in models for these disorders and may eventually provide novel opportunities for the treatment of patients.

  6. Succinate modulates Ca(2+) transient and cardiomyocyte viability through PKA-dependent pathway.

    Science.gov (United States)

    Aguiar, Carla J; Andrade, Vanessa L; Gomes, Enéas R M; Alves, Márcia N M; Ladeira, Marina S; Pinheiro, Ana Cristina N; Gomes, Dawidson A; Almeida, Alvair P; Goes, Alfredo M; Resende, Rodrigo R; Guatimosim, Silvia; Leite, M Fatima

    2010-01-01

    GPR91 is an orphan G-protein-coupled receptor (GPCR) that has been characterized as a receptor for succinate, a citric acid cycle intermediate, in several tissues. In the heart, the role of succinate is unknown. We now report that rat ventricular cardiomyocytes express GPR91. We found that succinate, through GPR91, increases the amplitude and the rate of decline of global Ca(2+) transient, by increasing the phosphorylation levels of ryanodine receptor and phospholamban, two well known Ca(2+) handling proteins. The effects of succinate on Ca(2+) transient were abolished by pre-treatment with adenylyl cyclase and cAMP-dependent protein kinase (PKA) inhibitors. Direct PKA activation by succinate was further confirmed using a FRET-based A-kinase activity reporter. Additionally, succinate decreases cardiomyocyte viability through a caspase-3 activation pathway, effect also prevented by PKA inhibition. Taken together, these observations show that succinate acts as a signaling molecule in cardiomyocytes, modulating global Ca(2+) transient and cell viability through a PKA-dependent pathway. 2009 Elsevier Ltd. All rights reserved.

  7. Study of the radiolysis of succinic acid - applications in the dosimetry of high doses

    International Nuclear Information System (INIS)

    Andrade e Silva, L.G.

    1978-01-01

    A study is made of the effect of the gama radiation dose and of particle size of succinic acid (fine powder of large crystals) in relation with the formation of CO 2 and CO + H 2 , which are the main gaseous products of radiolysis. A different yield of CO + H 2 is found when the succinic acid is used as powder compared to the material in the form of large crystals. The reason for this difference is searched, studying the influence of heating and sublimation of the succinic acid prior to irradiation. The influence, in the mentioned yield, of the surface area of succinic acid particles, of the presence of oxygen (air) and of the rapid recrystallization of the acid are also studied. The formation of intermediate species in the radiolysis of succinic acid is examined. The system used in ethanol-succinic acid at 77K. Analysis are made using an electronic paramagnetic resonance spectrometer. The possibility of using succinic acid as a dosimeter for high level gama radiation doses is discussed [pt

  8. Interaction of Palmitic Acid with Metoprolol Succinate at the Binding Sites of Bovine Serum Albumin

    Directory of Open Access Journals (Sweden)

    Mashiur Rahman

    2014-12-01

    Full Text Available Purpose: The aim of this study was to characterize the binding profile as well as to notify the interaction of palmitic acid with metoprolol succinate at its binding site on albumin. Methods: The binding of metoprolol succinate to bovine serum albumin (BSA was studied by equilibrium dialysis method (ED at 27°C and pH 7.4, in order to have an insight in the binding chemistry of the drug to BSA in presence and absence of palmitic acid. The study was carried out using ranitidine as site-1 and diazepam as site-2 specific probe. Results: Different analysis of binding of metoprolol succinate to bovine serum albumin suggested two sets of association constants: high affinity association constant (k1 = 11.0 x 105 M-1 with low capacity (n1 = 2 and low affinity association (k2 = 4.0×105 M-1 constant with high capacity (n2 = 8 at pH 7.4 and 27°C. During concurrent administration of palmitic acid and metoprolol succinate in presence or absence of ranitidine or diazepam, it was found that palmitic acid displaced metoprolol succinate from its binding site on BSA resulting reduced binding of metoprolol succinate to BSA. The increment in free fraction of metoprolol succinate was from 26.27% to 55.08% upon the addition of increased concentration of palmitic acid at a concentration of 0×10-5 M to 16×10-5 M. In presence of ranitidine and diazepam, palmitic acid further increases the free fraction of metoprolol succinate from 33.05% to 66.95% and 40.68% to 72.88%, respectively. Conclusion: This data provided the evidence of interaction at higher concentration of palmitic acid at the binding sites on BSA, which might change the pharmacokinetic properties of metoprolol succinate.

  9. Integrated production of cellulosic bioethanol and succinic acid from industrial hemp in a biorefinery concept

    DEFF Research Database (Denmark)

    Kuglarz, Mariusz; Alvarado-Morales, Merlin; Karakashev, Dimitar Borisov

    2016-01-01

    The aim of this study was to develop integrated biofuel (cellulosic bioethanol) and biochemical (succinic acid) production from industrial hemp (Cannabis sativa L.) in a biorefinery concept. Two types of pretreatments were studied (dilute-acid and alkaline oxidative method). High cellulose recovery...... productivity. With respect to succinic acid production, the highest productivity was obtained after liquid fraction fermentation originated from steam treatment with 1.5% of acid. The mass balance calculations clearly showed that 149 kg of EtOH and 115 kg of succinic acid can be obtained per 1 ton of dry hemp....... Results obtained in this study clearly document the potential of industrial hemp for a biorefinery....

  10. Synthesis, characterization of thiolated karaya gum and evaluation of effect of pH on its mucoadhesive and sustained release properties.

    Science.gov (United States)

    Bahulkar, Swati S; Munot, Neha M; Surwase, Sachin S

    2015-10-05

    Present study aims at synthesis and characterization of thiolated gum karaya by reacting karaya gum with 80% thioglycolic acid resulting in esterification and immobilization of thiol groups on polymeric backbone. Immobilized thiol groups were found to be 5.026 mM/g determined by Ellman's method. It was characterized by FTIR, DSC and XRD. Directly compressible tablets prepared using thiolated gum displayed more disintegration time, swelling and mucoadhesion with increase in pH of medium simulating gastric and intestinal environment than plain gum. Controlled drug release for more than 24h by Fickian diffusion following Korsemeyer-Peppas model was observed with Metoprolol Succinate as a model drug as compared to plain gum which released more than 90% of the drug within 2h. Synthesized thiomer showed no cytotoxicity determined using HepG2 cell line. According to these results, thiolated gum karaya seems to be promising excipient for the development of mucoadhesive drug delivery systems. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Synthesis and characterization of a novel multiblock copolyester containing poly(ethylene succinate) and poly(butylene succinate)

    International Nuclear Information System (INIS)

    Zhu Qunying; He Yisong; Zeng Jianbing; Huang Qing; Wang Yuzhong

    2011-01-01

    Highlights: → High-molecular-weight biodegradable multiblock copolyester containing PBS and PES segments was achieved. → PBS and PES are miscible with a single glass transition regardless of composition. → The multiblock copolyester showed excellent tensile strength and elongation at break. → The multiblock copolyester can serve as a potential substitute for conventional non-biodegradable commodity plastics. - Abstract: Multiblock copolyester (PBS-b-PES) containing poly(butylene succinate) (PBS) and poly(ethylene succinate) (PES) was successfully synthesized by chain-extension of dihydroxyl terminated PBS (HO-PBS-OH) and PES (HO-PES-OH) using 1,6-hexmethylene diisocyanate (HDI) as a chain extender. The chemical structures, molecular weights, crystallization behaviors, thermal and mechanical properties of the copolyesters were characterized by proton nuclear magnetic resonance spectroscopy ( 1 H NMR), gel permeation chromatography (GPC), differential scanning calorimetry (DSC), thermogravimetry analysis (TGA), wide-angle X-ray diffraction (WAXD), tensile testing and hydrolytic degradation. High-molecular-weight copolyesters with M w more than 2.0 x 10 5 g mol -1 were easily obtained through chain-extension. The copolyesters showed a single glass transition temperature (T g ) which increased with PES content. The melting point temperature (T m ) and relative degree of crystallinity (X c ) of the copolyesters decreased first and then increased with PES content. The copolyesters manifested excellent mechanical properties, for example, PBS 5 -b-PES 5 had fracture stress of 61.8 MPa and fracture strain of 1173%. The chain-extension reaction provided a very effective way to produce high molecular weight multiblock copolyesters.

  12. Nano self-assembly of recombinant human gelatin conjugated with α-tocopheryl succinate for Hsp90 inhibitor, 17-AAG, delivery.

    Science.gov (United States)

    Won, Young-Wook; Yoon, Sun-Mi; Sonn, Chung Hee; Lee, Kyung-Mi; Kim, Yong-Hee

    2011-05-24

    A wide variety of drug delivery systems have been developed for the delivery of anticancer agents. One of the most frequently used natural biomaterials in drug delivery systems is polysaccharides; however, they are difficult to digest and to eliminate from the body after systemic administration due to their high molecular weight natures and the absence of degrading enzymes. Therefore, the development of degradable and eliminable natural biomaterials is critical for successful in vivo applications. In the present study, we report the development of self-assembled biodegradable nanoparticles based on recombinant human gelatin (rHG) modified with alpha-tocopheryl succinate (TOS). The rHG-TOS nanoparticles efficiently encapsulated 17-AAG (17-allylamino-17-demethoxygeldanamycin), a small molecular anticancer drug targeting heat shock protein 90. The formation of 17-AAG-loaded nanoparticles was confirmed using TEM and dynamic light scattering analysis and found to be within the size of 90-220 nm. The loading efficiency, sustained release pattern, and stability of 17-AAG from the rHG-TOS nanoparticles were determined using HPLC. Furthermore, the passive targeting of rHG-TOS nanoparticles to the tumor area via enhanced permeability and retention effect was examined by noninvasive live animal imaging in a tumor mouse model. Finally, the 17-AAG-loaded nanoparticles were nonimmunogenic and more efficient than free 17-AAG in manifesting an anticancer effect in the tumor model. Overall, our data demonstrate rHG-TOS as a promising tool for the delivery of 17-AAG featuring therapeutic efficacy and biocompatibility.

  13. A fixed-dose combination tablet of gemigliptin and metformin sustained release has comparable pharmacodynamic, pharmacokinetic, and tolerability profiles to separate tablets in healthy subjects.

    Science.gov (United States)

    Park, Sang-In; Lee, Howard; Oh, Jaeseong; Lim, Kyoung Soo; Jang, In-Jin; Kim, Jeong-Ae; Jung, Jong Hyuk; Yu, Kyung-Sang

    2015-01-01

    sustained release can be a convenient therapeutic option in patients with type 2 diabetes mellitus requiring a combination approach.

  14. Nanocomposite hydrogels stabilized by self-assembled multivalent bisphosphonate-magnesium nanoparticles mediate sustained release of magnesium ion and promote in-situ bone regeneration.

    Science.gov (United States)

    Zhang, Kunyu; Lin, Sien; Feng, Qian; Dong, Chaoqun; Yang, Yanhua; Li, Gang; Bian, Liming

    2017-12-01

    Hydrogels are appealing biomaterials for applications in regenerative medicine due to their tunable physical and bioactive properties. Meanwhile, therapeutic metal ions, such as magnesium ion (Mg 2+ ), not only regulate the cellular behaviors but also stimulate local bone formation and healing. However, the effective delivery and tailored release of Mg 2+ remains a challenge, with few reports on hydrogels being used for Mg 2+ delivery. Bisphosphonate exhibits a variety of specific bioactivities and excellent binding affinity to multivalent cations such as Mg 2+ . Herein, we describe a nanocomposite hydrogel based on hyaluronic acid and self-assembled bisphosphonate-magnesium (BP-Mg) nanoparticles. These nanoparticles bearing acrylate groups on the surface not only function as effective multivalent crosslinkers to strengthen the hydrogel network structure, but also promote the mineralization of hydrogels and mediate sustained release of Mg 2+ . The released Mg 2+ ions facilitate stem cell adhesion and spreading on the hydrogel substrates in the absence of cell adhesion ligands, and promote osteogenesis of the seeded hMSCs in vitro. Furthermore, the acellular porous hydrogels alone can support in situ bone regeneration without using exogenous cells and inductive agents, thereby greatly simplifying the approaches of bone regeneration therapy. In this study, we developed a novel bioactive nanocomposite hydrogel based on hyaluronic acid and self-assembled bisphosphonate-magnesium (BP-Mg) nanoparticles. Such hydrogels are stabilized by the multivalent crosslinking domains formed by the aggregation of Ac-BP-Mg NPs, and therefore show enhanced mechanical properties, improved capacity for mineralization, and controlled release kinetics of Mg 2+ . Moreover, the released Mg 2+ can enhance cell adhesion and spreading, and further promote the osteogenic differentiation of hMSCs. Owing to these unique properties, these acellular hydrogels alone can well facilitate the in vivo

  15. Preparation of sustained release matrix pellets by melt agglomeration in the fluidized bed: influence of formulation variables and modelling of agglomerate growth.

    Science.gov (United States)

    Pauli-Bruns, Anette; Knop, Klaus; Lippold, Bernhard C

    2010-03-01

    The one-step preparation of sustained release matrix pellets, using a melting procedure in a fluidized bed apparatus, was tested in a 2(3) full factorial design of experiments, using microcrystalline wax as lipophilic binder, theophylline as model drug and talc as additional matrix forming agent. The three influence parameters were (A) size of binder particles, (B) fraction of theophylline in solid particles and (C) fraction of microcrystalline wax in formulation. The response variables were agglomerate size and size distribution, dissolution time, agglomerate crush resistance, sphericity, yield and porosity. Nearly spherical pellets comprising a smooth, closed surface could be obtained with the used method, exhibiting the hollow core typical for the immersion and layering mechanism. The reproducibility was very good concerning all responses. The size of agglomerates is proportional to the size of the binder particles, which serve as cores for pellet formation in the molten state in the fluidized bed. Additionally, the agglomerate size is influenced by the volume of the solid particles in relation to the binder particles, with more solid particles leading to larger agglomerates and vice versa. Dissolution times vary in a very wide range, resulting from the interplay between amount of drug in relation to the meltable matrix substance microcrystalline wax and the non-meltable matrix substance talc. The change of binder particle size does not lead to a structural change of the matrix; both dissolution times and porosity are not significantly altered. Agglomerate crush resistance is low due to the hollow core of the pellets. However, it is significantly increased if the volume fraction of microcrystalline wax in the matrix is high, which means that the matrix is mechanically better stabilized. A theoretical model has been established to quantitatively explain agglomerate growth and very good accordance of the full particle size distributions between predicted and

  16. Metabolic Effects of a Succinic Acid

    Directory of Open Access Journals (Sweden)

    B. N. Shakh

    2014-01-01

    Full Text Available The paper discusses promises for clinical use of substrate antihypoxants.Objective: to investigate the efficacy of succinate containing  substrate  antihypoxants  on  systemic  oxygen  consumption,  blood  buffer  capacity,  and  changes  in  the  mixed venous blood level of lactate when they are used in gravely sick patients and victims with marked metabolic posthypoxic disorders.Subjects and methods. The trial enrolled 30 patients and victims who had sustained an episode of severe hypoxia of mixed genesis, the severity of which was evaluated by the APACHE II scale and amounted to 23 to 30 scores with a 46 to 70.3% risk of death. The standard infusion program in this group involved the succinate-containing drug 1.5% reamberin solution  in  a  total  dose  of  800  ml.  A  comparison  group  included  15  patients  who  had  undergone  emergency  extensive surgery for abdominal diseases. 400 ml of 10% glucose solution was used as an infusion medium. Oxygen consumption (VO2ml/min and carbon dioxide production (VCO2ml/min were measured before infusion and monitored for 2 hours. Arterial blood gases and acid-base balance (ABB parameters and mixed venous blood lactate levels were examined. Measurements were made before and 30 minutes after the infusion of reamberin or glucose solution.Results. Infusion of 1.5% reamberin solution was followed by a significant increase in minute oxygen consumption from 281.5±21.2 to 310.4±24.4 ml/min. CO2 production declined (on average, from 223.3±6.5 to 206.5±7.59 ml/min. During infusion of 10% glucose solution, all the patients of the comparison group showed a rise in oxygen consumption from 303.6±33.86 to 443.13±32.1 ml/min, i.e. about 1.5-fold. VCO2 changed similarly. The intravenous infusion of 800 ml of 1.5% reamberin solution raised arterial blood buffer capacity, which was reflected by changes in pH, BE, and HCO3. There was a clear trend for lactate values to drop in the

  17. Multifunctional nanobiocomposite of Poly[(butylene succinate)-co-adipate] and clay

    CSIR Research Space (South Africa)

    Al-Thabaiti, SA

    2015-03-01

    Full Text Available The processing and characterization of multifunctional nanobiocomposite of biodegradable poly[(butylene succinate)-co-adipate] (PBSA) and organically modified synthetic fluorine mica (OSFM) are reported. The nanobiocomposite of PBSA with OSFM...

  18. Separation and Concentration of Succinic Adic from Multicomponent Aqueous Solutions by Nanofiltration Technique

    Directory of Open Access Journals (Sweden)

    Antczak Jerzy

    2014-06-01

    Full Text Available This paper applies the determined suitability of nanofiltration (NF membrane separation for selective isolation and concentration of succinic acid from aqueous solutions which are post-fermentation multicomponent fluids. The study analyzed the influence of concentration and the pH of the separated solutions on the efficiency and selectivity of NF process that runs in a module equipped with a ceramic membrane. Moreover, the effect of applied trans-membrane pressure on the retention of succinic acid and sodium succinate has been studied. The investigations have shown that in the used NF module the retention of succinic acid salt is equal almost 50% in the case of a three-component model solution, although the degree of retention depends on both the transmembrane pressure and the initial concentration of separated salt.

  19. 76 FR 59141 - Determination That LOXITANE (Loxapine Succinate) Capsules and Three Other Drug Products Were Not...

    Science.gov (United States)

    2011-09-23

    ... Applicant NDA 017525 LOXITANE (loxapine Watson Laboratories succinate) Inc., 417 Wakara Capsules, Way, Suite.../milliliter. NDA 020828 FORTOVASE Hoffmann La Roche (saquinavir) Inc., 340 Kingsland Capsule, 200 mg. St...

  20. Acetate:succinate CoA-transferase in the hydrogenosomes of Trichomonas vaginalis: Identification and characterization

    NARCIS (Netherlands)

    K.W.A. Grinsven; S. Rosnowsky (Silke); S.W.H. van Weelden (Susanne); S. Pütz (Simone); M. van der Giezen (Mark); W. Martin (William); J.J. van Hellemond (Jaap); A.G.M. Tielens (Aloysius); K. Henze (Katrin)

    2008-01-01

    textabstractAcetate:succinate CoA-transferases (ASCT) are acetate-producing enzymes in hydrogenosomes, anaerobically functioning mitochondria and in the aerobically functioning mitochondria of trypanosomatids. Although acetate is produced in the hydrogenosomes of a number of anaerobic microbial

  1. Industrial systems biology of Saccharomyces cerevisiae enables novel succinic acid cell factory.

    Directory of Open Access Journals (Sweden)

    José Manuel Otero

    Full Text Available Saccharomyces cerevisiae is the most well characterized eukaryote, the preferred microbial cell factory for the largest industrial biotechnology product (bioethanol, and a robust commerically compatible scaffold to be exploitted for diverse chemical production. Succinic acid is a highly sought after added-value chemical for which there is no native pre-disposition for production and accmulation in S. cerevisiae. The genome-scale metabolic network reconstruction of S. cerevisiae enabled in silico gene deletion predictions using an evolutionary programming method to couple biomass and succinate production. Glycine and serine, both essential amino acids required for biomass formation, are formed from both glycolytic and TCA cycle intermediates. Succinate formation results from the isocitrate lyase catalyzed conversion of isocitrate, and from the α-keto-glutarate dehydrogenase catalyzed conversion of α-keto-glutarate. Succinate is subsequently depleted by the succinate dehydrogenase complex. The metabolic engineering strategy identified included deletion of the primary succinate consuming reaction, Sdh3p, and interruption of glycolysis derived serine by deletion of 3-phosphoglycerate dehydrogenase, Ser3p/Ser33p. Pursuing these targets, a multi-gene deletion strain was constructed, and directed evolution with selection used to identify a succinate producing mutant. Physiological characterization coupled with integrated data analysis of transcriptome data in the metabolically engineered strain were used to identify 2(nd-round metabolic engineering targets. The resulting strain represents a 30-fold improvement in succinate titer, and a 43-fold improvement in succinate yield on biomass, with only a 2.8-fold decrease in the specific growth rate compared to the reference strain. Intuitive genetic targets for either over-expression or interruption of succinate producing or consuming pathways, respectively, do not lead to increased succinate. Rather, we

  2. Improved sugar-free succinate production by Synechocystis sp. PCC 6803 following identification of the limiting steps in glycogen catabolism

    Directory of Open Access Journals (Sweden)

    Tomohisa Hasunuma

    2016-12-01

    Full Text Available Succinate produced by microorganisms can replace currently used petroleum-based succinate but typically requires mono- or poly-saccharides as a feedstock. The cyanobacterium Synechocystis sp. PCC6803 can produce organic acids such as succinate from CO2 not supplemented with sugars under dark anoxic conditions using an unknown metabolic pathway. The TCA cycle in cyanobacteria branches into oxidative and reductive routes. Time-course analyses of the metabolome, transcriptome and metabolic turnover described here revealed dynamic changes in the metabolism of Synechocystis sp. PCC6803 cultivated under dark anoxic conditions, allowing identification of the carbon flow and rate-limiting steps in glycogen catabolism. Glycogen biosynthesized from CO2 assimilated during periods of light exposure is catabolized to succinate via glycolysis, the anaplerotic pathway, and the reductive TCA cycle under dark anoxic conditions. Expression of the phosphoenolpyruvate (PEP carboxylase gene (ppc was identified as a rate-limiting step in succinate biosynthesis and this rate limitation was alleviated by ppc overexpression, resulting in improved succinate excretion. The sugar-free succinate production was further enhanced by the addition of bicarbonate. In vivo labeling with NaH13CO3 clearly showed carbon incorporation into succinate via the anaplerotic pathway. Bicarbonate is in equilibrium with CO2. Succinate production by Synechocystis sp. PCC6803 therefore holds significant promise for CO2 capture and utilization. Keywords: Autofermentation, Cyanobacteria, Dynamic metabolic profiling, Metabolomics, Succinate, Synechocystis

  3. Production of succinic acid from oil palm empty fruit bunch cellulose using Actinobacillus succinogenes

    Science.gov (United States)

    Pasma, Satriani Aga; Daik, Rusli; Maskat, Mohamad Yusof

    2013-11-01

    Succinic acid is a common metabolite in plants, animals and microorganisms. It has been used widely in agricultural, food and pharmaceutical industries. Enzymatic hydrolysate glucose from oil palm empty fruit bunch (OPEFB) cellulose was used as a substrate for succinic acid production using Actinobacillus succinogenes. Using cellulose extraction from OPEFB can enhance the production of glucose as a main substrate for succinic acid production. The highest concentration of glucose produced from enzymatic hydrolysis is 167 mg/mL and the sugar recovery is 0.73 g/g of OPEFB. By optimizing the culture medium for succinic acid fermentation with enzymatic hydrolysate of OPEFB cellulose, the nitrogen sources could be reduced to just only 2.5 g yeast extract and 2.5 g corn step liquor. Batch fermentation was carried out using enzymatic hydrolysate of OPEFB cellulose with yeast extract, corn steep liquor and the salts mixture, 23.5 g/L succinic acid was obtained with consumption of 72 g/L glucose in enzymatic hydrolysate of OPEFB cellulose at 38 hours and 37°C. This study suggests that enzymatic hydrolysate of OPEFB cellulose maybe an alternative substrate for the efficient production of succinic acid by Actinobacillus succinogenes.

  4. Succinic acid production from xylose mother liquor by recombinant Escherichia coli strain.

    Science.gov (United States)

    Wang, Honghui; Pan, Jiachuan; Wang, Jing; Wang, Nan; Zhang, Jie; Li, Qiang; Wang, Dan; Zhou, Xiaohua

    2014-11-02

    Succinic acid (1,4-butanedioic acid) is identified as one of important building-block chemicals. Xylose mother liquor is an abundant industrial residue in xylitol biorefining industry. In this study, xylose mother liquor was utilized to produce succinic acid by recombinant Escherichia coli strain SD121, and the response surface methodology was used to optimize the fermentation media. The optimal conditions of succinic acid fermentation were as follows: 82.62 g L -1 total initial sugars, 42.27 g L -1 MgCO 3 and 17.84 g L -1 yeast extract. The maximum production of succinic acid was 52.09 ± 0.21 g L -1 after 84 h with a yield of 0.63 ± 0.03 g g -1 total sugar, approaching the predicted value (53.18 g L -1 ). It was 1.78-fold of the production of that obtained with the basic medium. This was the first report on succinic acid production from xylose mother liquor by recombinant E. coli strains with media optimization using response surface methodology. This work suggested that the xylose mother liquor could be an alternative substrate for the economical production of succinic acid by recombinant E. coli strains.

  5. Succinic acid production by Actinobacillus succinogenes using hydrolysates of spent yeast cells and corn fiber.

    Science.gov (United States)

    Chen, Ke-Quan; Li, Jian; Ma, Jiang-Feng; Jiang, Min; Wei, Ping; Liu, Zhong-Min; Ying, Han-Jie

    2011-01-01

    The enzymatic hydrolysate of spent yeast cells was evaluated as a nitrogen source for succinic acid production by Actinobacillus succinogenes NJ113, using corn fiber hydrolysate as a carbon source. When spent yeast cell hydrolysate was used directly as a nitrogen source, a maximum succinic acid concentration of 35.5 g/l was obtained from a glucose concentration of 50 g/l, with a glucose utilization of 95.2%. Supplementation with individual vitamins showed that biotin was the most likely factor to be limiting for succinic acid production with spent yeast cell hydrolysate. After supplementing spent yeast cell hydrolysate and 90 g/l of glucose with 150 μg/l of biotin, cell growth increased 32.5%, glucose utilization increased 37.6%, and succinic acid concentration was enhanced 49.0%. As a result, when biotin-supplemented spent yeast cell hydrolysate was used with corn fiber hydrolysate, a succinic acid yield of 67.7% was obtained from 70.3 g/l of total sugar concentration, with a productivity of 0.63 g/(l h). Our results suggest that biotin-supplemented spent yeast cell hydrolysate may be an alternative nitrogen source for the efficient production of succinic acid by A. succinogenes NJ113, using renewable resources. Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.

  6. Biotechnological route for sustainable succinate production utilizing oil palm frond and kenaf as potential carbon sources.

    Science.gov (United States)

    Luthfi, Abdullah Amru Indera; Manaf, Shareena Fairuz Abdul; Illias, Rosli Md; Harun, Shuhaida; Mohammad, Abdul Wahab; Jahim, Jamaliah Md

    2017-04-01

    Due to the world's dwindling energy supplies, greater thrust has been placed on the utilization of renewable resources for global succinate production. Exploration of such biotechnological route could be seen as an act of counterbalance to the continued fossil fuel dominance. Malaysia being a tropical country stands out among many other nations for its plenty of resources in the form of lignocellulosic biomass. To date, oil palm frond (OPF) contributes to the largest fraction of agricultural residues in Malaysia, while kenaf, a newly introduced fiber crop with relatively high growth rate, holds great potential for developing sustainable succinate production, apart from OPF. Utilization of non-food, inexhaustible, and low-cost derived biomass in the form of OPF and kenaf for bio-based succinate production remains largely untapped. Owing to the richness of carbohydrates in OPF and kenaf, bio-succinate commercialization using these sources appears as an attractive proposition for future sustainable developments. The aim of this paper was to review some research efforts in developing a biorefinery system based on OPF and kenaf as processing inputs. It presents the importance of the current progress in bio-succinate commercialization, in addition to describing the potential use of different succinate production hosts and various pretreatments-saccharifications under development for OPF and kenaf. Evaluations on the feasibility of OPF and kenaf as fermentation substrates are also discussed.

  7. Radioprotective properties of tocopherol succinate against ionizing radiation in mice

    International Nuclear Information System (INIS)

    Singh, V.K.; Singh, P.K.; Wise, S.Y.; Posarac, A.; Fatanmi, O.O.

    2013-01-01

    Threats of nuclear and other radiologic exposures have been increasing but no countermeasure for acute radiation syndrome has been approved by regulatory authorities. In prior publications we have demonstrated the efficacy of tocopherol succinate (TS) as a promising radiation countermeasure with the potential to protect against lethal doses of ionizing radiation exposure. The aim of this study was to gain further insight regarding how TS protects mice against a lethal dose of radiation. CD2F1 mice were injected subcutaneously with 400 mg/kg of TS, and 24 h later exposed to 60 Co γ-radiation. Intestinal tissues or spleen/thymus were harvested after irradiation and analyzed for CD68-positive inflammatory cells and apoptotic cells by immunostaining of jejunal cross-sections. Comet assay was used to analyze DNA damage in various tissues. Phospho-histone H3 (pH3) and the proliferating cell nuclear antigen (PCNA) were used as mitotic markers for immunostaining jejunal cross-sections. We observed that injecting TS significantly decreased the number of CD68-positive cells, DNA damage and apoptotic cells (bcl-associated X protein (BAX), caspase 3 and cleaved poly (ADP-ribose) polymerase-positive cells) as judged by various apoptotic pathway markers. TS treatment also increased proliferating cells in irradiated mice. Results of this study further support our contention that TS protects mice against lethal doses of ionizing radiation by inhibiting radiation-induced apoptosis and DNA damage while enhancing cell proliferation. (author)

  8. Metoprolol succinate extended release/hydrochlorothiazide combination tablets

    Directory of Open Access Journals (Sweden)

    James W Hainer

    2007-07-01

    Full Text Available James W Hainer, Jennifer SuggAstraZeneca LP, Wilmington, DE, USAAbstract: Lowering elevated blood pressure (BP with drug therapy reduces the risk for catastrophic fatal and nonfatal cardiovascular events such as stroke and myocardial infarction. Given the heterogeneity of hypertension as a disease, the marked variability in an individual patient’s BP response, and low response rates with monotherapy, expert groups such as the Joint National Committee (JNC emphasize the value of combination antihypertensive regimens, noting that combinations, usually of different classes, have additive antihypertensive effects. Metoprolol succinate extended-release tablet is a beta-1 (cardio-selective adrenoceptor-blocking agent formulated to provide controlled and predictable release of metoprolol. Hydrochlorothiazide (HCT is a well-established diuretic and antihypertensive agent, which promotes natruresis by acting on the distal renal tubule. The pharmacokinetics, efficacy, and safety/tolerability of the antihypertensive combination tablet, metoprolol extended release hydrochlorothiazide, essentially reflect the well-described independent characteristics of each of the component agents. Not only is the combination product more effective than monotherapy with the individual components but the combination product allows a low-dose multidrug regimen as an alternative to high-dose monotherapy, thereby, minimizing the likelihood of dose-related side-effects.Keywords: antihypertensive, blood pressure, cardiovascular disease, combination product

  9. Sustained-release liquisolid compact tablets containing artemether-lumefantrine as alternate-day regimen for malaria treatment to improve patient compliance

    Directory of Open Access Journals (Sweden)

    Nnamani PO

    2016-11-01

    yield and encapsulation efficiency were ~92% and 93% for Precirol® ATO 5/Transcutol® HP batch, then 81% and 95% for tallow fat/Transcutol® HP batch while LUM was amorphous in NLC matrix. In vitro AL release from liquisolid compacts revealed initial burst release and subsequent sustained release. Liquisolid tablet compacts formulated with Precirol® ATO 5/Transcutol® HP-AL4 achieved higher LUM release in simulated intestinal fluid (84.32% than tallow fat/Transcutol® HP-BL3 (77.9%. Non-Fickian (anomalous diffusion and super case II transport were the predominant mechanisms of drug release. Equal parasitemia reduction was observed for both batches of tablet compacts (~92%, superior to the reduction obtained with commercial antimalarial formulations: Coartem® tablets (86% and chloroquine phosphate tablets (66%. No significant difference (P<0.05 in parasite reduction between double (4/24 mg/kg and single (2/12 mg/kg strength doses of AL compacts was observed. Our result highlights that AL could be formulated in much lower doses (4/24 mg/kg, for once-in-two days oral administration to improve patient compliance, which is currently not obtainable with conventional AL dosage forms. Keywords: malaria, artemisinin-based combination therapy, antiplasmodial activity, liquisolid compacts, nanostructured lipid carriers

  10. A fixed-dose combination tablet of gemigliptin and metformin sustained release has comparable pharmacodynamic, pharmacokinetic, and tolerability profiles to separate tablets in healthy subjects

    Directory of Open Access Journals (Sweden)

    Park SI

    2015-02-01

    time curves of the FDC and the separate tablets almost overlapped, leading to a GMR (90% CI of the FDC to separate tablets for the plasma DPP-4 activity and its maximum inhibition of 1.00 (0.97–1.04 and 0.92 (0.82–1.05, respectively. Likewise, all of the GMRs (90% CIs of FDC to separate tablets for the area under the plasma concentration–time curve and maximum plasma concentration of gemigliptin and metformin fell entirely within the conventional bioequivalence range of 0.80–1.25. Both the FDC and separate tablets were well tolerated.Conclusion: The PD, PK, and tolerability profiles of gemigliptin and metformin XR in FDC and separate tablets were found to be comparable. The FDC tablet of gemigliptin and metformin sustained release can be a convenient therapeutic option in patients with type 2 diabetes mellitus requiring a combination approach. Keywords: dipeptidyl peptidase 4, DPP-4 inhibitor, type 2 diabetes mellitus, T2DM

  11. Efficacy and tolerability of bilateral sustained-release dexamethasone intravitreal implants for the treatment of noninfectious posterior uveitis and macular edema secondary to retinal vein occlusion

    Directory of Open Access Journals (Sweden)

    Ryder SJ

    2015-06-01

    Full Text Available Steven J Ryder,1 Danilo Iannetta,1 Swetangi D Bhaleeya,2 Szilárd Kiss1 1Department of Ophthalmology, Weill Cornell Medical College, New York, NY, USA; 2Department of Ophthalmology, University of South Florida, Tampa, FL, USA Purpose: To report our experience with bilateral placement of dexamethasone 0.7 mg (DEX sustained-release intravitreal implant in the management of noninfectious posterior uveitis or macular edema secondary to retinal vein occlusion.Methods: A retrospective chart review of patients with bilateral noninfectious posterior uveitis and macular edema secondary to retinal vein occlusion who were treated with DEX intravitreal implant was performed. Ocular side effects such as intraocular pressure (IOP, cataract, and tolerability of bilateral injections was reviewed.Results: Twenty-two eyes of eleven patients treated with a total of 32 DEX implants were included. Ten of eleven patients received bilateral implants due to active noninfectious uveitis while the other demonstrated macular edema in both eyes following separate central retinal vein occlusions. Among the patients with bilateral uveitis, the mean interval between DEX implant in the initial eye and the subsequent DEX in the fellow eye was 15.6 days (range 2–71 days. Seven of the ten patients received the second implant in the fellow eye within 8 days of the initial implantation. None of the patients had bilateral implantations on the same day. Seven eyes required reimplantation for recurrence of inflammation (mean interval between first and repeat implantation was 6.00±2.39 months. Following single or, in the case of the aforementioned seven eyes, repeat DEX implantation, all 20 uveitic eyes demonstrated clinical and/or angiographic evidence of decreased inflammation in the form of reduction in vitreous cells on slit lamp ophthalmoscopy, macular edema on ophthalmoscopy, or optical coherence tomography and/or disc and vascular leakage on fluorescein angiography. The mean

  12. Effectiveness and Safety of Transdermal Buprenorphine Versus Sustained-release Tramadol in Patients With Moderate to Severe Musculoskeletal Pain: An 8-Week, Randomized, Double-Blind, Double-Dummy, Multicenter, Active-controlled, Noninferiority Study.

    Science.gov (United States)

    Leng, Xiaomei; Li, Zhanguo; Lv, Houshan; Zheng, Yi; Liu, Yi; Dai, Kerong; Yao, Chen; Yan, Xiaoyan; Zeng, Xiaofeng

    2015-07-01

    The aim of this noninferiority study was to investigate clinical effectiveness and safety of buprenorphine transdermal system (BTDS) in patients with moderate to severe musculoskeletal pain inadequately controlled with nonsteroidal anti-inflammatory drugs, compared with sustained-release tramadol tablets. Eligible patients were randomized (1:1) to receive low-dose 7-day BTDS (5, 10, and 20 μg/h, maximum dosage of 20 μg/h) or sustained-release tramadol tablets (100 mg, maximum dosage of 400 mg/d) over an 8-week double-blind treatment period (3-week titration, 5-week maintenance). The primary endpoint was the difference in the visual analogue scale (VAS) pain scores from baseline to treatment completion. Noninferiority was assumed if the treatment difference on the VAS scale was within ±1.5 cm, this threshold indicating a clinically meaningful result. ClinicalTrials.gov identifier: NCT01476774. Two hundred eighty patients were randomized to BTDS (n=141) or to tramadol (n=139). Both treatments were associated with a significant reduction in pain by the end of the treatment. The least squares mean difference of the change from baseline in VAS scores between the BTDS and tramadol groups were 0.45 (95% confidence interval, -0.02 to 0.91), which was within the ±1.5 cm predefined threshold, indicating that the effectiveness of BTDS was not inferior to the effectiveness of sustained-release tramadol tablets. The incidence of adverse events was comparable between the 2 treatment groups. Our results suggest that BTDS is a good therapeutic option for patients experiencing chronic musculoskeletal pain of moderate to severe intensity that is insufficiently controlled by nonsteroidal anti-inflammatory drugs.

  13. Compatibility of ondansetron hydrochloride and methylprednisolone sodium succinate in multilayer polyolefin containers.

    Science.gov (United States)

    Bougouin, Christelle; Thelcide, Chloë; Crespin-Maillard, Fabienne; Maillard, Christian; Kinowski, Jean Marie; Favier, Mireille

    2005-10-01

    The compatibility of ondansetron hydrochloride and methylprednisolone sodium succinate in 5% dextrose injection and 0.9% sodium chloride injection was studied. Test solutions of ondansetron hydrochloride 0.16 mg/mL and methylprednisolone sodium succinate 2.4 mg/mL were prepared in triplicate and tested in duplicate. Total volumes of 4 and 2 mL of ondansetron hydrochloride solution and methylprednisolone sodium succinate solution, respectively, were added to 50-mL multilayer polyolefin bags containing 5% dextrose injection or 0.9% sodium chloride injection. Bags were stored for 24 hours at 20-25 degrees C and for 48 hours at 4-8 degrees C. Chemical compatibility was measured with high-performance liquid chromatography, and physical compatibility was determined visually. Ondansetron hydrochloride was stable for up to 24 hours at 20-25 degrees C and up to 48 hours at 4-8 degrees C. Methylprednisolone sodium succinate was stable for up to 48 hours at 4-8 degrees C. When stored at 20-25 degrees C, methylprednisolone sodium succinate was stable for up to 7 hours in 5% dextrose injection and up to 24 hours in 0.9% sodium chloride injection. Compatibility data for solutions containing ondansetron hydrochloride plus methylprednisolone sodium succinate revealed that each drug was stable for up to 24 hours at 20-25 degrees C and up to 48 hours at 4-8 degrees C. Ondansetron 0.16 mg/mL (as the hydrochloride) and methylprednisolone 2.4 mg/mL (as the sodium succinate) mixed in 50-mL multilayer polyolefin bags were stable in both 5% dextrose injection and 0.9% sodium chloride injection for up to 24 hours at 20-25 degrees C and up to 48 hours at 4-8 degrees C.

  14. Bio-oil based biorefinery strategy for the production of succinic acid

    Science.gov (United States)

    2013-01-01

    Background Succinic acid is one of the key platform chemicals which can be produced via biotechnology process instead of petrochemical process. Biomass derived bio-oil have been investigated intensively as an alternative of diesel and gasoline fuels. Bio-oil could be fractionized into organic phase and aqueous phase parts. The organic phase bio-oil can be easily upgraded to transport fuel. The aqueous phase bio-oil (AP-bio-oil) is of low value. There is no report for its usage or upgrading via biological methods. In this paper, the use of AP-bio-oil for the production of succinic acid was investigated. Results The transgenic E. coli strain could grow in modified M9 medium containing 20 v/v% AP-bio-oil with an increase in OD from 0.25 to 1.09. And 0.38 g/L succinic acid was produced. With the presence of 4 g/L glucose in the medium, succinic acid concentration increased from 1.4 to 2.4 g/L by addition of 20 v/v% AP-bio-oil. When enzymatic hydrolysate of corn stover was used as carbon source, 10.3 g/L succinic acid was produced. The obtained succinic acid concentration increased to 11.5 g/L when 12.5 v/v% AP-bio-oil was added. However, it decreased to 8 g/L when 50 v/v% AP-bio-oil was added. GC-MS analysis revealed that some low molecular carbon compounds in the AP-bio-oil were utilized by E. coli. Conclusions The results indicate that AP-bio-oil can be used by E. coli for cell growth and succinic acid production. PMID:23657107

  15. Genotoxicity of meso-2,3-dimercapto succinic acid-coated silver sulfide quantum dot

    Directory of Open Access Journals (Sweden)

    Deniz Özkan Vardar

    2015-06-01

    Full Text Available Nanotecnology products have been used in wide applications in chemistry, electronics, energy generation, and medicine. Despite significant interest in developing quantum dots (QDs for biomedical applications, many researchers are convinced that QDs will never be used for the treatment of patients because of their potential toxicity. In various in vitro cell culture studies, the cytotoxic properties of some QD have been demonstrated and they have been suggested to be toxic in humans. In this study, the cytotoxic properties of Ag2S-(Meso-2,3-Dimercapto Succinic acid nanomaterials in V79 cells (Chinese lung fibroblast cell line were determined by MTT assay. The genotoxic effects of Ag2S-(Meso-2,3-Dimercapto Succinic acid were evaluated by the alkaline single cell gel electrophoresis. The cells were treated with Ag2S-(Meso-2,3-Dimercapto Succinic acid at the concentrations of 5- 2000 µg/ml. No cytotoxic effect of Ag2S-(Meso-2,3-Dimercapto Succinic acid at all concentrations studied was observed. No significant increases in DNA damage were found at the studied concentrations when compared to negative control in V79 cells. In conclusion, further in vitro and in vivo studies are required to determine the safety doses of Ag2S-(Meso-2,3-Dimercapto Succinic acid.

  16. A novel process for recovery of fermentation-derived succinic acid: process design and economic analysis.

    Science.gov (United States)

    Orjuela, Alvaro; Orjuela, Andrea; Lira, Carl T; Miller, Dennis J

    2013-07-01

    Recovery and purification of organic acids produced in fermentation constitutes a significant fraction of total production cost. In this paper, the design and economic analysis of a process to recover succinic acid (SA) via dissolution and acidification of succinate salts in ethanol, followed by reactive distillation to form succinate esters, is presented. Process simulation was performed for a range of plant capacities (13-55 million kg/yr SA) and SA fermentation titers (50-100 kg/m(3)). Economics were evaluated for a recovery system installed within an existing fermentation facility producing succinate salts at a cost of $0.66/kg SA. For a SA processing capacity of 54.9 million kg/yr and a titer of 100 kg/m(3) SA, the model predicts a capital investment of $75 million and a net processing cost of $1.85 per kg SA. Required selling price of diethyl succinate for a 30% annual return on investment is $1.57 per kg. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Highly Carboxylated Cellulose Nanofibers via Succinic Anhydride Esterification of Wheat Fibers and Facile Mechanical Disintegration.

    Science.gov (United States)

    Sehaqui, H; Kulasinski, K; Pfenninger, N; Zimmermann, T; Tingaut, P

    2017-01-09

    We report herein the preparation of 4-6 nm wide carboxyl-functionalized cellulose nanofibers (CNF) via the esterification of wheat fibers with cyclic anhydrides (maleic, phtalic, and succinic) followed by an energy-efficient mechanical disintegration process. Remarkable results were achieved via succinic anhydride esterification that enabled CNF isolation by a single pass through the microfluidizer yielding a transparent and thick gel. These CNF carry the highest content of carboxyl groups ever reported for native cellulose nanofibers (3.8 mmol g -1 ). Compared to conventional carboxylated cellulose nanofibers prepared via Tempo-mediated oxidation of wheat fibers, the present esterified CNF display a higher molar-mass and a better thermal stability. Moreover, highly carboxylated CNF from succinic anhydride esterification were effectively integrated into paper filters for the removal of lead from aqueous solution and are potentially of interest as carrier of active molecules or as transparent films for packaging, biomedical or electronic applications.

  18. Thermodynamics of U(VI) complexation by succinate at variable temperatures

    Energy Technology Data Exchange (ETDEWEB)

    Rawat, Neetika [Radiochemistry Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India); Tomar, B.S., E-mail: bstomar@barc.gov.in [Radiochemistry Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India); Manchanda, V.K. [Radiochemistry Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India)

    2011-07-15

    Research highlights: > lg {beta} and {Delta}H{sub C} for U(VI)-succinate determined at variable temperatures. > Increase in lg {beta} with temperature well explained by Born equation. > {Delta}S{sub C} plays the dominant role in variation of {Delta}G{sub C} with temperature. > {Delta}H{sub C} for U(VI)-succinate increases linearly with temperature. > {Delta}C{sub P} of U(VI)-succinate is higher than that of oxalate and malonate complexes. - Abstract: Complexation of U(VI) by succinate has been studied at various temperatures in the range of (298 to 338) K by potentiometry and isothermal titration calorimetry at constant ionic strength (1.0 M). The potentiometric titrations revealed the formation of 1:1 uranyl succinate complex in the pH range of 1.5 to 4.5. The stability constant of uranyl succinate complex was found to increase with temperature. Similar trend was observed in the case of enthalpy of complex formation. However, the increase in entropy with temperature over-compensated the increase in enthalpy, thereby favouring the complexation reaction at higher temperatures. The linear increase of enthalpy of complexation with temperature indicates constancy of the change in heat capacity during complexation. The temperature dependence of stability constant data was well explained with the help of Born equation for electrostatic interaction between the metal ion and the ligand. The data have been compared with those for uranyl complexes with malonate and oxalate to study the effect of ligand size and hydrophobicity on the temperature dependence of thermodynamic quantities.

  19. Formation of itraconazole-succinic acid cocrystals by gas antisolvent cocrystallization.

    Science.gov (United States)

    Ober, Courtney A; Gupta, Ram B

    2012-12-01

    Cocrystals of itraconazole, an antifungal drug with poor bioavailability, and succinic acid, a water-soluble dicarboxylic acid, were formed by gas antisolvent (GAS) cocrystallization using pressurized CO(2) to improve itraconazole dissolution. In this study, itraconazole and succinic acid were simultaneously dissolved in a liquid solvent, tetrahydrofuran, at ambient conditions. The solution was then pressurized with CO(2), which decreased the solvating power of tetrahydrofuran and caused crystallization of itraconazole-succinic acid cocrystals. The cocrystals prepared by GAS cocrystallization were compared to those produced using a traditional liquid antisolvent, n-heptane, for crystallinity, chemical structure, thermal behavior, size and surface morphology, potential clinical relevance, and stability. Powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy analyses showed that itraconazole-succinic acid cocrystals with physical and chemical properties similar to cocrystals produced using a traditional liquid antisolvent technique can be prepared by CO(2) antisolvent cocrystallization. The dissolution profile of itraconazole was significantly enhanced through GAS cocrystallization with succinic acid, achieving over 90% dissolution in less than 2 h. The cocrystals appeared stable against thermal stress for up to 4 weeks under accelerated stability conditions, showing only moderate decreases in their degree of crystallinity but no change in their crystalline structure. This study shows the utility of an itraconazole-succinic acid cocrystal for improving itraconazole bioavailability while also demonstrating the potential for CO(2) to replace traditional liquid antisolvents in cocrystal preparation, thus making cocrystal production more environmentally benign and scale-up more feasible.

  20. Receptor structure-based discovery of non-metabolite agonists for the succinate receptor GPR91

    DEFF Research Database (Denmark)

    Trauelsen, Mette; Rexen Ulven, Elisabeth; Hjorth, Siv A

    2017-01-01

    therefore binds in a very different mode than generally believed. Importantly, an empty side-pocket is identified next to the succinate binding site. All this information formed the basis for a substructure-based search query, which, combined with molecular docking, was used in virtual screening of the ZINC...... database to pick two serial mini-libraries of a total of only 245 compounds from which sub-micromolar, selective GPR91 agonists of unique structures were identified. The best compounds were backbone-modified succinate analogs in which an amide-linked hydrophobic moiety docked into the side-pocket next...

  1. Metabolic Engineering of Saccharomyces cerevisiae Microbial Cell Factories for Succinic Acid Production

    DEFF Research Database (Denmark)

    Otero, José Manuel; Nielsen, Jens; Olsson, Lisbeth

    2007-01-01

    anhydride. There are several biomass platforms, all prokaryotic, for succinic acid production; however, overproduction of succinic acid in S. cerevisiae offers distinct process advantages. For example, S. cerevisiae has been awarded GRAS status for use in human consumables, grows well at low p......H significantly minimizing purification and acidification costs associated with organic acid production, and can utilize diverse carbon substrates in chemically defined medium. S. cerevisiae offers the unique advantage of being the most well characterized eukaryotic expression system. Here we describe the use...

  2. Modification of cellulose with succinic anhydride in TBAA/DMSO mixed solvent under catalyst-free conditions

    Science.gov (United States)

    Homogeneous modification of cellulose with succinic anhydride was performed in tetrabutylammonium acetate (TBAA)/dimethyl sulfoxide (DMSO) mixed solvent. The molar ratio of succinic anhydride (SA) to free hydroxyl groups in the anhydroglucose units (AGU) and TBAA dosage were investigated as paramete...

  3. Modification of cellulose with succinic anhydride in TBAA/DMSO mixed solvent under catalyst-free conditions

    Science.gov (United States)

    Ping-Ping Xin; Yao-Bing Huang; Chung-Yun Hse; Huai N. Cheng; Chaobo Huang; Hui. Pan

    2017-01-01

    Homogeneous modification of cellulose with succinic anhydride was performed using tetrabutylammonium acetate (TBAA)/dimethyl sulfoxide (DMSO) mixed solvent. The molar ratio of succinic anhydride (SA) to free hydroxyl groups in the anhydroglucose units (AGU), TBAA dosage, reaction temperature, and reaction time were investigated. The highest degree of substitution (DS)...

  4. Bio-oil based biorefinery strategy for the production of succinic acid

    DEFF Research Database (Denmark)

    Wang, Caixia; Thygesen, Anders; Liu, Yilan

    2013-01-01

    Background: Succinic acid is one of the key platform chemicals which can be produced via biotechnology process instead of petrochemical process. Biomass derived bio-oil have been investigated intensively as an alternative of diesel and gasoline fuels. Bio-oil could be fractionized into organic...

  5. Formation and stability of Vitamin E enriched nanoemulsions stabilized by Octenyl Succinic Anhydride modified starch

    Science.gov (United States)

    Vitamin E (VE) is highly susceptible to autoxidation; therefore, it requires systems to encapsulate and protect it from autoxidation.In this study,we developed VE delivery systems, which were stabilized by Capsul® (MS), a starch modified with octenyl succinic anhydride. Influences of interfacial ten...

  6. Succinate-based preparation alleviates manifestations of the climacteric syndrome in women.

    Science.gov (United States)

    Peskov, A B; Maevskii, E I; Uchitel', M L; Sakharova, N Yu; Vize-Khripunova, M A

    2005-09-01

    Clinical placebo-controlled study of Enerlit-Clima (bioactive succinate-based food additive) a showed positive effect of the preparation on general clinical and psychoemotional manifestations of the climacteric syndrome. A trend to an increase in estradiol level in early pathological climacteric and normalization of the endometrial status were observed.

  7. Intracellular product recycling in high succinic acid producing yeast at low pH

    NARCIS (Netherlands)

    Wahl, S.A.; Bernal Martinez, C.; Zhao, Zheng; van Gulik, W.M.; Jansen, Mickel L.A.

    2017-01-01

    Background: The metabolic engineering of Saccharomyces cerevisiae for the production of succinic acid has progressed dramatically, and a series of high-producing hosts are available. At low cultivation pH and high titers, the product transport can become bidirectional, i.e. the acid is reentering

  8. Integration of Succinic Acid Production in a Dry Mill Ethanol Facility

    Energy Technology Data Exchange (ETDEWEB)

    None

    2006-08-01

    This project seeks to address both issues for a dry mill ethanol biorefinery by lowering the cost of sugars with the development of an advanced pretreatment process, improving the economics of succinic acid (SA), and developing a model of an ethanol dry mill to evaluate the impact of adding different products and processes to a dry mill.

  9. Viscoelastic and electrical properties of carbon nanotubes filled poly(butylene succinate)

    CSIR Research Space (South Africa)

    Bandyopadhyay, J

    2014-03-01

    Full Text Available The carbon nanotubes (CNTs)-containing composites of poly(butylene succinate) (PBS) were prepared by melt-blending in a batch mixer with three concentrations by weight of CNTs: 1, 2 and 3 %. State of dispersion-distribution of the CNTs in the PBS...

  10. Succinic Acid as a Byproduct in a Corn-based Ethanol Biorefinery

    Energy Technology Data Exchange (ETDEWEB)

    MBI International

    2007-12-31

    MBI endeavored to develop a process for succinic acid production suitable for integration into a corn-based ethanol biorefinery. The project investigated the fermentative production of succinic acid using byproducts of corn mill operations. The fermentation process was attuned to include raw starch, endosperm, as the sugar source. A clean-not-sterile process was established to treat the endosperm and release the monomeric sugars. We developed the fermentation process to utilize a byproduct of corn ethanol fermentations, thin stillage, as the source of complex nitrogen and vitamin components needed to support succinic acid production in A. succinogenes. Further supplementations were eliminated without lowering titers and yields and a productivity above 0.6 g l-1 hr-1was achieved. Strain development was accomplished through generation of a recombinant strain that increased yields of succinic acid production. Isolation of additional strains with improved features was also pursued and frozen stocks were prepared from enriched, characterized cultures. Two recovery processes were evaluated at pilot scale and data obtained was incorporated into our economic analyses.

  11. Alpha-tocopheryl succinate inhibits malignant mesothelioma by disrupting the fibroblast growth factor autocrine loop

    Czech Academy of Sciences Publication Activity Database

    Stapelberg, M.; Gellert, N.; Swettenham, E.; Tomasetti, M.; Witting, P. K.; Procopio, A.; Neužil, Jiří

    2005-01-01

    Roč. 280, č. 27 (2005), s. 25369-25376 ISSN 0021-9258 Institutional research plan: CEZ:AV0Z50520514 Keywords : alpha-tocopheryl succinate * malignant mesothelioma * fibroblast growth factor Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.854, year: 2005

  12. Inhibition of mitochondrial glycerol-3-phosphate dehydrogenase by alpha-tocopheryl succinate

    Czech Academy of Sciences Publication Activity Database

    Rauchová, Hana; Vokurková, Martina; Drahota, Zdeněk

    2014-01-01

    Roč. 53, AUG (2014), s. 409-413 ISSN 1357-2725 R&D Projects: GA ČR(CZ) GAP304/12/0259 Institutional support: RVO:67985823 Keywords : brown adipose tissue mitochondria * oxygen consumption * glycerol-3-phosphate * succinate * reactive oxygen species Subject RIV: ED - Physiology Impact factor: 4.046, year: 2014

  13. Tocopherol-associated protein-1 accelerates apoptosis induced by alpha-tocopheryl succinate in mesothelioma cells

    Czech Academy of Sciences Publication Activity Database

    Neužil, Jiří; Dong, L.F.; Wang, X.F.; Zingg, J.M.

    2006-01-01

    Roč. 343, č. 4 (2006), s. 1113-1117 ISSN 0006-291X Institutional research plan: CEZ:AV0Z50520514 Keywords : apoptosis * tocopherol-associated protein * alpha-tocopheryl succinate Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.855, year: 2006

  14. Efficient production of succinic acid in immobilized fermentation with crude glycerol from Escherichia coli

    Directory of Open Access Journals (Sweden)

    Nik Nor Aziati, A.A.

    2017-10-01

    Full Text Available The increase in the price of commercial succinic acid has necessitated the need for its synthesis from waste materials such as glycerol. Glycerol residue is a waste product of Oleochemical production which is cheaply available and a very good source of carbon. The use of immobilized cells can further reduce the overall cost of the production process. This study primarily aims to produce succinic acid from glycerol residue through the use of immobilized Escherichia coli in a batch fermentation process. The parameters which affect bacterial fermentation process such as the mass substrate, temperature, inoculum size and duration of fermentation were screened using One-Factor-At-a-Time (OFAT method. The result of the screening process shows that a substrate (glycerol concentration of 30 g, inoculum size 20% v/v, and time 4 h produced the maximum succinic acid concentration of 117.99 g/L. The immobilized cells were found to be stable as well as retain their fermentative ability up to the 6th cycle of recycling, thereby presenting as an advantage over the free cell system. Therefore, conclude that using immobilized cells can contribute immensely to the cost-effective production of succinic acid from glycerol residue.

  15. Amorphous/crystal and polymer/filler interphases in biocomposites from poly(butylene succinate)

    Energy Technology Data Exchange (ETDEWEB)

    Signori, Francesca [Consiglio Nazionale delle Ricerche - Istituto per i Processi Chimico-Fisici (CNR-IPCF), Via G. Moruzzi 1, I-56124 Pisa (Italy); Pelagaggi, Martina [Universita di Pisa - Dipartimento di Chimica e Chimica Industriale, Via Risorgimento 35, I-56126 Pisa (Italy); Bronco, Simona [Consiglio Nazionale delle Ricerche - Istituto per i Processi Chimico-Fisici (CNR-IPCF), Via G. Moruzzi 1, I-56124 Pisa (Italy); Righetti, Maria Cristina, E-mail: righetti@ipcf.cnr.it [Consiglio Nazionale delle Ricerche - Istituto per i Processi Chimico-Fisici (CNR-IPCF), Via G. Moruzzi 1, I-56124 Pisa (Italy)

    2012-09-10

    Highlights: Black-Right-Pointing-Pointer The existence of intermolecular interactions between poly(butylene succinate) and hemp fibres was proved from specific heat capacities data. Black-Right-Pointing-Pointer Different degrees of mobility of the poly(butylene succinate) amorphous segments were evidenced at the amorphous/crystal interphase. Black-Right-Pointing-Pointer Devitrification of the rigid amorphous fraction in poly(butylene succinate) was found to occur before and simultaneously with the fusion. - Abstract: Poly(butylene succinate)-hemp composites (PBS-hemp), with hemp content in the range 0-40 wt.%, were prepared in the melt and characterized. This paper focuses on the detailed analysis of the thermal behaviour of the PBS-hemp composites, investigated by differential scanning calorimetry (DSC), to enlighten the polymer/fibre interphase features. The occurrence of specific intermolecular interactions between PBS and hemp was assessed from specific heat capacity data. Different degrees of mobility of the PBS amorphous segments were found at the amorphous/crystal interphases. A broadening of the bulk glass transition was observed, and attributed to the presence of polymer segments slightly constrained. Moreover, a rigid amorphous fraction that devitrifies at temperatures higher than the bulk glass transition, partly before the melting region and partly simultaneously with the fusion, was observed and quantified, and attributed to the presence of major constraints probably occurring in geometrically restricted areas.

  16. Fourier Transform Infrared Spectroscopy Study on Cation adsorption on Viscose Rayon Succinate

    Directory of Open Access Journals (Sweden)

    D Khasbaatar

    2014-09-01

    Full Text Available Ion-exchange materials have been considered as suitable material for the recovery of heavy metals in water. A viscose rayon succinate, synthesized from viscose rayon and succinic anhydride in presence of DMSO, to remove trace bivalent metal ions such as Ag+, Cu2+, Ni2+, Pb2+, Zn2+ and Cr3+, was studied using FT-IR for the behavior of metal adsorption. Both esterification and carboxyl bonding of viscose rayon succinate were assigned essentially at 1729 and 1693cm-1, respectively. And the essential band of bonding between metal and the material was determined at 1625cm-1. The available adsorption capacity of this fiber was 6.2 mequiv/g. The adsorption of metal ions on the viscose rayon succinate follows the order of Cu2+>Cr3+>Ni2+>Pb2+>Zn2+>Ag+ with maximum adsorptions capacities 4.2, 1.42, 0.91, 0.83, 0.69 and 0.35 mmol/g, respectively.DOI: http://dx.doi.org/10.5564/mjc.v12i0.189 Mongolian Journal of Chemistry Vol.12 2011: 136-141

  17. Volatility of Organic Aerosol: Evaporation of Ammonium Sulfate/Succinic Acid Aqueous Solution Droplets

    Science.gov (United States)

    2013-01-01

    Condensation and evaporation modify the properties and effects of atmospheric aerosol particles. We studied the evaporation of aqueous succinic acid and succinic acid/ammonium sulfate droplets to obtain insights on the effect of ammonium sulfate on the gas/particle partitioning of atmospheric organic acids. Droplet evaporation in a laminar flow tube was measured in a Tandem Differential Mobility Analyzer setup. A wide range of droplet compositions was investigated, and for some of the experiments the composition was tracked using an Aerosol Mass Spectrometer. The measured evaporation was compared to model predictions where the ammonium sulfate was assumed not to directly affect succinic acid evaporation. The model captured the evaporation rates for droplets with large organic content but overestimated the droplet size change when the molar concentration of succinic acid was similar to or lower than that of ammonium sulfate, suggesting that ammonium sulfate enhances the partitioning of dicarboxylic acids to aqueous particles more than currently expected from simple mixture thermodynamics. If extrapolated to the real atmosphere, these results imply enhanced partitioning of secondary organic compounds to particulate phase in environments dominated by inorganic aerosol. PMID:24107221

  18. Studies on Cross-linking of succinic acid with chitosan/collagen

    Directory of Open Access Journals (Sweden)

    Tapas Mitra

    2013-01-01

    Full Text Available The present study summarizes the cross-linking property of succinic acid with chitosan /collagen. In detail, the chemistry behind the cross-linking and the improvement in mechanical and thermal properties of the cross-linked material were discussed with suitable instruments and bioinformatics tools. The concentration of succinic acid with reference to the chosen polymers was optimized. A 3D scaffold prepared using an optimized concentration of succinic acid (0.2% (w/v with chitosan (1.0% (w/v and similarly with collagen (0.5% (w/v, was subjected to surface morphology, FT-IR analysis, tensile strength assessment, thermal stability and biocompatibility. Results revealed, cross-linking with succinic acid impart appreciable mechanical strength to the scaffold material. In silico analysis suggested the prevalence of non-covalent interactions, which played a crucial role in improving the mechanical and thermal properties of the cross-linked scaffold. The resultant 3D scaffold may find application as wound dressing material, as an implant in clinical applications and as a tissue engineering material.

  19. Sustained release of bactericidal concentrations of penicillin in the pleural space via an antibiotic-eluting pigtail catheter coated with electrospun nanofibers: results from in vivo and in vitro studies.

    Science.gov (United States)

    Chao, Yin-Kai; Lee, Cheng-Hung; Liu, Kuo-Sheng; Wang, Yi-Chuan; Wang, Chih-Wei; Liu, Shih-Jung

    2015-01-01

    Inadequate intrapleural drug concentrations caused by poor penetration of systemic antibiotics into the pleural cavity is a major cause of treatment failure in empyema. Herein, we describe a novel antibiotic-eluting pigtail catheter coated with electrospun nanofibers used for the sustained release of bactericidal concentrations of penicillin in the pleural space. Electrospun nanofibers prepared using polylactide-polyglycolide copolymer and penicillin G sodium dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol were used to coat the surface of an Fr6 pigtail catheter. The in vitro patterns of drug release were tested by placing the catheter in phosphate-buffered saline. In vivo studies were performed using rabbits treated with penicillin either intrapleurally (Group 1, 20 mg delivered through the catheter) or systemically (Group 2, intramuscular injection, 10 mg/kg). Penicillin concentrations in the serum and pleural fluid were then measured and compared. In vitro studies revealed a burst release of penicillin (10% of the total dose) occurring in the first 24 hours, followed by a sustained release in the subsequent 30 days. Intrapleural drug levels were significantly higher in Group 1 than in Group 2 (Ppenicillin concentrations remained above the minimum inhibitory concentration breakpoint throughout the entire study period. In contrast, serum penicillin levels were significantly higher in Group 2 than in Group 1 (P<0.001). Notably, all Group 2 rabbits showed signs of systemic toxicity (paralytic ileus and weight loss). We conclude that our antibiotic-eluting catheter may serve as a novel therapeutic option to treat empyema.

  20. Effectiveness, pharmacokinetics, and safety of a new sustained-release leuprolide acetate 3.75-mg depot formulation for testosterone suppression in patients with prostate cancer: a Phase III, open-label, international multicenter study.

    Science.gov (United States)

    Marberger, Michael; Kaisary, Amir V; Shore, Neal D; Karlin, Gary S; Savulsky, Claudio; Mis, Ricard; Leuratti, Chiara; Germa, Josep R

    2010-04-01

    A microencapsulated, sustained-release formulation of leuprolide acetate 3.75 mg has been developed. This study investigated the effectiveness, pharmacokinetics, and safety profile of a 1-month leuprolide acetate 3.75-mg depot formulation for suppressing testosterone concentrations in patients with prostate cancer. This was a Phase III, open-label, international multicenter clinical trial. Patients with prostate cancer who, in the judgment of the investigators, could benefit from androgen deprivation therapy received 6 monthly intramuscular injections of leuprolide acetate 3.75-mg depot. Plasma testosterone concentrations were determined at specific times throughout the study. The primary end point was the proportion of successful patients over the total number of evaluable patients (ie, patients with evaluable testosterone concentrations at all monthly assessments and no missing values due to treatment-related adverse events). Treatment success was defined as testosterone suppression below the clinical castration level (ie, n = 12), showed sustained release of leuprolide from the formulation. Values for AUC(0-t) calculated from day 0 to day 28, days 28 to 56, and days 56 to 84 were 25,976.5 (7892.0), 30,685.5 (9348.4), and 31,030.9 (10,745.0) pg/mL per day, respectively. The most common treatment-related adverse event was hot flashes (45.0% [72/160]). Fatigue, hyperhidrosis, night sweats, and headache each occurred in

  1. CLINICAL AND ECONOMICAL ASSESSMENTS OF METOPROLOL TARTRATE/SUCCINATE USAGE IN PATIENTS WITH ISCHEMIC HEART DISEASE

    Directory of Open Access Journals (Sweden)

    M. V. Soura

    2008-01-01

    Full Text Available Clinical and clinicoeconomical studies review is presented as well as results of author’s comparative cost analysis on metoprolol tartrate (Betaloc and metoprolol succinate (Betaloc ZOK usage in patients with ischemic heart disease. Efficacy of metoprolol therapy is proven in randomized clinical studies in patients with angina and myocardial infarction (MI. In angina patients metoprolol prevents cardiac attacks, MI, reduces nitroglycerine consumption, increases exercise tolerability, prolongs the exercise time before ST segment depression (succinate better than tartrate, decrease of angina intensity. In MI patients metoprolol therapy reduces mortality, sudden death, recurring MI and the rate of early post MI angina attacks. Nowadays metoprolol is the only β-blocker having indication on secondary MI prevention. Besides for the present metoprolol succinate is the only β-blocker with proven direct antisclerosis effect. According to Swedish clinicoeconomical study in patients after MI secondary prevention with metoprolol therapy saves the costs in comparison with placebo. American clinicoeconomical model of metoprolol and atenolol usage in all patients with MI could result in significant reduction in mortality and recurring MI rate, prolong the life and improve its quality, save financial resources. The cost of monthly treatment of angina patient with metoprolol tartrate (Betaloc and metoprolol succinate (Betaloc ZOK is 135 and 354 rubles, respectively. The price range of comparative β-blockers in ascending order is the following: atenolol (Atenolol Nicomed → metoprolol tartrate (Betaloc → metoprolol succinate (Betaloc ZOK → bisoprolol (Concor → nebivolol (Nebilet. In conclusion, metoprolol therapy is the one of mostly economically reasonable approach.

  2. Succinic acid production from orange peel and wheat straw by batch fermentations of Fibrobacter succinogenes S85.

    Science.gov (United States)

    Li, Qiang; Siles, Jose A; Thompson, Ian P

    2010-10-01

    Succinic acid is a platform molecule that has recently generated considerable interests. Production of succinate from waste orange peel and wheat straw by consolidated bioprocessing that combines cellulose hydrolysis and sugar fermentation, using a cellulolytic bacterium, Fibrobacter succinogenes S85, was studied. Orange peel contains D-limonene, which is a well-known antibacterial agent. Its effects on batch cultures of F. succinogenes S85 were examined. The minimal concentrations of limonene found to inhibit succinate and acetate generation and bacterial growth were 0.01%, 0.1%, and 0.06% (v/v), respectively. Both pre-treated orange peel by steam distillation to remove D: -limonene and intact wheat straw were used as feedstocks. Increasing the substrate concentrations of both feedstocks, from 5 to 60 g/L, elevated succinate concentration and productivity but lowered the yield. In addition, pre-treated orange peel generated greater succinate productivities than wheat straw but had similar resultant titres. The greatest succinate titres were 1.9 and 2.0 g/L for pre-treated orange peel and wheat straw, respectively. This work demonstrated that agricultural waste such as wheat straw and orange peel can be biotransformed to succinic acid by a one-step consolidated bioprocessing. Measures to increase fermentation efficiency are also discussed.

  3. Krebs cycle metabolite profiling for identification and stratification of pheochromocytomas/paragangliomas due to succinate dehydrogenase deficiency.

    Science.gov (United States)

    Richter, Susan; Peitzsch, Mirko; Rapizzi, Elena; Lenders, Jacques W; Qin, Nan; de Cubas, Aguirre A; Schiavi, Francesca; Rao, Jyotsna U; Beuschlein, Felix; Quinkler, Marcus; Timmers, Henri J; Opocher, Giuseppe; Mannelli, Massimo; Pacak, Karel; Robledo, Mercedes; Eisenhofer, Graeme

    2014-10-01

    Mutations of succinate dehydrogenase A/B/C/D genes (SDHx) increase susceptibility to development of pheochromocytomas and paragangliomas (PPGLs), with particularly high rates of malignancy associated with SDHB mutations. We assessed whether altered succinate dehydrogenase product-precursor relationships, manifested by differences in tumor ratios of succinate to fumarate or other metabolites, might aid in identifying and stratifying patients with SDHx mutations. PPGL tumor specimens from 233 patients, including 45 with SDHx mutations, were provided from eight tertiary referral centers for mass spectrometric analyses of Krebs cycle metabolites. Diagnostic performance of the succinate:fumarate ratio for identification of pathogenic SDHx mutations. SDH-deficient PPGLs were characterized by 25-fold higher succinate and 80% lower fumarate, cis-aconitate, and isocitrate tissue levels than PPGLs without SDHx mutations. Receiver-operating characteristic curves for use of ratios of succinate to fumarate or to cis-aconitate and isocitrate to identify SDHx mutations indicated areas under curves of 0.94 to 0.96; an optimal cut-off of 97.7 for the succinate:fumarate ratio provided a diagnostic sensitivity of 93% at a specificity of 97% to identify SDHX-mutated PPGLs. Succinate:fumarate ratios were higher in both SDHB-mutated and metastatic tumors than in those due to SDHD/C mutations or without metastases. Mass spectrometric-based measurements of ratios of succinate:fumarate and other metabolites in PPGLs offer a useful method to identify patients for testing of SDHx mutations, with additional utility to quantitatively assess functionality of mutations and metabolic factors responsible for malignant risk.

  4. Enterobacter sp. LU1 as a novel succinic acid producer - co-utilization of glycerol and lactose.

    Science.gov (United States)

    Podleśny, Marcin; Jarocki, Piotr; Wyrostek, Jakub; Czernecki, Tomasz; Kucharska, Jagoda; Nowak, Anna; Targoński, Zdzisław

    2017-03-01

    Succinic acid is an important C4-building chemical platform for many applications. A novel succinic acid-producing bacterial strain was isolated from goat rumen. Phylogenetic analysis based on the 16S rRNA sequence and physiological analysis indicated that the strain belongs to the genus Enterobacter. This is the first report of a wild bacterial strain from the genus Enterobacter that is capable of efficient succinic acid production. Co-fermentation of glycerol and lactose significantly improved glycerol utilization under anaerobic conditions, debottlenecking the utilization pathway of this valuable biodiesel waste product. Succinic acid production reached 35 g l -1 when Enterobacter sp. LU1 was cultured in medium containing 50 g l -1 of glycerol and 25 g l -1 of lactose as carbon sources. © 2016 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

  5. The impact of nanoclay on the crystal growth kinetics and morphology of biodegradable poly(ethylene succinate) composite

    CSIR Research Space (South Africa)

    Bandyopadhyay, J

    2012-07-01

    Full Text Available The impact of nanoclay on the isothermal crystal growth kinetics and morphology of biodegradable poly(ethylene succinate) (PES) is reported. A PES composite (PESNC) containing 5 wt% organically modified montmorillonite, was prepared via solvent...

  6. [Effects of Light Near-Infrared Radiation on Rats Assessed by Succinate Dehydrogenase Activity in Lymphocytes on Blood Smears].

    Science.gov (United States)

    Khunderyakova, N V; Zakharchenko, A V; Zakharchenko, M V; Muller, H; Fedotcheva, I; Kondrashova, M N

    2015-01-01

    Biological effects of light near infrared radiation (850 nm), with modulation acoustic frequency of 101 Hz, was studied. The study was conducted on rats, the effect was recorded by succinate dehydrogenase activity in lymphocytes on the blood smear after administration of the activating dose of adrenaline, which simulates the state of the organism in the early stages of the pathogenic effects (stress). A pronounced regulating effect of infrared radiation on the activity of succinate dehydrogenase in animals activated by adrenaline was shown. Infrared radiation has a normalizing effect reducing the degree of inhibition or activation of the enzyme induced by adrenaline and had no effect on the control animals. Thus, by modulating the activity of succinate dehydrogenase infrared radiation regulates energy production in the mitochondria supported by the most powerful oxidation substrate--succinic acid, which is especially pronounced under stress.

  7. Ferulenol specifically inhibits succinate ubiquinone reductase at the level of the ubiquinone cycle

    International Nuclear Information System (INIS)

    Lahouel, Mesbah; Zini, Roland; Zellagui, Ammar; Rhouati, Salah; Carrupt, Pierre-Alain; Morin, Didier

    2007-01-01

    The natural compound ferulenol, a sesquiterpene prenylated coumarin derivative, was purified from Ferula vesceritensis and its mitochondrial effects were studied. Ferulenol caused inhibition of oxidative phoshorylation. At low concentrations, ferulenol inhibited ATP synthesis by inhibition of the adenine nucleotide translocase without limitation of mitochondrial respiration. At higher concentrations, ferulenol inhibited oxygen consumption. Ferulenol caused specific inhibition of succinate ubiquinone reductase without altering succinate dehydrogenase activity of the complex II. This inhibition results from a limitation of electron transfers initiated by the reduction of ubiquinone to ubiquinol in the ubiquinone cycle. This original mechanism of action makes ferulenol a useful tool to study the physiological role and the mechanism of electron transfer in the complex II. In addition, these data provide an additional mechanism by which ferulenol may alter cell function and demonstrate that mitochondrial dysfunction is an important determinant in Ferula plant toxicity

  8. Promysalin Elicits Species-Selective Inhibition of Pseudomonas aeruginosa by Targeting Succinate Dehydrogenase.

    Science.gov (United States)

    Keohane, Colleen E; Steele, Andrew D; Fetzer, Christian; Khowsathit, Jittasak; Van Tyne, Daria; Moynié, Lucile; Gilmore, Michael S; Karanicolas, John; Sieber, Stephan A; Wuest, William M

    2018-02-07

    Natural products have served as an inspiration to scientists both for their complex three-dimensional architecture and exquisite biological activity. Promysalin is one such Pseudomonad secondary metabolite that exhibits narrow-spectrum antibacterial activity, originally isolated from the rhizosphere. We herein utilize affinity-based protein profiling (AfBPP) to identify succinate dehydrogenase (Sdh) as the biological target of the natural product. The target was further validated in silico, in vitro, in vivo, and through the selection, and sequencing, of a resistant mutant. Succinate dehydrogenase plays an essential role in primary metabolism of Pseudomonas aeruginosa as the only enzyme that is involved both in the tricarboxylic acid cycle (TCA) and in respiration via the electron transport chain. These findings add credence to other studies that suggest that the TCA cycle is an understudied target in the development of novel therapeutics to combat P. aeruginosa, a significant pathogen in clinical settings.

  9. Influence of VO2+ ions on structural and optical properties of potassium succinate-succinic acid single crystal for non-linear optical applications

    Science.gov (United States)

    Juliet sheela, K.; Subramanian, P.

    2018-04-01

    A transparent and good optical quality semi organic single crystal of vanadium doped potassium succinate-succinic acid (KSSA) was synthesized by slow evaporation technique at room temperature. The structural perfection was supported by the powder XRD of the KSSA-VO2+ single crystal. Optical behavior of the material was discovered from the absorption and transmission spectra of UV-vis-NIR characterization. Functional group and presence of metal ion in the specimen are depicted from FTIR traces. From the photoluminescence studies, emission of wavelength in the violet region (418 nm) at the excitation of 243 nm could be ascertained. EDAX, SEM measurements identify presence of elements and pictures the step-line growth and the imperfection presents in the grown crystal. EPR analysis extracts the information about the local site symmetry around the impurity ion, molecular orbital coefficients, admixture coefficients and ground state wave function of VO2+ doped KSSA single crystal. Second harmonic generation (SHG) efficiency of the grown crystal was investigated to explore the NLO characteristic of the material.

  10. Miscibility, crystallization and mechanical properties of biodegradable blends of poly(L-lactic acid) and poly(butylene succinate-b-ethylene succinate) multiblock copolymer

    International Nuclear Information System (INIS)

    Jiao, Ling; Huang, Cai-Li; Zeng, Jian-Bing; Wang, Yu-Zhong; Wang, Xiu-Li

    2012-01-01

    Highlights: ► The blend of PLLA and PBES showed limited miscibility. ► The crystallization rate of PLLA was accelerated by blending with PBES. ► The crystal structures of PLLA and PBES did not change. - Abstract: Poly(L-lactic acid) (PLLA) is regarded as one of the most promising biobased and biodegradable polymers. However, its application was restricted due to the brittle nature. In the present study, PLLA was blended with a novel biodegradable flexible multiblock copolymer, poly(butylene succinate-b-ethylene succinate) (PBES) to produce new biodegradable materials. PLLA/PBES blends with different composition were prepared by solution blending and casting method with chloroform as a mutual solvent. Miscibility, crystallization behavior, and mechanical properties of the blends were investigated by differential scanning calorimetry (DSC), wide-angle X-ray diffraction (WAXD), and tensile tests. The results indicated that PLLA and PBES showed limited miscibility in the amorphous phase. The crystallization rate of PLLA was accelerated with the increase of PBES in the blends while the crystallization mechanism did not change. The results of tensile tests suggest that the blends showed longer elongation at break than neat PLLA. The elongation at break of PLLA was obtained to be 10%, and those of PLLA/PBES 80/20, 60/40, 40/60 and 20/80 were 29, 110, 442, and 455%, respectively.

  11. Alpha-Tocopheryl succinate causes mitochondrial permeabilization by preferential formation of Bak channels

    Czech Academy of Sciences Publication Activity Database

    Procházka, L.; Dong, L.F.; Vališ, Karel; Freeman, R.; Ralph, S.J.; Turánek, J.; Neužil, Jiří

    2010-01-01

    Roč. 15, č. 7 (2010), s. 782-794 ISSN 1360-8185 R&D Projects: GA AV ČR(CZ) KAN200520703; GA AV ČR(CZ) IAA500520702; GA AV ČR(CZ) IAA500520602 Institutional research plan: CEZ:AV0Z50520701 Keywords : Vitamin E succinate * apoptosis * Noxa-Bak Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.397, year: 2010

  12. Industrial Systems Biology of Saccharomyces cerevisiae Enables Novel Succinic Acid Cell Factory

    DEFF Research Database (Denmark)

    Otero, José Manuel; Cimini, Donatella; Patil, Kiran Raosaheb

    2013-01-01

    Saccharomyces cerevisiae is the most well characterized eukaryote, the preferred microbial cell factory for the largest industrial biotechnology product (bioethanol), and a robust commerically compatible scaffold to be exploitted for diverse chemical production. Succinic acid is a highly sought......-direction of carbon fluxes in S. cerevisiae, and hence show proof of concept that this is a potentially attractive cell factory for over-producing different platform chemicals....

  13. Bisoprolol compared with carvedilol and metoprolol succinate in the treatment of patients with chronic heart failure.

    Science.gov (United States)

    Fröhlich, Hanna; Torres, Lorella; Täger, Tobias; Schellberg, Dieter; Corletto, Anna; Kazmi, Syed; Goode, Kevin; Grundtvig, Morten; Hole, Torstein; Katus, Hugo A; Cleland, John G F; Atar, Dan; Clark, Andrew L; Agewall, Stefan; Frankenstein, Lutz

    2017-09-01

    Beta-blockers are recommended for the treatment of chronic heart failure (CHF). However, it is disputed whether beta-blockers exert a class effect or whether there are differences in efficacy between agents. 6010 out-patients with stable CHF and a reduced left ventricular ejection fraction prescribed either bisoprolol, carvedilol or metoprolol succinate were identified from three registries in Norway, England, and Germany. In three separate matching procedures, patients were individually matched with respect to both dose equivalents and the respective propensity scores for beta-blocker treatment. During a follow-up of 26,963 patient-years, 302 (29.5%), 637 (37.0%), and 1232 (37.7%) patients died amongst those prescribed bisoprolol, carvedilol, and metoprolol, respectively. In univariable analysis of the general sample, bisoprolol and carvedilol were both associated with lower mortality as compared with metoprolol succinate (HR 0.80, 95% CI 0.71-0.91, p < 0.01, and HR 0.86, 95% CI 0.78-0.94, p < 0.01, respectively). Patients prescribed bisoprolol or carvedilol had similar mortality (HR 0.94, 95% CI 0.82-1.08, p = 0.37). However, there was no significant association between beta-blocker choice and all-cause mortality in any of the matched samples (HR 0.90; 95% CI 0.76-1.06; p = 0.20; HR 1.10, 95% CI 0.93-1.31, p = 0.24; and HR 1.08, 95% CI 0.95-1.22, p = 0.26 for bisoprolol vs. carvedilol, bisoprolol vs. metoprolol succinate, and carvedilol vs. metoprolol succinate, respectively). Results were confirmed in a number of important subgroups. Our results suggest that the three beta-blockers investigated have similar effects on mortality amongst patients with CHF.

  14. Effect of vitamin E succinate on inflammatory cytokines induced by high-intensity interval training

    Directory of Open Access Journals (Sweden)

    Hadi Sarir

    2015-01-01

    Full Text Available Aim and Scope: The anti-inflammatory effect of vitamin E under moderate exercises has been evaluated. However, the effect of vitamin E succinate, which has more potent anti-inflammatory effect than other isomers of vitamin E has not been evaluated. Therefore, the aim of the present study was to evaluate the effects of vitamin E succinate on tumor necrosis factor alpha (TNF-a and interleukin-6 (IL-6 production induced by high-intensity interval training (HIIT. Materials and Methods: In the present study, 24 rats were randomly divided into control (C, supplementation (S, HIIT, and HIIT + supplementation (HIIT+S groups. HIIT training protocol on a treadmill (at a speed of 40-54 m/min and vitamin E succinate supplementation (60 mg/kg/day was conducted for 6 weeks. Results: Serum IL-6 in the HIIT group significantly increased compared with the C group (350.42 ± 123.31 pg/mL vs 158.60 ± 41.96 pg/mL; P = 0.002. Also, serum TNF-a concentrations significantly enhanced (718.15 ± 133.42 pg/mL vs 350.87 ± 64.93 pg/mL; P = 0.001 in the HIIT group compared with the C group. Treatment of the training group with vitamin E numerically reduced IL-6 and TNF-a when compared with the HIIT group (217.31 ± 29.21 and 510.23 ± 217.88, respectively, P > 0.05. However, no significant changes were observed in serum TNF-a (P = 0.31 and IL-6 (P = 0.52 concentrations in the HIIT + S group compared with the C group. Conclusion: HIIT-induced IL-6 and TNF-α decreased by administration of Vitamin E succinate.

  15. Effect of vitamin E succinate on inflammatory cytokines induced by high-intensity interval training.

    Science.gov (United States)

    Sarir, Hadi; Emdadifard, Ghodsieh; Farhangfar, Homayoun; TaheriChadorneshin, Hossein

    2015-12-01

    The anti-inflammatory effect of vitamin E under moderate exercises has been evaluated. However, the effect of vitamin E succinate, which has more potent anti-inflammatory effect than other isomers of vitamin E has not been evaluated. Therefore, the aim of the present study was to evaluate the effects of vitamin E succinate on tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) production induced by high-intensity interval training (HIIT). In the present study, 24 rats were randomly divided into control (C), supplementation (S), HIIT, and HIIT + supplementation (HIIT+S) groups. HIIT training protocol on a treadmill (at a speed of 40-54 m/min) and vitamin E succinate supplementation (60 mg/kg/day) was conducted for 6 weeks. Serum IL-6 in the HIIT group significantly increased compared with the C group (350.42 ± 123.31 pg/mL vs 158.60 ± 41.96 pg/mL; P = 0.002). Also, serum TNF-α concentrations significantly enhanced (718.15 ± 133.42 pg/mL vs 350.87 ± 64.93 pg/mL; P = 0.001) in the HIIT group compared with the C group. Treatment of the training group with vitamin E numerically reduced IL-6 and TNF-α when compared with the HIIT group (217.31 ± 29.21 and 510.23 ± 217.88, respectively, P > 0.05). However, no significant changes were observed in serum TNF-α (P = 0.31) and IL-6 (P = 0.52) concentrations in the HIIT + S group compared with the C group. HIIT-induced IL-6 and TNF-α decreased by administration of Vitamin E succinate.

  16. A randomized, placebo controlled, trial of preoperative sustained release Betamethasone plus non-controlled intraoperative Ketorolac or Fentanyl on pain after diagnostic laparoscopy or laparoscopic tubal ligation [ISRCTN52633712

    Directory of Open Access Journals (Sweden)

    Piller Marsha D

    2003-08-01

    Full Text Available Abstract Background Gynecological laparoscopic surgery procedures are often complicated by postoperative pain resulting in an unpleasant experience for the patient, delayed discharge, and increased cost. Glucocorticosteroids have been suggested to reduce the severity and incidence of postoperative pain. Methods This study examines the efficacy of a sustained release betamethasone preparation to reduce postoperative pain and the requirement for pain relief drugs after either diagnostic laparoscopy or tubal ligation. Patients were recruited, as presenting, after obtaining informed consent. Prior to surgery, patients were randomly selected by a computer generated table to receive either pharmacy-coded betamethasone (12 mg IM Celestone™ or an optically identical placebo injection of Intralipid™ and isotonic saline mixture. The effect of non-controlled prophylactic intraoperative treatment with either fentanyl or ketorolac per surgeon's orders was also noted in this study. Blood samples taken at recovery and at discharge times were extracted and analyzed for circulating betamethasone. Visual analog scale data on pain was gathered at six post-recovery time points in a triple blind fashion and statistically compared. The postoperative requirement for pain relief drugs was also examined. Results Although the injection achieved a sustained therapeutic concentration, no beneficial effect of IM betamethasone on postoperative pain or reduction in pain relief drugs was observed during the postoperative period. Indeed, the mean combined pain scores during the 2 hour postoperative period, adjusted for postoperative opioids as the major confounding factor, were higher approaching statistical significance (P = 0.056 in the treatment group. Higher pain scores were also observed for the tubal ligation patients relative to diagnostic laparoscopy. Intraoperative fentanyl treatment did not significantly lower the average pain score during the 2 hour postoperative

  17. Succinate-induced neuronal mitochondrial fission and hexokinase II malfunction in ischemic stroke: Therapeutical effects of kaempferol.

    Science.gov (United States)

    Wu, Bin; Luo, Hong; Zhou, Xu; Cheng, Cai-Yi; Lin, Lin; Liu, Bao-Lin; Liu, Kang; Li, Ping; Yang, Hua

    2017-09-01

    Mitochondrial dysfunction is known as one of causative factors in ischemic stroke, leading to neuronal cell death. The present work was undertaken to investigate whether succinate induces neuron apoptosis by regulating mitochondrial morphology and function. In neurons, oxygen-glucose deprivation induced succinate accumulation due to the reversal of succinate dehydrogenase (SDH) activation, leading to mitochondrial fission. Kaempferol inhibited mitochondrial fission and maintained mitochondrial HK-II through activation of Akt, and thereby protected neurons from succinate-mediated ischemi injury. Knockdown of Akt2 with siRNA diminished the effect of kaempferol, indicating that kaempferol suppressed dynamin-related protein 1 (Drp1) activation and promoted HK-II mitochondrial binding dependently on Akt. Moreover, we demonstrated that kaempferol potentiated autophagy during oxygen and glucose deprivation, contributing to protecting neuron survival against succinate insult. In vivo, oral administration of kaempferol in mice attenuated the infract volume after ischemic and reperfusion (I/R) injury and reproduced the similar mitochondrial protective effect in the brain infract area. This study indicates that succinate accumulation plays a pivotal role in I/R injury-induced neuronal mitochondrial dysfunction, and suggests that modulation of Drp1 phosphorylation might be potential therapeutic strategy to protect neuron mitochondrial integrity and treat ischemic stroke. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Enhanced Bioactivity of α-Tocopheryl Succinate Based Block Copolymer Nanoparticles by Reduced Hydrophobicity.

    Science.gov (United States)

    Palao-Suay, Raquel; Aguilar, María Rosa; Parra-Ruiz, Francisco J; Maji, Samarendra; Hoogenboom, Richard; Rohner, Nathan A; Thomas, Susan N; Román, Julio San

    2016-12-01

    Well-structured amphiphilic copolymers are necessary to obtain self-assembled nanoparticles (NPs) based on synthetic polymers. Highly homogeneous and monodispersed macromolecules obtained by controlled polymerization have successfully been used for this purpose. However, disaggregation of the organized macromolecules is desired when a bioactive element, such as α-tocopheryl succinate, is introduced in self-assembled NPs and this element must be exposed or released to exert its action. The aim of this work is to demonstrate that the bioactivity of synthetic NPs based on defined reversible addition-fragmentation chain transfer polymerization copolymers can be enhanced by the introduction of hydrophilic comonomers in the hydrophobic segment. The amphiphilic terpolymers are based on poly(ethylene glycol) (PEG) as hydrophilic block, and a hydrophobic block based on a methacrylic derivative of α-tocopheryl succinate (MTOS) and small amounts of 2-hydroxyethyl methacrylate (HEMA) (PEG-b-poly(MTOS-co-HEMA)). The introduction of HEMA reduces hydrophobicity and introduces "disorder" both in the homogeneous blocks and the compact core of the corresponding NPs. These NPs are able to encapsulate additional α-tocopheryl succinate (α-TOS) with high efficiency and their biological activity is much higher than that described for the unmodified copolymers, proposedly due to more efficient degradation and release of α-TOS, demonstrating the importance of the hydrophilic-hydrophobic balance. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. [Effects of different neutralizing agents on succinate production by Actinobacillus succinogenes NJ113].

    Science.gov (United States)

    Yang, Zhuona; Jiang, Min; Li, Jian; Fang, Xiaojiang; Ye, Guizi; Bai, Xuefei; Zheng, Xiaoyu; Wei, Ping

    2010-11-01

    Different neutralizing agents were used as pH controller to investigate their effects on the growth and succinic acid production of Actinobacillus succinogenes NJ113. The fermentation results showed that Ca(OH)2, CaCO3 and NH4OH were not suitable for succinic acid production by A. succinogenes NJ113 because of their negative effects on cell growth. When Na-base was used, cells would flocculate and lump, and due to the sodium ion concentration reaching to a high level, OD660 dropped sharply after 12 h of fermentation. Mg-base was better because there was no significant inhibition by magnesium ion. Two combined neutralizing agents were used to maintain pH level, one with NaOH and Mg(OH)2 while the other with Na2CO3 and Mg(OH)2. The optimum ratios of the combined neutralizing agents were both 1:1 (g:g) when using 100 g/L glucose. When NaOH and Mg(OH)2 were chosen with the ratio of 1:1(g:g), 69.8 g/L of the succinic acid and 74.5% of the yield was obtained.

  20. Co-Consumption of Methanol and Succinate by Methylobacterium extorquens AM1

    Science.gov (United States)

    Peyraud, Rémi; Kiefer, Patrick; Christen, Philipp; Portais, Jean-Charles; Vorholt, Julia A.

    2012-01-01

    Methylobacterium extorquens AM1 is a facultative methylotrophic Alphaproteobacterium and has been subject to intense study under pure methylotrophic as well as pure heterotrophic growth conditions in the past. Here, we investigated the metabolism of M. extorquens AM1 under mixed substrate conditions, i.e., in the presence of methanol plus succinate. We found that both substrates were co-consumed, and the carbon conversion was two-thirds from succinate and one-third from methanol relative to mol carbon. 13C-methanol labeling and liquid chromatography mass spectrometry analyses revealed the different fates of the carbon from the two substrates. Methanol was primarily oxidized to CO2 for energy generation. However, a portion of the methanol entered biosynthetic reactions via reactions specific to the one-carbon carrier tetrahydrofolate. In contrast, succinate was primarily used to provide precursor metabolites for bulk biomass production. This work opens new perspectives on the role of methylotrophy when substrates are simultaneously available, a situation prevailing under environmental conditions. PMID:23133625

  1. Out of plane distortions of the heme b of Escherichia coli succinate dehydrogenase.

    Directory of Open Access Journals (Sweden)

    Quang M Tran

    Full Text Available The role of the heme b in Escherichia coli succinate dehydrogenase is highly ambiguous and its role in catalysis is questionable. To examine whether heme reduction is an essential step of the catalytic mechanism, we generated a series of site-directed mutations around the heme binding pocket, creating a library of variants with a stepwise decrease in the midpoint potential of the heme from the wild-type value of +20 mV down to -80 mV. This difference in midpoint potential is enough to alter the reactivity of the heme towards succinate and thus its redox state under turnover conditions. Our results show both the steady state succinate oxidase and fumarate reductase catalytic activity of the enzyme are not a function of the redox potential of the heme. As well, lower heme potential did not cause an increase in the rate of superoxide production both in vitro and in vivo. The electron paramagnetic resonance (EPR spectrum of the heme in the wild-type enzyme is a combination of two distinct signals. We link EPR spectra to structure, showing that one of the signals likely arises from an out-of-plane distortion of the heme, a saddled conformation, while the second signal originates from a more planar orientation of the porphyrin ring.

  2. Succinic acid production from acid hydrolysate of corn fiber by Actinobacillus succinogenes.

    Science.gov (United States)

    Chen, Kequan; Jiang, Min; Wei, Ping; Yao, Jiaming; Wu, Hao

    2010-01-01

    Dilute acid hydrolysate of corn fiber was used as carbon source for the production of succinic acid by Actinobacillus succinogenes NJ113. The optimized hydrolysis conditions were obtained by orthogonal experiments. When corn fiber particles were of 20 mesh in size and treated with 1.0% sulfuric acid at 121 degrees C for 2 h, the total sugar yield could reach 63.3%. It was found that CaCO(3) neutralization combined with activated carbon adsorption was an effective method to remove fermentation inhibitors especially furfural that presented in the acid hydrolysate of corn fiber. Only 5.2% of the total sugar was lost, while 91.9% of furfural was removed. The yield of succinic acid was higher than 72.0% with the detoxified corn fiber hydrolysate as the carbon source in anaerobic bottles or 7.5 L fermentor cultures. It was proved that the corn fiber hydrolysate could be an alternative to glucose for the production of succinic acid by A. succinogenes NJ113.

  3. Genome-scale modeling enables metabolic engineering of Saccharomyces cerevisiae for succinic acid production.

    Science.gov (United States)

    Agren, Rasmus; Otero, José Manuel; Nielsen, Jens

    2013-07-01

    In this work, we describe the application of a genome-scale metabolic model and flux balance analysis for the prediction of succinic acid overproduction strategies in Saccharomyces cerevisiae. The top three single gene deletion strategies, Δmdh1, Δoac1, and Δdic1, were tested using knock-out strains cultivated anaerobically on glucose, coupled with physiological and DNA microarray characterization. While Δmdh1 and Δoac1 strains failed to produce succinate, Δdic1 produced 0.02 C-mol/C-mol glucose, in close agreement with model predictions (0.03 C-mol/C-mol glucose). Transcriptional profiling suggests that succinate formation is coupled to mitochondrial redox balancing, and more specifically, reductive TCA cycle activity. While far from industrial titers, this proof-of-concept suggests that in silico predictions coupled with experimental validation can be used to identify novel and non-intuitive metabolic engineering strategies.

  4. Integrated production of cellulosic bioethanol and succinic acid from industrial hemp in a biorefinery concept.

    Science.gov (United States)

    Kuglarz, Mariusz; Alvarado-Morales, Merlin; Karakashev, Dimitar; Angelidaki, Irini

    2016-01-01

    The aim of this study was to develop integrated biofuel (cellulosic bioethanol) and biochemical (succinic acid) production from industrial hemp (Cannabis sativa L.) in a biorefinery concept. Two types of pretreatments were studied (dilute-acid and alkaline oxidative method). High cellulose recovery (>95%) as well as significant hemicelluloses solubilization (49-59%) after acid-based method and lignin solubilization (35-41%) after alkaline H2O2 method were registered. Alkaline pretreatment showed to be superior over the acid-based method with respect to the rate of enzymatic hydrolysis and ethanol productivity. With respect to succinic acid production, the highest productivity was obtained after liquid fraction fermentation originated from steam treatment with 1.5% of acid. The mass balance calculations clearly showed that 149kg of EtOH and 115kg of succinic acid can be obtained per 1ton of dry hemp. Results obtained in this study clearly document the potential of industrial hemp for a biorefinery. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Based Indomethacin Sustained-Release Tablets

    African Journals Online (AJOL)

    Owing to the short biological half-life of this drug, a sustained ... tendency. This work is aimed at formulating sustained ... Chemie GmbH, Germany), Phospholipon® 90H. (Phospholipid ... weighed out in an analytical balance and dispersed in ...

  6. Preparation and Characterization of Sustained Release Matrix ...

    African Journals Online (AJOL)

    tablet formulations showed a percent drug release ranging from 92.54 ± 1.02 to 98.56 ± 1.26 % at the end of 12 h. Using the spinal injury rat model, ... very common and significant problem. Nonsteroidal anti-inflammatory drugs (NSAIDs) ... animal studies, its mechanism of action involves depressing polysynaptic reflexes ...

  7. Orally Administered Bioadherent Sustained Release Microencapsulated Vaccines

    Science.gov (United States)

    1996-09-01

    microspheres consist of bovine serum albumin (BSA) and recombinant vitelline protein B (vpB) from the liver fluke Fasciola hepatica which is a known...from the liver fluke Fasciola hepatica." Biochemistry 26, 7819-7825. 10. Waite, J.H., Rice-Ficht, A.C. (1992) "Eggshell precursor proteins of Fasciola ...precursor proteins of Fasciola hepatica: I. Structure and expression of vitelline protein B." Mol. Bioch. Parasitol. 54, 127-143. 12. Yapel, A.F. (1985

  8. Formulation and Characterization of Sustained Release Floating ...

    African Journals Online (AJOL)

    Various approaches have been used to retain ... with distilled water and dried. ... gold film (200 nm) under reduced pressure ... size and wall thickness of microballoons ... microscopy (SEM) revealed pores on the ... Table 1: Effect of various processing parameters on the particle size, drug loading, incorporation efficiency.

  9. Direct Succinic Acid Production from Minimally Pretreated Biomass Using Sequential Solid-State and Slurry Fermentation with Mixed Fungal Cultures

    Directory of Open Access Journals (Sweden)

    Jerico Alcantara

    2017-06-01

    Full Text Available Conventional bio-based succinic acid production involves anaerobic bacterial fermentation of pure sugars. This study explored a new route for directly producing succinic acid from minimally-pretreated lignocellulosic biomass via a consolidated bioprocessing technology employing a mixed lignocellulolytic and acidogenic fungal co-culture. The process involved a solid-state pre-fermentation stage followed by a two-phase slurry fermentation stage. During the solid-state pre-fermentation stage, Aspergillus niger and Trichoderma reesei were co-cultured in a nitrogen-rich substrate (e.g., soybean hull to induce cellulolytic enzyme activity. The ligninolytic fungus Phanerochaete chrysosporium was grown separately on carbon-rich birch wood chips to induce ligninolytic enzymes, rendering the biomass more susceptible to cellulase attack. The solid-state pre-cultures were then combined in a slurry fermentation culture to achieve simultaneous enzymatic cellulolysis and succinic acid production. This approach generated succinic acid at maximum titers of 32.43 g/L after 72 h of batch slurry fermentation (~10 g/L production, and 61.12 g/L after 36 h of addition of fresh birch wood chips at the onset of the slurry fermentation stage (~26 g/L production. Based on this result, this approach is a promising alternative to current bacterial succinic acid production due to its minimal substrate pretreatment requirements, which could reduce production costs.

  10. Effects of food on the pharmacokinetics of gemigliptin/metformin sustained-release 50/1,000 mg (25/500 mg x 2 tablets) fixeddose combination tablet in healthy male volunteers.

    Science.gov (United States)

    Choi, Hee Youn; Noh, Yook-Hwan; Kim, Yo Han; Kim, Mi Jo; Lee, Shi Hyang; Kim, Jeong-Ae; Kim, Bogyeong; Lim, Hyeong-Seok; Bae, Kyun-Seop

    2014-05-01

    For patient convenience, a gemigliptin/metformin sustainedrelease fixed-dose combination (FDC) tablet was developed. This study was conducted to investigate the effects of food on the pharmacokinetic (PK) profile of the FDC tablets. This was an open-label, randomized, single dose, 2-period, 2-sequence crossover study in 24 healthy male volunteers. The FDC tablets (25/500 mg × 2 tablets) were administered in high-fat fed and fasted states on separate occasions, and each subject was randomly allocated to each sequence with a 7-day washout period. PK blood samplings were conducted from predose to 48 hours after dosing. Tolerability assessments were performed throughout the study. Nine adverse events (AEs) of mild intensity were reported from 8 subjects after study drug administration, and the AE frequency was similar between treatments. No serious AEs were reported. The PK parameters of gemigliptin and metformin were compared between fasting and fed states. For gemigliptin, the geometric mean ratios (GMRs) (fed : fasted state) of the Cmax and AUClast were 0.886 (90% confidence interval (CI) 0.781 - 1.006) and 1.021 (90% CI 0.949 - 1.099), respectively. For metformin, the GMRs of the Cmax and AUClast were 0.811 (90% CI 0.712 - 0.923) and 1.144 (90% CI 1.013 - 1.291), respectively. A prolonged tmax for metformin was observed. These results are similar to the effects of food on each component. The FDC tablet may have a similar PK profile as that of individual drugs and is generally tolerable when administered with food. These results indicate that the FDC tablet can be administered in the same dosing regimen as each component, especially that of metformin sustained-release.

  11. Development of a novel resin-based dental material with dual biocidal modes and sustained release of Ag+ ions based on photocurable core-shell AgBr/cationic polymer nanocomposites.

    Science.gov (United States)

    Cao, Weiwei; Zhang, Yu; Wang, Xi; Chen, Yinyan; Li, Qiang; Xing, Xiaodong; Xiao, Yuhong; Peng, Xuefeng; Ye, Zhiwen

    2017-07-01

    Research on the incorporation of cutting-edge nano-antibacterial agent for designing dental materials with potent and long-lasting antibacterial property is demanding and provoking work. In this study, a novel resin-based dental material containing photocurable core-shell AgBr/cationic polymer nanocomposite (AgBr/BHPVP) was designed and developed. The shell of polymerizable cationic polymer not only provided non-releasing antibacterial capability for dental resins, but also had the potential to polymerize with other methacrylate monomers and prevented nanoparticles from aggregating in the resin matrix. As a result, incorporation of AgBr/BHPVP nanocomposites did not adversely affect the flexural strength and modulus but greatly increased the Vicker's hardness of resin disks. By continuing to release Ag + ions without the impact of anaerobic environment, resins containing AgBr/BHPVP nanoparticles are particularly suitable to combat anaerobic cariogenic bacteria. By reason of the combined bactericidal effect of the contact-killing cationic polymers and the releasing-killing Ag + ions, AgBr/BHPVP-containing resin disks had potent bactericidal activity against S. mutans. The long-lasting antibacterial activity was also achieved through the sustained release of Ag + ions due to the core-shell structure of the nanocomposites. The results of macrophage cytotoxicity showed that the cell viability of dental resins loading less than 1.0 wt% AgBr/BHPVP was close to that of neat resins. The AgBr/BHPVP-containing dental resin with dual bactericidal capability and long term antimicrobial effect is a promising material aimed at preventing second caries and prolonging the longevity of resin composite restorations.

  12. Bioequivalence and Safety of Twice-Daily Sustained-Release Paracetamol (Acetaminophen) Compared With 3- and 4-Times-Daily Paracetamol: A Repeat-Dose, Crossover Pharmacokinetic Study in Healthy Volunteers.

    Science.gov (United States)

    Liu, Dongzhou J; Collaku, Agron

    2018-01-01

    Twice-daily sustained-release (SR) paracetamol (acetaminophen) offers convenient administration to chronic users. This study investigated at steady state (during the last 24 hours of a 3-day dosing period) the pharmacokinetics, bioequivalence, and safety of twice-daily SR paracetamol compared with extended-release (ER) and immediate-release (IR) paracetamol. In this open-label, randomized, multidose, 3-way crossover study, 28 healthy subjects received paracetamol SR (2 × 1000 mg twice daily), ER (2 × 665 mg 3 times daily), and IR (2 × 500 mg 4 times daily). At steady state, twice-daily SR paracetamol was bioequivalent to ER and IR paracetamol. The 90% confidence intervals for the ratios of geometric means were within the acceptance interval for SR/ER paracetamol (AUC 0-t , 0.973-1.033; AUC 0-24 , 0.974-1.034; AUC 0-∞ , 0.948-1.011; C max , 1.082-1.212; C av , 1.011-1.106) and SR/IR paracetamol (AUC 0-t , 0.969-1.029; AUC 0-24 , 0.968-1.027; AUC 0-∞ , 0.963-1.026; C max , 0.902-1.010; C av , 1.004-1.098). Given twice daily, the SR formulation demonstrated SR properties as expected. Mean time at or above a 4 μg/mL plasma concentration of paracetamol from 2 daily doses of the SR formulation was significantly longer than that from 4 daily doses of IR paracetamol. SR formulation also had a greater T max , a longer half-life, and lower C min compared with ER and IR paracetamol. All formulations were well tolerated. © 2017, The American College of Clinical Pharmacology.

  13. Microbiological and clinical effects of enamel matrix derivative and sustained-release micro-spherical minocycline application as an adjunct to non-surgical therapy in peri-implant mucosal inflammation.

    Science.gov (United States)

    Faramarzi, Masumeh; Goharfar, Zahra; Pourabbas, Reza; Kashefimehr, Atabak; Shirmohmmadi, Adileh

    2015-08-01

    The purpose of this study was to compare the microbial and clinical effects of mechanical debridement (MD) alone or in combination with the application of enamel matrix derivative (EMD) and sustained-release micro-spherical minocycline (MSM) for treatment of peri-implant mucosal infl ammation (PIMI). Subjects with at least one implant with PIMI were included and divided into control and two different test groups. In all three groups, MD was performed. In the MSM group, following MD, MSM was placed subgingivally around the implants. In the EMD group, after MD, EMD was placed in the sulcus around the implants. Sampling of peri-implant crevicular fl uid for microbial analysis with real-time polymerase chain reaction and recording of probing depth (PD) and bleeding on probing (BOP) were performed prior to as well as two weeks and three months after treatment. Median values and interquartile range were estimated for each variable during the various assessment intervals of the study. In all groups, at two weeks and three months, the counts of Porphyromonas gingivalis decreased significantly compared to baseline. Levels of P. gingivalis were significantly reduced in MSM (P<0.001) and EMD (P=0.026) groups compared to the control group. Also, clinical parameters improved significantly at two weeks and three months. Reduction of PD was significant in MSM (P<0.001) and EMD (P<0.001) groups. The decrease in BOP in the MSM, EMD, and control groups was 60%, 50%, and 20%, respectively. The use of MSM and EMD can be an adjunctive treatment for management of PIMI and improves clinical parameters and reduces P. gingivalis burden three months after treatment.

  14. Radiation-induced alterations in succinate dehydrogenase activity in the muscle of pigeon

    International Nuclear Information System (INIS)

    Gadhia, P.K.; Shah, V.C.

    1983-01-01

    The histochemical changes in succinate dehydrogenase were investigated in pectoralis major muscle of pigeon exposed to sub-lethal dose (400 rad) of γ-irradiation. Biochemical study was also carried out after 200, 300 and 400 rad of irradiation. In the present study the overall decrease in enzyme activity could be due to the structural and/or functional damage to mitochondria after treatment of pigeon to different sub-lethal doses of γ-irradiation. The significance of these results has been discussed with special reference to oxidative metabolism. (author)

  15. Mitochondrially Targeted Vitamin E Succinate Modulates Expression of Mitochondrial DNA Transcripts and Mitochondrial Biogenesis

    Czech Academy of Sciences Publication Activity Database

    Truksa, Jaroslav; Dong, L.F.; Rohlena, Jakub; Stursa, J.; Vondrusová, Magdaléna; Goodwin, J.; Nguyen, M.; Klučková, Katarína; Rychtarčíková, Zuzana; Lettlová, Sandra; Spáčilová, Jana; Stapelberg, M.; Zoratti, M.; Neužil, Jiří

    2015-01-01

    Roč. 22, č. 11 (2015), s. 883-900 ISSN 1523-0864 R&D Projects: GA ČR GAP301/10/1937; GA AV ČR KAN200520703; GA ČR GAP305/12/1708; GA ČR GAP301/12/1851; GA MŠk(CZ) ED1.1.00/02.0109 Institutional research plan: CEZ:AV0Z50520701 Institutional support: RVO:86652036 Keywords : ALPHA-TOCOPHERYL SUCCINATE * ELECTRON-TRANSPORT CHAIN * RESPIRATORY COMPLEX-II Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.093, year: 2015

  16. Evidence of redox imbalance in a patient with succinic semialdehyde dehydrogenase deficiency

    Directory of Open Access Journals (Sweden)

    Anna-Kaisa Niemi

    2014-01-01

    Full Text Available The pathophysiology of succinic semialdehyde dehydrogenase (SSADH deficiency is not completely understood. Oxidative stress, mitochondrial pathology, and low reduced glutathione levels have been demonstrated in mice, but no studies have been reported in humans. We report on a patient with SSADH deficiency in whom we found low levels of blood reduced glutathione (GSH, and elevations of dicarboxylic acids in urine, suggestive of possible redox imbalance and/or mitochondrial dysfunction. Thus, targeting the oxidative stress axis may be a potential therapeutic approach if our findings are confirmed in other patients.

  17. Influence of adrenaline on the activity of succinate dehydrogenase in peripheral blood lymphocytes of irradiated rats

    International Nuclear Information System (INIS)

    Koroleva, L.V.; Vasin, M.V.

    1988-01-01

    In experiments with albino mongrel female rats, the influence of adrenaline on succinate dehydrogenase (SDG) activity in the peripheral blood lymphocytes of irradiated and intact animals has been investigated. Two minutes after the intraperitoneal administration of adrenaline (1 mg/kg) to intact rats SDG activity sharply rises and 3-4 min it drastically falls. In 6 to 8 min the second peak in the enzyme activity is registered. Twenty minutes after irradiation of rats in the crano-caudal direction with a dose of 75 Gy delivered to head, the reaction to adrenaline, manifested by the rise in SDG activity, is absent

  18. Nb-Based Zeolites: Efficient bi-Functional Catalysts for the One-Pot Synthesis of Succinic Acid from Glucose

    Directory of Open Access Journals (Sweden)

    Magdi El Fergani

    2017-12-01

    Full Text Available The one-pot production of succinic acid from glucose was investigated in pure hot water as solvent using Nb (0.02 and 0.05 moles%-Beta zeolites obtained by a post-synthesis methodology. Structurally, they are comprised of residual framework Al-acid sites, extra-framework isolated Nb (V and Nb2O5 pore-encapsulated clusters. The Nb-modified Beta-zeolites acted as bi-functional catalysts in which glucose is dehydrated to levulinic acid (LA which, further, suffers an oxidation process to succinic acid (SA. After the optimization of the reaction conditions, that is, at 180 °C, 18 bar O2, and 12 h reaction time, the oxidation of glucose occurred with a selectivity to succinic acid as high as 84% for a total conversion.

  19. [Pathomorphology of regenerative processes in mandibular fracture after sodium succinate treatment and laser magnetotherapy in an experimental setting].

    Science.gov (United States)

    Faustov, L A; Nedel'ko, N A; Morozova, M V

    2001-01-01

    Morphological reactions in tissue adjacent to mandibular angular fracture were studied in guinea pigs treated with sodium succinate and laser magnetotherapy. Due to succinate therapy the exudative component of inflammation was less expressed in comparison with the control, macrophagal reaction and neoangiogenesis were activated, the volume of damaged muscle tissue and the incidence of suppurations decreased. The number of osteoblasts increased and new bone structures acquired a lamellar pattern earlier than in the control. Sodium succinate therapy in combination with laser magnetotherapy had a more pronounced positive effect as regards activation of macrophagal reaction and neoangiogenesis and a decrease in the area of fibrosclerotic changes in the zone of damaged muscles, where newly formed myosymplasts differentiated into myotubes and even in muscle fibers. Suppuration of the wound was prevented. Bone tissue in the fracture zone formed without preliminary formation of cartilaginous tissue, which resulted in more rapid osteogenesis (lamellar bone growth in the fracture zone).

  20. Succinate production positively correlates with the affinity of the global transcription factor Cra for its effector FBP in Escherichia coli.

    Science.gov (United States)

    Wei, Li-Na; Zhu, Li-Wen; Tang, Ya-Jie

    2016-01-01

    Effector binding is important for transcription factors, affecting both the pattern and function of transcriptional regulation to alter cell phenotype. Our previous work suggested that the affinity of the global transcription factor catabolite repressor/activator (Cra) for its effector fructose-1,6-bisphosphate (FBP) may contribute to succinate biosynthesis. To support this hypothesis, single-point and three-point mutations were proposed through the semi-rational design of Cra to improve its affinity for FBP. For the first time, a positive correlation between succinate production and the affinity of Cra for FBP was revealed in Escherichia coli . Using the best-fit regression function, a cubic equation was used to examine and describe the relationship between succinate production and the affinity of Cra for FBP, demonstrating a significant positive correlation between the two factors (coefficient of determination R 2  = 0.894, P  = 0.000 Cra and DNA showed that Cra bound to the promoter regions of pck and aceB to activate the corresponding genes. Normally, Cra-regulated operons under positive control are deactivated in the presence of FBP. Therefore, theoretically, the enhanced affinity of Cra for FBP will inhibit the activation of pck and aceB . However, the activation of genes involved in CO 2 fixation and the glyoxylate pathway was further improved by the Cra mutant, ultimately contributing to succinate biosynthesis. Enhanced binding of Cra to FBP or active site mutations may eliminate the repressive effect caused by FBP, thus leading to increased activation of genes associated with succinate biosynthesis in the Cra mutant. This work demonstrates an important transcriptional regulation strategy in the metabolic engineering of succinate production and provides useful information for better understanding of the regulatory mechanisms of transcription factors.

  1. Study on fluorescence properties of carbogenic nanoparticles and their application for the determination of ferrous succinate

    Energy Technology Data Exchange (ETDEWEB)

    Sun Wen [Department of Analytical Chemistry, China Pharmaceutical University, Nanjing 210009 (China); Du Yingxiang, E-mail: du_yingxiang@126.co [Department of Analytical Chemistry, China Pharmaceutical University, Nanjing 210009 (China) and Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing 210009 (China) and Key Laboratory of Modern Chinese Medicines, Ministry of Education, China Pharmaceutical University, Nanjing 210009 (China); Wang Yunqing [Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003 (China)

    2010-08-15

    A new type of fluorescent nanomaterial named carbogenic nanoparticles (NPs) has drawn considerable attention recently. In this study, we adopted a direct and simple synthetic method to produce the carbogenic NPs and investigated the fluorescence properties of the as-prepared carbogenic NPs in detail. It was found that the fluorescence of carbogenic NPs was stable with the variance of environmental conditions such as pH, temperature and UV irradiation. More interestingly, we found carbogenic NPs exhibited high selectivity and sensitivity towards ferric ions. Under optimum conditions, a good linear relationship could be obtained between the fluorescence intensity and concentration of ferric ions in the range of 5.0x10{sup -5}-5.0x10{sup -4} mol L{sup -1}, and the limit of detection is 11.2 {mu}mol L{sup -1}. Based on the fluorescence quenching of carbogenic NPs, a rapid and specific quantitative method was proposed for the determination of ferrous succinate. The content of ferrous succinate in commercial tablets determined by the present method was agreed with the spectrophotometric method results and the reproducibility and the recovery of the proposed method were satisfactory.

  2. Crystallization and degradation behaviors of poly(butylene succinate)/poly(Z-L-lysine) composites

    International Nuclear Information System (INIS)

    Tan, Licheng; Hu, Jun; Ye, Suwen; Wei, Junchao; Chen, Yiwang

    2014-01-01

    Highlights: • A new biodegradable poly(butylene succinate) (PBS)/poly(Z-L-lysine) (PZlys) composites were successfully prepared through physical blend. • PZlys may greatly affected the crystallization behaviors of PBS without changing its crystalline structure. • The degradation speed of PBS may be greatly accelerated by introduction of PZlys in PBS matrix. - Abstract: A new type of biodegradable poly(butylene succinate) (PBS)/poly(Z-L-lysine) (PZlys) composites were prepared. The crystallization behaviors were investigated by differential scanning calorimetry (DSC), wide angle X-ray diffraction (WAXD) and polarizing optical microscopy (POM) and the results showed that PZlys can restrict the crystallization of PBS, the crystallization speed of PBS/PZlys were slower than that of PBS, and the crystallization degree of the composites were smaller than that of PBS. However, the WAXD results showed that the incorporation of PZlys did not change the crystalline structure of PBS. The in vitro degradation experiments demonstrated that the degradation speed of the composites were faster than that of PBS. Moreover, the mechanical properties of the composites showed that the composites with a proper composition (for example, 80/20) can keep the mechanical properties of PBS without evident difference, which implied that the composites might be potentially useful as biodegradable materials

  3. Succinate Functionalization of Hyperbranched Polyglycerol-Coated Magnetic Nanoparticles as a Draw Solute During Forward Osmosis.

    Science.gov (United States)

    Yang, Hee-Man; Choi, Hye Min; Jang, Sung-Chan; Han, Myeong Jin; Seo, Bum-Kyoung; Moon, Jei-Kwon; Lee, Kune-Woo

    2015-10-01

    Hyperbranched polyglycerol-coated magnetic nanoparticles (SHPG-MNPs) were functionalized with succinate groups to form a draw solute for use in a forward osmosis (FO). After the one-step synthesis of hyperbranched polyglycerol-coated magnetic nanoparticles (HPG-MNPs), the polyglycerol groups on the surfaces of the HPG-MNPs were functionalized with succinic anhydride moieties. The resulting SHPG-MNPs showed no change of size and magnetic property compared with HPG-MNPs and displayed excellent dispersibility in water up to the concentration of 400 g/L. SHPG-MNPs solution showed higher osmotic pressure than that of HPG-MNPs solution due to the presence of surface carboxyl groups in SHPG-MNPs and could draw water from a feed solution across an FO membrane without any reverse draw solute leakage during FO process. Moreover, the water flux remained nearly constant over several SHPG-MNP darw solute regeneration cycles applied to the ultrafiltration (UF) process. The SHPG-MNPs demonstrate strong potential for use as a draw solute in FO processes.

  4. Review of succinate dehydrogenase-deficient renal cell carcinoma with focus on clinical and pathobiological aspects

    Directory of Open Access Journals (Sweden)

    Naoto Kuroda

    2016-05-01

    Full Text Available Succinate dehydrogenase (SDH-deficient renal cell carcinoma (RCC was first identified in 2004 and has been integrated into the 2016 WHO classification of RCC. Succinate dehydrogenase (SDH is an enzyme complex composed of four protein subunits (SDHA, SDHB, SDHC and SDHD. The tumor which presents this enzyme mutation accounts for 0.05 to 0.2% of all renal carcinomas. Multiple tumors may occur in approximately 30% of affected patients. SDHB-deficient RCC is the most frequent, and the tumor histologically consists of cuboidal cells with eosinophilic cytoplasm, vacuolization, flocculent intracytoplasmic inclusion and indistinct cell borders. Ultrastructurally, the tumor contains abundant mitochondria. Immunohistochemically, tumor cells are positive for SDHA, but negative for SDHB in SDHB-, SDHC- and SDHD-deficient RCCs. However, SDHA-deficient RCC shows negativity for both SDHA and SDHB. In molecular genetic analyses, a germline mutation in the SDHB , SDHC or SDHD gene (in keeping with most patients having germline mutations in an SDH gene has been identified in patients with or without a family history of renal tumors, paraganglioma/pheochromocytoma or gastrointestinal stromal tumor. While most tumors are low grade, some tumors may behave in an aggressive fashion, particularly if they are high nuclear grade, and have coagulative necrosis or sarcomatoid differentiation.

  5. Role of O2 in the Growth of Rhizobium leguminosarum bv. viciae 3841 on Glucose and Succinate

    OpenAIRE

    Wheatley, Rachel M.; Ramachandran, Vinoy K.; Geddes, Barney A.; Perry, Benjamin J.; Yost, Chris K.; Poole, Philip S.

    2016-01-01

    Insertion sequencing (INSeq) analysis of Rhizobium leguminosarum bv. viciae 3841 (Rlv3841) grown on glucose or succinate at both 21% and 1% O2 was used to understand how O2 concentration alters metabolism. Two transcriptional regulators were required for growth on glucose (pRL120207 [eryD] and RL0547 [phoB]), five were required on succinate (pRL100388, RL1641, RL1642, RL3427, and RL4524 [ecfL]), and three were required on 1% O2 (pRL110072, RL0545 [phoU], and RL4042). A novel toxin-antitoxin s...

  6. Two-step irradiance schedule versus single-dose tramadol sustained-release tablets for pain control during topical 5-aminolevulinic acid-photodynamic therapy of condyloma acuminatum in Chinese patients: a randomized comparative study.

    Science.gov (United States)

    Mchepange, Uwesu O; Huang, Chun-Yan; Sun, Yi; Tu, Ya-Ting; Tao, Juan

    2014-07-01

    Photodynamic therapy with 5-aminolevulinic acid (ALA-PDT) offers promising results for the treatment of condyloma acuminatum. However, patients have to dwell with pain to benefit from this otherwise effective and safe "off-label" treatment modality. Several techniques have been explored to control ALA-PDT-induced pain, but the desperate search for a universally accepted method is still ongoing. This study compares the two-step irradiance approach with single-dose administration of 100 mg tramadol sustained-release tablets for pain induced by ALA-PDT of condyloma acuminatum in Chinese patients. Adult Chinese patients with condyloma acuminatum were enrolled in a randomized comparative study. Pain levels were compared using the Numeric Rating Scale (NRS) at pre-defined assessment points during and after irradiation. The pain was dominated by characteristics such as burning and pricking and was almost always local and superficial. The median pain scores were lower in the two-step irradiance group at 1 minute (U = 621.5, P = 0.002) but higher at 20 minutes (U = 585.5, P = 0.002). The median pain scores between the two groups did not differ significantly at other assessment points. The pain was moderate in both groups and peaked earlier in the analgesics group (median: 5 minutes) but later in the two-step irradiance group (median: 15 minutes). The pain was generally mild. The median pain scores were equal at each assessment point, except at 3 hours where the median was lower in the analgesics group (1.0) as compared with the two-step irradiance group (2.0) (U = 725.0, P = 0.056). Pain in the two-step irradiance protocol is irradiance-dependent. The two-step irradiance approach produces significant benefits over analgesics during the initial stages of therapy but analgesics offer significant benefits thereafter. There are potential benefits of combining the two approaches in minimizing ALA-PDT-induced pain. © 2014 Wiley Periodicals

  7. A novel mutation in the succinate dehydrogenase subunit D gene in siblings with the hereditary paraganglioma–pheochromocytoma syndrome

    Directory of Open Access Journals (Sweden)

    Chaithra Prasad

    2014-10-01

    Full Text Available Germline mutations in the succinate dehydrogenase complex subunit D gene are now known to be associated with hereditary paraganglioma–pheochromocytoma syndromes. Since the initial succinate dehydrogenase complex subunit D gene mutation was identified about a decade ago, more than 131 unique variants have been reported. We report the case of two siblings presenting with multiple paragangliomas and pheochromocytomas; they were both found to carry a mutation in the succinate dehydrogenase complex subunit D gene involving a substitution of thymine to guanine at nucleotide 236 in exon 3. This particular mutation of the succinate dehydrogenase complex subunit D gene has only been reported in one previous patient in Japan; this is, therefore, the first report of this pathogenic mutation in siblings and the first report of this mutation in North America. With continued screening of more individuals, we will be able to create a robust mutation database that can help us understand disease patterns associated with particular variants and may be a starting point in the development of new therapies for familial paraganglioma syndromes.

  8. Influence of salicylic and succinic acids on antioxidant enzymes activity, heat resistance and productivity of Panicum miliaceum L.

    Directory of Open Access Journals (Sweden)

    Miroshnichenko N.N.

    2011-05-01

    Full Text Available The influence of treatment of millet (Panicum miliaceum L. seeds with the solutions of salicylic and succinic acids on the heat resistance of plantlets and activity of antioxidant enzymes – superoxide dismutase (SOD, catalase and peroxidase – in them have been investigated. In the micro-field experiment the influence of these acids on the millet yield was estimated. The action of salicylic (10 μM and succinic (1 mM acids caused the increase of plantlets resistance to the damaging heating that expressed in the rise of relative quantity of survived plantlets in 5 days after heating at the temperature of 47°С and in the reduced content of lipid peroxidation product malonic dialdehyde during the poststress period. The increase of activity of SOD, catalase and peroxidase took place in millet plantlets under the influence of salicylic and succinic acids. The increase of productivity of millet grain under the action of salicylic and succinic acids on 13,3-52,0 and 6,4-38,8% respectively depending on weather conditions in the field experiments was noted.

  9. Linkage and radiation hybrid mapping of the porcine gene for subunit C of succinate dehydrogenase complex (SDHC)

    Czech Academy of Sciences Publication Activity Database

    Stratil, Antonín; Reiner, G.; Peelman, L. J.; Poucke, M.; Geldermann, H.

    2001-01-01

    Roč. 32, č. 2 (2001), s. 110-112 ISSN 0268-9146 R&D Projects: GA AV ČR KSK5052113; GA ČR GA523/00/0669 Keywords : succinate dehydrogenase complex Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.020, year: 2001

  10. Discovering novel Alternaria solani succinate dehydrogenase inhibitors by in silico modeling and virtual screening strategies to combat early blight

    NARCIS (Netherlands)

    Iftikhar, Sehrish; Shahid, Ahmad A.; Halim, Sobia A.; Wolters, Pieter J.; Vleeshouwers, Vivianne G.A.A.; Khan, Ajmal; Al-Harrasi, Ahmed; Ahmad, Shahbaz

    2017-01-01

    Alternaria blight is an important foliage disease caused by Alternaria solani. The enzyme Succinate dehydrogenase (SDH) is a potential drug target because of its role in tricarboxylic acid cycle. Hence targeting Alternaria solani SDH enzyme could be efficient tool to design novel fungicides against

  11. Utilization of CO2 fixating bacterium Actinobacillus succinogenes 130Z for simultaneous biogas upgrading and bio-succinic acid production

    DEFF Research Database (Denmark)

    Gunnarsson, Ingólfur Bragi; Alvarado-Morales, Merlin; Angelidaki, Irini

    2014-01-01

    Biogas is an attractive renewable energy carrier. However, it contains CO2 which limits certain applications of biogas. Here we report a novel approach for removing CO2 from biogas and capturing it as a biochemical through a biological process. This approach entails converting CO2 into bio...... and titre, CO2 consumption rate and CH4 purity. When using biogas as the only CO2 source at 140 kPa, the CO2 consumption rate corresponded to 2.59 L CO2 L-1 d-1 with a final succinic acid titre of 14.4 g L-1. Under this pressure condition the highest succinic acid yield and biogas quality reached......-succinic acid using the bacterial strain Actinobacillus succinogenes 130Z, and simultaneously producing high purity CH4 (>95%). Results showed that when pressure during fermentation was increased from 101.325 to 140 kPa, higher CO2 solubility was achieved, thereby positively affecting final succinic acid yield...

  12. Enhancing succinic acid biosynthesis in Escherichia coli by engineering its global transcription factor, catabolite repressor/activator (Cra).

    Science.gov (United States)

    Zhu, Li-Wen; Xia, Shi-Tao; Wei, Li-Na; Li, Hong-Mei; Yuan, Zhan-Peng; Tang, Ya-Jie

    2016-11-04

    This study was initiated to improve E. coli succinate production by engineering the E. coli global transcription factor, Cra (catabolite repressor/activator). Random mutagenesis libraries were generated through error-prone PCR of cra. After re-screening and mutation site integration, the best mutant strain was Tang1541, which provided a final succinate concentration of 79.8 ± 3.1 g/L: i.e., 22.8% greater than that obtained using an empty vector control. The genes and enzymes involved in phosphoenolpyruvate (PEP) carboxylation and the glyoxylate pathway were activated, either directly or indirectly, through the mutation of Cra. The parameters for interaction of Cra and DNA indicated that the Cra mutant was bound to aceBAK, thereby activating the genes involved in glyoxylate pathway and further improving succinate production even in the presence of its effector fructose-1,6-bisphosphate (FBP). It suggested that some of the negative effect of FBP on Cra might have been counteracted through the enhanced binding affinity of the Cra mutant for FBP or the change of Cra structure. This work provides useful information about understanding the transcriptional regulation of succinate biosynthesis.

  13. Mitochondrially targeted vitamin E succinate efficiently kills breast tumour-initiating cells in a complex II-dependent manner

    Czech Academy of Sciences Publication Activity Database

    Yan, B.; Stantic, M.; Zobalová, Renata; Bezawork-Geleta, A.; Stapelberg, M.; Stursa, J.; Prokopová, Kateřina; Dong, L.; Neužil, Jiří

    2015-01-01

    Roč. 15, č. 401 (2015) ISSN 1471-2407 R&D Projects: GA MZd NT14078; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : Tumour-initiating cells * Mitochondrially targeted vitamin E succinate * Complex II Subject RIV: FD - Oncology ; Hematology Impact factor: 3.265, year: 2015

  14. Bid integrates intrinsic and extrinsic signaling in apoptosis induced by alpha-tocopheryl succinate in human gastric carcinoma cells

    Czech Academy of Sciences Publication Activity Database

    Zhao, Y.; Li, R.; Xia, W.; Neužil, Jiří; Lu, Y.; Zhang, H.; Zhao, X.; Zhang, X.; Sun, C.; Wu, K.

    2010-01-01

    Roč. 288, č. 1 (2010), s. 42-49 ISSN 0304-3835 R&D Projects: GA ČR(CZ) GA204/08/0811 Institutional research plan: CEZ:AV0Z50520701 Keywords : Alpha-tocopheryl succinate * signaling * apoptosis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.864, year: 2010

  15. Alpha-Tocopheryl succinate induces cytostasis and apoptosis in osteosarcoma cells: the role of E2F1

    Czech Academy of Sciences Publication Activity Database

    Alleva, R.; Benassi, M.S.; Tomasetti, M.; Gellert, N.; Ponticelli, F.; Borghi, B.; Picci, P.; Neužil, Jiří

    2005-01-01

    Roč. 331, č. 4 (2005), s. 1515-1521 ISSN 0006-291X Institutional research plan: CEZ:AV0Z50520514; CEZ:AV0Z5052915 Keywords : osteosarcoma * alpha-tocopheryl succinate * E2F1 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.000, year: 2005

  16. Physical and chemical stability of palonosetron hydrochloride with dacarbazine and with methylprednisolone sodium succinate during simulated y-site administration.

    Science.gov (United States)

    Trissel, Lawrence A; Zhang, Yanping; Xu, Quanyun A

    2006-01-01

    The objective of this study was to evaluate the physical and chemical stability of mixtures of undiluted palonosetron hydrochloride 50 micrograms/mL with dacarbazine 4 mg/mL and with methylprednisolone sodium succinate 5 mg/mL in 5% dextrose injection during simulated Y-site administration. Triplicate test samples were prepared by admixing 7.5 mL of palonosetron hydrochloride with 7.5 mL of dacarbazine solution and, separately, methylprednisolone sodium succinate solution. Physical stability was assessed by using a multistep evaluation procedure that included both turbidimetric and particulate measurement as well as visual inspection. Chemical stability was assessed by using stability-indicating high-performance liquid chromatographic analytical techniques that determined drug concentrations. Evaluations were performed immediately after mixing and 1 and 4 hours after mixing. The palonosetron hydrochloride-dacarbazine samples were clear and colorless when viewed in normal fluorescent room light and when viewed with a Tyndall beam. Measured turbidities remained unchanged; particulate contents were low and exhibited little change. High-performance liquid chromatography analysis revealed that palonosetron hydrochloride and dacarbazine remained stable throughout the 4-hour test with no drug loss. Palonosetron hydrochloride is, therefore, physically compatible and chemically stable with dacarbazine during Y-site administration. Within 4 hours, the mixtures of palonosetron hydrochloride and methylprednisolone sodium succinate developed a microprecipitate that became a white precipitate visible to the unaided eye. The precipitate was analyzed and identified as methylprednisolone. Palonosetron hydrochloride is incompatible with methylprednisolone sodium succinate.

  17. Development of chitosan/gelatin/keratin composite containing hydrocortisone sodium succinate as a buccal mucoadhesive patch to treat desquamative gingivitis.

    Science.gov (United States)

    Davoudi, Zahra; Rabiee, Mohammad; Houshmand, Behzad; Eslahi, Niloofar; Khoshroo, Kimia; Rasoulianboroujeni, Morteza; Tahriri, Mohammadreza; Tayebi, Lobat

    2018-01-01

    The aim of this research was to develop chitosan/gelatin/keratin composite containing hydrocortisone sodium succinate as a buccal mucoadhesive patch to treat desquamative gingivitis, which was fabricated through an environmental friendly process. Mucoadhesive films increase the advantage of higher efficiency and drug localization in the affected region. In this research, mucoadhesive films, for the release of hydrocortisone sodium succinate, were prepared using different ratios of chitosan, gelatin and keratin. In the first step, chitosan and gelatin proportions were optimized after evaluating the mechanical properties, swelling capacity, water uptake, stability, and biodegradation of the films. Then, keratin was added at different percentages to the optimum composite of chitosan and gelatin together with the drug. The results of surface pH showed that none of the samples were harmful to the buccal cavity. FTIR analysis confirmed the influence of keratin on the structure of the composite. The presence of a higher amount of keratin in the composite films resulted in high mechanical, mucoadhesive properties and stability, low water uptake and biodegradation in phosphate buffer saline (pH = 7.4) containing 10 4  U/ml lysozyme. The release profile of the films ascertained that keratin is a rate controller in the release of the hydrocortisone sodium succinate. Finally, chitosan/gelatin/keratin composite containing hydrocortisone sodium succinate can be employed in dental applications.

  18. Hepatoprotective Activity of a Complex Compound of 5-Hydroxy-6-Methyluracil and Succinic Acid in Experimental Peritonitis

    Directory of Open Access Journals (Sweden)

    D. A. Yenikeyev

    2008-01-01

    Full Text Available Objective: to evaluate the hepatoprotective efficacy of a complex compound of 5-hydroxy-6-methyluracil and succinic acid in experimental peritonitis. Materials and methods. Experiments were carried out on 48 male albino rats in which peritonitis was simulated via intraperitoneal administration of 7% fecal suspension in a dose of 0.6 ml per 100 g bodyweight. The rate of free radical oxidation processes, the activity of antioxidative protection, the degree of endogenous intoxication and cytolytic syndrome, and the effect of the test compound on these parameters were estimated in the experiment. Results. With the development of an abdominal inflammatory process, there were increases in rates of endogenous intoxication and free radical oxidation (FRO, a change in the activity of antioxidative protection enzymes, and a reduction in the levels of ceruloplasmin and sulfahydryl groups. The complex compound, that comprised 5-hydroxy-6-methyluracil and succinic acid used as monotherapy, reduced the degree of endogenous intoxication, FRO, and lipid peroxidation-antioxidative defense system imbalance. Conclusion. The experimental data suggest that the use of the complex compound containing succinic acid and 5-hydroxy-6-methy-luracil is pathogenetically warranted. Key words: peritonitis, lipid peroxidation, antioxidants, succinic acid, pyrim-idine derivatives.

  19. Two transgenic mouse models for β-subunit components of succinate-CoA ligase yielding pleiotropic metabolic alterations

    DEFF Research Database (Denmark)

    Kacso, Gergely; Ravasz, Dora; Doczi, Judit

    2016-01-01

    Succinate-CoA ligase (SUCL) is a heterodimer enzyme composed of Suclg1 α-subunit and a substrate-specific Sucla2 or Suclg2 β-subunit yielding ATP or GTP, respectively. In humans, the deficiency of this enzyme leads to encephalomyopathy with or without methylmalonyl aciduria, in addition to result...

  20. Surface Functionalization of WO3 Thin Films with (3-Aminopropyl)triethoxysilane and Succinic Anhydride

    Science.gov (United States)

    Ta, Thi Kieu Hanh; Tran, Thi Nhu Hoa; Tran, Quang Minh Nhat; Pham, Duy Phong; Pham, Kim Ngoc; Cao, Thi Thanh; Kim, Yong Soo; Tran, Dai Lam; Ju, Heongkyu; Phan, Bach Thang

    2017-06-01

    We report effects of oxygen plasma treatment on the surface functionalization of WO3 thin films with (3-aminopropyl)triethoxysilane (APTES) and succinic anhydride (SA). X-ray diffraction and x-ray photoelectron spectroscopy results indicate the existence of the WO3 phase. Fourier transform infrared spectroscopy measurement shows clear bands at 1040 cm-1 (Si-O-Si), 1556 cm-1 (N-H), 1655 cm-1 (C=O), 2937 cm-1 (C-H) and 3298 cm-1 (N-H), confirming the surface functionalization efficiency enhanced by prior treatment of oxygen plasma. It thus follows that the prior oxygen plasma treatment activates hydroxylation with more -OH groups on the WO3 surface, which can pave a highly efficient way to the surface functionalization by APTES and SA.

  1. Vickers microhardness studies on solution-grown single crystals of potassium boro-succinate

    Science.gov (United States)

    Lakshmipriya, M.; Rajan Babu, D.; Ezhil Vizhi, R.

    2015-02-01

    The semiorganic crystals of potassium boro-succinate (KBS) were grown by slow evaporation method. KBS crystallizes in monoclinic system which was confirmed by powder XRD analysis. Vickers microhardness study has been carried out over a load range of 25-100 g. The Vickers hardness numbers (Hv) of the material increases as the load increases so the material is suitable for device fabrication. The Meyer index 'n' is estimated to be greater than 1.6, the crystal system belongs to the soft material category. The elastic stiffness coefficient, c11, has also been calculated using Wooster's empirical relation from the hardness data. The fracture toughness values 'Kc', determined from measurements of crack lengths, were estimated to be 0.15166 MN/m3/2. The brittleness indices 'Bi' were estimated as 276 m-1/2.

  2. Enhanced performance of biodegradable poly(butylene succinate)/graphene oxide nanocomposites via in situ polymerization.

    Science.gov (United States)

    Wang, X W; Zhang, C-A; Wang, P L; Zhao, J; Zhang, W; Ji, J H; Hua, K; Zhou, J; Yang, X B; Li, X P

    2012-05-08

    Poly(butylene succinate) (PBS)/graphene oxide (GO) nanocomposites were facilely prepared via in situ polymerization. The properties of the nanocomposites were studied using FTIR, XRD, and (1)H NMR, and the state of dispersion of GO in the PBS matrix was examined by SEM. The crystallization and melting behavior of the PBS matrix in the presence of dispersed GO nanosheets have been studied by DSC and polarized optical microscopy. Through the mechnical testing machine and DMA, PBS/GO nanocomposites with 3% GO have shown a 43% increase in tensile strength and a 45% improvement in storage modulus. This high performance of the nanocomposites is mainly attributed to the high strength of graphene oxide combined with the strong interfacial interactions in the uniformly dispersed PBS/GO nanocomposites.

  3. Preparation of nanocomposites based on poly(Butylene Succinate) and montmorillonite organoclay via in situ polymerization

    International Nuclear Information System (INIS)

    Ferreira, Leticia P.; Moreira, Andrei N.; Souza Junior, Fernando G. de; Pinto, Jose Carlos Costa da Silva

    2014-01-01

    Nanocomposites based on poly(butylene succinate) (PBS) and organophilic montmorillonite were synthesized via in situ polymerization using three different clay compositions (4, 6 and 8 wt%). The products were characterized by several different techniques. X-ray diffraction was useful to confirm the increase of the interlayer spacing of the clay due to the presence of the polymer chains among layers. Thermal analysis indicated that the polymerization method chosen led to materials with lower thermal stability compared to the pure PBS, due to the difficulty of chain growth in the presence of the clay. Low-field NMR technique was used to assess clay dispersion in the polymer, with exfoliated structures predominating in the nanocomposites. (author)

  4. Unconventional biomasses as feedstocks for production of biofuels and succinic acid in a biorefinery concept

    DEFF Research Database (Denmark)

    Gunnarsson, Ingólfur Bragi

    composition of the specific biomass feedstock, as well as which pretreatment, saccharification, fermentation and extraction techniques are used. Furthermore, integrating biological processes into the biorefinery that effectively consume CO2 will become increasingly important. Such process integration could...... significantly improve the sustainability indicators of the overall biorefinery process. In this study, unconventional lignocellulosic- and aquatic biomasses were investigated as biorefinery feedstocks. The studied biomasses were Jerusalem artichoke, industrial hemp and macroalgae species Laminaria digitata....... The chemical composition of biomasses was determined in order to demonstrate their biorefinery potential. Bioethanol and biogas along with succinic acid production were the explored bioconversion routes, while potential production of other compounds was also investigated. Differences and changes in biomass...

  5. Dissolving polyvinylpyrrolidone-based microneedle systems for in-vitro delivery of sumatriptan succinate.

    Science.gov (United States)

    Ronnander, P; Simon, L; Spilgies, H; Koch, A; Scherr, S

    2018-03-01

    In-vitro permeation studies were conducted to assess the feasibility of fabricating dissolving-microneedle-array systems to release sumatriptan succinate. The formulations consisted mainly of the encapsulated active ingredient and a water-soluble biologically compatible polymer, polyvinylpyrrolidone (PVP), approved by the U.S. Food and Drug Administration (FDA). Tests with Franz-type diffusion cells and Göttingen minipig skins showed an increase of the transdermal flux compared to passive diffusion. A preparation, containing 30% by mass of PVP and 8.7mg sumatriptan, produced a delivery rate of 395±31μg/cm 2 h over a 7-hour period after a negligible lag time of approximately 39min. Theoretically, a 10.7cm 2 microneedle-array patch loaded with 118.8mg of the drug would provide the required plasma concentration, 72ng/mL, for nearly 7h. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. The ALDH21 gene found in lower plants and some vascular plants codes for a NADP+ -dependent succinic semialdehyde dehydrogenase.

    Science.gov (United States)

    Kopečná, Martina; Vigouroux, Armelle; Vilím, Jan; Končitíková, Radka; Briozzo, Pierre; Hájková, Eva; Jašková, Lenka; von Schwartzenberg, Klaus; Šebela, Marek; Moréra, Solange; Kopečný, David

    2017-10-01

    Lower plant species including some green algae, non-vascular plants (bryophytes) as well as the oldest vascular plants (lycopods) and ferns (monilophytes) possess a unique aldehyde dehydrogenase (ALDH) gene named ALDH21, which is upregulated during dehydration. However, the gene is absent in flowering plants. Here, we show that ALDH21 from the moss Physcomitrella patens codes for a tetrameric NADP + -dependent succinic semialdehyde dehydrogenase (SSALDH), which converts succinic semialdehyde, an intermediate of the γ-aminobutyric acid (GABA) shunt pathway, into succinate in the cytosol. NAD + is a very poor coenzyme for ALDH21 unlike for mitochondrial SSALDHs (ALDH5), which are the closest related ALDH members. Structural comparison between the apoform and the coenzyme complex reveal that NADP + binding induces a conformational change of the loop carrying Arg-228, which seals the NADP + in the coenzyme cavity via its 2'-phosphate and α-phosphate groups. The crystal structure with the bound product succinate shows that its carboxylate group establishes salt bridges with both Arg-121 and Arg-457, and a hydrogen bond with Tyr-296. While both arginine residues are pre-formed for substrate/product binding, Tyr-296 moves by more than 1 Å. Both R121A and R457A variants are almost inactive, demonstrating a key role of each arginine in catalysis. Our study implies that bryophytes but presumably also some green algae, lycopods and ferns, which carry both ALDH21 and ALDH5 genes, can oxidize SSAL to succinate in both cytosol and mitochondria, indicating a more diverse GABA shunt pathway compared with higher plants carrying only the mitochondrial ALDH5. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  7. Determination of vitamin E acid succinate in biodegradable microspheres by reversed-phase high-performance liquid chromatography.

    Science.gov (United States)

    Martínez Sancho, C; Herrero Vanrell, R; Negro, S

    2004-01-01

    A simple, rapid, and reproducible reversed-phase high-performance liquid chromatographic (HPLC) method is applied to the routine assay of vitamin E acid succinate in biodegradable microspheres. Vitamin E acid-succinate-containing poly-(D,L-lactic-co-glycolic acid) microspheres are prepared by the solvent evaporation method. The starting drug-polymer ratio is 1:10 (w/w) and the total amount of drug and polymer processed is always 440 mg. The content of vitamin E acid succinate in the microspheres is evaluated by HPLC. Chromatography is carried out isocratically at 25 degrees C +/- 0.5 degrees C on an Extrasil ODS-2 column with a mobile phase composed of methanol-water (97:3, v/v) (pH 5.6) at a flow rate of 2 mL/min and UV detection at 284 nm. Parameters such as linearity, limits of quantitation (LOQ) and detection (LOD), precision, accuracy, recovery, specificity, and ruggedness are studied as reported in the International Conference on Harmonization guidelines. The stability of vitamin E acid succinate is also studied with satisfactory results after 48 h at 25 degrees C. The method is selective and linear for drug concentrations in the range 15-210 micro g/mL. The LOQ and LOD are 15 and 3 micro g/mL, respectively. The results for accuracy studies are good. Values for coefficient of variation for intra- and interassay are 2.08% and 2.32%, respectively. The mean percentage of vitamin E acid succinate in the recovery studies is 99.52% +/- 0.81%. The mean loading efficiency for microspheres is 96.53% +/- 1.31%.

  8. Gamma radiation effects on random copolymers based on poly(butylene succinate) for packaging applications

    Science.gov (United States)

    Negrin, M.; Macerata, E.; Consolati, G.; Quasso, F.; Genovese, L.; Soccio, M.; Giola, M.; Lotti, N.; Munari, A.; Mariani, M.

    2018-01-01

    Within the context of new bioplastic materials, poly(butylene succinate) (PBS) and four novel poly(butylene/thiodiethylene succinate) random copolymers (PBS-PTDGS), in sheets as well as in films, were exposed to gamma radiation, in air and in water, and their behavior along with the effect on their biodegradability was investigated. The molecular weight data obtained from gel permeation chromatography indicate that the sensibility to radiation increases with the amount of sulfur-containing co-unit (TDGS). At 200 kGy the average molecular weight of PBS film halves, while for P(BS60TDGS40) the residual molecular weight is about 20%. The calculated intermolecular crosslink Gx and scissioning Gs yields confirmed that degradation is predominant over crosslink for all the aliphatic systems. As shown by thermal analyses, gamma radiation affects the thermal properties, leading to an increased crystallinity of the systems, remarkable for PBS, and lower decomposition temperatures. Variations of crystallinity with the increasing absorbed dose were confirmed also by PALS analyses. Water contact angle measurements revealed post-irradiation wettability alterations that could positively affect polymer biodegradability. In particular, when irradiated in water at 100 kGy PBS film exhibits a water contact angle decrease of about 17%, indicating an enhanced wettability. After degradation in compost, changes in the surface morphology were observed by means of SEM and sample weight losses were determined, at different extent, according to the irradiation environment. Interestingly, after 52 days in compost PBS films, both pristine and irradiated in air at 25 kGy, showed a residual weight of about 60%, while the ones irradiated in water at 25 kGy of about 44%. Experimental data confirmed that gamma irradiation could represent a viable treatment to enhance biodegradation in compost of PBS and PBS-based copolymers.

  9. Metabolism of 14C-labeled doxylamine succinate (Bendectin) in the rhesus monkey (Macaca mulatta)

    International Nuclear Information System (INIS)

    Slikker, W. Jr.; Holder, C.L.; Lipe, G.W.; Korfmacher, W.A.; Thompson, H.C. Jr.; Bailey, J.R.

    1986-01-01

    The time-course of the metabolic fate of [ 14 C]doxylamine was determined after the p.o. administration of 13 mg/kg doxylamine succinate as Bendectin plus [ 14 C]doxylamine succinate to the rhesus monkey. Urine and plasma samples were analyzed by reversed-phase high performance liquid chromatography (HPLC), chemical derivatization, and mass spectrometry. The cumulative 48-hr urinary metabolic profile contained 81% of the administered radiolabeled dose and consisted of at least six radiolabeled peaks. They were peak 1: unknown polar metabolites (8% of dose); peak 2: 2-[1-phenyl-1-(2-pyridinyl)ethoxy] acetic acid, 1-[1-phenyl-1(2-pyridinyl)ethoxy] methanol, and another minor metabolite(s) (31%); peak 3: doxylamine-N-oxide (1%); peak 4a: N,N-didesmethyldoxylamine (17%); peak 4b: doxylamine (4%); and peak 5: N-desmethyldoxylamine (20%). The plasma metabolic profile was the same as the urinary profile except for the absence of doxylamine-N-oxide. The maximum plasma concentrations and elapsed time to attain these concentrations were as follows. Peak 1: 540 ng/mL, 4 hr; peak 2: 1700 ng/mL, 1 hr; peak 4a: 430 ng/mL, 4 hr; peak 4b: 930 ng/mL, 2 hr; and peak 5: 790 ng/mL, 2 hr. These data suggest that in the monkey, doxylamine metabolism follows at least four pathways: a minor pathway to the N-oxide; a minor pathway to unknown polar metabolites; a major pathway to mono- and didesmethyldoxylamine via successive N-demethylation; and a major pathway to side-chain cleavage products (peak 2) via direct side-chain oxidation and/or deamination

  10. Succinate overproduction: A case study of computational strain design using a comprehensive Escherichia coli kinetic model

    Directory of Open Access Journals (Sweden)

    Ali eKhodayari

    2015-01-01

    Full Text Available Computational strain design prediction accuracy has been the focus for many recent efforts through the selective integration of kinetic information into metabolic models. In general, kinetic model prediction quality is determined by the range and scope of genetic and/or environmental perturbations used during parameterization. In this effort, we apply the k-OptForce procedure on a kinetic model of E. coli core metabolism constructed using the Ensemble Modeling (EM method and parameterized using multiple mutant strains data under aerobic respiration with glucose as the carbon source. Minimal interventions are identified that improve succinate yield under both aerobic and anaerobic conditions to test the fidelity of model predictions under both genetic and environmental perturbations. Under aerobic condition, k-OptForce identifies interventions that match existing experimental strategies pointing at a number of unexplored flux redirections such as routing glyoxylate flux through the glycerate metabolism to improve succinate yield. Many of the identified interventions rely on the kinetic descriptions and would not be discoverable by a purely stoichiometric description. In contrast, under fermentative (anaerobic conditions, k-OptForce fails to identify key interventions including up-regulation of anaplerotic reactions and elimination of competitive fermentative products. This is due to the fact that the pathways activated under anaerobic conditions were not properly parameterized as only aerobic flux data were used in the model construction. This study shed light on the importance of condition-specific model parameterization and provides insight onto how to augment kinetic models so as to correctly respond to multiple environmental perturbations.

  11. Mechanical and thermal properties of basalt fiber reinforced poly(butylene succinate) composites

    International Nuclear Information System (INIS)

    Zhang Yihe; Yu Chunxiao; Chu, Paul K.; Lv Fengzhu; Zhang Changan; Ji Junhui; Zhang Rui; Wang Heli

    2012-01-01

    Highlights: ► Novel basalt fiber-reinforced biodegradable poly(butylene succinate) composites have been successfully fabricated with various fiber loadings. ► The tensile and flexural properties of the PBS matrix resin are improved significantly by increasing the fiber loading in the composites. ► The impact strength of the BF/PBS composite decreases with the addition fibers primarily and increases with increasing fiber loading due to energy dissipation when the fibers are pulled out. ► Heat deflection temperature tests clearly show that the HDT of the basalt fiber reinforced PBS composites is significantly higher than the HDT of the PBS resin. - Abstract: Basalt fiber (BF) reinforced poly(butylene succinate) (PBS) composites have been fabricated with different fiber contents by a injection molding method and their tensile, flexural and impact properties, as well as thermal stability have been investigated. The tensile and flexural properties of the PBS matrix resin are improved markedly by increasing the fiber contents in the composites. The values are relatively higher than the natural fiber/PP systems reported earlier by other research groups. The heat deflection temperature (HDT) and Vicat softening temperature (VST) of the composites are significantly higher than those of the neat PBS resin. Scanning electron microscopy (SEM) conducted on the fracture surfaces of the composites reveals superior interfacial linkage between the basalt fibers and PBS matrix. The results suggest that the BF/PBS composites may be a potential candidate of PP or PP composites to manufacturing some daily commodities to solve the “white pollution” in environmental management.

  12. Differences between the succinate dehydrogenase sequences of isopyrazam sensitive Zymoseptoria tritici and insensitive Fusarium graminearum strains.

    Science.gov (United States)

    Dubos, Tiphaine; Pasquali, Matias; Pogoda, Friederike; Casanova, Angèle; Hoffmann, Lucien; Beyer, Marco

    2013-01-01

    Forty-one Zymoseptoria tritici strains isolated in Luxembourg between 2009 and 2010 were highly sensitive towards the new succinate dehydrogenase inhibitor (SDHI) isopyrazam, with concentrations inhibiting fungal growth by 50% (EC50) ranging from 0.0281 to 4.53μM, whereas 41 Fusarium graminearum strains isolated in Europe and Northern America between 1969 and 2009 were insensitive with the average rate of inhibition converging towards 28% with increasing isopyrazam concentration. Seven isolates of both species covering the range of isopyrazam sensitivities observed in the present study were selected for the sequencing of the subunits B, C and D of the succinate dehydrogenase (sdh) gene. Predicted sdh amino acid sequences of subunits B, C and D were identical among F. graminearum strains. By comparing with fungal strains where resistance towards SDHIs was previously reported, three variations were unique to F. graminearum; B-D130N located in the iron-sulfur cluster [2Fe-2S], B-A275T located in the [3Fe-4S] cluster and an additional S at amino acid position 83-84 of sdhC, probably modifying structurally the ubiquinone binding site and therefore the biological activity of the fungicide. No variation was found among the Z. tritici strains in subunits B and D. Two variations were observed within the subunit C sequences of Z. tritici strains: C-N33T and C-N34T. The difference in EC50 values between Z. tritici strains with the NN and TT configuration was non-significant at P=0.289. Two outliers in the Z. tritici group with significantly higher EC50 values that were not related to mutations in the sdhB, sdhC, or sdhD were detected. The role of isopyrazam for the control of F. graminearum and Z. tritici in Luxembourg is discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Binary and ternary solid-liquid phase equilibrium for the systems formed by succinic acid, urea and diethylene glycol: Determination and modelling

    International Nuclear Information System (INIS)

    Li, Yanxun; Li, Congcong; Han, Shuo; Zhao, Hongkun

    2017-01-01

    Highlights: • Solubility of succinic acid in diethylene glycol was determined. • Solubility of succinic acid + urea + diethylene glycol was determined. • Three ternary phase diagrams were constructed for the ternary system. • The ternary phase diagrams were correlated using NRTL model. - Abstract: In this work, the solid-liquid phase equilibrium for binary system of succinic acid + diethylene glycol at the temperatures ranging from (298.15 to 333.15) K and ternary system of (succinic acid + urea + diethylene glycol) at 298.15 K, 313.15 K and 333.15 K was built by using the isothermal saturation method under atmospheric pressure (101.2 kPa), and the solubilities were determined by a high-performance liquid chromatography. The solid-phases formed in the ternary system of ((succinic acid + urea + diethylene glycol)) were confirmed by Schreinemaker’s method of wet residue, which corresponded to urea, succinic acid, and adduct 2:1 urea-succinic acid (mole ratio). Three isothermal phase diagrams for the ternary system were constructed based on the measured mutual solubility. Each isothermal phase diagram included six crystallization fields, three invariant curves, two invariant points and two co-saturated points. The crystalline region of adduct 2:1 urea-succinic acid is larger than those of the other two solids. The solubility of succinic acid in diethylene glycol was correlated with the modified Apelblat equation, λh equation and NRTL model; and the mutual solubility of the ternary ((succinic acid + urea + diethylene glycol)) system was correlated and calculated by the NRTL model. The interaction parameters’ values of succinic acid-urea were acquired. The value of RMSD was 7.11 × 10 −3 for the ternary system. The calculation results had good agreement with the experiment values. Furthermore, the densities of equilibrium liquid phase were acquired. The phase diagrams and the thermodynamic model of the ternary system could provide the basis for design of

  14. Succinate-CoA ligase deficiency due to mutations in SUCLA2 and SUCLG1

    DEFF Research Database (Denmark)

    Carrozzo, Rosalba; Verrigni, Daniela; Rasmussen, Magnhild

    2016-01-01

    BACKGROUND: The encephalomyopathic mtDNA depletion syndrome with methylmalonic aciduria is associated with deficiency of succinate-CoA ligase, caused by mutations in SUCLA2 or SUCLG1. We report here 25 new patients with succinate-CoA ligase deficiency, and review the clinical and molecular findings...... deficiency of complexes I and IV, but normal histological and biochemical findings in muscle did not preclude a diagnosis of succinate-CoA ligase deficiency. In five patients, the urinary excretion of methylmalonic acid was only marginally elevated, whereas elevated plasma methylmalonic acid was consistently...

  15. Polymer blends of polylactic acid (PLA) and polybutylene succinate-adipate

    Science.gov (United States)

    Ma, Wenguang

    A series of blends consisting of polylactic acid (PLA) and aliphatic succinate polyester (BionolleRTM #3000) had been prepared and investigated. The results of mechanical property investigations showed that using 20 wt% Bionolle#3000 can significantly increase the toughness of PLA. BionolleRTM #3000 also reduces the physical aging rate of PLA so blends remain tough longer. Conversely, the stiffness of BionolleRTM #3000 can be significantly increased by blending in PLA. DMA and DSC results show that PLA/BionolleRTM 3000 blends are not thermodynamically miscible, but are compatible blends. Studies have also been performed to determine the amount and rate of aerobic biodegradation of PLA/aliphatic succinate polyester blends in biologically active composting, enzymatic, and soil environments. The changes in molecular weight, molecular structure and thermal properties in the composting environment were also studied by GPC, NMR and DSC analyses. The research results showed BionolleRTM #3000 had a high degradation rate, while PLA had a low degradation rate. PLA/BionolleRTM #3000 blends had moderate degradation rates that increased with BionolleRTM #3000 content. The melt flow behavior of PLA/BionolleRTM #3000 blends has been studied by capillary rheometry. The relationship of the blends' viscosity with their composition, shear stress, shear rate, and temperature has been investigated. Power law index and activation energy of PLA, BionolleRTM #3000 and their blends have been calculated. The experimental and theoretical data can let us understand the processability of PLA/BionolleRTM #3000 blends. A scanning electron microscope (SEM) was used to investigate the morphological structure of the PLA/BionolleRTM #3000 blends. Micrographs of the samples made from different methods (blown film, extrudate and compression molding sheet) were taken; their differences in morphology were compared. For comparison, the micrographs of blend PLA/BionolleRTM #6000 was also studied. The

  16. Vitamin E succinate-conjugated F68 micelles for mitoxantrone delivery in enhancing anticancer activity

    Directory of Open Access Journals (Sweden)

    Liu Y

    2016-07-01

    Full Text Available Yuling Liu,1,* Yingqi Xu,2,* Minghui Wu,3 Lijiao Fan,1 Chengwei He,2 Jian-Bo Wan,2 Peng Li,2 Meiwan Chen,2 Hui Li11Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People’s Republic of China; 3Department of Cell Biology and Anatomy, School of Medicine, University of Florida, Gainesville, FL, USA *These authors contributed equally to this work Abstract: Mitoxantrone (MIT is a chemotherapeutic agent with promising anticancer efficacy. In this study, Pluronic F68-vitamine E succinate (F68-VES amphiphilic polymer micelles were developed for delivering MIT and enhancing its anticancer activity. MIT-loaded F68–VES (F68–VES/MIT micelles were prepared via the solvent evaporation method with self-assembly under aqueous conditions. F68–VES/MIT micelles were found to be of optimal particle size with the narrow size distribution. Transmission electron microscopy images of F68–VES/MIT micelles showed homogeneous spherical shapes and smooth surfaces. F68–VES micelles had a low critical micelle concentration value of 3.311 mg/L, as well as high encapsulation efficiency and drug loading. Moreover, F68–VES/MIT micelles were stable in the presence of fetal bovine serum for 24 hours and maintained sustained drug release in vitro. Remarkably, the half maximal inhibitory concentration (IC50 value of F68–VES/MIT micelles was lower than that of free MIT in both MDA-MB-231 and MCF-7 cells (two human breast cancer cell lines. In addition, compared with free MIT, there was an increased trend of apoptosis and cellular uptake of F68–VES/MIT micelles in MDA-MB-231 cells. Taken together, these results indicated that F68–VES polymer micelles were able to effectively deliver MIT and largely improve its potency in cancer therapy. Keywords: F68, vitamin E

  17. Mapping of Saccharomyces cerevisiae metabolites in fermenting wheat straight-dough reveals succinic acid as pH-determining factor.

    Science.gov (United States)

    Jayaram, Vinay B; Cuyvers, Sven; Lagrain, Bert; Verstrepen, Kevin J; Delcour, Jan A; Courtin, Christophe M

    2013-01-15

    Fermenting yeast does not merely cause dough leavening, but also contributes to the bread aroma and might alter dough rheology. Here, the yeast carbon metabolism was mapped during bread straight-dough fermentation. The concentration of most metabolites changed quasi linearly as a function of fermentation time. Ethanol and carbon dioxide concentrations reached up to 60 mmol/100g flour. Interestingly, high levels of glycerol (up to 10 mmol/100g flour) and succinic acid (up to 1.6 mmol/100g flour) were produced during dough fermentation. Further tests showed that, contrary to current belief, the pH decrease in fermenting dough is primarily caused by the production of succinic acid by the yeast instead of carbon dioxide dissolution or bacterial organic acids. Together, our results provide a comprehensive overview of metabolite production during dough fermentation and yield insight into the importance of some of these metabolites for dough properties. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Recent advances in the metabolic engineering of Corynebacterium glutamicum for the production of lactate and succinate from renewable resources.

    Science.gov (United States)

    Tsuge, Yota; Hasunuma, Tomohisa; Kondo, Akihiko

    2015-03-01

    Recent increasing attention to environmental issues and the shortage of oil resources have spurred political and industrial interest in the development of environmental friendly and cost-effective processes for the production of bio-based chemicals from renewable resources. Thus, microbial production of commercially important chemicals is viewed as a desirable way to replace current petrochemical production. Corynebacterium glutamicum, a Gram-positive soil bacterium, is one of the most important industrial microorganisms as a platform for the production of various amino acids. Recent research has explored the use of C. glutamicum as a potential cell factory for producing organic acids such as lactate and succinate, both of which are commercially important bulk chemicals. Here, we summarize current understanding in this field and recent metabolic engineering efforts to develop C. glutamicum strains that efficiently produce L- and D-lactate, and succinate from renewable resources.

  19. The H+/O ratio of proton translocation linked to the oxidation of succinate by mitochondria. Reply to a commentary.

    Science.gov (United States)

    Lehninger, A L; Reynafarje, B; Hendler, R W; Shrager, R I

    1985-11-18

    Costa, L.E., Reynafarje, B. and Lehninger, A.L. [(1984) J. Biol. Chem. 259, 4802-4811] have reported 'second-generation' measurements of the H+/O ratio approaching 8.0 for vectorial H+ translocation coupled to succinate oxidation by rat liver mitochondria. In a Commentary in this Journal [Krab, K., Soos, J. and Wikström, M. (1984) FEBS Lett. 178, 187-192] it was concluded that the measurements of Costa et al. significantly overestimated the true H+/O stoichiometry. It is shown here that the mathematical simulation on which Krab et al. based this claim is faulty and that data reported by Costa et al. had already excluded the criticism advanced by Krab et al. Also reported are new data, obtained under conditions in which the arguments of Krab et al. are irrelevant, which confirm that the H+/O ratio for succinate oxidation extrapolated to level flow is close to 8.

  20. Gold-nanoparticle-based catalysts for the oxidative esterification of 1,4-butanediol into dimethyl succinate.

    Science.gov (United States)

    Brett, Gemma L; Miedziak, Peter J; He, Qian; Knight, David W; Edwards, Jennifer K; Taylor, Stuart H; Kiely, Christopher J; Hutchings, Graham J

    2013-10-01

    The oxidation of 1,4-butanediol and butyrolactone have been investigated by using supported gold, palladium and gold-palladium nanoparticles. The products of such reactions are valuable chemical intermediates and, for example, can present a viable pathway for the sustainable production of polymers. If both gold and palladium were present, a significant synergistic effect on the selective formation of dimethyl succinate was observed. The support played a significant role in the reaction, with magnesium hydroxide leading to the highest yield of dimethyl succinate. Based on structural characterisation of the fresh and used catalysts, it was determined that small gold-palladium nanoalloys supported on a basic Mg(OH)2 support provided the best catalysts for this reaction. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Contribution of the tricarboxylic acid (TCA) cycle and the glyoxylate shunt in Saccharomyces cerevisiae to succinic acid production during dough fermentation.

    Science.gov (United States)

    Rezaei, Mohammad N; Aslankoohi, Elham; Verstrepen, Kevin J; Courtin, Christophe M

    2015-07-02

    Succinic acid produced by yeast during bread dough fermentation can significantly affect the rheological properties of the dough. By introducing mutations in the model S288C yeast strain, we show that the oxidative pathway of the TCA cycle and the glyoxylate shunt contribute significantly to succinic acid production during dough fermentation. More specifically, deletion of ACO1 and double deletion of ACO1 and ICL1 resulted in a 36 and 77% decrease in succinic acid levels in fermented dough, respectively. Similarly, double deletion of IDH1 and IDP1 decreased succinic acid production by 85%, while also affecting the fermentation rate. By contrast, double deletion of SDH1 and SDH2 resulted in a two-fold higher succinic acid accumulation compared to the wild-type. Deletion of fumarate reductase activity (FRD1 and OSM1) in the reductive pathway of the TCA cycle did not affect the fermentation rate and succinic acid production. The changes in the levels of succinic acid produced by mutants Δidh1Δidp1 (low level) and Δsdh1Δsdh2 (high level) in fermented dough only resulted in small pH differences, reflecting the buffering capacity of dough at a pH of around 5.1. Moreover, Rheofermentometer analysis using these mutants revealed no difference in maximum dough height and gas retention capacity with the dough prepared with S288C. The impact of the changed succinic acid profile on the organoleptic or antimicrobial properties of bread remains to be demonstrated. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Bagasse hydrolyzates from Agave tequilana as substrates for succinic acid production by Actinobacillus succinogenes in batch and repeated batch reactor.

    Science.gov (United States)

    Corona-González, Rosa Isela; Varela-Almanza, Karla María; Arriola-Guevara, Enrique; Martínez-Gómez, Álvaro de Jesús; Pelayo-Ortiz, Carlos; Toriz, Guillermo

    2016-04-01

    The aim of this work was to obtain fermentable sugars by enzymatic or acid hydrolyses of Agave tequilana Weber bagasse in order to produce succinic acid with Actinobacillus succinogenes. Hydrolyses were carried out with mineral acids (sulfuric and hydrochloric acids) or a commercial cellulolytic enzyme, and were optimized statistically by a response surface methodology, having as factors the concentration of acid/enzyme and time of hydrolysis. The concentration of sugars obtained at optimal conditions for each hydrolysis were 21.7, 22.4y 19.8g/L for H2SO4, HCl and the enzymatic preparation respectively. Concerning succinic acid production, the enzymatic hydrolyzates resulted in the highest yield (0.446g/g) and productivity (0.57g/Lh) using A. succinogenes in a batch reactor system. Repeated batch fermentation with immobilized A. succinogenes in agar and with the enzymatic hydrolyzates resulted in a maximum concentration of succinic acid of 33.6g/L from 87.2g/L monosaccharides after 5 cycles in 40h, obtaining a productivity of 1.32g/Lh. Copyright © 2016. Published by Elsevier Ltd.

  3. Citrate- and Succinate-Modified Carbonate Apatite Nanoparticles with Loaded Doxorubicin Exhibit Potent Anticancer Activity against Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Sultana Mehbuba Hossain

    2018-03-01

    Full Text Available Biodegradable inorganic apatite-based particle complex is popular for its pH-sensitivity at the endosomal acidic environment to facilitate drug release following cellular uptake. Despite being a powerful anticancer drug, doxorubicin shows severe off-target effects and therefore would need a carrier for the highest effectiveness. We aimed to chemically modify carbonate apatite (CA with Krebs cycle intermediates, such as citrate and succinate in order to control the growth of the resultant particles to more efficiently carry and transport the anticancer drug into the cancer cells. Citrate- or succinate-modified CA particles were synthesized with different concentrations of sodium citrate or sodium succinate, respectively, in the absence or presence of doxorubicin. The drug loading efficiency of the particles and their cellular uptake were observed by quantifying fluorescence intensity. The average diameter and surface charge of the particles were determined using Zetasizer. Cell viability was assessed by MTT assay. Citrate-modified carbonate apatite (CMCA exhibited the highest (31.38% binding affinity for doxorubicin and promoted rapid cellular uptake of the drug, leading to the half-maximal inhibitory concentration 1000 times less than that of the free drug in MCF-7 cells. Hence, CMCA nanoparticles with greater surface area enhance cytotoxicity in different breast cancer cells by enabling higher loading and more efficient cellular uptake of the drug.

  4. Phase Transformation of Adefovir Dipivoxil/Succinic Acid Cocrystals Regulated by Polymeric Additives

    Directory of Open Access Journals (Sweden)

    Sungyup Jung

    2013-12-01

    Full Text Available The polymorphic phase transformation in the cocrystallization of adefovir dipivoxil (AD and succinic acid (SUC was investigated. Inspired by biological and biomimetic crystallization, polymeric additives were utilized to control the phase transformation. With addition of poly(acrylic acid, the metastable phase newly identified through the analysis of X-ray diffraction was clearly isolated from the previously reported stable form. Without additives, mixed phases were obtained even at the early stage of cocrystallization. Also, infrared spectroscopy analysis verified the alteration of the hydrogen bonding that was mainly responsible for the cocrystal formation between AD and SUC. The hydrogen bonding in the metastable phase was relatively stronger than that in the stable form, which indicated the locally strong AD/SUC coupling in the initial stage of cocrystallization followed by the overall stabilization during the phase transformation. The stronger hydrogen bonding could be responsible for the faster nucleation of the initially observed metastable phase. The present study demonstrated that the polymeric additives could function as effective regulators for the polymorph-selective cocrystallization.

  5. Synthesized cellulose/succinic anhydride as an ion exchanger. Calorimetry of divalent cations in aqueous suspension

    Energy Technology Data Exchange (ETDEWEB)

    Melo, Julio C.P. [Institute of Chemistry, University of Campinas, UNICAMP, P.O. Box 6154, 13084-971 Campinas, SP (Brazil); Silva Filho, Edson C. [LIMAV, Federal University of Piaui, 64049-550 Teresina, Piaui (Brazil); Santana, Sirlane A.A. [Departamento de Quimica/CCET, Universidade Federal do Maranhao, Av. dos Portugueses S/N, Campus do Bacanga, 65080-540 Sao Luiz, MA (Brazil); Airoldi, Claudio, E-mail: airoldi@iqm.unicamp.br [Institute of Chemistry, University of Campinas, UNICAMP, P.O. Box 6154, 13084-971 Campinas, SP (Brazil)

    2011-09-20

    Highlights: {yields} Synthetic route based on anhydride melting point. {yields} Cellulosic biopolymer/anhydride as ion exchanger. {yields} Calorimetry of cation exchange at solid/liquid interface. {yields} Favorable thermodynamic data of exchanging process. - Abstract: A synthetic route to a biopolymer/anhydride ion exchanger adds cellulose directly to molten succinic anhydride in a quasi solvent-free procedure. An amount of 3.07 {+-} 0.05 mmol of pendant groups incorporated onto the polymeric structure, which was characterized by elemental analysis, solid state carbon NMR, infrared, X-ray and thermogravimetry. The new polysaccharide is able to exchange cations from aqueous solution through a batchwise methodology, to obtain 2.46 {+-} 0.09 mmol g{sup -1} for divalent cobalt and nickel cations. The net thermal effects obtained from calorimetric titrations gave endothermic values of 3.81 {+-} 0.02 and 2.35 {+-} 0.01 kJ mol{sup -1}. The spontaneity of this ion-exchange process reflected in negative Gibbs energies and also a positive entropic contribution. These thermodynamic data at the solid/liquid interface suggests a favorable ion exchange process for this anchored biopolymer, for cation removal from the environment.

  6. Processing Conditions, Thermal and Mechanical Responses of Stretchable Poly (Lactic Acid)/Poly (Butylene Succinate) Films.

    Science.gov (United States)

    Fortunati, Elena; Puglia, Debora; Iannoni, Antonio; Terenzi, Andrea; Kenny, José Maria; Torre, Luigi

    2017-07-16

    Poly (lactic acid) (PLA) and poly (butylene succinate) (PBS) based films containing two different plasticizers [Acetyl Tributyl Citrate (ATBC) and isosorbide diester (ISE)] at three different contents (15 wt %, 20 wt % and 30 wt %) were produced by extrusion method. Thermal, morphological, mechanical and wettability behavior of produced materials was investigated as a function of plasticizer content. Filmature parameters were also adjusted and optimized for different formulations, in order to obtain similar thickness for different systems. Differential scanning calorimeter (DSC) results and evaluation of solubility parameter confirmed that similar miscibility was obtained for ATBC and ISE in PLA, while the two selected plasticizers resulted as not efficient for plasticization of PBS, to the limit that the PBS-30ATBC resulted as not processable. On the basis of these results, isosorbide-based plasticizer was considered a suitable agent for modification of a selected blend (PLA/PBS 80:20) and two mixing approaches were used to identify the role of ISE in the plasticization process: results from mechanical analysis confirmed that both produced PLA-PBS blends (PLA85-ISE15)-PBS20 and (PLA80-PBS20)-ISE15 could guarantee advantages in terms of deformability, with respect to the PLA80-PBS20 reference film, suggesting that the promising use of these stretchable PLA-PBS based films plasticized with isosorbide can provide novel solutions for food packaging applications.

  7. Mechanical properties and crystallization behavior of hydroxyapatite/poly(butylenes succinate) composites.

    Science.gov (United States)

    Guo, Wenmin; Zhang, Yihe; Zhang, Wei

    2013-09-01

    Biodegradable synthetic polymers have attracted much attention nowadays, and more and more researches have been done on biodegradable polymers due to their excellent mechanical properties, biocompatibility, and biodegradability. In this work, hydroxyapatite (HA) particles were melt-mixing with poly (butylenes succinate) (PBS) to prepare the material, which could be used in the biomedical industry. To develop high-performance PBS for cryogenic engineering applications, it is necessary to investigate the cryogenic mechanical properties and crystallization behavior of HA/PBS composites. Cryogenic mechanical behaviors of the composites were studied in terms of tensile and impact strength at the glass transition temperature (-30°C) and compared to their corresponding behaviors at room temperature. With the increase of HA content, the crystallization of HA/PBS composites decreased and crystallization onset temperature shifted to a lower temperature. The diameter of spherulites increased at first and decreased with a further HA content. At the same time, the crystallization rate became slow when the HA content was no more than 15wt% and increased when HA content reached 20wt%. In all, the results we obtained demonstrate that HA/PBS composites reveal a better tensile strength at -30°C in contrast to the strength at room temperature. HA particles with different amount affect the crystallization of PBS in different ways. Copyright © 2013 Wiley Periodicals, Inc.

  8. Cloning and functional analysis of succinate dehydrogenase gene PsSDHA in Phytophthora sojae.

    Science.gov (United States)

    Pan, Yuemin; Ye, Tao; Gao, Zhimou

    2017-07-01

    Succinate dehydrogenase (SDH) is one of the key enzymes of the tricarboxylic acid cycle (TCA cycle) and a proven target of fungicides for true fungi. To explore the roles of the SDHA gene in Phytophthora sojae, we first cloned PsSDHA to construct the PsSDHA silenced expression vector pHAM34-PsSDHA, and then utilized PEG to mediate the P. sojae protoplast transformation experiment. Through transformation screening, we obtained the silenced mutants A1 and A3, which have significant suppressive effect. Further study showed that the hyphae of the silenced mutant strains were shorter and more bifurcated; the growth of the silenced mutants was clearly inhibited in 10% V8 agar medium containing sodium chloride (NaCl), hydrogen peroxide (H 2 O 2 ) or Congo Red, respectively. The pathogenicity of the silenced mutants was significantly reduced compared with the wild-type strain and the mock. The results could help us better to understand the position and function of SDH in P. sojae and provide a proven target of fungicides for the oomycete. Copyright © 2017. Published by Elsevier Ltd.

  9. [Antihypoxic effect of 3-hydroxypyridine and succinic acid derivatives and their nootropic action in alloxan diabetes].

    Science.gov (United States)

    Volchegorskiĭ, I A; Rassokhina, L M; Miroshnichenko, I Iu

    2011-01-01

    Relationship between the antihypoxic effect of 3-hydroxypyridine and succinic acid derivatives (emoxipine, reamberin and mexidol) and their effect on conditional learning, glycemia, and lipidemia was studied in rats with alloxan-induced diabetes. In parallel, the analogous relationship was investigated for alpha-lipoic acid that is regarded as a "gold standard" in treatment of diabetic neuropathy. It was established that single administration of emoxipine and mexidol in mice in doses equivalent to therapeutic-range doses in humans produces antihypoxic effect manifested by increased resistance to acute hypoxic hypoxia in test animals. Alpha-lipoic acid is inferior to emoxipin and mexidol in the degree of antihypoxic action. Reamberin does not exhibit this effect. The introduction of emoxipin, reamberin, mexidol, and alpha-lipoic acid in rats with alloxan diabetes during 7 or 14 days in doses equivalent to therapeutic-range doses in humans corrects conditional learning disorders in direct relationship with the antihypoxic activity of these drugs. The development of the nootropic effect of emoxipin, mexidol, and alpha-lipoic acid is related to a decrease in hyperglycemia and hyperlipidemia in rats with alloxan diabetes. The nootropic action of reamberin is accompanied by a transient hypoglycemizing effect and aggravation of dyslipidemic disorders. The antihypoxic activity of investigated drugs determines the direction and expression of their lipidemic effect, but is not correlated with the hypoglycemizing action these drugs on test animals with alloxan diabetes.

  10. Ovicidal activity of succinic acid isolated from sisal waste (Agave sisalana against gastrointestinal nematodes of goats

    Directory of Open Access Journals (Sweden)

    Nathália Silva de Souza Santos

    Full Text Available ABSTRACT: This study was conducted to evaluate the in vitro anthelmintic activity of the succinic acid (SA isolated from sisal waste against gastrointestinal nematodes of goats, using the egg hatching and larvae motility assays. In addition, potential cytotoxicity of SA on Vero cell cultures was investigated by means of MTT (3-4,5-dimethylthiazol-2-yl, 2,5diphenyltetrazolium bromide test. The SA induced a significant inhibition of egg hatching (P<0.05 at all concentrations tested (60 to 250µg mL-1, and the concentrations to inhibit 50% (EC50 and 90% (EC90 values (mean ± standard deviation were 90.3±2.8 and 130.6±3.5µg mL-1, respectively. The SA has not shown larvicidal activity. The SA was less toxic to the Vero cells, with the mean percentage of cell viability equal to 85±6.2% at the concentration of 130µg mL-1. The results suggested that SA has potential anthelmintic effect; although, more research is needed to confirm its activity in vivo.

  11. Succinate Dehydrogenase B Subunit Immunohistochemical Expression Predicts Aggressiveness in Well Differentiated Neuroendocrine Tumors of the Ileum

    Energy Technology Data Exchange (ETDEWEB)

    Milione, Massimo [Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan I-20133 (Italy); Pusceddu, Sara [Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan I-20133 (Italy); Gasparini, Patrizia [Molecular Cytogenetics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan I-20133 (Italy); Melotti, Flavia [Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan I-20133 (Italy); Maisonneuve, Patrick [Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan 20141 (Italy); Mazzaferro, Vincenzo [Division of Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan I-20133 (Italy); Braud, Filippo G. de [Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan I-20133 (Italy); Pelosi, Giuseppe, E-mail: giuseppe.pelosi@unimi.it [Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan I-20133 (Italy); Department of Medicine, Surgery and Dentistry, Università degli Studi, Facoltà di Medicina, Milan 20122 (Italy)

    2012-08-16

    Immunohistochemical loss of the succinate dehydrogenase subunit B (SDHB) has recently been reported as a surrogate biomarker of malignancy in sporadic and familial pheocromocytomas and paragangliomas through the activation of hypoxia pathways. However, data on the prevalence and the clinical implications of SDHB immunoreactivity in ileal neuroendocrine tumors are still lacking. Thirty-one consecutive, advanced primary midgut neuroendocrine tumors and related lymph node or liver metastases from 24 males and seven females were immunohistochemically assessed for SDHB. All patients were G1 tumors (Ki-67 labeling index ≤2%). SDHB immunohistochemistry results were expressed as immunostaining intensity and scored as low or strong according to the internal control represented by normal intestinal cells. Strong positivity for SDHB, with granular cytoplasmatic reactivity, was found in 77% of primary tumors (T), whilst low SDHB expression was detected in 90% of metastases (M). The combined analysis (T+M) confirmed the loss of SDHB expression in 82% of metastases compared to 18% of primary tumors. SDHB expression was inversely correlated with Ki-67 labeling index, which accounted for 1.54% in metastastic sites and 0.7% in primary tumors. A correlation between SDHB expression loss, increased Ki-67 labeling index and biological aggressiveness was shown in advanced midgut neuroendocrine tumors, suggesting a role of tumor suppressor gene.

  12. Succinate Dehydrogenase B Subunit Immunohistochemical Expression Predicts Aggressiveness in Well Differentiated Neuroendocrine Tumors of the Ileum

    International Nuclear Information System (INIS)

    Milione, Massimo; Pusceddu, Sara; Gasparini, Patrizia; Melotti, Flavia; Maisonneuve, Patrick; Mazzaferro, Vincenzo; Braud, Filippo G. de; Pelosi, Giuseppe

    2012-01-01

    Immunohistochemical loss of the succinate dehydrogenase subunit B (SDHB) has recently been reported as a surrogate biomarker of malignancy in sporadic and familial pheocromocytomas and paragangliomas through the activation of hypoxia pathways. However, data on the prevalence and the clinical implications of SDHB immunoreactivity in ileal neuroendocrine tumors are still lacking. Thirty-one consecutive, advanced primary midgut neuroendocrine tumors and related lymph node or liver metastases from 24 males and seven females were immunohistochemically assessed for SDHB. All patients were G1 tumors (Ki-67 labeling index ≤2%). SDHB immunohistochemistry results were expressed as immunostaining intensity and scored as low or strong according to the internal control represented by normal intestinal cells. Strong positivity for SDHB, with granular cytoplasmatic reactivity, was found in 77% of primary tumors (T), whilst low SDHB expression was detected in 90% of metastases (M). The combined analysis (T+M) confirmed the loss of SDHB expression in 82% of metastases compared to 18% of primary tumors. SDHB expression was inversely correlated with Ki-67 labeling index, which accounted for 1.54% in metastastic sites and 0.7% in primary tumors. A correlation between SDHB expression loss, increased Ki-67 labeling index and biological aggressiveness was shown in advanced midgut neuroendocrine tumors, suggesting a role of tumor suppressor gene

  13. Effects of Radiation on Mechanical Properties of Poly (butylene succinate) and Cassava Starch Blends

    International Nuclear Information System (INIS)

    Hemvichian, K.; Dechasasawat, K.; Kangsumrith, W.; Suwanmala, P.

    2014-01-01

    This research compared the effects of gamma and electron beam irradiation at different doses on the mechanical properties of polymer blends between poly(butylene succinate) (PBS) and cassava starch. Two types of starch were used to prepare thermoplastic starch (TPS), native cassava starch and hydrophobic starch. PBS/TPS blends were compounded at five different weight ratios using a twin-screw extruder. Mechanical properties and degradation were evaluated in comparison to unirradiated samples. Results indicated that the incorpora- tion of TPS prepared from native cassava starch decreased the mechanical properties of PBS/TPS blends, whereas the addition of TPS prepared from hydrophobic starch improved the mechanical properties of the blends. In addition, the maximum mechanical properties of PBS/TPS blends were achieved when samples were exposed to irradiation at 120 kGy. Using soil burial evaluation, the degradation rate of blends was found to increase with the addition of TPS. Therefore we have demonstrated in this study that the type of TPS and irradiation treatment can significantly alter the mechanical properties and degradation of PBS/TPS blends.

  14. The use of chemical modified chitosan with succinic anhydride in the methylene blue adsorption

    International Nuclear Information System (INIS)

    Lima, Ilauro S.; Ribeiro, Emerson S.; Airoldi, Claudio

    2006-01-01

    The adsorption capacity of a-chitosan and its modified form with succinic anhydride was compared with the traditional adsorbent active carbon by using the dye methylene blue, employed in the textile industry. The isotherms for both biopolymers were classified as SSA systems in the Giles model, more specifically in L class and subgroup 3. The dye concentration in the supernatant in the adsorption assay was determined through electronic spectroscopy. By calorimetric titration thermodynamic data of the interaction between methylene blue and the chemically modified chitosan at the solid/liquid interface were obtained. The enthalpy of the dye/chitosan interaction gave 2.47 ± 0.02 kJ mol-1 with an equilibrium constant of 7350 ± 10 and for the carbon/dye interaction this constant gave 5951 ± 8. The spontaneity of these adsorptions are reflected by the free Gibbs energies of -22.1 ± 0.4 and -21.5 ± 0.2 kJ mol-1, respectively, found for these systems. This new adsorbent derived from a natural polysaccharide is as efficient as activated carbon. However 97% of the bonded dye can be eluted by sodium chloride solution, while this same operation elutes only 42% from carbon. Chitosan is efficient in dye removal with the additional advantage of being cheap, non-toxic, biocompatible and biodegradable. (author)

  15. Preparation And Physicochemical Properties of Octenyl Succinic Anhydride (OSA) Modified Sago Starch

    International Nuclear Information System (INIS)

    Nur Farhana Zainal Abiddin; Anida Yusoff; Noorlaila Ahmad

    2016-01-01

    Starch from sago (Metroxylon sagu) was esterified with octenyl succinic anhydride (OSA) in order to regulate its shortcoming by adding amphiphilic properties. The objective of this work is to determine the physicochemical properties of native sago and OSA sago starches. The OSA sago starch was produced according to the optimum condition generated via response surface methodology (RSM) with 5.00 % OSA at pH 7.20 and a reaction time of 9.65 hours. The esterified sago starch gives a degree of substitution (DS) value of 0.012. The physicochemical properties of OSA sago starch was determined by measuring the amylose content, laser diffraction particle size analyzer, scanning electron microscopy (SEM) and Fourier transform infrared (FT-IR). The amylose content for OSA sago starch was found to be reduced after esterification reaction. The particle size of OSA sago starch was found to increase significantly (p<0.05) compared to their native starches. Scanning electron microscopy (SEM) revealed that OSA starch developed slightly rough surface and their edges lost some definition. FT-IR spectroscopy shows that there was appearance of new absorption correspond to ester carbonyl group (1717 cm -1 ) and carboxylate RCOO- (1569 cm -1 ). This study showed that the physicochemical properties of modified starches were influenced not only by DS but also on the botanical origin of the starches. (author)

  16. Synthesis and antifungal activity of nicotinamide derivatives as succinate dehydrogenase inhibitors.

    Science.gov (United States)

    Ye, Yong-Hao; Ma, Liang; Dai, Zhi-Cheng; Xiao, Yu; Zhang, Ying-Ying; Li, Dong-Dong; Wang, Jian-Xin; Zhu, Hai-Liang

    2014-05-07

    Thirty-eight nicotinamide derivatives were designed and synthesized as potential succinate dehydrogenase inhibitors (SDHI) and precisely characterized by (1)H NMR, ESI-MS, and elemental analysis. The compounds were evaluated against two phytopathogenic fungi, Rhizoctonia solani and Sclerotinia sclerotiorum, by mycelia growth inhibition assay in vitro. Most of the compounds displayed moderate activity, in which, 3a-17 exhibited the most potent antifungal activity against R. solani and S. sclerotiorum with IC50 values of 15.8 and 20.3 μM, respectively, comparable to those of the commonly used fungicides boscalid and carbendazim. The structure-activity relationship (SAR) of nicotinamide derivatives demonstrated that the meta-position of aniline was a key position contributing to the antifungal activity. Inhibition activities against two fungal SDHs were tested and achieved the same tendency with the data acquired from in vitro antifungal assay. Significantly, 3a-17 was demonstrated to successfully suppress disease development in S. sclerotiorum infected cole in vivo. In the molecular docking simulation, sulfur and chlorine of 3a-17 were bound with PHE291 and PRO150 of the SDH homology model, respectively, which could explain the probable mechanism of action between the inhibitory and target protein.

  17. Thermal and Mechanical Properties of Poly(butylene succinate Films Reinforced with Silica

    Directory of Open Access Journals (Sweden)

    Sangviroon Nanthaporn

    2015-01-01

    Full Text Available In recent year, bioplastics have become more popular resulting from the growing concerns on environmental issues and the rising fossil fuel price. However, their applications were limited by its mechanical and thermal properties. The aim of this research is thus to improve mechanical and thermal properties of PBS bioplastic films by reinforcing with silica. Due to the poor interfacial interaction between the PBS matrix and silica, glycidyl methacrylate grafted poly(butylene succinate (PBS-g-GMA was used as a compatibilizer in order to improve the interaction between bioplastic films and filler. PBS-g-GMA was prepared in a twin-screw extruder and analyzed by the FTIR spectrometer. PBS and silica were then mixed in a twin-screw extruder and processed into films by a chill-roll cast extruder. The effects of silica loading on thermal and mechanical properties of the prepared bioplastic films were investigated. It was found that the mechanical properties of PBS/silica composite films were improved when 1%wt of silica was added. However, the mechanical properties decreased with increasing silica loading due to the agglomeration of silica particles. The results also show that the silica/PBS films with PBS-g-GMA possessed improved mechanical properties over the films without the compatibilizer.

  18. Influence of protoporphyrin IX loaded phloroglucinol succinic acid dendrimer in photodynamic therapy

    Science.gov (United States)

    Kumar, M. Suresh; Aruna, P.; Ganesan, S.

    2018-03-01

    One of the major problems reported clinically for photosensitizers (PS) in Photodynamic therapy (PDT) is, the cause of side-effects to normal tissue due to dark toxicity. The usefulness of photosensitizers can be made possible by reducing its dark toxicity nature. In such scenario, biocompatible carriers can be used as a drug delivery system to evade the problems that arises while using free (dark toxic) drugs. So in this study, we have developed a nano drug delivery system called Phloroglucinol Succinic acid (PGSA) dendrimer, entrapped a photosensitizer, protoporphyrin IX (PpIX) inside the system and investigated whether the photodynamic efficacy of the anionic surface charged dendrimer-PpIX nano formulation is enhanced than achieved by the free PpIX in HeLa cancer cell lines. Moreover, the Reactive oxygen species (ROS) production was monitored using 2‧,7‧-dichlorodihydrofluorescein diacetate (H2DCF-DA)- ROS Marker with phase contrast microscopy for the IC50 values of free and dendrimer-PpIX nano formulation. Similarly, the mode of cell death has been confirmed by cell cycle analysis for the same. For the in vitro PDT application, we have used a simple light source (Light Emitting Diode) with a power of 30-50 mW for 20 min irradiation. Hence, in this study we have taken steps to report this anionic drug delivery system is good to consider for the photodynamic therapy applications with the photosensitizer, PpIX which satisfied the prime requirement of PDT.

  19. Self-assembled nanoformulation of methylprednisolone succinate with carboxylated block copolymer for local glucocorticoid therapy.

    Science.gov (United States)

    Kamalov, Marat I; Đặng, Trinh; Petrova, Natalia V; Laikov, Alexander V; Luong, Duong; Akhmadishina, Rezeda A; Lukashkin, Andrei N; Abdullin, Timur I

    2018-04-01

    A new self-assembled formulation of methylprednisolone succinate (MPS) based on a carboxylated trifunctional block copolymer of ethylene oxide and propylene oxide (TBC-COOH) was developed. TBC-COOH and MPS associated spontaneously at increased concentrations in aqueous solutions to form almost monodisperse mixed micelles (TBC-COOH/MPS) with a hydrodynamic diameter of 19.6 nm, zeta potential of -27.8 mV and optimal weight ratio ∼1:6.3. Conditions for the effective formation of TBC-COOH/MPS were elucidated by comparing copolymers and glucocorticoids with different structure. The micellar structure of TBC-COOH/MPS persisted upon dilution, temperature fluctuations and interaction with blood serum components. TBC-COOH increased antiradical activity of MPS and promoted its intrinsic cytotoxicity in vitro attributed to enhanced cellular availability of the mixed micelles. Intracellular transportation and hydrolysis of MPS were analyzed using optimized liquid chromatography tandem mass spectrometry with multiple reaction monitoring which showed increased level of both MPS and methylprednisolone in neuronal cells treated with the formulated glucocorticoid. Our results identify TBC-COOH/MPS as an advanced in situ prepared nanoformulation and encourage its further investigation for a potential local glucocorticoid therapy. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Impaired succinic dehydrogenase activity of rat Purkinje cell mitochondria during aging.

    Science.gov (United States)

    Fattoretti, P; Bertoni-Freddari, C; Caselli, U; Paoloni, R; Meier-Ruge, W

    1998-03-16

    The perikaryal Purkinje cell mitochondria positive to the copper ferrocyanide histochemical reaction for succinic dehydrogenase (SDH) have been investigated by means of semiautomatic morphometric methods in rats of 3, 12 and 24 months of age. The number of organelles/microm3 of Purkinje cell cytoplasm (Numeric density: Nv), the average mitochondrial volume (V) and the mitochondrial volume fraction (Volume density: Vv) were the ultrastructural parameters taken into account. Nv was significantly higher at 12 than at 3 and 24 months of age. V was significantly decreased at 12 and 24 months of age, but no difference was envisaged between adult and old rats. Vv was significantly decreased in old animals vs. the other age groups. In young and old rats, the percentage of organelles larger than 0.32 microm3 was 13.5 and 11%, respectively, while these enlarged mitochondria accounted for less than 1% in the adult group. Since SDH activity is of critical importance when energy demand is high, the marked decrease of Vv supports an impaired capacity of the old Purkinje cells to match actual energy supply at sustained transmission of the nervous impulse. However, the high percentage of enlarged organelles found in old rats may witness a morphofunctional compensatory response.

  1. Effect of Rubberwood Content on Biodegradability of Poly(butylene succinate Biocomposites

    Directory of Open Access Journals (Sweden)

    Hemhong Anankaphong

    2015-01-01

    Full Text Available Poly(butylene succinate (PBS biocomposites incorporated with rubberwood powder (RWP were fabricated with various RWP weight fractions (i.e., 0 to 40% wt by injection moulding process. The soil burial test was employed to examine the biodegradability of such biocomposites under outdoor environment for 60 days. The physical appearance, percentage weight loss, chemical structure, and mechanical properties before and after the soil burial test were determined. Apparent changes in physical appearance of the biocomposites from optical micrographs were detected in terms of surface morphology and colour. The percentage of crystallinity of PBS/RWP biocomposites was studied by the X-ray diffraction (XRD technique, and the XRD pattern revealed a decrease in percentage of crystallinity due to enhancing RWP weight fractions. This may be attributed to a presence of rubberwood powders providing more disordered molecular chain arrangement of PBS matrix and also an agglomeration of the rubberwood powder content at greater concentration as seen in SEM micrographs. With increasing RWP weight fractions and burial time, the results exhibited a considerable change in chemical structure (essentially ester linkage due to biodegradation mechanism of PBS, relatively greater percentage weight loss, and a substantial decrease in flexural properties. Consequently, the results indicate that incorporating RWP enhances biodegradability of PBS/RWP biocomposites; that is, the biodegradation rate of biocomposites increases with increasing RWP weight fractions and burial time.

  2. Stoichiometry of mitochondrial H+ translocation coupled to succinate oxidation at level flow.

    Science.gov (United States)

    Costa, L E; Reynafarje, B; Lehninger, A L

    1984-04-25

    The mechanistic stoichiometry of vectorial H+ translocation coupled to succinate oxidation by rat liver mitochondria in the presence of a permeant cation has been determined under level flow conditions with a membraneless fast responding O2 electrode kinetically matched with a glass pH electrode. The reactions were initiated by rapid injection of O2 into the anaerobically preincubated test system under conditions in which interfering H+ backflow was minimized. The rates of O2 uptake and H+ ejection, obtained from computer-fitted regression lines, were monotonic and first order over 75% of the course of O2 consumption. Extrapolation of the observed rates to zero time, at which zero delta mu H+ and thus level flow prevails, yielded vectorial H+/O flow ratios above 7 and closely approaching 8. The mitochondria undergo no irreversible change and give identical H+/O ratios on repeated tests. In a further refinement, the lower and upper limits of the mechanistic H+/O ratio were determined to be 7.55 and 8.56, respectively, from plots of the rates of O2 uptake versus H+ ejection at increasing malonate and increasing valinomycin concentrations, respectively. It is therefore concluded that the mechanistic H+/O ratio for energy-conserving sites 2 + 3 is 8, in confirmation of earlier measurements. KCl concentration is critical for maximal observed H+/O ratios. Optimum conditions and possible errors in determination of mechanistic H+/O translocation ratios are discussed.

  3. Application of finite inverse gas chromatography in hypromellose acetate succinate-water-acetone systems.

    Science.gov (United States)

    Chiu, Sheng-Wei; Sturm, Derek R; Moser, Justin D; Danner, Ronald P

    2016-09-30

    A modification of a GC was developed to investigate both infinitely dilute and finite concentrations of solvents in polymers. Thermodynamic properties of hypromellose acetate succinate (HPMCAS-L)-acetone-water systems are important for the optimization of spray-drying processes used in pharmaceutical manufacturing of solid dispersion formulations. These properties, at temperatures below the glass transition temperature, were investigated using capillary column inverse gas chromatography (CCIGC). Water was much less soluble in the HPMCAS-L than acetone. Experiments were also conducted at infinitely dilute concentrations of one of the solvents in HPMCAS-L that was already saturated with the other solvent. Overall the partitioning of the water was not significantly affected by the presence of either water or acetone in the polymer. The acetone partition coefficient decreased as either acetone or water was added to the HPMCAS-L. A representation of the HPMCAS-L structure in terms of UNIFAC groups has been developed. With these groups, the UNIFAC-vdw-FV model did a reasonable job of predicting the phase equilibria in the binary and ternary systems. The Flory-Huggins correlation with fitted interaction parameters represented the data well. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Rheological, pasting, thermal and retrogradation properties of octenyl succinic anhydride modified potato starch

    Directory of Open Access Journals (Sweden)

    Chuin WON

    Full Text Available Abstract The objective of the present study was to investigate the rheological, pasting, and thermal properties of octenyl succinic anhydrate (OSA-modified potato starch. Potato starch was modified using different concentrations of OSA (0, 1, 3, and 5%, v/v. The degree of substitution (DS for the OSA-modified starch ranged from 0.0012 to 0.0055. The amylose leaching values of native and OSA-modified potato starch with different DS levels were in the range of 47.09-87.32%. The gel strength values of the OSA-modified starch were lower than those of native potato starch. Rapid Visco Analyzer data showed that peak, hot pasting, final and setback viscosities of the native starch decreased after OSA modification. Dynamic shear rheological tests, conducted at 4 °C, indicated that OSA-modified potato starch had weak gel-like behavior with the storage moduli (G' higher than the loss moduli (G” over most of the frequency ranges (0.63-63.8 rad·s-1.

  5. Structural control of co-continuous poly(L-lactide)/poly(butylene succinate)/clay nanocomposites.

    Science.gov (United States)

    Zhao, Li; Li, Yongjin; Shimizu, Hiroshi

    2009-04-01

    Poly(L-lactide) (PLLA)/poly(butylene succinate) (PBS) (55/45 w/w) blends with different amounts of nanoclay loadings were prepared using a specially designed high-shear extruder, HSE3000mini, which can reach a maximum shear rate of 4400 sec(-1). The resulted co-continuous structural morphologies were observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). SEM observation revealed that through the combination of various amounts of nanoclay loadings and processing under various shear conditions, the phase size of co-continuous structures of PLLA/PBS blends can be controlled over a wide range from several tens of micrometers to submicrometers. TEM observation shows that all the nanoclays are selectively dispersed in the PBS phase. We also found that clays in low-shear processed sample were mainly located at the interface of PBS phase, while in high-shear sample, the clays were mainly located inside of the PBS phase. It was considered that the dependence of nanoclay location in the PBS phase on the shear conditions, as well as the changing of the viscosity ratio of PBS and PLLA phase with different amounts of clay loading, play important roles in controlling the phase size of the co-continuous structures of PLLA/PBS blends.

  6. Structural properties of pepsin-solubilized collagen acylated by lauroyl chloride along with succinic anhydride

    International Nuclear Information System (INIS)

    Li, Conghu; Tian, Zhenhua; Liu, Wentao; Li, Guoying

    2015-01-01

    The structural properties of pepsin-solubilized calf skin collagen acylated by lauroyl chloride along with succinic anhydride were investigated in this paper. Compared with native collagen, acylated collagen retained the unique triple helix conformation, as determined by amino acid analysis, circular dichroism and X-ray diffraction. Meanwhile, the thermostability of acylated collagen using thermogravimetric measurements was enhanced as the residual weight increased by 5%. With the temperature increased from 25 to 115 °C, the secondary structure of native and acylated collagens using Fourier transform infrared spectroscopy measurements was destroyed since the intensity of the major amide bands decreased and the positions of the major amide bands shifted to lower wavenumber, respectively. Meanwhile, two-dimensional correlation spectroscopy revealed that the most sensitive bands for acylated and native collagens were amide I and II bands, respectively. Additionally, the corresponding order of the groups between native and acylated collagens was different and the correlation degree for acylated collagen was weaker than that of native collagen, suggesting that temperature played a small influence on the conformation of acylated collagen, which might be concluded that the hydrophobic interaction improved the thermostability of collagen. - Highlights: • Acylated collagen retained the unique triple helix conformation. • Acylated collagen had stronger thermostability than native collagen. • Amide I was the most sensitive band to the temperature for acylated collagen. • Amide II was the most sensitive band to the temperature for native collagen. • Auto-peak at 1680 cm −1 for acylated collagen disappeared at higher temperature

  7. Analysis of Gas Permeability Characteristics of Poly(Lactic Acid/Poly(Butylene Succinate Nanocomposites

    Directory of Open Access Journals (Sweden)

    Amita Bhatia

    2012-01-01

    Full Text Available Gas permeability and morphological properties of nanocomposites prepared by the mixing of poly(lactic acid (PLA, poly(butylene succinate (PBS, and clay was investigated. While the composition of PLA and PBS polymers was fixed as 80% and 20% by weight, respectively, for all the nanocomposites, clay contents varied from 1 to 10 wt%. From the morphological studies using both wide angle X-ray diffraction and transmission electron microscopy, the nanocomposite having 1 wt% of clay was considered to have a mixed morphology of intercalated and delaminated structure, while some clusters or agglomerated particles were detected for nanocomposites having 3 and more than 3 wt% of clay content. However, the average particle size of the dispersed PBS phase was reduced significantly from 7 μm to 30–40 nm with the addition of clay in the blend. The oxygen barrier property was improved significantly as compared to the water vapor. A model based on gas barrier property was used for the validation of the oxygen relative permeabilities of PLA/PBS/clay nanocomposites. PLA/PBS/clay nanocomposites validated the Bharadwaj model up to 3 wt% of clay contents only, while for nanocomposites of higher clay contents the Bharadwaj model was invalid due to the clusters and agglomerates formed.

  8. Sugar-Based Ethanol Biorefinery: Ethanol, Succinic Acid and By-Product Production

    Energy Technology Data Exchange (ETDEWEB)

    Donal F. Day

    2009-03-31

    The work conducted in this project is an extension of the developments itemized in DE-FG-36-04GO14236. This program is designed to help the development of a biorefinery based around a raw sugar mill, which in Louisiana is an underutilized asset. Some technical questions were answered regarding the addition of a biomass to ethanol facility to existing sugar mills. The focus of this work is on developing technology to produce ethanol and valuable by-products from bagasse. Three major areas are addressed, feedstock storage, potential by-products and the technology for producing ethanol from dilute ammonia pre-treated bagasse. Sugar mills normally store bagasse in a simple pile. During the off season there is a natural degradation of the bagasse, due to the composting action of microorganisms in the pile. This has serious implications if bagasse must be stored to operate a bagasse/biorefinery for a 300+ day operating cycle. Deterioration of the fermentables in bagasse was found to be 6.5% per month, on pile storage. This indicates that long term storage of adequate amounts of bagasse for year-round operation is probably not feasible. Lignin from pretreatment seemed to offer a potential source of valuable by-products. Although a wide range of phenolic compounds were present in the effluent from dilute ammonia pretreatment, the concentrations of each (except for benzoic acid) were too low to consider for extraction. The cellulosic hydrolysis system was modified to produce commercially recoverable quantities of cellobiose, which has a small but growing market in the food process industries. A spin-off of this led to the production of a specific oligosaccharide which appears to have both medical and commercial implications as a fungal growth inhibitor. An alternate use of sugars produced from biomass hydrolysis would be to produce succinic acid as a chemical feedstock for other conversions. An organism was developed which can do this bioconversion, but the economics of

  9. In-vitro responses of T lymphocytes to poly(butylene succinate) based biomaterials.

    Science.gov (United States)

    Toso, Montree; Patntirapong, Somying; Janvikul, Wanida; Singhatanadgit, Weerachai

    2017-04-01

    Polybutylene succinate (PBSu) and PBSu/β-tricalcium phosphate (TCP) composites are biocompatible and good candidates as bone graft materials. However, little is known about the responses of T lymphocytes to these biomaterials, which play an important role in the success of bone grafting. Activated T lymphocytes were cultured onto 32 mm diameter films (PBSu/TCP films), that had previously been placed in 6-well culture plates, for 8, 24 and 72 hours. A plastic-well culture plate was used as a control surface. The effects of PBSu-based biomaterials on T lymphocytes were examined by the using flow cytometry and reverse-transcription polymerase chain reaction. These biomaterials were non-toxic to T lymphocytes, allowing their normal DNA synthesis and activation. All materials induced only transient activation of T lymphocytes, which existed no longer than 72 hours. Proportions of four main CD4/CD8 T lymphocyte subpopulations were not affected by these biomaterials. Moreover, PBSu and PBSu/TCP significantly suppressed the expression of IL-1β and IL-6 genes by 15-35% and 21-26%, respectively. In contrast, a PBSu/TCP composite (at PBSu:TCP=60:40) significantly stimulated the expression of IL-10 and IL-13 genes by 17% and 19%, respectively. PBSu and PBSu/TCP composites were non-toxic to T lymphocytes and did not induce unfavorable responses of T lymphocytes. The tested biomaterials down-regulated key proinflammatory cytokine genes and up-regulated anti-inflammatory cytokine genes in T lymphocytes. These suggest that the biomaterials studied are good candidates as bone graft materials.

  10. CRISPR-Cas9 for the genome engineering of cyanobacteria and succinate production.

    Science.gov (United States)

    Li, Hung; Shen, Claire R; Huang, Chun-Hung; Sung, Li-Yu; Wu, Meng-Ying; Hu, Yu-Chen

    2016-11-01

    Cyanobacteria hold promise as a cell factory for producing biofuels and bio-derived chemicals, but genome engineering of cyanobacteria such as Synechococcus elongatus PCC 7942 poses challenges because of their oligoploidy nature and long-term instability of the introduced gene. CRISPR-Cas9 is a newly developed RNA-guided genome editing system, yet its application for cyanobacteria engineering has yet to be reported. Here we demonstrated that CRISPR-Cas9 system can effectively trigger programmable double strand break (DSB) at the chromosome of PCC 7942 and provoke cell death. With the co-transformation of template plasmid harboring the gene cassette and flanking homology arms, CRISPR-Cas9-mediated DSB enabled precise gene integration, ameliorated the homologous recombination efficiency and allowed the use of lower amount of template DNA and shorter homology arms. The CRISPR-Cas9-induced cell death imposed selective pressure and enhanced the chance of concomitant integration of gene cassettes into all chromosomes of PCC 7942, hence accelerating the process of obtaining homogeneous and stable recombinant strains. We further explored the feasibility of engineering cyanobacteria by CRISPR-Cas9-assisted simultaneous glgc knock-out and gltA/ppc knock-in, which improved the succinate titer to 435.0±35.0μg/L, an ≈11-fold increase when compared with that of the wild-type cells. These data altogether justify the use of CRISPR-Cas9 for genome engineering and manipulation of metabolic pathways in cyanobacteria. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  11. Novel bioactive polyester scaffolds prepared from unsaturated resins based on isosorbide and succinic acid

    Energy Technology Data Exchange (ETDEWEB)

    Śmiga-Matuszowicz, Monika, E-mail: monika.smiga-matuszowicz@polsl.pl [Silesian University of Technology, Department of Physical Chemistry and Technology of Polymers, M. Strzody Street 9, 44-100 Gliwice (Poland); Janicki, Bartosz; Jaszcz, Katarzyna; Łukaszczyk, Jan [Silesian University of Technology, Department of Physical Chemistry and Technology of Polymers, M. Strzody Street 9, 44-100 Gliwice (Poland); Kaczmarek, Marcin [Silesian University of Technology, Department of Biomaterials and Medical Devices Engineering, de Gaulle' a Street 66, 41-800 Zabrze (Poland); Lesiak, Marta; Sieroń, Aleksander L. [Medical University of Silesia, Department of General and Molecular Biology and Genetics, Medyków Street 18, 40-752 Katowice (Poland); Simka, Wojciech [Silesian University of Technology, Department of Chemistry, Inorganic Technology and Fuels, B. Krzywoustego Street 6, 44-100 Gliwice (Poland); Mierzwiński, Maciej; Kusz, Damian [Medical University of Silesia, Department of Orthopedics and Traumatology, Ziołowa Street 45, 40-635 Katowice (Poland)

    2014-12-01

    In this study new biodegradable materials obtained by crosslinking poly(3-allyloxy-1,2-propylene succinate) (PSAGE) with oligo(isosorbide maleate) (OMIS) and small amount of methyl methacrylate were investigated. The porous scaffolds were obtained in the presence of a foaming system consisted of calcium carbonate/carboxylic acid mixture, creating in situ porous structure during crosslinking of liquid formulations. The maximum crosslinking temperature and setting time, the cured porous materials morphology as well as the effect of their porosity on mechanical properties and hydrolytic degradation process were evaluated. It was found that the kind of carboxylic acid used in the foaming system influenced compressive strength and compressive modulus of porous scaffolds. The MTS cytotoxicity assay was carried out for OMIS using hFOB1.19 cell line. OMIS resin was found to be non-toxic in wide range of concentrations. On the ground of scanning electron microscopy (SEM) observations and energy X-ray dispersive analysis (EDX) it was found that hydroxyapatite (HA) formation at the scaffolds surfaces within short period of soaking in phosphate buffer solution occurs. After 3 h immersion a compact layer of HA was observed at the surface of the samples. The obtained results suggest potential applicability of resulted new porous crosslinked polymeric materials as temporary bone void fillers. - Highlights: • Isosorbide-based resin was used as a component of biodegradable scaffolds. • CAC/carboxylic acid system was proven as facile method to obtain porous scaffolds. • Porous scaffolds displayed the formation of hydroxyapatite at their surfaces.

  12. Emulsion stabilizing capacity of intact starch granules modified by heat treatment or octenyl succinic anhydride.

    Science.gov (United States)

    Timgren, Anna; Rayner, Marilyn; Dejmek, Petr; Marku, Diana; Sjöö, Malin

    2013-03-01

    Starch granules are an interesting stabilizer candidate for food-grade Pickering emulsions. The stabilizing capacity of seven different intact starch granules for making oil-in-water emulsions has been the topic of this screening study. The starches were from quinoa; rice; maize; waxy varieties of rice, maize, and barley; and high-amylose maize. The starches were studied in their native state, heat treated, and modified by octenyl succinic anhydride (OSA). The effect of varying the continuous phase, both with and without salt in a phosphate buffer, was also studied. Quinoa, which had the smallest granule size, had the best capacity to stabilize oil drops, especially when the granules had been hydrophobically modified by heat treatment or by OSA. The average drop diameter (d 32) in these emulsions varied from 270 to 50 μm, where decreasing drop size and less aggregation was promoted by high starch concentration and absence of salt in the system. Of all the starch varieties studied, quinoa had the best overall emulsifying capacity, and OSA modified quinoa starch in particular. Although the size of the drops was relatively large, the drops themselves were in many instances extremely stable. In the cases where the system could stabilize droplets, even when they were so large that they were visible to the naked eye, they remained stable and the measured droplet sizes after 2 years of storage were essentially unchanged from the initial droplet size. This somewhat surprising result has been attributed to the thickness of the adsorbed starch layer providing steric stabilization. The starch particle-stabilized Pickering emulsion systems studied in this work has potential practical application such as being suitable for encapsulation of ingredients in food and pharmaceutical products.

  13. Alpha-tocopherol succinate- and AMD3100-mobilized progenitors mitigate radiation combined injury in mice

    International Nuclear Information System (INIS)

    Singh, Vijay K.; Wise, Stephen Y.; Fatanmi, Oluseyi O.; Beattie, Lindsay A.; Ducey, Elizabeth J.; Seed, Thomas M.

    2014-01-01

    The purpose of this study was to elucidate the role of alpha-tocopherol succinate (TS)- and AMD3100-mobilized progenitors in mitigating combined injury associated with acute radiation exposure in combination with secondary physical wounding. CD2F1 mice were exposed to high doses of cobalt-60 gamma-radiation and then transfused intravenously with 5 million peripheral blood mononuclear cells (PBMCs) from TS- and AMD3100-injected mice after irradiation. Within 1 h after irradiation, mice were exposed to secondary wounding. Mice were observed for 30 d after irradiation and cytokine analysis was conducted by multiplex Luminex assay at various time-points after irradiation and wounding. Our results initially demonstrated that transfusion of TS-mobilized progenitors from normal mice enhanced survival of acutely irradiated mice exposed 24 h prior to transfusion to supralethal doses (11.5–12.5 Gy) of 60 Co gamma-radiation. Subsequently, comparable transfusions of TS-mobilized progenitors were shown to significantly mitigate severe combined injuries in acutely irradiated mice. TS administered 24 h before irradiation was able to protect mice against combined injury as well. Cytokine results demonstrated that wounding modulates irradiation-induced cytokines. This study further supports the conclusion that the infusion of TS-mobilized progenitor-containing PBMCs acts as a bridging therapy in radiation-combined-injury mice. We suggest that this novel bridging therapeutic approach involving the infusion of TS-mobilized hematopoietic progenitors following acute radiation exposure or combined injury might be applicable to humans. (author)

  14. Health expenditure comparison of extended-release metoprolol succinate and immediate-release metoprolol tartarate

    Directory of Open Access Journals (Sweden)

    Vaidya V

    2012-02-01

    Full Text Available Varun Vaidya, Pranav PatelCollege of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USABackground: Metoprolol, a selective beta-1 blocker, is available in two different salt forms in the market – metoprolol succinate (MS and metoprolol tartarate (MT. Both the formulations are Food and Drug Administration approved for the treatment of hypertension. Several studies have shown similar efficacies between the two salts; however, they differ in their pharmacokinetic properties and are therefore priced differently. The primary objective of this study was to compare the overall health care expenditures of hypertensive patients on MT and MS to see if the price difference in the two preparations is offset by savings in overall expenditure.Methods: Two cohorts of patients using MT and MS were selected from the 2008 Medical Expenditure Panel Survey. Propensity score matching technique was used to balance the cohorts on various parameters such as demographic information, insurance status, and comorbidity score. Patients using MT were matched to patients using MS on the logit of propensity score using calipers of width equal to 0.2 of the standard deviation of the logit of the propensity score. Multiple regression analysis was carried out to examine the association between health expenditure and type of metoprolol salt, adjusting for other covariates.Results: A total of 742 patients were found to use metoprolol (MT-388, MS-354. After propensity score matching, a total of 582 patients were left in the sample for final analysis (291 patients in each cohort. The average annual health care expenditure was slightly higher in the MT cohort; however, after adjusting for covariates in a multivariate analysis, the difference was found to be statistically insignificant (P = 0.23.Conclusion: Both the products of metoprolol were found to have similar average annual total health care expenditure; however, MS once a day has higher out

  15. Chiral separation of (d- and (l-enantiomers of doxylamine succinate in rat plasma

    Directory of Open Access Journals (Sweden)

    Tadiboyina Sirisha

    2015-12-01

    Full Text Available A selective chiral ultra fast liquid chromatography (UFLC-DAD method was developed and validated to separate and quantify the (d- and (l-enantiomers of doxylamine in rat plasma. After extraction of the plasma samples with acetonitrile, the separation of doxylamine succinate enantiomers and internal standard (I.S., diphenhydramine hydrochloride was achieved on a cellulose Tris (4-chloro,3-methylphenylcarbamate column with a mobile phase of 20 mM ammonium bicarbonate buffer–acetonitrile (65:35 v/v with 0.15% diethylamine in the buffer at a flow rate of 1.0 mL/min. The diode array (DAD detection wavelength was set at 220 nm. The peaks obtained were identified as (d and (l by injecting the pure (d form into the liquid chromatography and comparing the chromatograms. The effect of column oven temperature on the retention of doxylamine and mobile phase variables which have an effect on the enantiomers separation like ionic strength, type and concentration of organic modifier was studied. Linear calibration curves were obtained over the range of 100–1400 ng/mL in plasma for both enantiomers (R2 > 0.995. The mean extraction recoveries were 94.5–104.7% of rat plasma. The mean relative standard deviation (RSD% of accuracy and intra-day and inter-day precision for both enantiomers were ⩽10%. The method can be further applied to determine the pharmacokinetics of (d- and (l-enantiomers in rat plasma.

  16. Influences of hyperbranched poly(amide-ester) on the properties of poly(butylene succinate)

    International Nuclear Information System (INIS)

    Run, Mingtao; Wang, Jian; Yao, Meng; Guo, Lijie; Wang, Hai-jun; Ba, Xinwu

    2013-01-01

    The polymer blends of hyperbranched poly(amide-ester) and poly(butylene succinate) (HBP/PBS) were prepared by melt-blending method. The molecular interaction within the blends, phase morphology, crystal morphology, mechanical, rheological and dynamic mechanical properties were investigated by using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), tensile machine, polarized optical microscopy, rotational rheometer and dynamic mechanical analyzer (DMA), respectively. The results suggest that PBS and HBP have a certain compatibility at amorphous state. A certain number of H-bonding was detected between PBS and HBP phases and it influences the material properties. HBP not only serves partially as a nucleating agent for the crystallization of PBS but also plays a role of plasticizer for the rheology of PBS. The glass transition temperatures of the blends slightly decrease with increasing HBP content. The proper amount of HBP (4–6%) has a reinforcement effect on the PBS matrix at glassy state. However, the blend with 10%HBP content has an improved impact strength mainly due to the plasticization effect or H-bonding effect of HBP on PBS matrix. The storage modulus is increased with increasing HBP contents, and the loss modulus is much smaller than the storage modulus in each blend at glassy state. At rubbery state the storage modulus of different samples is independent of HBP content. The complex viscosity of the melt decreases with increasing HBP content; however, the blend with 10%HBP is a special sample because of its abnormal larger complex viscosity at low shear frequencies. In addition, the melt’s elasticity behavior increases slightly with increasing HBP content. - Highlights: ► H-bonding was detected between PBS and HBP phases by FTIR. ► HBP serves partly as a nucleating agent for the crystallization of PBS. ► HBP plays a role of plasticizer for PBS. ► The blend with 10%HBP has abnormal larger complex viscosity

  17. The Effect of Nebivolol versus Metoprolol Succinate Extended Release on Asymmetric Dimethylarginine in Hypertension

    Science.gov (United States)

    Kandavar, Ramprasad; Higashi, Yusuke; Chen, Wei; Blackstock, Christopher; Vaughn, Charlotte; Sukhanov, Sergiy; Sander, Gary E.; Roffidal, Louise E.; Delafontaine, Patrice; Giles, Thomas D.

    2011-01-01

    Objectives This study sought to determine if metoprolol succinate ER (MET), and nebivolol (NEB), a β1-AR with increased bioavailability of nitric oxide (NO), would have differing effects on plasma asymmetric dimethylarginine concentration in hypertensives. Background It was hypothesized that NEB, a β1-AR antagonist and β3-AR agonist with NO- releasing properties and MET, only a β1-AR antagonist, would have different effects on plasma ADMA concentration. Methods Forty-one hypertensive subjects randomly received either 50 mg of MET (n = 19) or 5 mg of NEB (n = 22) for 4 weeks followed by 100 mg MET and 10 mg NEB for 4 weeks. ADMA and IGF-1 were measured by ELISA kit; endothelial progenitor cells were estimated using fluorescein-labeled monoclonal antibody to KDR and CD133 receptors; arterial augmentation index was measured by radial tonometry. Results Baseline systolic/diastolic blood pressure was 155.1 ± 18.7/85.3 ± 12.5 mm Hg for MET subjects and 157.6 ± 20.7/87.1 ± 14.0 mm Hg for NEB subjects. Baseline ADMA was 0.32 ± 0.123 μmol/L in the MET group and 0.4035 ± 0.1378 in the NEB group. ADMA increased 44.78% and 72% in the MET group at weeks 4 and 8 (p < 0.05 for both), respectively, without increase in the NEB group. At week 8 augmentation index was increased in the MET group (p<0.05). IGF-1 and EPC were unchanged by treatment. Conclusions Plasma ADMA and augmentation index are increased in a dose-dependent fashion by MET but not with NEB. PMID:21251896

  18. Successful chemotherapy of hepatic metastases in a case of succinate dehydrogenase subunit B-related paraganglioma.

    Science.gov (United States)

    He, J; Makey, D; Fojo, T; Adams, K T; Havekes, B; Eisenhofer, G; Sullivan, P; Lai, E W; Pacak, K

    2009-10-01

    Compared to other familial pheochromocytoma/paragangliomas (PHEO/PGLs), the succinate dehydrogenase subunit B (SDHB)-related PHEO/PGLs often present with aggressive and rapidly growing metastatic lesions. Currently, there is no proven effective treatment for malignant PHEO/PGLs. Here, we present a 35-year-old white man with primary malignant abdominal extra-adrenal 11 cm paraganglioma underwent surgical successful resection. But 6 months later, he developed extensive bone, liver, and lymph nodes metastasis, which were demonstrated by computed tomography scan and the (18)F-fluorodeoxyglucose positron emission tomography. However, his (123)I-metaiodobenzylguanidine scintigraphy was negative; therefore, the cyclophosphamide, vincristine, and dacarbazine (CVD) combination chemotherapy was initiated. The combination chemotherapy was very effective showing 80% overall reduction in the liver lesions and 75% overall reduction in the retroperitoneal mass and adenopathy, and normalization of plasma catecholamine and metanephrine levels. However, plasma levels of dopamine (DA) and methoxytyramine (MTY) were only partially affected and remained consistently elevated throughout the remaining period of follow-up evaluation. Genetic testing revealed an SDHB gene mutation. Here, we present an SDHB-related PHEO/PGL patient with extensive tumor burden, numerous organ lesions, and rapidly growing tumors, which responded extremely well to CVD therapy. We conclude patients with SDHB-related PHEO/PGLs can be particularly sensitive to CVD chemotherapy and may have an excellent outcome if this therapy is used and continued on periodic basis. The data in this patient also illustrate the importance of measuring plasma levels of DA and MTY to provide a more complete and accurate assessment of the biochemical response to therapy than provided by measurements restricted to other catecholamines and O-methylated metabolites.

  19. Mutants of GABA transaminase (POP2 suppress the severe phenotype of succinic semialdehyde dehydrogenase (ssadh mutants in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Frank Ludewig

    Full Text Available BACKGROUND: The gamma-aminubutyrate (GABA shunt bypasses two steps of the tricarboxylic acid cycle, and is present in both prokaryotes and eukaryotes. In plants, the pathway is composed of the calcium/calmodulin-regulated cytosolic enzyme glutamate decarboxylase (GAD, the mitochondrial enzymes GABA transaminase (GABA-T; POP2 and succinic semialdehyde dehydrogenase (SSADH. We have previously shown that compromising the function of the GABA-shunt, by disrupting the SSADH gene of Arabidopsis, causes enhanced accumulation of reactive oxygen intermediates (ROIs and cell death in response to light and heat stress. However, to date, genetic investigations of the relationships between enzymes of the GABA shunt have not been reported. PRINCIPAL FINDINGS: To elucidate the role of succinic semialdehyde (SSA, gamma-hydroxybutyrate (GHB and GABA in the accumulation of ROIs, we combined two genetic approaches to suppress the severe phenotype of ssadh mutants. Analysis of double pop2 ssadh mutants revealed that pop2 is epistatic to ssadh. Moreover, we isolated EMS-generated mutants suppressing the phenotype of ssadh revealing two new pop2 alleles. By measuring thermoluminescence at high temperature, the peroxide contents of ssadh and pop2 mutants were evaluated, showing that only ssadh plants accumulate peroxides. In addition, pop2 ssadh seedlings are more sensitive to exogenous SSA or GHB relative to wild type, because GHB and/or SSA accumulate in these plants. SIGNIFICANCE: We conclude that the lack of supply of succinate and NADH to the TCA cycle is not responsible for the oxidative stress and growth retardations of ssadh mutants. Rather, we suggest that the accumulation of SSA, GHB, or both, produced downstream of the GABA-T transamination step, is toxic to the plants, resulting in high ROI levels and impaired development.

  20. Structural studies on the actinide carboxylates. 4. The crystal and molecular structure of succinate dioxouranium(VI) monohydrate

    Energy Technology Data Exchange (ETDEWEB)

    Bombieri, G; Benetollo, F [Consiglio Nazionale delle Ricerche, Padua (Italy). Lab. di Chimica e Tecnologia dei Radioelementi; Del Pra, A; Rojas, R

    1979-01-01

    The structure of the title compound, UO/sub 2/(CH/sub 2/COO)/sub 2/.H/sub 2/O, has been determined from three-dimensional X-ray data. The crystals are orthorhombic, space group Pbcn with four formula units in a cell. The coordination geometry about the uranium atom is pentagonal bipyramidal. The uranyl ions are equatorially surrounded by one water oxygen and by four carboxylate oxygen atoms of different succinic ligands. Each ligand is shared by four uranyl units giving rise to a polymeric-like structure.

  1. Comparative analysis of succinate dehydrogenase activity in mammalian peripheral blood lymphocytes and radiomodifying action of gas hypoxis mixtures

    International Nuclear Information System (INIS)

    Gajdamakin, A.N.; Abramov, M.M.

    1987-01-01

    Radiprotective efficiency of gas hypoxic mixtures (GHM) containing 5-12% of oxygen and the rate of the reaction of succinate dehydrogenase (V SDG ) activity in peripheral blood lymphocytes upon breathing GHM were comparatively studied in rats and dogs. V SDG was 4393.5 (%O 2 ) -2,58 and 130.76 (%O 2 ) -1.42 in dogs and rats respectively. Taking into account that DMF in rats is a function of oxygen concentration in the mixture one can obtain a formula for determining a dose modifying factors (DMF) as a function of the rate of SDG activity reaction

  2. Blend membrane of succinic acid-crosslinked chitosan grafted with heparin/PVA-PEG (polyvinyl alcohol-polyethylene glycol) and its characterization

    Science.gov (United States)

    Sangkota, V. D. A.; Lusiana, R. A.; Astuti, Y.

    2018-04-01

    Crosslinking and grafting reactions are required to modify the functional groups on chitosan to increase the number of its active groups. In this study, crosslinking reaction of succinic acid and grafting reaction of heparin on chitosan were conducted to produce a membrane as a candidate of a hemodialysis membrane. The mole ratio between chitosan and succinate acids was varied to obtain the best composition of modified materials. By blending all the material composition with PVA-PEG, the blend was transformed into a membrane. The resulted membrane was then characterized by various test methods such as tests of thickness, weight, water uptake, pH resistance, tensile strength and membrane hydrophilicity. The results showed that the best composition of the membrane reached in the addition of 0.011 gram of succinic acid proved by its highest mechanical strength compared to the other membranes.

  3. The Deletion of the Succinate Dehydrogenase Gene KlSDH1 in Kluyveromyces lactis Does Not Lead to Respiratory Deficiency

    Science.gov (United States)

    Saliola, Michele; Bartoccioni, Paola Chiara; De Maria, Ilaria; Lodi, Tiziana; Falcone, Claudio

    2004-01-01

    We have isolated a Kluyveromyces lactis mutant unable to grow on all respiratory carbon sources with the exception of lactate. Functional complementation of this mutant led to the isolation of KlSDH1, the gene encoding the flavoprotein subunit of the succinate dehydrogenase (SDH) complex, which is essential for the aerobic utilization of carbon sources. Despite the high sequence conservation of the SDH genes in Saccharomyces cerevisiae and K. lactis, they do not have the same relevance in the metabolism of the two yeasts. In fact, unlike SDH1, KlSDH1 was highly expressed under both fermentative and nonfermentative conditions. In addition to this, but in contrast with S. cerevisiae, K. lactis strains lacking KlSDH1 were still able to grow in the presence of lactate. In these mutants, oxygen consumption was one-eighth that of the wild type in the presence of lactate and was normal with glucose and ethanol, indicating that the respiratory chain was fully functional. Northern analysis suggested that alternative pathway(s), which involves pyruvate decarboxylase and the glyoxylate cycle, could overcome the absence of SDH and allow (i) lactate utilization and (ii) the accumulation of succinate instead of ethanol during growth on glucose. PMID:15189981

  4. 99mtechnetium-dimercapto-succinic acid renal scanning and excretory urography in diagnosis of renal scars in children

    International Nuclear Information System (INIS)

    McLorie, G.A.; Aliabadi, H.; Churchill, B.M.; Ash, J.M.; Gilday, D.L.

    1989-01-01

    We compared the ability of excretory urography (without tomography) and 99mtechnetium-dimercapto-succinic acid renal scanning to detect renal scars in 32 children with primary vesicoureteral reflux. These children did not have hydronephrosis, renal failure or urinary tract obstruction. In all cases both studies were conducted within a 10-month period. The findings from both modalities were in agreement for 51 of the 64 renal units evaluated (80%). Evaluation of the excretory urogram indicated 6 cases of diffuse and 2 of focal scarring that were not detected by evaluation of the renal scan. The sensitivity of excretory urography to detect renal scars was 84% and the specificity was 83%. The 99mtechnetium-dimercapto-succinic acid renal scan showed 5 cases of focal renal scarring not detected by excretory urography. The sensitivity of the renal scan to detect renal scars was 77% and the specificity was 75%. We conclude that neither study alone could effectively replace the other for the detection of renal scars, and recommend that both be included in the initial evaluation and followup of patients with renal scars

  5. [Changes in cell respiration of postural muscle fibers under long-term gravitational unloading after dietary succinate supplementation].

    Science.gov (United States)

    Ogneva, I V; Veselova, O M; Larina, I M

    2011-01-01

    The intensity of cell respiration of the rat m. soleus, m. gastrocnemius c.m. and tibialis anterior fibers during 35-day gravitational unloading, with the addition of succinate in the diet at a dosage rate of 50 mg per 1 kg animal weight has been investigated. The gravitational unloading was modeled by antiorthostatic hindlimb suspension. The intensity of cell respiration was estimated by polarography. It was shown that the rate of oxygen consumption by soleus and gastrocnemius fibers on endogenous and exogenous substrates and with the addition of ADP decreases after the discharge. This may be associated with the transition to the glycolytic energy path due to a decrease in the EMG-activity. At the same time, the respiration rate after the addition of exogenous substrates in soleus fibers did not increase, indicating a disturbance in the function of the NCCR-section of the respiratory chain and more pronounced changes in the structure of muscle fibers. In tibialis anterior fibers, no changes in oxygen consumption velocity were observed. The introduction of succinate to the diet of rats makes it possible to prevent the negative effects of hypokinesia, although it reduces the basal level of intensity of cell respiration.

  6. Mixed ligand complexes of essential metal ions with L-glutamine and succinic acid in SLS-water mixtures

    Directory of Open Access Journals (Sweden)

    Bindu Hima Gandham

    2012-01-01

    Full Text Available Speciation of mixed ligand complexes of Co(II, Ni(II and Cu(II with L-glutamine and succinic acid was studied in varying amounts (0.0-2.5% w/v of sodium lauryl sulphate in aqueous solutions maintaining an ionic strength of 0.16 mol L-1 (NaCl at 303.0 K. Titrations were carried out in the presence of different relative concentrations (M : L : X = 1 : 2 : 2, 1 : 4 : 2, 1 : 2 : 4 of metal (M to L-glutamine (L to succinic acid (X with sodium hydroxide. Stability constants of ternary complexes were refined with MINIQUAD75. The best-fit chemical models were selected based on statistical parameters and residual analysis. The species detected were ML2X, MLX, MLXH and MLXH2 for Co(II, Ni(II and Cu(II. Extra stability of ternary complexes compared to their binary complexes was believed to be due to electrostatic interactions of the side chains of ligands, charge neutralization, chelate effect, stacking interactions and hydrogen bonding. The species distribution with pH at different compositions of SLS and plausible equilibria for the formation of species were also presented.

  7. Physical Stability of Octenyl Succinate-Modified Polysaccharides and Whey Proteins for Potential Use as Bioactive Carriers in Food Systems.

    Science.gov (United States)

    Puerta-Gomez, Alex F; Castell-Perez, M Elena

    2015-06-01

    The high cost and potential toxicity of biodegradable polymers like poly(lactic-co-glycolic)acid (PLGA) has increased the interest in natural and modified biopolymers as bioactive carriers. This study characterized the physical stability (water sorption and state transition behavior) of selected starch and proteins: octenyl succinate-modified depolymerized waxy corn starch (DWxCn), waxy rice starch (DWxRc), phytoglycogen, whey protein concentrate (80%, WPC), whey protein isolate (WPI), and α-lactalbumin (α-L) to determine their potential as carriers of bioactive compounds under different environmental conditions. After enzyme modification and particle size characterization, glass transition temperature and moisture isotherms were used to characterize the systems. DWxCn and DWxRc had increased water sorption compared to native starch. The level of octenyl succinate anhydrate (OSA) modification (3% and 7%) did not reduce the water sorption of the DWxCn and phytoglycogen samples. The Guggenheim-Andersen-de Boer model indicated that native waxy corn had significantly (P whey proteins had higher glass transition temperature (Tg) values. On the other hand, depolymerized waxy starches at 7%-OSA modification had a "melted" appearance when exposed to environments with high relative humidity (above 70%) after 10 days at 23 °C. The use of depolymerized and OSA-modified polysaccharides blended with proteins created more stable blends of biopolymers. Hence, this biopolymer would be suitable for materials exposed to high humidity environments in food applications. © 2015 Institute of Food Technologists®

  8. Effect of stretching on the mechanical properties in melt-spun poly(butylene succinate)/microfibrillated cellulose (MFC) nanocomposites.

    Science.gov (United States)

    Zhou, Mi; Fan, Mao; Zhao, Yongsheng; Jin, Tianxiang; Fu, Qiang

    2016-04-20

    In order to prepare poly(butylene succinate)/microfibrillated cellulose composites with high performance, in this work, microfibrillated cellulose (MFC) was first treated by acetylchloride with ball-milling to improve its interfacial compatibility with poly(butylene succinate) (PBS). Then melt stretching processing was adopted to further improve the dispersion and orientation of MFC in as-spun PBS fiber. And the effect of MFC on the crystalline structure and mechanical properties were systematically investigated for the melt-spun fibers prepared with two different draw ratios. The dispersion, alignment of the MFC and interfacial crystalline structure in the composite fibers are significantly influenced by the stretching force during the melt spinning. The possible formation of nanohybrid shish kebab (NHSK) superstructure where aligned MFC as shish and PBS lamellae as kebab has been suggested via SEM and SAXS in the composite fibers prepared at the high draw ratio. Large improvement in tensile strength has been realized at the high draw ratio due to the enhanced orientation and dispersion of MFC as well as the formation of NHSK. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. No evidence for promoter region methylation of the succinate dehydrogenase and fumarate hydratase tumour suppressor genes in breast cancer

    Directory of Open Access Journals (Sweden)

    Dobrovic Alexander

    2009-09-01

    Full Text Available Abstract Background Succinate dehydrogenase (SDH and fumarate hydratase (FH are tricarboxylic acid (TCA cycle enzymes that are also known to act as tumour suppressor genes. Increased succinate or fumarate levels as a consequence of SDH and FH deficiency inhibit hypoxia inducible factor-1α (HIF-1α prolyl hydroxylases leading to sustained HIF-1α expression in tumours. Since HIF-1α is frequently expressed in breast carcinomas, DNA methylation at the promoter regions of the SDHA, SDHB, SDHC and SDHD and FH genes was evaluated as a possible mechanism in silencing of SDH and FH expression in breast carcinomas. Findings No DNA methylation was identified in the promoter regions of the SDHA, SDHB, SDHC, SDHD and FH genes in 72 breast carcinomas and 10 breast cancer cell lines using methylation-sensitive high resolution melting which detects both homogeneous and heterogeneous methylation. Conclusion These results show that inactivation via DNA methylation of the promoter CpG islands of SDH and FH is unlikely to play a major role in sporadic breast carcinomas.

  10. Succinate Dehydrogenase Activity Assay in situ with Blue Tetrazolium Salt in Crabtree-Positive Saccharomyces cerevisiae Strain

    Directory of Open Access Journals (Sweden)

    Joanna Berlowska

    2008-01-01

    Full Text Available A spectrophotometric method for determining succinate dehydrogenase (SDH activity assay in azide-sensitive yeast Saccharomyces cerevisiae has been developed. The permeabilization of yeast cells by 0.05 % digitonin permitted to study yeast enzymatic activity in situ. The reduction of blue tetrazolium salt (BT to blue tetrazolium formazan (BTf was conducted in the presence of phenazine methosulphate (PMS as an exogenous electron carrier, and sodium azide (SA as an inhibitor of cytochrome oxidase (Cyt pathway. Various factors such as type of substrate, BT concentration, cell number, temperature and time of incubation, and different Cyt pathway blockers were optimized. In earlier studies, dimethyl sulfoxide (DMSO had been selected as the best solvent for extraction of BTf from yeast cells. The linear correlation between permeabilized yeast cell density and amount of formed formazan was evidenced in the range from 9·10^7 to 5·10^8 cells per sample solution. Below the yeast cell concentration of 10^7 the absorbance values were too low to detect formazans with good precision. This standarized procedure allows the estimation of SDH activity in whole cells, depending on vitality level of yeast populations. Significant increases of succinate dehydrogenase activities were observed in sequential passages as the result of the increase of activity of the strain and adaptation to cultivation conditions.

  11. Rapid liquid–liquid extraction of thallium(III from succinate media with 2-octylaminopyridine in chloroform as the extractant

    Directory of Open Access Journals (Sweden)

    SANDIP V. MAHAMUNI

    2008-04-01

    Full Text Available A simple solvent extraction study of thallium(III was conducted. Selective and quantitative extraction of thallium(III by 2-octylaminopyridine (2-OAP in chloroform occurred from aqueous sodium succinate medium (0.0075 M at pH 3.0. Thallium(III was back extracted with acetate buffer (pH 4.63. The effect of the concentration of succinate and 2-OAP, the role of various diluents, stripping agents, loading capacity of 2-OAP, equilibrium time and aqueous:organic volume ratio on the extraction of thallium(III was studied. The stoichiometry of the extracted species was determined based on the slope analysis method and found to be 1: 2: 1 (metal:acid:extractant. The temperature dependence of the extraction equilibrium constant was also examined to estimate the apparent thermodynamic functions ∆H, ∆G and ∆S for the extraction reaction. The method is free from interference of a large number of cations and anions. The method was used for the selective extraction of thallium(III from its binary mixture with Zn(II, Cd(II, Hg(II, Bi(III, Pb(II, Se(IV, Te(IV, Sb(III, Ga(III, In(III, Al(III, Tl(I and Fe(III. The proposed method was applied to the synthetic mixtures and alloys. It is simple, selective, rapid and eco-friendly.

  12. Extraction behaviour of 2-octylaminopyridine towards lead(II) from succinate media and its separation from other toxic metals

    International Nuclear Information System (INIS)

    Mane, Chandrashekhar P.; Anuse, Mansing A.

    2008-01-01

    Liquid-liquid extraction of lead(II) from succinate media was carried out with 2-octylaminopyridine (2-OAP) in chloroform. Lead(II) was quantitatively extracted with 0.036 M 2-OAP in chloroform from 0.005-0.007 M sodium succinate when equilibrated for 5 min. Lead(II) from the organic phase was stripped with three 10 mL portions of 0.4 M acetic acid and determined titrimetrically with EDTA. The nature of extracted species was determined from the log-log plot. The optimum conditions have been evaluated based on a critical study of weak acid concentration, extractant concentration, period of equilibration and effect of diluents. The metal loading capacity of the reagent was found to be 8 mg of lead(II) with 10 mL 0.036 M of the extractant. The extraction of the lead(II) was carried out in presence of various ions to ascertain the tolerance limit of individual. Temperature dependence of the extraction equilibrium constants was examined to estimate the apparent thermodynamic functions (ΔH, ΔS and ΔG) for extraction reaction. Lead(II) was successfully separated from commonly associated metal ions such as Bi(III), Hg(II), Cr(VI), Cd(II), Zn(II), Al(III), Ca(II), Ba(II) and from binary and ternary mixtures. The method was extended for determination of lead(II) in real samples

  13. Diglycolic acid inhibits succinate dehydrogenase activity in human proximal tubule cells leading to mitochondrial dysfunction and cell death.

    Science.gov (United States)

    Landry, Greg M; Dunning, Cody L; Conrad, Taylor; Hitt, Mallory J; McMartin, Kenneth E

    2013-08-29

    Diethylene glycol (DEG) is a solvent used in consumer products allowing the increased risk for consumer exposure. DEG metabolism produces two primary metabolites, 2-hydroxyethoxyacetic acid (2-HEAA) and diglycolic acid (DGA). DGA has been shown to be the toxic metabolite responsible for the proximal tubule cell necrosis seen in DEG poisoning. The mechanism of DGA toxicity in the proximal tubule cell is not yet known. The chemical structure of DGA is very similar to citric acid cycle intermediates. Studies were designed to assess whether its mechanism of toxicity involves disruption of cellular metabolic pathways resulting in mitochondrial dysfunction. First, DGA preferentially inhibited succinate dehydrogenase, including human kidney cell enzyme, but had no effect on other citric acid cycle enzyme activities. DGA produces a cellular ATP depletion that precedes cell death. Human proximal tubule (HPT) cells, pre-treated with increasing DGA concentrations, showed significantly decreased oxygen consumption. DGA did not increase lactate levels, indicating no effect on glycolytic activity. DGA increased reactive oxygen species (ROS) production in HPT cells in a concentration and time dependent manner. These results indicate that DGA produced proximal tubule cell dysfunction by specific inhibition of succinate dehydrogenase and oxygen consumption. Disruption of these processes results in decreased energy production and proximal tubule cell death. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. Influence of the course prescription of sodium succinate on functional state and general physical working ability of footballers organism during the training sessions

    Directory of Open Access Journals (Sweden)

    Олексій Володимирович Чернєв

    2015-09-01

    Full Text Available Pharmacological purpose of metabotropic preparations including burshtin acid and its derivative succinate sodium copes with the number of tasks the main of which is an activation of alternative ways of energoproduction at the work of submaximal and maximal force and preliminary training of the separate links of metabolism.The task of research is to ascertain changes that take place in functional state of sportsmen during long physical loadings and optimization of the work of cardiovascular system (CVS and prophylaxis of psychical strains with the help of succinate sodium.Methods and organization of research. There were examined 84 sportsmen to ascertain changes that take place in the functional state of sportsmen during the long physical loadings and optimization of the work of CVS with the help of succinate sodium. Examinations took place during the training sessions (TS in January, February and July 2012-2013 years.Results of research and its discussion. There was studied an efficiency of the course use of succinate sodium in footballers 100 mg 3 times a day during 14 days. Energetic supply of processes of intracellular homeostasis in erythrocytes realizes by means of ATP that is created in the process of glycolysis. According to the results of research after course prescription of succinate sodium in sportsmen the content of ATP in erythrocytes increased and an amount of ADP and AMP decreased. An improvement of general metabolic situation under an influence of succinate sodium was proved by the decrease of products of reactions of peroxidation in blood plasma of footballers.These results indicated an essential antiacidotic effect of the course use of succinate sodium by footballers after loading in anaerobic and glycolytic zone of intensity. At the same time there was ascertain in our research that the use of succinate sodium had a positive effect on the dynamics of lactate content during the processes of renewal after training in aerobic

  15. Acetate and succinate production in amoebae, helminths, diplomonads, trichomonads and trypanosomatids: common and diverse metabolic strategies used by parasitic lower eukaryotes.

    Science.gov (United States)

    Bringaud, F; Ebikeme, C; Boshart, M

    2010-08-01

    Parasites that often grow anaerobically in their hosts have adopted a fermentative strategy relying on the production of partially oxidized end products, including lactate, glycerol, ethanol, succinate and acetate. This review focuses on recent progress in understanding acetate production in protist parasites, such as amoebae, diplomonads, trichomonads, trypanosomatids and in the metazoan parasites helminths, as well as the succinate production pathway(s) present in some of them. We also describe the unconventional organisation of the tricarboxylic acid cycle associated with the fermentative strategy adopted by the procyclic trypanosomes, which may resemble the probable structure of the primordial TCA cycle in prokaryotes.

  16. Succinic acid production derived from carbohydrates: An energy and greenhouse gas assessment of a platform chemical toward a bio-based economy

    NARCIS (Netherlands)

    Cok, B.|info:eu-repo/dai/nl/371750679; Tsiropoulos, I.; Roes, A.L.|info:eu-repo/dai/nl/303022388; Patel, M.K.|info:eu-repo/dai/nl/18988097X

    2014-01-01

    Bio-based succinic acid has the potential to become a platform chemical, i.e. a key building block for deriving both commodity and high-value chemicals, which makes it an attractive compound in a bio-based economy. A few companies and industrial consortia have begun to develop its industrial

  17. Hepatic processing determines dual activity of alpha-tocopheryl succinate: a novel paradigm for a shift in biological activity due to provitamin-to-vitamin conversion

    Czech Academy of Sciences Publication Activity Database

    Neužil, Jiří; Massa, H.

    2005-01-01

    Roč. 327, č. 4 (2005), s. 1024-1027 ISSN 0006-291X Institutional research plan: CEZ:AV0Z5052915; CEZ:AV0Z50520514 Keywords : vitamin E * alpha-tocopheryl succinate * hepatic processing Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.000, year: 2005

  18. Polystyrene/TiO2 composite electrospun fibers as fillers for poly(butylene succinate-co-adipate): Structure, morphology and properties

    CSIR Research Space (South Africa)

    Neppalli, R

    2014-01-01

    Full Text Available In this work, composite polystyrene/titanium dioxide (PS/TiO(sub2)) electrospun fibers were used as a reinforcement for a poly(butylene succinate-co-adipate) (PBSA) matrix. The structure, morphology, mechanical properties and degradation behavior...

  19. Effect of nanoclay loading on the thermal and mechanical properties of biodegradable Polylactide/Poly[(butylene succinate)- co-adipate] blend composites

    CSIR Research Space (South Africa)

    Ojijo, Vincent O

    2012-04-01

    Full Text Available Polylactide/poly[(butylene succinate)-co-adipate] (PLA/PBSA)-organoclay composites were prepared via melt compounding in a batch mixer. The weight ratio of PLA to PBSA was kept at 70:30, while the weight fraction of the organoclay was varied from 0...

  20. Discovering Novel Alternaria solani Succinate Dehydrogenase Inhibitors by in Silico Modeling and Virtual Screening Strategies to Combat Early Blight

    Directory of Open Access Journals (Sweden)

    Sehrish Iftikhar

    2017-11-01

    Full Text Available Alternaria blight is an important foliage disease caused by Alternaria solani. The enzyme Succinate dehydrogenase (SDH is a potential drug target because of its role in tricarboxylic acid cycle. Hence targeting Alternaria solani SDH enzyme could be efficient tool to design novel fungicides against A. solani. We employed computational methodologies to design new SDH inhibitors using homology modeling; pharmacophore modeling and structure based virtual screening. The three dimensional SDH model showed good stereo-chemical and structural properties. Based on virtual screening results twelve commercially available compounds were purchased and tested in vitro and in vivo. The compounds were found to inhibit mycelial growth of A. solani. Moreover in vitro trials showed that inhibitory effects were enhanced with increase in concentrations. Similarly increased disease control was observed in pre-treated potato tubers. Hence the applied in silico strategy led us to identify novel fungicides.

  1. Succinate, iron chelation, and monovalent cations affect the transformation efficiency of Acinetobacter baylyi ATCC 33305 during growth in complex media.

    Science.gov (United States)

    Leong, Colleen G; Boyd, Caroline M; Roush, Kaleb S; Tenente, Ricardo; Lang, Kristine M; Lostroh, C Phoebe

    2017-10-01

    Natural transformation is the acquisition of new genetic material via the uptake of exogenous DNA by competent bacteria. Acinetobacter baylyi is model for natural transformation. Here we focus on the natural transformation of A. baylyi ATCC 33305 grown in complex media and seek environmental conditions that appreciably affect transformation efficiency. We find that the transformation efficiency for A. baylyi is a resilient characteristic that remains high under most conditions tested. We do find several distinct conditions that alter natural transformation efficiency including addition of succinate, Fe 2+ (ferrous) iron chelation, and substitution of sodium ions with potassium ones. These distinct conditions could be useful to fine tune transformation efficiency for researchers using A. baylyi as a model organism to study natural transformation.

  2. Preparation and structural characterisation of novel and versatile amphiphilic octenyl succinic anhydride-modified hyaluronic acid derivatives

    DEFF Research Database (Denmark)

    Eenschooten, Corinne Diane; Guillaumie, Fanny; Kontogeorgis, Georgios

    2010-01-01

    and structurally characterised by Fourier transform-infrared spectroscopy and proton nuclear magnetic resonance spectroscopy (1H NMR). The influence of four reaction parameters on the DS of the derivatives was studied by means of an experimental design. The results showed that the OSA/HA molar ratio, the buffer......The purpose of the present study was to prepare amphiphilic hyaluronic acid (HA) derivatives and to study the influence of a selection of reaction parameters on the degree of substitution (DS) of the derivatives. Octenyl succinic anhydride (OSA)–modified HA (OSA–HA) derivatives were prepared...... (NaHCO3) concentration and their interaction had the largest influence while the HA concentration and the reaction time only had a negligible effect. According to 1H NMR the maximum DS achieved within the experimental conditions tested was 43% per disaccharide unit. Moreover optimal reaction...

  3. Effect of Anorganic Substance on Physical Properties of Poly (Butylene Succinate -co- Adipate) Irradiated by Electron Beam

    International Nuclear Information System (INIS)

    Meri Suhartini

    2004-01-01

    Poly(butylene succinate-co-adipate), PBSA were electron beam irradiated in the presence of inorganic materials. The samples gave high gel fraction by irradiation in the presence of 2% silicon dioxide and 2% carbon black. It was found that addition of carbon black (CB) was effective for improving the heat stability of the sample. This is because of three-dimensional carbon black- polymer networks. Irradiated PBSA sheets broke immediately at 110 o C with load 6.67 kgf/cm 2 , while irradiated the same sample mixed with 2% carbon black did not break at the same condition. Biodegradability of crosslinked PBSA by soil burial tests was accelerated by addition of carbon black. (author)

  4. Effect of low dose x irradiation on the succinate dehydrogenase activity of guinea pig, rat and mouse tissues

    Energy Technology Data Exchange (ETDEWEB)

    Shah, V C; Bhatavdekar, J M; Aravinda Babu, K [Gujarat Univ., Ahmedabad (India). Dept. of Zoology

    1976-07-01

    The histochemical changes in succinate dehydrogenase (SDH) were investigated in pectoralis major muscle of guinea pig, rat and mouse after level X-irradiation (72 R and 240 R) and compared with control animals. Biochemical studies were carried out on liver, kidney, muscle (pectoralis major), adrenal and spleen of these animals after low dose local X-irradiation and compared with control animals. Changes in SDH activity were studied up to 72-h post-irradiation, which shows that low dose local X-irradiation leads to increased enzymic activity. The increase in enzymic activity was remarkable in mouse tissues as compared with guinea pig and rat. Adrenals of all the three animals showed significant activation after all the doses of radiation studied. The significance of these results, with special reference to oxidative metabolism, has been discussed.

  5. Acylation Modification of Antheraea pernyi Silk Fibroin Using Succinic Anhydride and Its Effects on Enzymatic Degradation Behavior

    Directory of Open Access Journals (Sweden)

    Xiufang Li

    2013-01-01

    Full Text Available The degradation rate of tissue engineering scaffolds should match the regeneration rate of new tissues. Controlling the degradation behavior of silk fibroin is an important subject for silk-based tissue engineering scaffolds. In this study, Antheraea pernyi silk fibroin was successfully modified with succinic anhydride and then characterized by zeta potential, ninhydrin method, and FTIR. In vitro, three-dimensional scaffolds prepared with modified silk fibroin were incubated in collagenase IA solution for 18 days to evaluate the impact of acylation on the degradation behavior. The results demonstrated that the degradation rate of modified silk fibroin scaffolds was more rapid than unmodified ones. The content of the β-sheet structure in silk fibroin obviously decreased after acylation, resulting in a high degradation rate. Above all, the degradation behavior of silk fibroin scaffolds could be regulated by acylation to match the requirements of various tissues regeneration.

  6. RRR-alpha-tocopheryl succinate inhibits EL4 thymic lymphoma cell growth by inducing apoptosis and DNA synthesis arrest.

    Science.gov (United States)

    Yu, W; Sanders, B G; Kline, K

    1997-01-01

    RRR-alpha-tocopheryl succinate (vitamin E succinate, VES) treatment of murine EL4 T lymphoma cells induced the cells to undergo apoptosis. After 48 hours of VES treatment at 20 micrograms/ml, 95% of cells were apoptotic. Evidence for the induction of apoptosis by VES treatments is based on staining of DNA for detection of chromatin condensation/fragmentation, two-color flow-cytometric analyses of DNA content, and end-labeled DNA and electrophoretic analyses for detection of DNA ladder formation. VES-treated EL4 cells were blocked in the G1 cell cycle phase; however, apoptotic cells came from all cell cycle phases. Analyses of mRNA expression of genes involved in apoptosis revealed decreased c-myc and increased bcl-2, c-fos, and c-jun mRNAs within three to six hours after treatment. Western analyses showed increased c-Jun, c-Fos, and Bcl-2 protein levels. Electrophoretic mobility shift assays showed increased AP-1 binding at 6, 12, and 24 hours after treatment and decreased c-Myc binding after 12 and 24 hours of VES treatment. Treatments of EL4 cells with VES+RRR-alpha-to-copherol reduced apoptosis without effecting DNA synthesis arrest. Treatments of EL4 cells with VES+rac-6-hydroxyl-2, 5,7,8-tetramethyl-chroman-2-carboxylic acid, butylated hydroxytoluene, or butylated hydroxyanisole had no effect on apoptosis or DNA synthesis arrest caused by VES treatments. Analyses of bcl-2, c-myc, c-jun, and c-fos mRNA levels in cells receiving VES + RRR-alpha-tocopherol treatments showed no change from cells receiving VES treatments alone, implying that these changes are correlated with VES treatments but are not causal for apoptosis. However, treatments with VES + RRR-alpha-tocopherol decreased AP-1 binding to consensus DNA oligomer, suggesting AP-1 involvement in apoptosis induced by VES treatments.

  7. Preparation of venlafaxine hydrochloride sustained-release tablets

    Directory of Open Access Journals (Sweden)

    ZHANG Yang

    2013-02-01

    Full Text Available A novel non-enzymatic glucose sensor was developed by electrodepositing copper film onto the graphene(GR substrate.The morphologies and structures of the nanocomposites were characterized by field emission scanning electron microscope (FESEM.The electrochemical performances of the Cu/GR nanocomposite film were investigated.The Cu/GR nanocomposite film showed good electrocatalytic activity towards glucose oxidation in alkaline solution.The Cu/GR nanocomposite film-based sensor displayed a linear concentration range from 8×10-6 to 9.4×10-4 mol/L with the sensitivity of 0.225 A·L·mol-1 and the detection limit (S/N=3 of 2.5 μmol/L for the detection of glucose.With an enhanced electrocatalytic property,high sensitivity and good stability.The as-prepared sensor is promising for the future development of nonenzymatic sensors.

  8. Optimization of sustained release aceclofenac microspheres using response surface methodology

    Energy Technology Data Exchange (ETDEWEB)

    Deshmukh, Rameshwar K.; Naik, Jitendra B., E-mail: jitunaik@gmail.com

    2015-03-01

    Polymeric microspheres containing aceclofenac were prepared by single emulsion (oil-in-water) solvent evaporation method using response surface methodology (RSM). Microspheres were prepared by changing formulation variables such as the amount of Eudragit® RS100 and the amount of polyvinyl alcohol (PVA) by statistical experimental design in order to enhance the encapsulation efficiency (E.E.) of the microspheres. The resultant microspheres were evaluated for their size, morphology, E.E., and in vitro drug release. The amount of Eudragit® RS100 and the amount of PVA were found to be significant factors respectively for determining the E.E. of the microspheres. A linear mathematical model equation fitted to the data was used to predict the E.E. in the optimal region. Optimized formulation of microspheres was prepared using optimal process variables setting in order to evaluate the optimization capability of the models generated according to IV-optimal design. The microspheres showed high E.E. (74.14 ± 0.015% to 85.34 ± 0.011%) and suitably sustained drug release (minimum; 40% to 60%; maximum) over a period of 12 h. The optimized microspheres formulation showed E.E. of 84.87 ± 0.005 with small error value (1.39). The low magnitudes of error and the significant value of R{sup 2} in the present investigation prove the high prognostic ability of the design. The absence of interactions between drug and polymers was confirmed by Fourier transform infrared (FTIR) spectroscopy. Differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRPD) revealed the dispersion of drug within microspheres formulation. The microspheres were found to be discrete, spherical with smooth surface. The results demonstrate that these microspheres could be promising delivery system to sustain the drug release and improve the E.E. thus prolong drug action and achieve the highest healing effect with minimal gastrointestinal side effects. - Highlights: • Aceclofenac microspheres were prepared by the o/w solvent evaporation method. • Two independent variables were investigated by IV-optimal design. • The microspheres showed high % encapsulation efficiency (74.14% to 85.34%). • In-vitro study of the microspheres showed a sustained drug release pattern. • Response surface methodology is an efficient tool in the optimization experiments.

  9. Diclofenac transdermal patch versus the sustained release tablet: A ...

    African Journals Online (AJOL)

    polyvinyl pyrrolidone K30, with turpentine oil and sesame oil as penetration enhancers. ... therapeutic advantages over conventional oral tablets in terms of prolonged release and improvement of ..... is simple to adopt and cost-effective. In this ...

  10. Formulation of Sustained-Release Diltiazem Matrix Tablets Using ...

    African Journals Online (AJOL)

    Erah

    surface, their drug release behavior appears simple, but ... matrix material for the formulation of ..... formulation F5 (,) and reference formulations. ( , □). 0. 50. 100. 150. 200. 250. 300. 0. 3. 6 .... Coviello T, Matricardi P, Marianecci C, Alhaique F.

  11. Application of mathematical modeling in sustained release delivery systems.

    Science.gov (United States)

    Grassi, Mario; Grassi, Gabriele

    2014-08-01

    This review, presenting as starting point the concept of the mathematical modeling, is aimed at the physical and mathematical description of the most important mechanisms regulating drug delivery from matrix systems. The precise knowledge of the delivery mechanisms allows us to set up powerful mathematical models which, in turn, are essential for the design and optimization of appropriate drug delivery systems. The fundamental mechanisms for drug delivery from matrices are represented by drug diffusion, matrix swelling, matrix erosion, drug dissolution with possible recrystallization (e.g., as in the case of amorphous and nanocrystalline drugs), initial drug distribution inside the matrix, matrix geometry, matrix size distribution (in the case of spherical matrices of different diameter) and osmotic pressure. Depending on matrix characteristics, the above-reported variables may play a different role in drug delivery; thus the mathematical model needs to be built solely on the most relevant mechanisms of the particular matrix considered. Despite the somewhat diffident behavior of the industrial world, in the light of the most recent findings, we believe that mathematical modeling may have a tremendous potential impact in the pharmaceutical field. We do believe that mathematical modeling will be more and more important in the future especially in the light of the rapid advent of personalized medicine, a novel therapeutic approach intended to treat each single patient instead of the 'average' patient.

  12. Formulation of Sustained-Release Matrix Tablets Using Cross ...

    African Journals Online (AJOL)

    MK and the formulations were also characterized by scanning electron microscopy (SEM), Fourier transform infra-red spectroscopy (FTIR) and differential scanning calorimetry (DSC). Results: Tablets with MK showed higher mean dissolution time (MDT) and lower dissolution efficiency than those prepared with karaya gum.

  13. Sustained Release of a Water-Soluble Drug from Directly ...

    African Journals Online (AJOL)

    Okra gum was evaluated as a controlled-release agent in modified release matrices in comparison with sodium carboxymethylcellulose (NaCMC) using aspirin as the model drug. Tablets were produced by direct compression and the in vitro drug release was assessed under conditions similar to those in the gastrointestinal ...

  14. Preparation and pre-clinical characterization of sustained- release ...

    African Journals Online (AJOL)

    This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and .... with the help of screw gauge (n = 3). Hardness .... performed by ANOVA using GraphPad Prism©. 4.0. Values of p ...

  15. Sustained release formulations of citronella oil nanoemulsion using cavitational techniques.

    Science.gov (United States)

    Agrawal, Naveen; Maddikeri, Ganesh L; Pandit, Aniruddha B

    2017-05-01

    Nanoemulsion synthesis has proven to be an effective way for transportation of immobile, insoluble bioactive compounds. Citronella Oil (lemongrass oil), a natural plant extract, can be used as a mosquito repellent and has less harmful effects compared to its available market counterpart DEET (N, N-Diethyl-meta-toluamide). Nanoemulsion of citronella oil in water was prepared using cavitation-assisted techniques while investigating the effect of system parameters like HLB (Hydrophilic Lipophilic Balance), surfactant concentration, input energy density and mode of power input on emulsion quality. The present work also examines the effect of emulsification on release rate to understand the relationship between droplet size and the release rate. Minimum droplet size (60nm) of the emulsion was obtained at HLB of 14, S/O 1 ratio of 1.0, ultrasound amplitude of 50% and irradiation time of 5min. This study revealed that hydrodynamic cavitation-assisted emulsification is more energy efficient compared to ultrasonic emulsification. It was also found that the release rate of nanoemulsion enhanced as the droplet size of emulsion reduced. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Biodegradable Bioadherent Microcapsules for Orally Administered Sustained Release Vaccines

    Science.gov (United States)

    1997-05-01

    Fasciola hepatica which is a known bioadhesive’’. The encapsulation method is the classical, well described water in oil technique for the preparation of...immunization, Vaccine 12 (1994) 387-340. 6. Waite, J.H., Rice-Ficht, A.C., Presclerotized eggshell protein from the liver fluke Fasciola hepatica...Biochemistry 26 (1987) 7819-7825. 7. Waite, J.H., Rice-Ficht, A.C., Eggshell precursor proteins of Fasciola hepatica: II. Microheterogeneity in vitelline

  17. Eudragit RS PO nanoparticles for sustained release of pyridostigmine bromide

    International Nuclear Information System (INIS)

    Hoobakht, Fatemeh; Ganji, Fariba; Vasheghani-Farahani, Ebrahim; Mousavi, Seyyed Mohammad

    2013-01-01

    Pyridostigmine bromide (PB) is an inhibitor of cholinesterase, which is used in the treatment of myasthenia gravis and administered for protection against exposure to toxic nerve agents. Tests were done to investigate prolonging the half-life of PB and improving its release behavior. PB was loaded in nanoparticles (NPs) of Eudragit RS PO (Eu-RS) prepared using the technique of quasi emulsion solvent diffusion. Variables of output power of the sonicator, bath temperature and mixing time, were chosen as the optimization factors to obtain the minimum sized NPs. In addition, emulsions were tested at different ratios of drug-to-polymer by dynamic light scattering to determine size and zeta potential of NPs. UV-spectroscopy was used to determine PB content of the NPs. Drug-loaded NPs were characterized by scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectra. Results determined that mixing time had a significant impact on the size of Eu-RS NPs, but power output of sonicator and bath temperature had no significant effect. The particle size obtained at the optimum condition (power output of 70 W, bath temperature of 33 °C, and mixing time of 7 min) was less than 200 nm (optimum sizes were 138.9 and 179.5 nm for Eu-RS and PB-loaded Eu-RS NPs, respectively). The optimum PB-loaded Eu-RS NPs at the PB to Eu-RS weight ratio of 1–4 and 20 % of loaded PB released from the nanocarriers within 100 h

  18. Radiation crosslinked hydrogels as sustained release drug delivery systems

    International Nuclear Information System (INIS)

    Pekala, W.; Rosiak, J.; Rucinska-Rybus, A.; Burczak, K.; Galant, S.; Czolczynska, T.

    1986-01-01

    Radiation methods have been used for: i/modification of vascular prostheses, ii/ obtaining burn dressing materials enabling controlled drug release, iii/ the preparation of polymer ocular insert discs. The surface of polyester vascular prostheses, has been modified by deposition of acrylamide and inducing its polymerization in the solid state by γ-radiation. As a result of this treatment, tightness of the prosthesis walls and its surface hydrophilicity have been improved. Toxicological examinations and blood hemolysis studies of modified prostheses showed its good biocompatibility. Various burn dressings have been prepared and the most promising of all investigated turned to be composition consisting of a cotton gauze base and an active polyacrylamide hydrogel layer with addition of glycerin and immobilized Provital/protein preparation/. Preliminary clinical evaluations of this particular dressing showed that the process of burn healing is indeed fast and fully satisfactory. Ocular insert discs made of polymer and containing pilocarpin hydrochloride which is released at controlled rate have been prepared. It has been found that high hydrophilicity and good swelling properties of the ocular insert discs made possible to incorporate pilocarpin hydrochloride into hydrogel matrix. This work has been carried out under IAEA research contract RB 3379/R-1 POL. (author)

  19. Eudragit RS PO nanoparticles for sustained release of pyridostigmine bromide

    Energy Technology Data Exchange (ETDEWEB)

    Hoobakht, Fatemeh; Ganji, Fariba, E-mail: fganji@modares.ac.ir; Vasheghani-Farahani, Ebrahim [Tarbiat Modares University, Biomedical Engineering Group, Chemical Engineering Department (Iran, Islamic Republic of); Mousavi, Seyyed Mohammad [Tarbiat Modares University, Biotechnology Group, Chemical Engineering Department (Iran, Islamic Republic of)

    2013-09-15

    Pyridostigmine bromide (PB) is an inhibitor of cholinesterase, which is used in the treatment of myasthenia gravis and administered for protection against exposure to toxic nerve agents. Tests were done to investigate prolonging the half-life of PB and improving its release behavior. PB was loaded in nanoparticles (NPs) of Eudragit RS PO (Eu-RS) prepared using the technique of quasi emulsion solvent diffusion. Variables of output power of the sonicator, bath temperature and mixing time, were chosen as the optimization factors to obtain the minimum sized NPs. In addition, emulsions were tested at different ratios of drug-to-polymer by dynamic light scattering to determine size and zeta potential of NPs. UV-spectroscopy was used to determine PB content of the NPs. Drug-loaded NPs were characterized by scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectra. Results determined that mixing time had a significant impact on the size of Eu-RS NPs, but power output of sonicator and bath temperature had no significant effect. The particle size obtained at the optimum condition (power output of 70 W, bath temperature of 33 Degree-Sign C, and mixing time of 7 min) was less than 200 nm (optimum sizes were 138.9 and 179.5 nm for Eu-RS and PB-loaded Eu-RS NPs, respectively). The optimum PB-loaded Eu-RS NPs at the PB to Eu-RS weight ratio of 1-4 and 20 % of loaded PB released from the nanocarriers within 100 h.

  20. Alginate-Chitosan Particulate System for Sustained Release of ...

    African Journals Online (AJOL)

    Erah

    1School of Pharmacy and Health Sciences, International Medical University, Kuala Lumpur, Malaysia, 2Division of ... Both calcium alginate beads and the beads treated with chitosan failed to relea