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Sample records for vitro controlled release

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

    Science.gov (United States)

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

    2014-05-01

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

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

    NARCIS (Netherlands)

    VANDERVEEN, J; EISSENS, AC; LERK, CF

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

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

    OpenAIRE

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

    2003-01-01

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

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

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    Xiangyang Xie

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

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

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    Hernawan Hernawan

    2013-12-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

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    Tang, Yu; Singh, Jagdish

    2008-06-05

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

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

    Science.gov (United States)

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

    2012-10-15

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

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

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    Ikrima Khalid

    2014-09-01

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

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

    Science.gov (United States)

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

    2016-09-01

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

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

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    Praveen Kumar Gaur

    2014-12-01

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

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

    Science.gov (United States)

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

    2003-07-01

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

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

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

    2017-09-01

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

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

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

    2014-01-01

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

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

    NARCIS (Netherlands)

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

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

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

    Science.gov (United States)

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

    2016-05-01

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

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

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    Carol L. Berkower

    2013-01-01

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

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

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    Feng S

    2017-06-01

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

  19. An in vitro evaluation of fenugreek mucilage as a potential excipient for oral controlled-release matrix tablet.

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    Nokhodchi, Ali; Nazemiyeh, Hossein; Khodaparast, Afagh; Sorkh-Shahan, Tarifeh; Valizadeh, Hadi; Ford, J L

    2008-03-01

    A polysaccharide mucilage derived from the seeds of fenugreek, Trigonella foenum-graceum L (family Fabaceae) was investigated for use in matrix formulations containing propranolol hydrochloride. Methocel hypomellose K4M was used as a standard controlled release polymer for comparison purposes. In this study the effect of lactose on the release behaviour of propranolol hydrochloride from matrices formulated to contain the fenugreek mucilage also was investigated. An increase in concentration of the mucilage in matrices resulted in a reduction in the release rate of propranolol hydrochloride comparable to that observed with hypomellose matrices. The rate of release of propranolol hydrochloride from fenugreek mucilage matrices was mainly controlled by the drug:mucilage ratio. However, the mechanism of release from matrices containing drug:mucilage ratios of 1:1, 1:1.25, 1:1.5, and 1:2 remained the same. The kinetics of release, utilising the release exponent n, showed that the values of n were between 0.46-0.57 indicating that the release from fenugreek mucilage matrices was predominantly by diffusion. The presence of lactose in matrices containing mucilage increased the release rate of propranolol hydrochloride. This is due to a reduction in tortuoisity and increased pore size of channels caused by lactose through which propranolol diffuses and therefore diffusion of water into the tablet is facilitated.

  20. Chronotherapeutic drug delivery of Tamarind gum, Chitosan and Okra gum controlled release colon targeted directly compressed Propranolol HCl matrix tablets and in-vitro evaluation.

    Science.gov (United States)

    Newton, A M J; Indana, V L; Kumar, Jatinder

    2015-08-01

    The main objective of this investigation is to develop a chronotherapeutic drug delivery of various natural polymers based colon targeted drug delivery systems to treat early morning sign in BP. The polymers such as Tamarind gum, Okra gum and Chitosan were used in the formulation design. A model drug Propranolol HCl was incorporated in the formulation in order to assess the controlled release and time dependent release potential of various natural polymers. A novel polymer Tamarind gum was extracted and used as a prime polymer in this study to prove the superiority of this polymer over other leading natural polymer. Propranolol HCl was used as a model drug which undergoes hepatic metabolism and witnesses the poor bioavailability. The matrix tablets of Propranolol HCl were prepared by direct compression. The tablets were evaluated for various quality control parameters and found to be within the limits. Carbopol 940 was used as an auxiliary polymer to modify the drug release and physicochemical characteristics of the tablets. The in vitro release studies were performed in 0.1N HCl for 1.5h, followed by pH 6.8 phosphate buffer for 2h and pH 7.4 phosphate buffer till maximum amount of drug release. The in vitro release profile of the formulations were fitted with various pharmacokinetic mathematical models and analyzed for release profile. The formulations prepared with Tamarind gum prolonged the release for an extended period of time compared to other polymer based formulation and showed an excellent compression characteristic. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Design and in vitro and in vivo characterization of mucoadhesive matrix pellets of metformin hydrochloride for oral controlled release: a technical note.

    Science.gov (United States)

    Ige, Pradum Pundlikrao; Gattani, Surendra Ganeshlal

    2012-03-01

    The aim of the current work was to design and develop matrix pellets of hydroxy propyl methyl cellulose K200M and microcrystalline cellulose in an admixture for a mucoadhesive gastroretentive drug delivery system. Pellets containing metformin hydrochloride (500 mg) were prepared by the pelletization technique using an extruder-spheronizer. Pellets were characterized by differential scanning calorimetry (DSC), x-ray diffraction (XRD), scanning electron microscopy (SEM), circularity, roundness, percent drug content, percent production yield, in vitro swelling, ex vivo mucoadhesion, in vitro drug release and in vivo x-ray imaging studies. Optimized pellets were sufficiently porous spheroids, free flowing, had smooth surfaces, had yields up to 75.45 ± 0.52% and had drug content up to 96.45 ± 0.19%. The average particle size of formulations MF2 and MF6 were 1.13 ± 0.41 mm and 1.22 ± 0.18 mm, respectively. Formulation MF6 exhibited strong adhesion, about 94.67%, to goat mucosal tissue, and the desired in vitro swelling, with a sustained drug release profile for 12 h and with retention in the upper small intestine of rabbits for 10 h. We conclude that hydroxy propyl methyl cellulose K200M and microcrystalline cellulose at a 2.80:1.00 w/w ratio could be an effective carrier for multiple unit controlled delivery of metformin hydrochloride.

  2. Plantago ovata F. Mucilage-Alginate Mucoadhesive Beads for Controlled Release of Glibenclamide: Development, Optimization, and In Vitro-In Vivo Evaluation

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    Amit Kumar Nayak

    2013-01-01

    Full Text Available The current study deals with the development and optimization of ispaghula (Plantago ovata F. husk mucilage- (IHM- alginate mucoadhesive beads containing glibenclamide by ionotropic gelation technique. The effects of sodium alginate (SA to IHM and cross-linker (CaCl2 concentration on the drug encapsulation efficiency (DEE, %, as well as cumulative drug release after 10 hours (R10 h, %, were optimized using 32 factorial design based on response surface methodology. The observed responses were coincided well with the predicted values by the experimental design. The optimized mucoadhesive beads exhibited 94.43±4.80% w/w of DEE and good mucoadhesivity with the biological membrane in wash-off test and sustained drug release profile over 10 hours. The beads were also characterized by SEM and FTIR analyses. The in vitro drug release from these beads was followed by controlled release (zero-order pattern with super case-II transport mechanism. The optimized glibenclamide-loaded IHM-alginate mucoadhesive beads showed significant antidiabetic effect in alloxan-induced diabetic rats over prolonged period after oral administration.

  3. Protein release from hippocampus in vitro.

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

    1984-07-02

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

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

    Science.gov (United States)

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

    2016-07-01

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

  5. Contribution of carboxyl modified chiral mesoporous silica nanoparticles in delivering doxorubicin hydrochloride in vitro: pH-response controlled release, enhanced drug cellular uptake and cytotoxicity.

    Science.gov (United States)

    Li, Jing; Du, Xiaotong; Zheng, Nan; Xu, Lu; Xu, Jinghua; Li, Sanming

    2016-05-01

    In this study, dual functionalized mesoporous silica nanoparticle (Dual-MSN) with functions of carboxyl modification and chirality was successfully developed and its special contribution in delivering doxorubicin hydrochloride (DOX) in vitro was mainly studied. Characteristics of Dual-MSN and its application as DOX carrier were intensively explored by comparing with naked non-functionalized MSN (Naked MSN). The results indicated that both Naked MSN and Dual-MSN significantly controlled DOX release due to the release hindrance caused by mesopores. As expected, Dual-MSN exhibited obvious enhanced pH-response because of its negative charges of carboxyl groups. DOX loaded Naked MSN and DOX loaded Dual-MSN presented better cytotoxicity than DOX due to carrier-mediated endocytosis and the favorable intercalation of DOX into DNA in the nuclei. The cytotoxicity of DOX loaded Dual-MSN was better than DOX loaded Naked MSN owing to its enhanced cellular uptake induced by chirality of Dual-MSN, demonstrating that double functions of Dual-MSN had unique advantages in improving antitumor effect of DOX towards MCF-7 cells and thus confirming its special contribution in DOX delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Synthesis of Gelatin-γ-Polyglutamic Acid-Based Hydrogel for the In Vitro Controlled Release of Epigallocatechin Gallate (EGCG from Camellia sinensis

    Directory of Open Access Journals (Sweden)

    John Philip Domondon Garcia

    2013-12-01

    Full Text Available The antioxidant property and other health benefits of the most abundant catechin, epigallocatechin gallate (EGCG, are limited because of poor stability and permeability across intestine. Protecting the EGCG from the harsh gastrointestinal tract (GIT environment can help to increase its bioavailability following oral administration. In this study, EGCG was loaded to hydrogel prepared from ionic interaction between an optimized concentration of gelatin and γ-polyglutamic acid (γ-PGA, with ethylcarbodiimide (EDC as the crosslinker. Physicochemical characterization of hydrogel was done using Fourier transform-infrared spectroscopy (FT-IR, differential scanning calorimetry (DSC and scanning electron microscopy (SEM. The dependence of the swelling degree (SD of the hydrogel to the amount of gelatin, γ-PGA, EDC, swelling time and pH was determined. A high SD of the crosslinked hydrogel was noted at pH 4.5, 6.8 and 9.0 compared to pH 7.4, which describes pH-responsiveness. Approximately 67% of the EGCG from the prepared solution was loaded to the hydrogel after 12 h post-loading, in which loading efficiency was related to the amount of EDC. The in vitro release profile of EGCG at pH 1.2, 6.8 and 7.4, simulating GIT conditions, resulted in different sustained release curves. Wherein, the released EGCG was not degraded instantly compared to free-EGCG at controlled temperature of 37 °C at different pH monitored against time. Therefore, this study proves the potential of pH-responsive gelatin-γ-PGA-based hydrogel as a biopolymer vehicle to deliver EGCG.

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

    Science.gov (United States)

    Bhoopathy, Dhivya; Bhaskaran Ravi, Latha

    2017-12-01

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

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

    Science.gov (United States)

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

    2018-01-15

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

  9. Stimulus-Responsive, Biodegradable, Biocompatible, Covalently Cross-Linked Hydrogel Based on Dextrin and Poly(N-isopropylacrylamide) for in Vitro/in Vivo Controlled Drug Release.

    Science.gov (United States)

    Das, Dipankar; Ghosh, Paulomi; Ghosh, Animesh; Haldar, Chanchal; Dhara, Santanu; Panda, Asit Baran; Pal, Sagar

    2015-07-08

    A novel stimulus-sensitive covalently cross-linked hydrogel derived from dextrin, N-isopropylacrylamide, and N,N'-methylene bis(acrylamide) (c-Dxt/pNIPAm), has been synthesized via Michael type addition reaction for controlled drug release application. The chemical structure of c-Dxt/pNIPAm has been confirmed through Fourier transform infrared (FTIR) spectroscopy and (1)H and (13)C NMR spectral analyses. The surface morphology of the hydrogel has been studied by field emission scanning electron microscopic (FE-SEM) and environmental scanning electron microscopic (E-SEM) analyses. The stimulus responsiveness of the hydrogel was studied through equilibrium swelling in various pH media at 25 and 37 °C. Rheological study was performed to measure the gel strength and gelation time. Noncytotoxicity of c-Dxt/pNIPAm hydrogel has been studied using human mesenchymal stem cells (hMSCs). The biodegradability of c-Dxt/pNIPAm was confirmed using hen egg lysozyme. The in vitro and in vivo release studies of ornidazole and ciprofloxacin imply that c-Dxt/pNIPAm delivers both drugs in a controlled way and would be an excellent alternative for a dual drug carrier. The FTIR, powder X-ray diffraction (XRD), and UV-vis-near infrared (NIR) spectra along with the computational study predict that the drugs remain in the matrix through physical interaction. A stability study signifies that the drugs (ornidazole ∼97% and ciprofloxacin ∼98%) are stable in the tablet formulations for up to 3 months.

  10. In vitro and in vivo evaluation of controlled-release matrix tablets of highly water-soluble drug applying different Mw polyethylene oxides (PEO) as retardants.

    Science.gov (United States)

    Wen, Haoyang; Li, Xue; Li, Yuenan; Wang, Haiying; Yanyan, Wang; Tuanjie, Wang; Pan, Weisan; Yang, Xinggang

    2017-11-13

    The aim of the work presented is to prepare a controlled-release hydrophilic matrix tablet (CMT) controlling release of highly water-soluble drug applying pure combination of high and low Mw PEO as matrix materials, to avoid the lag time of drug release, and to overcome incomplete release in later stages. The influences of types and amounts of different Mw PEOs used, drug loading, pH of release medium and agitation rate on drug release were evaluated. The study of uptake and erosion of matrix was conducted and mechanism of improving drug release was discussed. In vivo pharmacokinetics of the CMT and reference preparation self-made controlled-release osmotic pump tablets (COPT) were performed in beagle dogs. The optimized formulation containing 43% PEO WSR 303 and 32% PEO N750 showed a zero order release from 1h to 12h. In vivo results demonstrated that the CMT had similar AUC0-48h and Cmax with the COPT but smaller Tmax than the COPT and provided a more stable therapeutic concentration compared to the COPT. In conclusion, hydrophilic matrix tablet combining only different Mw PEOs as matrix materials had very good potential to be developed into a controlled-release drug delivery system for highly water-soluble drug. Besides, its manufacturing processes were succinct which would be preferable for modern medicine industry.

  11. Workload Control with Continuous Release

    NARCIS (Netherlands)

    Phan, B. S. Nguyen; Land, M. J.; Gaalman, G. J. C.

    2009-01-01

    Workload Control (WLC) is a production planning and control concept which is suitable for the needs of make-to-order job shops. Release decisions based on the workload norms form the core of the concept. This paper develops continuous time WLC release variants and investigates their due date

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

    African Journals Online (AJOL)

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

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

    Science.gov (United States)

    Bohrey, Sarvesh; Chourasiya, Vibha; Pandey, Archna

    2016-03-01

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

  14. Continuous production of controlled release dosage forms based on hot-melt extruded gum arabic: Formulation development, in vitro characterization and evaluation of potential application fields.

    Science.gov (United States)

    Kipping, Thomas; Rein, Hubert

    2016-01-30

    Controlled release matrices based on gum arabic are prepared by applying a continuous hot-melt extrusion technology: the pre-mixture consisting of gum arabic and the incorporated API is plasticized by a co-rotating twin-screw extruder, an intermediate strand is formed by a round nozzle. Single dosed matrices are prepared by cutting the semi elastic strand with a rotary fly cutter. Paracetamol and phenazone are used as model drug substances. High drug loadings up to 70% can be realized. Matrices are characterized concerning their crystalline structure, in vitro dissolution, disintegration time and various physical parameters including glass transition temperature (Tg). Release characteristic behavior is mainly influenced by erosion of the matrices. At higher drug loadings also diffusion based transport gain importance. The solubility of the API shows an influence on the erosion rate of the matrix and should therefore be considered during formulation development. Tg is mainly influenced by the solubility of the API in the surrounding matrix. High soluble phenazone shows a decrease, whereas paracetamol addition has nearly no influence on the Tg of the polymeric system. Activation energy (EA) of the glass transition is determined via dynamic mechanical analysis. The addition of APIs leads to a reduction of EA indicating an increased molecular movement at Tg region compared to placebo extrudates. X-ray diffraction is used to determine the crystalline state of the extruded matrices and interaction between matrix and incorporated APIs. The production of thin layer matrices is an interesting option to provide a fast drug delivery to the oral cavity. High mechanical strength combined with fast disintegration times can be a great advantage for the development of oro-dispersible tablets. A great benefit of the evaluated processing technology is the simple adaption of the final dose by varying either the cutting length or the diameter of the nozzle resulting in a cost

  15. A controlled release of antibiotics from calcium phosphate-coated poly(lactic-co-glycolic acid) particles and their in vitro efficacy against Staphylococcus aureus biofilm.

    Science.gov (United States)

    Bastari, Kelsen; Arshath, Mohamed; Ng, Zhi Hui Melissa; Chia, Jia Hua; Yow, Zhi Xian Daniel; Sana, Barindra; Tan, Meng Fong Cherine; Lim, Sierin; Loo, Say Chye Joachim

    2014-03-01

    Ceramic-polymer hybrid particles, intended for osteomyelitis treatment, were fabricated by preparing poly(lactic-co-glycolic acid) particles through an emulsion solvent evaporation technique, followed by calcium phosphate (CaP) coating via a surface adsorption-nucleation method. The presence of CaP coating on the surface of the particles was confirmed by scanning electron microscopy, energy-dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy. Subsequently, two antibiotics for treating bone infection, nafcillin (hydrophilic) and levofloxacin (amphiphilic), were loaded into these hybrid particles and their in vitro drug release studies were investigated. The CaP coating was shown to reduce burst release, while providing sustained release of the antibiotics for up to 4 weeks. In vitro bacterial study against Staphylococcus aureus demonstrated the capability of these antibiotic-loaded hybrid particles to inhibit biofilm formation as well as deteriorate established biofilm, making this hybrid system a potential candidate for further investigation for osteomyelitis treatment.

  16. Controlled release from recombinant polymers.

    Science.gov (United States)

    Price, Robert; Poursaid, Azadeh; Ghandehari, Hamidreza

    2014-09-28

    Recombinant polymers provide a high degree of molecular definition for correlating structure with function in controlled release. The wide array of amino acids available as building blocks for these materials lend many advantages including biorecognition, biodegradability, potential biocompatibility, and control over mechanical properties among other attributes. Genetic engineering and DNA manipulation techniques enable the optimization of structure for precise control over spatial and temporal release. Unlike the majority of chemical synthetic strategies used, recombinant DNA technology has allowed for the production of monodisperse polymers with specifically defined sequences. Several classes of recombinant polymers have been used for controlled drug delivery. These include, but are not limited to, elastin-like, silk-like, and silk-elastinlike proteins, as well as emerging cationic polymers for gene delivery. In this article, progress and prospects of recombinant polymers used in controlled release will be reviewed. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Controlled Release from Recombinant Polymers

    Science.gov (United States)

    Price, Robert; Poursaid, Azadeh; Ghandehari, Hamidreza

    2014-01-01

    Recombinant polymers provide a high degree of molecular definition for correlating structure with function in controlled release. The wide array of amino acids available as building blocks for these materials lend many advantages including biorecognition, biodegradability, potential biocompatibility, and control over mechanical properties among other attributes. Genetic engineering and DNA manipulation techniques enable the optimization of structure for precise control over spatial and temporal release. Unlike the majority of chemical synthetic strategies used, recombinant DNA technology has allowed for the production of monodisperse polymers with specifically defined sequences. Several classes of recombinant polymers have been used for controlled drug delivery. These include, but are not limited to, elastin-like, silk-like, and silk-elastinlike proteins, as well as emerging cationic polymers for gene delivery. In this article, progress and prospects of recombinant polymers used in controlled release will be reviewed. PMID:24956486

  18. [Preparation of Shuxiong pulsatile controlled-release dropping pill].

    Science.gov (United States)

    Chen, Hui; Chen, Yan-Zhong; Xie, Qing-Chun; Lin, Shi-Yuan; Lin, Jia-Cheng; Jianc, Wei-Ning

    2013-07-01

    To prepare Shuxiong pulsatile controlled-release dropping pill and study the influencing factors in vitro. Dropping pills with suitable size (10 - 15 mg) were coated with swelling layer containing croscarmellose sodium and controlled-release layer containing ethylcellulos aqueous dispersion respectively to prepare Shuxiong pulsatile controlled-release dropping pill. The effects of the materials of swelling layer, the weight of swelling layer and controlled-release layer on the release of drugs were investigated to optimize the process technology and validate formula. The release behavior was influenced strikingly by the types and weight of coating layer. The optimal formula was as follows: Shuxiong pulsatile controlled-release dropping pills were prepared using croscarmellose sodium as inner layer with 15% (weight) coating level and ethylcellulose aqueous dispersion (Surelease) as outer controlled-release layer with 7% (weight) coating level. The lag time of prepared pulsatile controlled-release dropping pills was about 4 h and accumulative release rate reached 80% within 4 h. The drug release of Shuxiong pulsatile controlled-release dropping pill is shown in pulsatile way in vitro.

  19. In Vitro Investigation of Self-Assembled Nanoparticles Based on Hyaluronic Acid-Deoxycholic Acid Conjugates for Controlled Release Doxorubicin: Effect of Degree of Substitution of Deoxycholic Acid

    Directory of Open Access Journals (Sweden)

    Wen-Hao Wei

    2015-03-01

    Full Text Available Self-assembled nanoparticles based on a hyaluronic acid-deoxycholic acid (HD chemical conjugate with different degree of substitution (DS of deoxycholic acid (DOCA were prepared. The degree of substitution (DS was determined by titration method. The nanoparticles were loaded with doxorubicin (DOX as the model drug. The human cervical cancer (HeLa cell line was utilized for in vitro studies and cell cytotoxicity of DOX incorporated in the HD nanoparticles was accessed by the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay. In addition, cellular uptake of fluorescently labeled nanoparticles was also investigated. An increase in the degree of deoxycholic acid substitution reduced the size of the nanoparticles and also enhanced their drug encapsulation efficiency (EE, which increased with the increase of DS. A higher degree of deoxycholic acid substitution also lead to a lower release rate and an initial burst release of doxorubicin from the nanoparticles. In summary, the degree of substitution allows the modulation of the particle size, drug encapsulation efficiency, drug release rate, and cell uptake efficiency of the nanoparticles. The herein developed hyaluronic acid-deoxycholic acid conjugates are a good candidate for drug delivery and could potentiate therapeutic formulations for doxorubicin–mediated cancer therapy.

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

    Science.gov (United States)

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

    2017-04-01

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

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

    African Journals Online (AJOL)

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

  2. Controlled release of moxifloxacin from intraocular lenses modified by Ar plasma-assisted grafting with AMPS or SBMA: An in vitro study.

    Science.gov (United States)

    Pimenta, A F R; Vieira, A P; Colaço, R; Saramago, B; Gil, M H; Coimbra, P; Alves, P; Bozukova, D; Correia, T R; Correia, I J; Guiomar, A J; Serro, A P

    2017-08-01

    Intraocular lenses (IOLs) present an alternative for extended, local drug delivery in the prevention of post-operative acute endophthalmitis. In the present work, we modified the surface of a hydrophilic acrylic material, used for manufacturing of IOLs, through plasma-assisted grafting copolymerization of 2-acrylamido-2-methylpropane sulfonic acid (AMPS) or [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SBMA), with the aim of achieving a controlled and effective drug release. The material was loaded with moxifloxacin (MFX), a commonly used antibiotic for endophthalmitis prevention. The characterization of the modified material showed that relevant properties, like swelling capacity, wettability, refractive index and transmittance, were not affected by the surface modification. Concerning the drug release profiles, the most promising result was obtained when AMPS grafting was done in the presence of MFX. This modification led to a higher amount of drug being released for a longer period of time, which is a requirement for the prevention of endophthalmitis. The material was found to be non-cytotoxic for rabbit corneal endothelial cells. In a second step, prototype IOLs were modified with AMPS and loaded with MFX as previously and, after sterilization and storage (30days), they were tested under dynamic conditions, in a microfluidic cell with volume and renovation rate similar to the eye aqueous humour. MFX solutions collected in this assay were tested against Staphylococcus aureus and Staphylococcus epidermidis and the released antibiotic proved to be effective against both bacteria until the 12th day of release. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Controlled-release effervescent floating matrix tablets of ciprofloxacin hydrochloride: development, optimization and in vitro-in vivo evaluation in healthy human volunteers.

    Science.gov (United States)

    Tadros, Mina Ibrahim

    2010-02-01

    Ciprofloxacin hydrochloride has a short elimination half-life, a narrow absorption window and is mainly absorbed in proximal areas of GIT. The purpose of this study was to develop a gastroretentive controlled-release drug delivery system with swelling, floating, and adhesive properties. Ten tablet formulations were designed using hydroxypropylmethylcellulose (HPMC K15M) and/or sodium alginate (Na alginate) as release-retarding polymer(s) and sodium bicarbonate (NaHCO(3)) or calcium carbonate (CaCO(3)) as a gas former. Swelling ability, floating behaviour, adhesion period and drug release studies were conducted in 0.1 N HCl (pH 1.2) at 37+/-0.5 degrees C. The tablets showed acceptable physicochemical properties. Drug release profiles of all formulae followed non-Fickian diffusion. Statistical analyses of data revealed that tablets containing HPMC K15M (21.42%, w/w), Na alginate (7.14%, w/w) and NaHCO(3) (20%, w/w) (formula F7) or CaCO(3) (20%, w/w) (formula F10) were promising systems exhibiting excellent floating properties, extended adhesion periods and sustained drug release characteristics. Both formulae were stored at 40 degrees C/75% RH for 3months according to ICH guidelines. Formula F10 showed better physical stability. Abdominal X-ray imaging of formula F10, loaded with barium sulfate, in six healthy volunteers revealed a mean gastric retention period of 5.50+/-0.77h. Copyright (c) 2009 Elsevier B.V. All rights reserved.

  4. Studies on renin release in vitro

    DEFF Research Database (Denmark)

    Skøtt, O

    1989-01-01

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

  5. Modelling and simulations of controlled release fertilizer

    Science.gov (United States)

    Irfan, Sayed Ameenuddin; Razali, Radzuan; Shaari, Ku Zilati Ku; Mansor, Nurlidia

    2016-11-01

    The recent advancement in controlled release fertilizer has provided an alternative solution to the conventional urea, controlled release fertilizer has a good plant nutrient uptake they are environment friendly. To have an optimum plant intake of nutrients from controlled release fertilizer it is very essential to understand the release characteristics. A mathematical model is developed to predict the release characteristics from polymer coated granule. Numerical simulations are performed by varying the parameters radius of granule, soil water content and soil porosity to study their effect on fertilizer release. Understanding these parameters helps in the better design and improve the efficiency of controlled release fertilizer.

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

    Science.gov (United States)

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

    2017-09-01

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

  7. vitro Release of Saraca indica Caesalpiniaceae Bark Powder Tablets

    African Journals Online (AJOL)

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

  8. A systemic evaluation of drug in acrylic pressure sensitive adhesive patch in vitro and in vivo: The roles of intermolecular interaction and adhesive mobility variation in drug controlled release.

    Science.gov (United States)

    Liu, Chao; Quan, Peng; Li, Shanshan; Zhao, Yongshan; Fang, Liang

    2017-04-28

    Though acrylic pressure sensitive adhesives (PSAs) are widely used in transdermal drug delivery system, molecular details of drug-PSA interactions, PSA molecular mobility variations and their influences on drug skin permeation are unclear. In this study, three classes of acrylic PSAs containing hydroxyl (AAOH), carboxyl (AACOOH) and non-functional group (AAnone) were synthesized. Their abilities of controlling drug release were evaluated using propranolol (PRO) and zaltoprofen (ZAL) in vitro and in vivo. Interaction details were identified by FT-IR, solid-state NMR and molecular modeling. Thermodynamic activity of drug and strength of drug-PSA interaction were characterized using miscibility study. PSA mobility was characterized using thermal analysis and rheology study. Thus, ionic interaction reduced the thermodynamic activity of PRO and mobility of AACOOH, which made PRO-AACOOH obtain a significant lower bioavailability (11.8±0.7%) than these of PRO-AAnone (40.7±2.5%) and PRO-AAOH (42.3±2.9%). Though thermodynamic activity of ZAL in AACOOH was lower than that in AAOH due to the hydrogen bonding, bioavailability of ZAL-AAOH (19.0±4.1%) exhibited no significant difference with ZAL-AACOOH (15.4±2.8%), mainly because AAOH mobility was decreased by ZAL. In conclusion, the strength, types and involved functional groups of drug-PSA interactions were identified. On this basis, it was found that different control patterns of drug release were not only caused by the thermodynamic or kinetic hindrance effects of drug-PSA interactions, but also influenced by the interactions introduced PSA mobility variations, which was an innovative mechanism of controlled release in transdermal patch. The conclusions extended our understanding about the mechanism of controlled drug release of drug-in-adhesive patch. In addition, they contributed to the design of TDDS and custom acrylic PSAs. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. In vitro and in vivo metal ion release.

    Science.gov (United States)

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

    1988-04-01

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

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

    Science.gov (United States)

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

    2010-04-01

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

  11. Controlled release of an extract of Calendula officinalis flowers from a system based on the incorporation of gelatin-collagen microparticles into collagen I scaffolds: design and in vitro performance.

    Science.gov (United States)

    Jiménez, Ronald A; Millán, Diana; Suesca, Edward; Sosnik, Alejandro; Fontanilla, Marta R

    2015-06-01

    Aiming to develop biological skin dresses with improved performance in the treatment of skin wounds, acellular collagen I scaffolds were modified with polymeric microparticles and the subsequent loading of a hydroglycolic extract of Calendula officinalis flowers. Microparticles made of gelatin-collagen were produced by a water-in-oil emulsion/cross-linking method. Thereafter, these microparticles were mixed with collagen suspensions at three increasing concentrations and the resulting mixtures lyophilized to make microparticle-loaded porous collagen scaffolds. Resistance to enzymatic degradation, ability to associate with the C. officinalis extract, and the extract release profile of the three gelatin-collagen microparticle-scaffold prototypes were assessed in vitro and compared to collagen scaffolds without microparticles used as control. Data indicated that the incorporation of gelatin-collagen microparticles increased the resistance of the scaffolds to in vitro enzymatic degradation, as well as their association with the C. officinalis flower extract. In addition, a sharp decrease in cytotoxicity, as well as more prolonged release of the extract, was attained. Overall results support the potential of these systems to develop innovative dermal substitutes with improved features. Furthermore, the gelatin-collagen mixture represents a low-cost and scalable alternative with high clinical transferability, especially appealing in developing countries.

  12. Design and in vitro evaluation of self-assembled indometacin prodrug nanoparticles for sustained/controlled release and reduced normal cell toxicity

    Science.gov (United States)

    Lin, Jinyan; Pan, Zhou; Song, Liang; Zhang, Yanmei; Li, Yang; Hou, Zhenqing; Lin, Changjian

    2017-12-01

    Despite the great efficacy of indomethacin (IND) as an anti-inflammatory agent, its clinical translation has been obstructed by the water insolubility, severe side effects, and exceedingly low bioavailability. Indomethacin prodrug-based nanoparticles (NPs) combining the strengths of both nanotechnology and prodrugs that might overcome this crucial problem are presented. Here, using the carbodiimide-mediated couple reaction, IND was conjugated to clinically approved poly(ethylene glycol) (PEG) polymer via peptide linkage that was cleavaged in the presence of cathepsin B, which was significantly induced after inflammatory. The synthesized IND-PEG-IND conjugate was characterized by UV-vis, FTIR, 1H NMR, XRD, and MALDI-TOF-MS analyses. For its intrinsic amphiphilic property, the IND prodrug self-assembled into NPs in aqueous solution and served two roles-as an anti-inflammatory prodrug and a drug carrier. The constructed IND-PEG-IND NPs had naoscaled particle size of approximately 80 nm, negative surface, spherical shape, good water-dispersity, and high and fixed drug-loading content of 20.1 wt%. In addition, IND-PEG-IND NPs demonstrated sustained and cathepsin B-controlled drug release behavior. More importantly, IND-PEG-IND NPs significantly reduced the acute totoxicity agaist normal osteoblast cells and displayed the more potent anti-inflammatory effect against macrophage cells compared to the free IND. Taken together, the nanoprodrug might exhibit increased potency for nanomedicine-prospective therapeutic use in clinical treatement of implant inflammatory diseases.

  13. Honey/PVA hybrid wound dressings with controlled release of antibiotics: Structural, physico-mechanical and in-vitro biomedical studies.

    Science.gov (United States)

    Tavakoli, Javad; Tang, Youhong

    2017-08-01

    Hydrogel/honey hybrids manifest an attractive design with an exclusive therapeutic property that promotes wound healing process. The greater the concentration of honey within the formulation, the better the biomedical properties that will be achieved. However, an increase in the percentage of honey can negatively affect the physico-chemical and mechanical properties of hybrid hydrogels. The need exists, therefore, to prepare wound dressings that contain high honey density with optimal biomedical, mechanical and physicochemical properties. In this study, a simple method for the preparation of a highly concentrated honey/PVA hybrid hydrogel with borax as the crosslinking agent is reported. Comprehensive evaluations of the morphology, swelling kinetics, permeability, bio-adhesion, mechanical characteristics, cytotoxicity, antibacterial property, cell proliferation ability and their controlling release properties were conducted as a function of crosslinking density. All the borax-induced hydrogels showed acceptable biocompatibility, and the incorporation of 1% borax in the hydrogel formulation produced optimal behaviours for wound addressing applications. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2017-03-30

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

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

    Science.gov (United States)

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

    2012-01-01

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

  16. Stimuli responsive nanomaterials for controlled release applications

    KAUST Repository

    Li, Song

    2012-01-01

    The controlled release of therapeutics has been one of the major challenges for scientists and engineers during the past three decades. Coupled with excellent biocompatibility profiles, various nanomaterials have showed great promise for biomedical applications. Stimuli-responsive nanomaterials guarantee the controlled release of cargo to a given location, at a specific time, and with an accurate amount. In this review, we have combined the major stimuli that are currently used to achieve the ultimate goal of controlled and targeted release by "smart" nanomaterials. The most heavily explored strategies include (1) pH, (2) enzymes, (3) redox, (4) magnetic, and (5) light-triggered release.

  17. Controlled release tablet formulation containing natural Δ(9)-tetrahydrocannabinol.

    Science.gov (United States)

    Punyamurthula, Nagendra S; Hingorani, Tushar; Adelli, Goutham; Gul, Waseem; ElSohly, Mahmoud A; Repka, Michael A; Majumdar, Soumyajit

    2016-01-01

    Cannabinoids are increasingly being used in the treatment of chemotherapy-induced nausea and vomiting (CINV) because of their action on the cannabinoid receptors, CB1 and CB2. The currently marketed capsule formulations (sesame oil based and crystalline powder) are required to be administered frequently to maintain therapeutic levels, which leads to non-compliance. In the present study, oral controlled release tablet formulations of Δ(9)-tetrahydrocannabinol (THC) were prepared using the lipids Precirol® and Compritol®. Release profiles using THC-lipid matrices and/or with the lipids in the external phase (blend) were evaluated. The effect of directly compressible diluents lactose mixture (Ludipress®), dicalcium phosphate anhydrous (Emcompress®) and microcrystalline cellulose (Avicel® 102) on tablet characteristics and in vitro drug release was also investigated. Further, in vitro THC release in the presence of a lipase inhibitor, Pluronic® F68, was also studied. A 24 h zero-order THC release profile was obtained with a combination of Precirol® and Compritol® in the compression blend. Addition of Pluronic® F68 did not alter THC release in vitro. These optimized tablets were chemically and physically stable for 3 months, the last time point tested, at 25 °C/60% RH. The overall results demonstrate the feasibility of preparing oral THC tablets for once a day administration which can improve CINV management.

  18. Lignin based controlled release coatings

    NARCIS (Netherlands)

    Mulder, W.J.; Gosselink, R.J.A.; Vingerhoeds, M.H.; Harmsen, P.F.H.; Eastham, D.

    2011-01-01

    Urea is a commonly used fertilizer. Due to its high water-solubility, misuse easily leads to excess nitrogen levels in the soil. The aim of this research was to develop an economically feasible and biodegradable slow-release coating for urea. For this purpose, lignin was selected as coating

  19. Controlled Release from Zein Matrices

    NARCIS (Netherlands)

    Bouman, Jacob; Belton, Peter; Venema, Paul; Linden, Van Der Erik; Vries, De Renko; Qi, Sheng

    2016-01-01

    Purpose: In earlier studies, the corn protein zein is found to be suitable as a sustained release agent, yet the range of drugs for which zein has been studied remains small. Here, zein is used as a sole excipient for drugs differing in hydrophobicity and isoelectric point: indomethacin,

  20. Coherently Controlled Release of Drugs in Ophthalmology

    Science.gov (United States)

    Buckup, Tiago; Möhring, Jens; Settels, Volker; Träger, Jens; Kim, Hee-Cheo; Hampp, Norbert; Motzkus, Marcus

    The photocleavage of a coumarin derivative dimer is a promising mechanism for laser controlled drug release in medical applications. We investigate the efficiency of the twophoton induced cleavage in open- and closed-loop control schemes.

  1. Photoresponsive lipid-polymer hybrid nanoparticles for controlled doxorubicin release

    Science.gov (United States)

    Yao, Cuiping; Wu, Ming; Zhang, Cecheng; Lin, Xinyi; Wei, Zuwu; Zheng, Youshi; Zhang, Da; Zhang, Zhenxi; Liu, Xiaolong

    2017-06-01

    Currently, photoresponsive nanomaterials are particularly attractive due to their spatial and temporal controlled drug release abilities. In this work, we report a photoresponsive lipid-polymer hybrid nanoparticle for remote controlled delivery of anticancer drugs. This hybrid nanoparticle comprises three distinct functional components: (i) a poly(D,L-lactide-co-glycolide) (PLGA) core to encapsulate doxorubicin; (ii) a soybean lecithin monolayer at the interface of the core and shell to act as a molecular fence to prevent drug leakage; (iii) a photoresponsive polymeric shell with anti-biofouling properties to enhance nanoparticle stability, which could be detached from the nanoparticle to trigger the drug release via a decrease in the nanoparticle’s stability under light irradiation. In vitro results revealed that this core-shell nanoparticle had excellent light-controlled drug release behavior (76% release with light irradiation versus 10% release without light irradiation). The confocal microscopy and flow cytometry results also further demonstrated the light-controlled drug release behavior inside the cancer cells. Furthermore, a CCK8 assay demonstrated that light irradiation could significantly improve the efficiency of killing cancer cells. Meanwhile, whole-animal fluorescence imaging of a tumor-bearing mouse also confirmed that light irradiation could trigger drug release in vivo. Taken together, our data suggested that a hybrid nanoparticle could be a novel light controlled drug delivery system for cancer therapy.

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

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Avadi

    2017-06-01

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

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

    Science.gov (United States)

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

    2015-02-01

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

  4. Release Control of Dye from Agar Ball

    OpenAIRE

    板屋, 智之; 山村, 俊貴; 唐澤, 有太朗

    2013-01-01

    Agar is a special product of Nagano prefecture. To utilize agar gel as adsorbing or releasing material of dyes or drugs, spherical agar gel “agar ball” was prepared by dropping aqueous agar solution into salad oil. And releasing behavior of a dye (rhodamine B) from agar ball was studied. The dye is released easily from agar ball, but the release can be controlled by hybiridazation of agar and galatin. In addition, it was found that agar ball could extract the dye from oil phase containing the...

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

    Science.gov (United States)

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

    2016-10-01

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

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

    Science.gov (United States)

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

    2013-07-15

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

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

    Directory of Open Access Journals (Sweden)

    Roya Mashayekhi

    2013-07-01

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

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

    Science.gov (United States)

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

    2012-02-14

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

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

    Science.gov (United States)

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

    1999-07-01

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

  10. Mucoadhesive tablets for controlled release of acyclovir.

    Science.gov (United States)

    Ruiz-Caro, Roberto; Gago-Guillan, Manuel; Otero-Espinar, Francisco Javier; Veiga, María Dolores

    2012-01-01

    Mucoadhesive chitosan (CS) and/or hydroxypropyl-methylcellulose (HPMC) tablets for gastric drug delivery of acyclovir (ACV) have been developed in order to improve the ACV oral bioavailability. Swelling, bioadhesive and dissolution studies were carried out in two acidic media (pH 1.5 and 4) in order to determine the tablets behaviour in both fed and fasted states. All the designed tablets showed good mucoadhesive properties on gastric mucosa due to the presence of CS and/or HPMC. In vitro dissolution of ACV from tablets was influenced by the swelling behaviour of each polymer. All data release of the studied tablets fitted to Hopfenberg model, which describes drug release from tablets displaying heterogeneous erosion. HPMC and CS/HPMC tablets revealed a sustained release for 24 h, but a complete dissolution of the tablets was not produced at this time. On the contrary, tablets which contained only CS as polymer were able to release the total amount of ACV for 4 h, due to the CS imbibition and erosion processes in pH 1.5 medium. These results allowed us to conclude that CS is the excipient to be chosen to obtain gastroretentive formulations, due to its demonstrated gastric compatibility.

  11. Local control of striatal dopamine release

    Directory of Open Access Journals (Sweden)

    Roger eCachope

    2014-05-01

    Full Text Available The mesolimbic and nigrostriatal dopamine (DA systems play a key role in the physiology of reward seeking, motivation and motor control. Importantly, they are also involved in the pathophysiology of Parkinson’s and Huntington’s disease, schizophrenia and addiction. Control of DA release in the striatum is tightly linked to firing of DA neurons in the ventral tegmental area (VTA and the substantia nigra (SN. However, local influences in the striatum affect release by exerting their action directly on axon terminals. For example, endogenous glutamatergic and cholinergic activity is sufficient to trigger striatal DA release independently of cell body firing. Recent developments involving genetic manipulation, pharmacological selectivity or selective stimulation have allowed for better characterization of these phenomena. Such termino-terminal forms of control of DA release transform considerably our understanding of the mesolimbic and nigrostriatal systems, and have strong implications as potential mechanisms to modify impaired control of DA release in the diseased brain. Here, we review these and related mechanisms and their implications in the physiology of ascending DA systems.

  12. Sol-gel encapsulation for controlled drug release and biosensing

    Science.gov (United States)

    Fang, Jonathan

    The main focus of this dissertation is to investigate the use of sol-gel encapsulation of biomolecules for controlled drug release and biosensing. Controlled drug release has advantages over conventional therapies in that it maintains a constant, therapeutic drug level in the body for prolonged periods of time. The anti-hypertensive drug Captopril was encapsulated in sol-gel materials of various forms, such as silica xerogels and nanoparticles. The primary objective was to show that sol-gel silica materials are promising drug carriers for controlled release by releasing Captopril at a release rate that is within a therapeutic range. We were able to demonstrate desired release for over a week from Captopril-doped silica xerogels and overall release from Captopril-doped silica nanoparticles. As an aside, the antibiotic Vancomycin was also encapsulated in these porous silica nanoparticles and desired release was obtained for several days in-vitro. The second part of the dissertation focuses on immobilizing antibodies and proteins in sol-gel to detect various analytes, such as hormones and amino acids. Sol-gel competitive immunoassays on antibody-doped silica xerogels were used for hormone detection. Calibration for insulin and C-peptide in standard solutions was obtained in the nM range. In addition, NASA-Ames is also interested in developing a reagentless biosensor using bacterial periplasmic binding proteins (bPBPs) to detect specific biomarkers, such as amino acids and phosphate. These bPBPs were doubly labeled with two different fluorophores and encapsulated in silica xerogels. Ligand-binding experiments were performed on the bPBPs in solution and in sol-gel. Ligand-binding was monitored by fluorescence resonance energy transfer (FRET) between the two fluorophores on the bPBP. Titration data show that one bPBP has retained its ligand-binding properties in sol-gel.

  13. Electrosprayed nanoparticle delivery system for controlled release

    Energy Technology Data Exchange (ETDEWEB)

    Eltayeb, Megdi, E-mail: megdi.eltayeb@sustech.edu [Department of Biomedical Engineering, Sudan University of Science and Technology, PO Box 407, Khartoum (Sudan); Stride, Eleanor, E-mail: eleanor.stride@eng.ox.ac.uk [Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Old Road Campus Research Building, Headington OX3 7DQ (United Kingdom); Edirisinghe, Mohan, E-mail: m.edirisinghe@ucl.ac.uk [Department of Mechanical Engineering, University College London, Torrington Place, London WC1E 7JE (United Kingdom); Harker, Anthony, E-mail: a.harker@ucl.ac.uk [London Centre for Nanotechnology, Gordon Street, London WC1H 0AH (United Kingdom); Department of Physics & Astronomy, University College London, Gower Street, London WC1E 6BT (United Kingdom)

    2016-09-01

    This study utilises an electrohydrodynamic technique to prepare core-shell lipid nanoparticles with a tunable size and high active ingredient loading capacity, encapsulation efficiency and controlled release. Using stearic acid and ethylvanillin as model shell and active ingredients respectively, we identify the processing conditions and ratios of lipid:ethylvanillin required to form nanoparticles. Nanoparticles with a mean size ranging from 60 to 70 nm at the rate of 1.37 × 10{sup 9} nanoparticles per minute were prepared with different lipid:ethylvanillin ratios. The polydispersity index was ≈ 21% and the encapsulation efficiency ≈ 70%. It was found that the rate of ethylvanillin release was a function of the nanoparticle size, and lipid:ethylvanillin ratio. The internal structure of the lipid nanoparticles was studied by transmission electron microscopy which confirmed that the ethylvanillin was encapsulated within a stearic acid shell. Fourier transform infrared spectroscopy analysis indicated that the ethylvanillin had not been affected. Extensive analysis of the release of ethylvanillin was performed using several existing models and a new diffusive release model incorporating a tanh function. The results were consistent with a core-shell structure. - Highlights: • Electrohydrodynamic spraying is used to produce lipid-coated nanoparticles. • A new model is proposed for the release rates of active components from nanoparticles. • The technique has potential applications in food science and medicine. • Electrohydrodynamic processing controlled release lipid nanoparticles.

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

    Science.gov (United States)

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

    1997-01-01

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

  15. Controlled release matrix tablets of glipizide: Influence of different grades of ethocel and Co-excipient on drug release.

    Science.gov (United States)

    Mehsud, Saif Ullah; Khan, Gul Majid; Hussain, Abid; Akram, Muhammad; Akhlaq, Muhammad; Khan, Kamran Ahmad; Shakoor, Abdul

    2016-05-01

    The aim of the current study was to formulate and evaluate glipizide controlled release matrix tablets by means of different grades of polymer Ethoceland different co-excipients in order to evaluate their effect on drug release profiles during in vitro dissolution studies. Type II diabetes mellitus is usually treated with Glipizide. Glipizide belongs to sulfonylurea group. Gastric disturbance and severe hypoglycemia has been observed after taking glipizide orally. To overcome these problems, controlled release matrices were developed using different grades of ethyl cellulose polymer with a drug-polymer ratio of 1:3by the direct compression method. The effect on drug release of partial replacement of lactose by different co-excipients, HPMC K100M, starch and CMC, were also studied. Diameter, thickness, hardness, friability, weight variations, drug contents of formulations were tested, these properties were within prescribed limits. Co-excipients and polymer containing formulations were compared to the without co-excipients and polymer containing formulations with respect to their release profile. After a 24-hour release study, ethyl cellulose polymer containing formulation exhibited prolonged release for 5-16 hours; however the polymer Ethocel (R) standard FP 7 Premium without co-excipient containing formulation exhibited controlled release for 24 hours. Incompatibility was investigated between drugs, co-excipient DSC and polymer study was performed and any type of interaction was not found. Different kinetic models were used to study the release mechanism. An enhanced release rate was observed in case of excipients containing formulations.

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

    Science.gov (United States)

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

    2006-02-01

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

  17. Preventing and controlling accidental gas releases

    Science.gov (United States)

    Moskowitz, P. D.; Fthenakis, V. M.; Kalb, P. D.

    1988-07-01

    Toxic, flammable, and explosive gases may be used in photovoltaic cell research laboratories and in commercial manufacturing facilities. Accidental release of these materials can present hazards to life and property. Accidents can arise from a variety of mechanical and human related failures. These can occur from the time materials are received at the loading dock of the facility to the time treated gases are discharged to the atmosphere through a stack. Each type of initiating event may require a different control approach. These may range from the training and certification of plant workers charged with the handling of gas cylinder hookups to installation of emergency pollution control systems. Since engineering options for controlling released materials are limited, emphasis should be placed on administrative and engineering approaches for preventing such accidents. These are likely to be the most effective approaches for protecting life and property.

  18. Externally controlled triggered-release of drug from PLGA micro and nanoparticles.

    Science.gov (United States)

    Hua, Xin; Tan, Shengnan; Bandara, H M H N; Fu, Yujie; Liu, Siguo; Smyth, Hugh D C

    2014-01-01

    Biofilm infections are extremely hard to eradicate and controlled, triggered and controlled drug release properties may prolong drug release time. In this study, the ability to externally control drug release from micro and nanoparticles was investigated. We prepared micro/nanoparticles containing ciprofloxacin (CIP) and magnetic nanoparticles encapsulated in poly (lactic-co-glycolic acid) PLGA. Both micro/nanoparticles were observed to have narrow size distributions. We investigated and compared their passive and externally triggered drug release properties based on their different encapsulation structures for the nano and micro systems. In passive release studies, CIP demonstrated a fast rate of release in first 2 days which then slowed and sustained release for approximately 4 weeks. Significantly, magnetic nanoparticles containing systems all showed ability to have triggered drug release when exposed to an external oscillating magnetic field (OMF). An experiment where the OMF was turned on and off also confirmed the ability to control the drug release in a pulsatile manner. The magnetically triggered release resulted in a 2-fold drug release increase compared with normal passive release. To confirm drug integrity following release, the antibacterial activity of released drug was evaluated in Pseudomonas aeruginosa biofilms in vitro. CIP maintained its antimicrobial activity after encapsulation and triggered release.

  19. Externally controlled triggered-release of drug from PLGA micro and nanoparticles.

    Directory of Open Access Journals (Sweden)

    Xin Hua

    Full Text Available Biofilm infections are extremely hard to eradicate and controlled, triggered and controlled drug release properties may prolong drug release time. In this study, the ability to externally control drug release from micro and nanoparticles was investigated. We prepared micro/nanoparticles containing ciprofloxacin (CIP and magnetic nanoparticles encapsulated in poly (lactic-co-glycolic acid PLGA. Both micro/nanoparticles were observed to have narrow size distributions. We investigated and compared their passive and externally triggered drug release properties based on their different encapsulation structures for the nano and micro systems. In passive release studies, CIP demonstrated a fast rate of release in first 2 days which then slowed and sustained release for approximately 4 weeks. Significantly, magnetic nanoparticles containing systems all showed ability to have triggered drug release when exposed to an external oscillating magnetic field (OMF. An experiment where the OMF was turned on and off also confirmed the ability to control the drug release in a pulsatile manner. The magnetically triggered release resulted in a 2-fold drug release increase compared with normal passive release. To confirm drug integrity following release, the antibacterial activity of released drug was evaluated in Pseudomonas aeruginosa biofilms in vitro. CIP maintained its antimicrobial activity after encapsulation and triggered release.

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

    Science.gov (United States)

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

    2007-03-01

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

  1. Simultaneous control of capsaicinoids release from polymeric nanocapsules.

    Science.gov (United States)

    Contri, Renata V; Kaiser, Moacir; Poletto, Fernanda S; Pohlmann, Adriana R; Guterres, Silvia S

    2011-03-01

    The nanoencapsulation of capsaicinoids (capsaicin and dihydrocapsaicin) was proposed in this work as a strategy to control their release due to the reservoir characteristics of the nanocapsules. This reservoir property could prolong the topical analgesic effect and reduce the burning sensation and skin irritation caused by the capsaicinoids. The nanocapsules were physicochemically characterized and presented z-average diameter of 153 +/- 7 (PDI capsaicinoids content was 0.5 mg mL(-1) (64% of capsaicin and 33% of dihydrocapsaicin) and their encapsulation efficiencies were close to 100%. The formulation was stable over 90 days. The in vitro release profiles demonstrated that the release of capsaicin and dihydrocapsaicin was prolonged by means of nanoencapsulation. Moreover, comparing the half-life values, it was observed that the polymeric wall significantly affected the release rates for both capsaicinoids. According to Fick's first law, capsaicin presented higher flux (5.6 +/- 0.1 (x10(-4)) mg cm(-2) h(-1)) than that of dihydrocapsaicin (2.1 +/- 0.2 (x 10(-4)) mg cm(-2) h(-1)), which was probably related to its higher gradient concentration. Drug diffusion and polymer relaxation were responsible for the capsaicinoids release from the nanocapsules, which fitted the monoexponential mathematical model. This innovative formulation was designed considering its potential action of prolonging the analgesic effect of the capsaicionoids on the skin.

  2. Collagen Scaffolds with Controlled Insulin Release and Controlled Pore Structure for Cartilage Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Himansu Sekhar Nanda

    2014-01-01

    Full Text Available Controlled and local release of growth factors and nutrients from porous scaffolds is important for maintenance of cell survival, proliferation, and promotion of tissue regeneration. The purpose of the present research was to design a controlled release porous collagen-microbead hybrid scaffold with controlled pore structure capable of releasing insulin for application to cartilage tissue regeneration. Collagen-microbead hybrid scaffold was prepared by hybridization of insulin loaded PLGA microbeads with collagen using a freeze-drying technique. The pore structure of the hybrid scaffold was controlled by using preprepared ice particulates having a diameter range of 150–250 μm. Hybrid scaffold had a controlled pore structure with pore size equivalent to ice particulates and good interconnection. The microbeads showed an even spatial distribution throughout the pore walls. In vitro insulin release profile from the hybrid scaffold exhibited a zero order release kinetics up to a period of 4 weeks without initial burst release. Culture of bovine articular chondrocytes in the hybrid scaffold demonstrated high bioactivity of the released insulin. The hybrid scaffold facilitated cell seeding and spatial cell distribution and promoted cell proliferation.

  3. Influence of cellulose polymers type on in vitro controlled release tablets containing theophylline Desenvolvimento e avaliação de comprimidos matriciais de teofilina baseados em ésteres da celulose

    Directory of Open Access Journals (Sweden)

    Evelyn Ojoe

    2007-12-01

    Full Text Available In this study, the effect of ethylcellulose (EC and 6 types of hydroxypropylmethylcellulose (Methocel® K100M, K100MPRCR, K15MPRCR, K4MPRCR, K4M PR and E4MCR on release profile of theophylline from matrix tablets was evaluated. Formulations tablets were prepared by either wet granulation or direct compression technique. The tablets were evaluated for physical characteristics and in vitro release of drug was performed as described in USP 30 ed. (Test 3. All formulations with cellulose polymer produced tablets easily and with physicals characteristics in accordance with official limits. Drug dissolution tests showed that formulations with 15% of Methocel® K4MPR, 15% of Methocel® K4MPRCR and 30% of Ethocel® N10STD, obtained by direct compression method, complied with official specifications, in terms of release profile and diffusion was the main mechanism involved in theophylline delivery.Os efeitos das variáveis das formulações na liberação da teofilina a partir da hidroxipropilmetilcelulose (HPMC e etilcelulose (EC em comprimidos matriciais foram estudados. Formulações de comprimidos foram preparadas pelos métodos da granulação úmida ou compressão direta usando diferentes viscosidades de HPMC. Propriedades físico-químicas dos comprimidos e liberação do fármaco foram estudadas conforme dissolução descrita no Teste 3 da Farmacopéia Americana 30ed. Ensaios "in vitro" mostraram que as formulações com 15% de Methocel® K4MPR, 15% de Methocel® K4MPRCR e 30% de Ethocel® N10STD obtidas por compressão direta apresentaram bom perfil de liberação de teofilina e a difusão foi o principal mecanismo envolvido na liberação.

  4. Meltable magnetic biocomposites for controlled release

    Science.gov (United States)

    Müller, R.; Zhou, M.; Dellith, A.; Liebert, T.; Heinze, T.

    2017-06-01

    New biocompatible composites with adjustable melting point in the range of 30-140 °C, consisting of magnetite nanoparticles embedded into a matrix of meltable dextran fatty acid ester are presented which can be softened under an induced alternating magnetic field (AMF). The chosen thermoplastic magnetic composites have a melting range close to human body temperature and can be easily shaped into disk or coating film under melting. The composite disks were loaded with green fluorescent protein (GFP) as a model protein. Controlled release of the protein was realized with high frequent alternating magnetic field of 20 kA/m at 400 kHz. These results showed that under an AMF the release of GFP from magnetic composite was accelerated compared to the control sample without exposure to AMF. Furthermore a texturing of particles in the polymer matrix by a static magnetic field was investigated.

  5. A Proof-of-Concept Clinical Trial of A Single Luteal Use of Long-Acting Gonadotropin-Releasing Hormone Antagonist Degarelix in Controlled Ovarian Stimulation for In Vitro Fertilization: Long Antagonist Protocol

    Directory of Open Access Journals (Sweden)

    Evangelos G. Papanikolaou

    2018-03-01

    Full Text Available IntroductionA drawback of gonadotropin-releasing hormone (GnRH antagonist protocols in in vitro fertilization (IVF is that they have limited flexibility in cycle programming. This proof of concept study explored the efficacy of a single-dose, long-acting GnRH antagonist IVF protocol. Trial registration number is NCT03240159, retrospectively registered on March 08, 2017.Materials and methodsThe efficacy of a single-dose long-acting antagonist, degarelix, was explored initially in healthy donors and subsequently in infertile patients. In the first part, five healthy oocyte donors underwent ovarian stimulation with this new protocol: in the late luteal phase, at day 24, a bolus injection of degarelix was administered subcutaneously to control the LH surge in the follicular phase. Ovarian stimulation with gonadotropins was initiated subsequently from day 7 to day 10. End points were first to inhibit the LH surge later in the follicular phase and, second, to retrieve mature oocytes for IVF. In the second part, five infertile women received the same bolus injection of degarelix administered during the luteal phase at day 24. Different gonadotropin starting days (day 2 through day 8 were tested in order to observe possible differences in ovarian stimulation. In these infertile patients, fresh embryo transfers were performed to assess the pregnancy efficacy of this protocol on pregnancy outcomes and to address any possible negative effects on endometrium receptivity.ResultsIn the first part of the study, all donors were effectively downregulated with a single luteal dose of 0.5 ml of degarelix for up to 22 days until the final oocyte maturation triggering day. Mature oocytes were retrieved after 36 h from all patients and all produced 2–7 blastocysts. In the second part, all five infertile patients achieved sufficient LH downregulation and completed ovarian stimulation without any LH surge. All patients (except one with freeze all strategy had

  6. Controlled Release System for Localized and Sustained Drug Delivery Applications

    Science.gov (United States)

    Rodriguez, Lidia Betsabe

    Current controlled release formulations has many drawbacks such as excess of initial burst release, low drug efficiency, non-degradability of the system and low reproducibility. The present project aims to offer an alternative by developing a technique to prepare uniform, biodegradable particles ( ˜19 mum ) that can sustainably release a drug for a specific period of time. Chitosan is a natural polysaccharide that has many characteristics to be used for biomedical applications. In the last two decades, there have been a considerable number of studies affirming that chitosan could be used for pharmaceutical applications. However, chitosan suffers from inherent weaknesses such as low mechanical stability and dissolution of the system in acidic media. In the present study, chitosan microparticles were prepared by emulsification process. The model drug chosen was acetylsalicylic acid as it is a small and challenging molecule. The maximum loading capacity obtained for the microparticles was approximately 96%. The parameters for the preparation of uniform particles with a narrow size distribution were identified in a triangular phase diagram. Moreover, chitosan particles were successfully coated with thin layers of poly lactic-coglycolic acid (PLGA) and poly lactic acid (PLA). The performance of different layerswas tested for in vitro drug release and degradation studies. Additionally, the degradability of the system was evaluated by measuring the weight loss of the system when exposed to enzyme and without enzyme. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM) and inductively coupled plasma optical emission spectrometry (ICP-OES) were used to characterize the controlled release system. Additionally, the in vitro drug release was monitored by ultraviolet-visible spectrophotometry (UV-Vis) and liquid chromatography mass spectrometry (LC-MS). The results obtained from this project showed that it is

  7. pH-controlled drug release for dental applications

    Science.gov (United States)

    Wironen, John Francis

    A large proportion of the dental fillings replaced at present are revised because of the perceived presence of a recurrent caries under or adjacent to the restoration. Many of these perceived caries may not exist, while others may go undetected. This work describes the preparation of drug loaded polymer microspheres that sense the presence of the bacteria that cause caries by the associated presence of acid by-products of digestion. These microspheres are designed to swell and release their antimicrobial drugs once the pH drops to a level that would normally cause caries. The preparation of the microspheres as well as their loading with potassium fluoride, chlorhexidine digluconate, chlorhexidine dihydrochloride, chlorhexidine diacetate, and tetracycline hydrochloride are described. A detailed study of the controlled release behavior of fluoride as a function of polymer composition and pH is presented first. A study of the release kinetics of potassium fluoride, chlorhexidine digluconate, diacetate, dihydrochloride, and tetracycline hydrochloride as a function of pH in the same polymer system is then presented. Additional studies of the swelling kinetics of chlorhexidine-loaded microspheres in various pH buffers are discussed with special reference to correlations with the controlled-release data. Finally, an experiment in which the microspheres are tested in an in vitro bacteria model that includes Streptococcus mutans is presented and discussed in detail.

  8. Meltable magnetic biocomposites for controlled release

    Energy Technology Data Exchange (ETDEWEB)

    Müller, R., E-mail: robert.mueller@ipht-jena.de [Leibniz Institute of Photonic Technology (IPHT), P.O.B. 100239, Jena, D-07702 Germany (Germany); Zhou, M. [Institute of Organic Chemistry and Macromolecular Chemistry, Friedrich Schiller University of Jena, Humboldtstrasse 10, Jena, D-07743 Germany (Germany); Dellith, A. [Leibniz Institute of Photonic Technology (IPHT), P.O.B. 100239, Jena, D-07702 Germany (Germany); Liebert, T.; Heinze, T. [Institute of Organic Chemistry and Macromolecular Chemistry, Friedrich Schiller University of Jena, Humboldtstrasse 10, Jena, D-07743 Germany (Germany)

    2017-06-01

    New biocompatible composites with adjustable melting point in the range of 30–140 °C, consisting of magnetite nanoparticles embedded into a matrix of meltable dextran fatty acid ester are presented which can be softened under an induced alternating magnetic field (AMF). The chosen thermoplastic magnetic composites have a melting range close to human body temperature and can be easily shaped into disk or coating film under melting. The composite disks were loaded with green fluorescent protein (GFP) as a model protein. Controlled release of the protein was realized with high frequent alternating magnetic field of 20 kA/m at 400 kHz. These results showed that under an AMF the release of GFP from magnetic composite was accelerated compared to the control sample without exposure to AMF. Furthermore a texturing of particles in the polymer matrix by a static magnetic field was investigated. - Highlights: • Thermoplastic biocomposite are prepared from dextran ester and magnetite particles. • The composite can be heated by an AC magnetic field above the melting temperature. • In molten state texturing of particles is possible and improves the heating ability. • The biopolymer could be used as a remote controlled matrix for protein release.

  9. Controlled release fertilizer workshop, 1991: Proceedings

    Energy Technology Data Exchange (ETDEWEB)

    Scheib, R.M. (ed.)

    1991-11-01

    Over the last 20 years the Tennessee Valley Authority's National Fertilizer and Environmental Research Center (NFERC) has carried out a number of programs to develop controlled release fertilizers. They pioneered the development and commercialization of sulfur coated urea and conducted extensive research in an attempt to develop an economical synthesis for oxamide. In recent years there has developed an increasing interest in the environmental impact of fertilizers, particularly on the potential for ground water contamination by nitrate derived from fertilizer materials. In response to this interest NFERC's Chemical Research Department organized a five member Controlled Release Fertilizer (CRF) Team to reassess the potential for controlled release materials in agriculture with a view to minimizing any adverse environmental impact and increasing the efficiency of nutrient utilization by the crop. This workshop was part of that reassessment program. The workshop goals were: To determine the present status of CRF research, production and use; to assess the future needs of CRF producers and consumers; and to promote communication and exchange of information. To accomplish these goals the team invited speakers from across' the United States representing academics, experimental station researchers, fertilizer producers, environmentalists, and marketing experts to present papers.

  10. Controlled release fertilizer workshop, 1991: Proceedings

    Energy Technology Data Exchange (ETDEWEB)

    Scheib, R.M. [ed.

    1991-11-01

    Over the last 20 years the Tennessee Valley Authority`s National Fertilizer and Environmental Research Center (NFERC) has carried out a number of programs to develop controlled release fertilizers. They pioneered the development and commercialization of sulfur coated urea and conducted extensive research in an attempt to develop an economical synthesis for oxamide. In recent years there has developed an increasing interest in the environmental impact of fertilizers, particularly on the potential for ground water contamination by nitrate derived from fertilizer materials. In response to this interest NFERC`s Chemical Research Department organized a five member Controlled Release Fertilizer (CRF) Team to reassess the potential for controlled release materials in agriculture with a view to minimizing any adverse environmental impact and increasing the efficiency of nutrient utilization by the crop. This workshop was part of that reassessment program. The workshop goals were: To determine the present status of CRF research, production and use; to assess the future needs of CRF producers and consumers; and to promote communication and exchange of information. To accomplish these goals the team invited speakers from across` the United States representing academics, experimental station researchers, fertilizer producers, environmentalists, and marketing experts to present papers.

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

    African Journals Online (AJOL)

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

  12. Meticulous Overview on the Controlled Release Fertilizers

    Directory of Open Access Journals (Sweden)

    Siafu Ibahati Sempeho

    2014-01-01

    Full Text Available Owing to the high demand for fertilizer formulations that will exhaust the possibilities of nutrient use efficiency (NUE, regulate fertilizer consumption, and lessen agrophysicochemical properties and environmental adverse effects instigated by conventional nutrient supply to crops, this review recapitulates controlled release fertilizers (CRFs as a cutting-edge and safe way to supply crops’ nutrients over the conventional ways. Essentially, CRFs entail fertilizer particles intercalated within excipients aiming at reducing the frequency of fertilizer application thereby abating potential adverse effects linked with conventional fertilizer use. Application of nanotechnology and materials engineering in agriculture particularly in the design of CRFs, the distinctions and classification of CRFs, and the economical, agronomical, and environmental aspects of CRFs has been revised putting into account the development and synthesis of CRFs, laboratory CRFs syntheses and testing, and both linear and sigmoid release features of CRF formulations. Methodical account on the mechanism of nutrient release centring on the empirical and mechanistic approaches of predicting nutrient release is given in view of selected mathematical models. Compositions and laboratory preparations of CRFs basing on in situ and graft polymerization are provided alongside the physical methods used in CRFs encapsulation, with an emphasis on the natural polymers, modified clays, and superabsorbent nanocomposite excipients.

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

    Science.gov (United States)

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

    2017-11-28

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

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

    Science.gov (United States)

    Risbud, M V; Bhonde, R R

    2000-01-01

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

  15. Controlled Release Formulations of Auxinic Herbicides

    Science.gov (United States)

    Kowalski, Witold J.; Siłowiecki, Andrzej.; Romanowska, Iwona; Glazek, Mariola; Bajor, Justyna; Cieciwa, Katarzyna; Rychter, Piotr

    2013-04-01

    Controlled release formulations are applied extensively for the release of active ingredients such as plant protection agents and fertilizers in response to growing concern for ecological problems associated with increased use of plant protection chemicals required for intensive agricultural practices [1]. We synthesized oligomeric mixtures of (R,S)-3-hydroxy butyric acid chemically bonded with 2,4-D, Dicamba and MCPA herbicides (HBA) respectively, and determined their molecular structure and molecular weight dispersion by the size exclusion chromatography, proton magnetic resonance spectrometry and electro-spray ionization mass spectrometry. Further we carried out bioassays of herbicidal effectiveness of the HBA herbicides vs. series of dicotyledonous weeds and crop injury tests [2, 3, 4]. Field bioassays were accomplished according to the EPPO standards [5]. Groups of representative weeds (the development stages in the BCCH scale: 10 - 30) were selected as targets. Statistical variabilities were assessed by the Fisher LSD test for plants treated with the studied herbicides in form of HBA oligomers, the reference herbicides in form of dimethyl ammonium salts (DMA), and untreated plants. No statistically significant differences in the crop injuries caused by the HBA vs. the DMA reference formulation were observed. The effectiveness of the HBA herbicides was lower through the initial period (ca. 2 weeks) relative to the DMA salts, but a significant increase in the effectiveness of the HBA systems followed during the remaining fraction of each assay. After 6 weeks all observed efficiencies approached 100%. The death of weeds treated with the HBA herbicides was delayed when compared with the DMA reference herbicides. The delayed uptake observed for the HBA oligomers relative to the DMA salts was due to controlled release phenomena. In case of the DMA salts the total amount of active ingredients was available at the target site. By contrast, the amount of an active

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

    African Journals Online (AJOL)

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

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

    National Research Council Canada - National Science Library

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

    2012-01-01

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

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

    National Research Council Canada - National Science Library

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

    2013-01-01

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

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

    National Research Council Canada - National Science Library

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

    2009-01-01

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

  20. Oral controlled release formulation of diclofenac sodium by microencapsulation with ethyl cellulose.

    Science.gov (United States)

    Sajeev, C; Vinay, G; Archna, R; Saha, R N

    2002-01-01

    The aim of this study was to formulate and evaluate microencapsulated controlled release preparations of diclofenac sodium (DFS) using different proportions of ethyl cellulose (EC) as the retardant material to extend the release. The formulated microcapsules were then compressed into tablets to obtain controlled release oral formulations. Phase separation-coacervation technique was employed to prepare microcapsules of DFS using different proportions of EC in cyclohexane. Physical characteristics of microcapsules and their tablets, in vitro release pattern of the designed microcapsules and their tablets prepared from them were studied using USP dissolution apparatus (USP 2000) type 2 (paddle method) in triple distilled water. The prepared microcapsules were white, free flowing and spherical in shape, with the particle size varying from 49.94-52.72 microm. The duration of DFS release from microcapsules was found to be directly proportional to the proportion of EC and, thus, coat thickness. All tablets were of good quality with respect to appearance, drug content uniformity, hardness, weight variation, friability and thickness uniformity. In vitro release study of the tabletted microcapsules in triple distilled water showed a zero order release kinetics and extended release beyond 24 h. A good correlation was obtained between drug release (t(60)) and proportion of EC in the microcapsules. In the case of tabletted microcapsules, very good correlation could be established between t(60), proportion of EC, weight of the tablets and between release rate constant (K) and proportion of EC. All the formulations were highly stable and possessed reproducible release kinetics across the batches.

  1. Role of nitric oxide in control of prolactin release by the adenohypophysis.

    OpenAIRE

    Duvilanski, B H; Zambruno, C; Seilicovich, A; Pisera, D.; Lasaga, M; Diaz, M.C.; Belova, N; Rettori, V; McCann, S M

    1995-01-01

    Nitric oxide synthase-containing cells were visualized in the anterior pituitary gland by immunocytochemistry. Consequently, we began an evaluation of the possible role of NO in the control of anterior pituitary function. Prolactin is normally under inhibitory hypothalamic control, and in vitro the gland secretes large quantities of the hormone. When hemipituitaries were incubated for 30 min in the presence of sodium nitroprusside, a releaser of NO, prolactin release was inhibited. This suppr...

  2. A Responsive Battery with Controlled Energy Release.

    Science.gov (United States)

    Wang, Xiaopeng; Gao, Jian; Cheng, Zhihua; Chen, Nan; Qu, Liangti

    2016-11-14

    A new type of responsive battery with the fascinating feature of pressure perceptibility has been developed, which can spontaneously, timely and reliably control the power outputs (e.g., current and voltage) in response to pressure changes. The device design is based on the structure of the Zn-air battery, in which graphene-coated sponge serves as pressure-sensitive air cathode that endows the whole system with the capability of self-controlled energy release. The responsive batteries exhibit superior battery performance with high open-circuit voltage (1.3 V), and competitive areal capacity of 1.25 mAh cm -2 . This work presents an important move towards next-generation intelligent energy storage devices with energy management function. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    African Journals Online (AJOL)

    HP

    2013-07-15

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

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

    Science.gov (United States)

    Ochoa, Juan G. Diaz

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

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

    Directory of Open Access Journals (Sweden)

    Kathryn A. Seabaugh

    2017-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Robert Edward Sims

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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    African Journals Online (AJOL)

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

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

    Science.gov (United States)

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

    2011-10-01

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

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

    African Journals Online (AJOL)

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

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

    African Journals Online (AJOL)

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

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

    Directory of Open Access Journals (Sweden)

    Matheus Melo Pithon

    2009-04-01

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

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

    African Journals Online (AJOL)

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

  14. Hydrophobic Drug-Loaded PEGylated Magnetic Liposomes for Drug-Controlled Release

    Science.gov (United States)

    Hardiansyah, Andri; Yang, Ming-Chien; Liu, Ting-Yu; Kuo, Chih-Yu; Huang, Li-Ying; Chan, Tzu-Yi

    2017-05-01

    Less targeted and limited solubility of hydrophobic-based drug are one of the serious obstacles in drug delivery system. Thus, new strategies to enhance the solubility of hydrophobic drug and controlled release behaviors would be developed. Herein, curcumin, a model of hydrophobic drug, has been loaded into PEGylated magnetic liposomes as a drug carrier platform for drug controlled release system. Inductive magnetic heating (hyperthermia)-stimulated drug release, in vitro cellular cytotoxicity assay of curcumin-loaded PEGylated magnetic liposomes and cellular internalization-induced by magnetic guidance would be investigated. The resultant of drug carriers could disperse homogeneously in aqueous solution, showing a superparamagnetic characteristic and could inductive magnetic heating with external high-frequency magnetic field (HFMF). In vitro curcumin release studies confirmed that the drug carriers exhibited no significant release at 37 °C, whereas exhibited rapid releasing at 45 °C. However, it would display enormous (three times higher) curcumin releasing under the HFMF exposure, compared with that without HFMF exposure at 45 °C. In vitro cytotoxicity test shows that curcumin-loaded PEGylated magnetic liposomes could efficiently kill MCF-7 cells in parallel with increasing curcumin concentration. Fluorescence microscopy observed that these drug carriers could internalize efficiently into the cellular compartment of MCF-7 cells. Thus, it would be anticipated that the novel hydrophobic drug-loaded PEGylated magnetic liposomes in combination with inductive magnetic heating are promising to apply in the combination of chemotherapy and thermotherapy for cancer therapy.

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

    Science.gov (United States)

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

    1986-01-01

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

  16. Biological control of weeds release sites : Kulm Wetland Management District

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Table of release sites of insects for biological control of invasive plants at Kulm Wetland Management District (WMD). Insects were released on Kulm WMD to...

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

    Science.gov (United States)

    Huang, Y; Sun, Y; Wang, Q

    2015-11-20

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

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

    Directory of Open Access Journals (Sweden)

    Zhengtao Yang

    2018-01-01

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

  19. Electrically controlled drug release from nanostructured polypyrrole coated on titanium

    Energy Technology Data Exchange (ETDEWEB)

    Sirivisoot, Sirinrath; Pareta, Rajesh; Webster, Thomas J, E-mail: Thomas_Webster@Brown.edu [School of Engineering, Brown University, Providence, RI 02912 (United States)

    2011-02-25

    Previous studies have demonstrated that multi-walled carbon nanotubes grown out of anodized nanotubular titanium (MWNT-Ti) can be used as a sensing electrode for various biomedical applications; such sensors detected the redox reactions of certain molecules, specifically proteins deposited by osteoblasts during extracellular matrix bone formation. Since it is known that polypyrrole (PPy) can release drugs upon electrical stimulation, in this study antibiotics (penicillin/streptomycin, P/S) or an anti-inflammatory drug (dexamethasone, Dex), termed PPy[P/S] or PPy[Dex], respectively, were electrodeposited in PPy on titanium. The objective of the present study was to determine if such drugs can be released from PPy on demand and (by applying a voltage) control cellular behavior important for orthopedic applications. Results showed that PPy films possessed nanometer-scale roughness as analyzed by atomic force microscopy. X-ray photoelectron spectroscopy confirmed the presence of P/S and Dex encapsulated within the PPy films. Results from cyclic voltammetry showed that 80% of the drugs were released on demand when sweep voltages were applied for five cycles at a scan rate of 0.1 V s{sup -1}. Furthermore, osteoblast (bone-forming cells) and fibroblast (fibrous tissue-forming cells) adhesion were determined on the PPy films. Results showed that PPy[Dex] enhanced osteoblast adhesion after 4 h of culture compared to plain Ti. PPy-Ti (with or without anionic drug doping) inhibited fibroblast adhesion compared to plain Ti. These in vitro results confirmed that electrodeposited PPy[P/S] and PPy[Dex] can release drugs on demand to potentially fight bacterial infection, reduce inflammation, promote bone growth or reduce fibroblast functions, further implicating the use of such materials as implant sensors.

  20. Electrically controlled drug release from nanostructured polypyrrole coated on titanium

    Science.gov (United States)

    Sirivisoot, Sirinrath; Pareta, Rajesh; Webster, Thomas J.

    2011-02-01

    Previous studies have demonstrated that multi-walled carbon nanotubes grown out of anodized nanotubular titanium (MWNT-Ti) can be used as a sensing electrode for various biomedical applications; such sensors detected the redox reactions of certain molecules, specifically proteins deposited by osteoblasts during extracellular matrix bone formation. Since it is known that polypyrrole (PPy) can release drugs upon electrical stimulation, in this study antibiotics (penicillin/streptomycin, P/S) or an anti-inflammatory drug (dexamethasone, Dex), termed PPy[P/S] or PPy[Dex], respectively, were electrodeposited in PPy on titanium. The objective of the present study was to determine if such drugs can be released from PPy on demand and (by applying a voltage) control cellular behavior important for orthopedic applications. Results showed that PPy films possessed nanometer-scale roughness as analyzed by atomic force microscopy. X-ray photoelectron spectroscopy confirmed the presence of P/S and Dex encapsulated within the PPy films. Results from cyclic voltammetry showed that 80% of the drugs were released on demand when sweep voltages were applied for five cycles at a scan rate of 0.1 V s - 1. Furthermore, osteoblast (bone-forming cells) and fibroblast (fibrous tissue-forming cells) adhesion were determined on the PPy films. Results showed that PPy[Dex] enhanced osteoblast adhesion after 4 h of culture compared to plain Ti. PPy-Ti (with or without anionic drug doping) inhibited fibroblast adhesion compared to plain Ti. These in vitro results confirmed that electrodeposited PPy[P/S] and PPy[Dex] can release drugs on demand to potentially fight bacterial infection, reduce inflammation, promote bone growth or reduce fibroblast functions, further implicating the use of such materials as implant sensors.

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

    Science.gov (United States)

    Mohammadi, Saman; Jones, Lyndon; Gorbet, Maud

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Saman Mohammadi

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

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

    Science.gov (United States)

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

    2015-07-10

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

  4. Preparation and Physicochemical Evaluation of Controlled-release Carbon Source Tablet for Groundwater in situ Denitrification

    Science.gov (United States)

    Kim, Y.; Kang, J. H.; Yeum, Y.; Han, K. J.; Kim, D. W.; Park, C. W.

    2015-12-01

    Nitric nitrogen could be the one of typical pollution source such asNO3-through domestic sewage, livestock and agricultural wastewater. Resident microflorain aquifer has known to remove the nitric nitrogen spontaneously following the denitration process with the carbon source (CS) as reactant. However, it could be reacted very slowly with the rack of CS and there have been some studies for controlled addition of CS (Ref #1-3). The aim of this study was to prepare the controlled-release carbon source (CR-CS) tablet and to evaluate in vitro release profile for groundwater in situ denitrification. CR-CS tablet could be manufactured by direct compression method using hydraulic laboratory press (Caver® 3850) with 8 mm rounded concave punch/ die.Seven kinds of CR-CS tablet were prepared to determine the nature of the additives and their ratio such as sodium silicate, dicalcium phosphate, bentonite and sand#8.For each formulation, the LOD% and flowability of pre-mixed powders and the hardness of compressed tablets were analyzed. In vitro release study was performed to confirm the dissolution profiles following the USP Apparatus 2 method with Distilled water of 900mL, 20 °C. As a result, for each lubricated powders, they were compared in terms of ability to give an acceptable dry pre-mixed powder for tableting process. The hardness of the compressed tablets is acceptable whatever the formulations tested. After in vitro release study, it could confirm that the different formulations of CR-CS tablet have a various release rate patterns, which could release 100% at 3 hrs, 6 hrs and 12 hrs. The in vitro dissolution profiles were in good correlation of Higuchi release kinetic model. In conclusion, this study could be used as a background for development and evaluation of the controlled-release carbon source (CR-CS) tablet for the purification of groundwater following the in situ denitrification.

  5. Development and Optimization of controlled drug release ...

    African Journals Online (AJOL)

    Formulation variables like type of osmotic agent (sodium chloride, mannitol, lactose), level of pore former and plasticizer and percent weight gain were found to affect the drug release from the developed formulations. The release performance of diclofenac sodium from the optimized formulations was studied over a period of ...

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

    African Journals Online (AJOL)

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

  7. Controlled release of vancomycin from poloxamer 407 gels.

    Science.gov (United States)

    Veyries, M L; Couarraze, G; Geiger, S; Agnely, F; Massias, L; Kunzli, B; Faurisson, F; Rouveix, B

    1999-12-10

    The purpose of this study was to investigate Poloxamer 407 25% (w/w) formulations aimed at prolonging the residence time of vancomycin, a time-dependent antibiotic, in a body site with a high infectious risk. Reversible thermal gelation of the formulations permitted their local injection in liquid form and in situ gelation as they warmed to body temperature. Neither the rheological properties of the Poloxamer matrices nor the antibacterial activity of vancomycin was altered by their combination. In vitro, the dispersed form exhibited prolonged release, with a lower diffusion coefficient of vancomycin compared to the solubilized form (4.7x10(-8) vs 2. 1x10(-7) cm(2) s(-1)131 mg l(-1) for the solubilized form), followed by lower but effective antibacterial levels for at least 8 days. Controlled-release profiles, good preservation of vancomycin activity, good tolerability in rats, and ease of administration suggest that Poloxamer 407 may be useful as a vancomycin delivery vehicle for local prophylaxis of infections, especially in prosthetic surgery.

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

    Directory of Open Access Journals (Sweden)

    Alija Uzunović

    2010-08-01

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

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

    DEFF Research Database (Denmark)

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

    2002-01-01

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

  10. Analytical solution of diffusion model for nutrient release from controlled release fertilizer

    Science.gov (United States)

    Ameenuddin Irfan, Sayed; Razali, Radzuan; KuShaari, KuZilati; Mansor, Nurlidia; Azeem, Babar

    2017-09-01

    An analytical method has been developed to solve the initial value problem which arises from Fick’s diffusion equation encountered in the modelling of the Controlled Release Fertilizers. The proposed analytical solution is developed using the modified Adomian decomposition method. This method does not require the discretization method, reliability and efficiency of this method is more and it also reduces the calculation time. The model has predicted the effect of granule radius and diffusion coefficient on the nutrient release and total release time of Controlled Release Fertilizer. Model has predicted that increase in the radius of granule reduces the release and vice versa in case of diffusion coefficient. Detailed understanding of these parameters helps in improved designing of Controlled Release Fertilizer.

  11. Controlled release of 5-flurouracil from biomedical polyurethanes

    Indian Academy of Sciences (India)

    Administrator

    kles on their surfaces. The release of 5-FU through the microspheres was investigated in pH 7⋅4- phosphate buffer. An increase in release rate was observed with increasing molar ratio of PLF68 with respect to castor oil. Keywords. Biomedical polyurethane; controlled release; 5-flurouracil; drug delivery. 1. Introduction.

  12. Controlled Release of Lysozyme from Double-Walled Poly(Lactide-Co-Glycolide (PLGA Microspheres

    Directory of Open Access Journals (Sweden)

    Rezaul H. Ansary

    2017-10-01

    Full Text Available Double-walled microspheres based on poly(lactide-co-glycolide (PLGA are potential delivery systems for reducing a very high initial burst release of encapsulated protein and peptide drugs. In this study, double-walled microspheres made of glucose core, hydroxyl-terminated poly(lactide-co-glycolide (Glu-PLGA, and carboxyl-terminated PLGA were fabricated using a modified water-in-oil-in-oil-in-water (w1/o/o/w2 emulsion solvent evaporation technique for the controlled release of a model protein, lysozyme. Microspheres size, morphology, encapsulation efficiency, lysozyme in vitro release profiles, bioactivity, and structural integrity, were evaluated. Scanning electron microscopy (SEM images revealed that double-walled microspheres comprising of Glu-PLGA and PLGA with a mass ratio of 1:1 have a spherical shape and smooth surfaces. A statistically significant increase in the encapsulation efficiency (82.52% ± 3.28% was achieved when 1% (w/v polyvinyl alcohol (PVA and 2.5% (w/v trehalose were incorporated in the internal and external aqueous phase, respectively, during emulsification. Double-walled microspheres prepared together with excipients (PVA and trehalose showed a better control release of lysozyme. The released lysozyme was fully bioactive, and its structural integrity was slightly affected during microspheres fabrication and in vitro release studies. Therefore, double-walled microspheres made of Glu-PLGA and PLGA together with excipients (PVA and trehalose provide a controlled and sustained release for lysozyme.

  13. Chemical Control of FGF-2 Release for Promoting Calvarial Healing with Adipose Stem Cells*

    OpenAIRE

    Kwan, Matthew D.; Sellmyer, Mark A.; Quarto, Natalina; Ho, Andrew M.; Wandless, Thomas J.; Longaker, Michael T.

    2011-01-01

    Chemical control of protein secretion using a small molecule approach provides a powerful tool to optimize tissue engineering strategies by regulating the spatial and temporal dimensions that are exposed to a specific protein. We placed fibroblast growth factor 2 (FGF-2) under conditional control of a small molecule and demonstrated greater than 50-fold regulation of FGF-2 release as well as tunability, reversibility, and functionality in vitro. We then applied conditional control of FGF-2 se...

  14. Preparation and investigation of controlled-release glipizide novel oral device with three-dimensional printing.

    Science.gov (United States)

    Li, Qijun; Wen, Haoyang; Jia, Danyang; Guan, Xiaoying; Pan, Hao; Yang, Yue; Yu, Shihui; Zhu, Zhihong; Xiang, Rongwu; Pan, Weisan

    2017-06-15

    The purpose of this study was to explore the feasibility of combining fused deposition modeling (FDM) 3D printing technology with hot melt extrusion (HME) to fabricate a novel controlled-release drug delivery device. Glipizide used in the treatment of diabetes was selected as model drug, and was successfully loaded into commercial polyvinyl alcohol (PVA) filaments by HME method. The drug-loaded filaments were printed through a dual-nozzle 3D printer, and finally formed a double-chamber device composed by a tablet embedded within a larger tablet (DuoTablet), each chamber contains different contents of glipizide. The drug-loaded 3D printed device was evaluated for drug release under in vitro dissolution condition, and we found the release profile fit Korsmeyer-Peppas release kinetics. With the double-chamber design, it is feasible to design either controlled drug release or delayed drug release behavior by reasonably arranging the concentration distribution of the drug in the device. The characteristics of the external layer performed main influence on the release profile of the internal compartment such as lag-time or rate of release. The results of this study suggest the potential of 3D printing to fabricate controlled-release drug delivery system containing multiple drug concentration distributions via hot melt extrusion method and specialized design configurations. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Environmental Release Prevention and Control Plan

    Energy Technology Data Exchange (ETDEWEB)

    Mamatey, A.; Arnett, M.

    1997-10-01

    During the history of SRS, continual improvements in facilities, process, and operations, and changes in the site`s mission have reduced the amount of radioactive liquid releases. In the early years of SRS (1958 to 1965), the amount of tritium discharged to the Savannah River averaged approximately 61,000 curies a year. During the mid-1980`s (1983 to 1988), liquid releases of tritium averaged 27,000 curies a year. By 1996, liquid releases of tritium are projected to be just 3000 curies for the year. This large projected decrease is the result of the planned shut-down of all reactors and the anticipated significant decline in the amount of tritium migrating from the site seepage basins and the Solid Waste Disposal Facility.

  16. Nutrient Sensing Overrides Somatostatin and Growth Hormone-Releasing Hormone to Control Pulsatile Growth Hormone Release.

    Science.gov (United States)

    Steyn, F J

    2015-07-01

    Pharmacological studies reveal that interactions between hypothalamic inhibitory somatostatin and stimulatory growth hormone-releasing hormone (GHRH) govern pulsatile GH release. However, in vivo analysis of somatostatin and GHRH release into the pituitary portal vasculature and peripheral GH output demonstrates that the withdrawal of somatostatin or the appearance of GHRH into pituitary portal blood does not reliably dictate GH release. Consequently, additional intermediates acting at the level of the hypothalamus and within the anterior pituitary gland are likely to contribute to the release of GH, entraining GH secretory patterns to meet physiological demand. The identification and validation of the actions of such intermediates is particularly important, given that the pattern of GH release defines several of the physiological actions of GH. This review highlights the actions of neuropeptide Y in regulating GH release. It is acknowledged that pulsatile GH release may not occur selectively in response to hypothalamic control of pituitary function. As such, interactions between somatotroph networks, the median eminence and pituitary microvasculature and blood flow, and the emerging role of tanycytes and pericytes as critical regulators of pulsatility are considered. It is argued that collective interactions between the hypothalamus, the median eminence and pituitary vasculature, and structural components within the pituitary gland dictate somatotroph function and thereby pulsatile GH release. These interactions may override hypothalamic somatostatin and GHRH-mediated GH release, and modify pulsatile GH release relative to the peripheral glucose supply, and thereby physiological demand. © 2015 British Society for Neuroendocrinology.

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

    Indian Academy of Sciences (India)

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

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

    NARCIS (Netherlands)

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

    2008-01-01

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

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

    Science.gov (United States)

    Chojnacka, Katarzyna; Mikulewicz, Marcin

    2014-11-01

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

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

    DEFF Research Database (Denmark)

    Larsen, T

    1990-01-01

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

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

    African Journals Online (AJOL)

    p2492989

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

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

    Science.gov (United States)

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

    2009-01-05

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

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

    Directory of Open Access Journals (Sweden)

    J Emami

    2004-04-01

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

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

    Science.gov (United States)

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

    2010-06-01

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

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

    Science.gov (United States)

    Nallagundla, Sumalatha; Patnala, Srinivas; Kanfer, Isadore

    2014-08-01

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

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

    Science.gov (United States)

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

    1999-06-01

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

  7. Controlled release formulations of metribuzin: release kinetics in water and soil.

    Science.gov (United States)

    Kumar, Jitendra; Nisar, Keyath; Shakil, N A; Walia, Suresh; Parsad, Rajender

    2010-05-01

    Controlled release (CR) formulations of metribuzin in Polyvinyl chloride [(PVC) (emulsion)], carboxy methyl cellulose (CMC), and carboxy methyl cellulose-kaolinite composite (CMC-KAO), are reported. Kinetics of its release in water and soil was studied in comparison with the commercial formulation (75 DF). Metribuzin from the commercial formulation became non-detectable after 35 days whereas it attained maxima between 35-49 days and became non-detectable after 63 days in the developed products. Amongst the CR formulations, the release in both water and soil was the fastest in CMC and slowest in PVC. The CMC-KAO composite reduced the rate of release as compared to CMC alone. The diffusion exponent (n value) of metribuzin in water and soil ranged from 0.515 to 0.745 and 0.662 to 1.296, respectively in the various formulations. The release was diffusion controlled with half release time (t(1/2)) from different controlled release matrices of 12.98 to 47.63 days in water and 16.90 to 51.79 days in soil. It was 3.25 and 4.66 days, respectively in the commercial formulation. The period of optimum availability of metribuzin in water and soil from controlled released formulations ranged from 15.09 to 31.68 and 17.99 to 34.72 days as against 5.03 and 8.80 days in the commercial formulation.

  8. Design of magnetic molecularly imprinted polymer nanoparticles for controlled release of doxorubicin under an alternative magnetic field in athermal conditions

    Science.gov (United States)

    Griffete, N.; Fresnais, J.; Espinosa, A.; Wilhelm, C.; Bée, A.; Ménager, C.

    2015-11-01

    An innovative magnetic delivery nanomaterial for triggered cancer therapy showing active control over drug release by using an alternative magnetic field is proposed. In vitro and In vivo release of doxorubicin (DOX) were investigated and showed a massive DOX release under an alternative magnetic field without temperature elevation of the medium.An innovative magnetic delivery nanomaterial for triggered cancer therapy showing active control over drug release by using an alternative magnetic field is proposed. In vitro and In vivo release of doxorubicin (DOX) were investigated and showed a massive DOX release under an alternative magnetic field without temperature elevation of the medium. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06133d

  9. Overview study of LNG release prevention and control systems

    Energy Technology Data Exchange (ETDEWEB)

    Pelto, P.J.; Baker, E.G.; Holter, G.M.; Powers, T.B.

    1982-03-01

    The liquefied natural gas (LNG) industry employs a variety of release prevention and control techniques to reduce the likelihood and the consequences of accidental LNG releases. A study of the effectiveness of these release prevention and control systems is being performed. Reference descriptions for the basic types of LNG facilities were developed. Then an overview study was performed to identify areas that merit subsequent and more detailed analyses. The specific objectives were to characterize the LNG facilities of interest and their release prevention and control systems, identify possible weak links and research needs, and provide an analytical framework for subsequent detailed analyses. The LNG facilities analyzed include a reference export terminal, marine vessel, import terminal, peakshaving facility, truck tanker, and satellite facility. A reference description for these facilities, a preliminary hazards analysis (PHA), and a list of representative release scenarios are included. The reference facility descriptions outline basic process flows, plant layouts, and safety features. The PHA identifies the important release prevention operations. Representative release scenarios provide a format for discussing potential initiating events, effects of the release prevention and control systems, information needs, and potential design changes. These scenarios range from relatively frequent but low consequence releases to unlikely but large releases and are the principal basis for the next stage of analysis.

  10. Formulation development and evaluation of lamivudine controlled release tablets using cross-linked sago starch.

    Science.gov (United States)

    Singh, Akhilesh Vikram; Nath, Lila Kanta

    2013-02-01

    Modified starches based polymeric substances find utmost applicability in pharmaceutical formulation development. Cross-linked starches showed very promising results in drug delivery application. The present investigation concerns with the development of controlled release tablets of lamivudine using cross-linked sago starch. The cross-linked derivative was synthesized with phosphorous oxychloride and native sago starch in basic pH medium. The cross-linked sago starch was tested for acute toxicity and drug-excipient compatibility study. The formulated tablets were evaluated for various physical characteristics, in vitro dissolution release study and in vivo pharmacokinetic study in rabbit model. In vitro release study showed that the optimized formulation exhibited highest correlation (R) in case of zero order kinetic model and the release mechanism followed a combination of diffusion and erosion process. There was a significant difference in the pharmacokinetic parameters (T(max), C(max), AUC, V(d), T(1/2), and MDT) of the optimized formulation as compared to the marketed conventional tablet Lamivir®. The cross-linked starch showed promising results in terms of controlling the release behavior of the active drug from the matrix. The hydrophilic matrix synthesized by cross-linking could be used with a variety of active pharmaceutical ingredients for making their controlled/sustained release formulations.

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

    Science.gov (United States)

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

    2016-12-30

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

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

    Directory of Open Access Journals (Sweden)

    Oksana Megasari

    2007-07-01

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

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

    Science.gov (United States)

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

    2014-03-25

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

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

    Science.gov (United States)

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

    2017-08-01

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

  15. Formulation and evaluation of controlled release matrix mucoadhesive tablets of domperidone using Salvia plebeian gum

    Directory of Open Access Journals (Sweden)

    Gurpreet Arora

    2011-01-01

    Full Text Available The aim of study was to prepare controlled release matrix mucoadhesive tablets of domperidone using Salvia plebeian gum as natural polymer. Tablets were formulated by direct compression technology employing the natural polymer in different concentrations (5, 10, 15 and 20% w/w. The prepared batches were evaluated for drug assay, diameter, thickness, hardness and tensile strength, swelling index, mucoadhesive strength (using texture analyzer and subjected to in vitro drug release studies. Real-time stability studies were also conducted on prepared batches. In vitro drug release data were fitted in various release kinetic models for studying the mechanism of drug release. Tensile strength was found to increase from 0.808 ± 0.098 to 1.527 ± 0.10 mN/cm 2 and mucoadhesive strength increased from 13.673 ± 1.542 to 40.378 ± 2.345 N, with an increase in the polymer concentration from 5 to 20% (A1 to A4. Swelling index was reported to increase with both increase in the concentration of gum and the time duration. The in vitro drug release decreased from 97.76 to 83.4% (A1 to A4 with the increase in polymer concentration. The drug release from the matrix tablets was found to follow zero-order and Higuchi models, indicating the matrix-forming potential of natural polymer. The value of n was found to be between 0.5221 and 0.8992, indicating the involvement of more than one drug release mechanism from the formulation and possibly the combination of both diffusion and erosion. These research findings clearly indicate the potential of S. plebeian gum to be used as binder, release retardant and mucoadhesive natural material in tablet formulations.

  16. Controlled Drug Release from Biodegradable Shape-Memory Polymers

    Science.gov (United States)

    Wischke, Christian; Neffe, Axel T.; Lendlein, Andreas

    Biodegradable shape-memory polymers (SMPs) have attracted significant interest for biomedical applications. Modern concepts for biofunctional implants often comprise the controlled release of bioactive compounds to gain specific biofunctionalities. Therefore, a general strategy has been suggested for polymer systems combining degradability and shape-memory capability with controlled release of drugs. This chapter provides a detailed description of the molecular basis for such multifunctional SMPs including the selection of building blocks, the polymer morphology, and the three dimensional architecture. Moreover, drug loading and release, drug effects on thermomechanical properties of SMPs, and drug release patterns in a physiological environment are described and potential applications in minimally-invasive surgery are discussed.

  17. Photo-controlled release of fipronil from a coumarin triggered precursor.

    Science.gov (United States)

    Gao, Zhenhong; Yuan, Pengtao; Wang, Donghui; Xu, Zhiping; Li, Zhong; Shao, Xusheng

    2017-06-01

    Developing efficient controlled release system of insecticide can facilitate the better use of insecticide. We described here a first example of photo-controlled release of an insecticide by linking fipronil with photoresponsive coumarin covalently. The generated coumarin-fipronil (CF) precursor could undergo cleavage to release free fipronil in the presence of blue light (420nm) or sunlight. Photophysical studies of CF showed that it exhibited strong fluorescence properties. The CF had no obvious activity against mosquito larvae under dark, but it can be activated by light inside the mosquito larvae. The released Fip from CF by blue light irradiation in vitro retained its activity to armyworm (Mythimna separate) with LC50 value of 24.64μmolL-1. This photocaged molecule provided an alternative delivery method for fipronil. Copyright © 2017. Published by Elsevier Ltd.

  18. Formulation optimization of hydrodynamically balanced oral controlled release bioadhesive tablets of tramadol hydrochloride.

    Science.gov (United States)

    Singh, Bhupinder; Rani, Ashu; Babita; Ahuja, Naveen; Kapil, Rishi

    2010-01-01

    The directly compressible floating-bioadhesive tablets of tramadol were formulated using varying amounts Carbopol 971P (CP) and hydroxy-propylmethyl cellulose (HPMC), along with other requisite excipients. In vitro drug release profile, floatational characteristics and ex vivo bioadhesive strength using texture analyzer were determined, and systematically optimized using a 3(2) central composite design (CCD). The studies indicated successful formulation of gastroretentive compressed matrices with excellent controlled release, mucoadhesion and hydrodynamic balance. Comparison of the dissolution profiles of the optimized formulation, with optimal composition of CP:HPMC :: 80.0:125.0, with that of the marketed controlled release formulation other indicated analogy of drug release performance with each other. Validation of optimization study using eight confirmatory experimental runs indicated very high degree of prognostic ability of CCD with mean  SEM of â0.06%  0.37. Further, the study successfully unravels the effect of the polymers on the selected response variables.

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

    Science.gov (United States)

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

    2017-05-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  1. [Controlled release of pseudoephedrine HCl from pellets].

    Science.gov (United States)

    Vertommen, J

    1997-01-01

    This study describes the development work on a dosage form, which should release the drug pseudoephedrine HCl over twelve hours. Pellets were chosen as the dosage form. The pellets contained 20, respectively, 45 percent pseudoephedrine HCL and were produced using a high shear mixer-granulator. These pellets were coated in a fluidized bed and in a high shear mixer-granulator equipped with a microwave drying installation. The results of the experiments indicate that it is possible to produce pellets in a high shear mixer-granulator. Strong pellets with a narrow size distribution were obtained. A high shear mixer-granulator appears, therefore, to be a valuable alternative to the more commonly used pellet-forming technique of extrusion-sphere formation. The pellets could be coated as well in a fluidized bed as in a high shear mixer-granulator equipped with a microwave drying installation. A major advantage of the high shear mixer-granulator equipped with a microwave drying installation is the possibility to perform several unit operations such as mixing, pellet formation drying, and coating in one piece of equipment. With respect to the requirement of getting a release of pseudoephedrine HCl over twelve hours, the pellets containing 20 percent pseudoephedrine HCl fulfilled this requirement. For pellets containing 45 percent pseudoephedrine HCl it appears to be hard to obtain a sufficient delay in release using the commonly used coating formulations. This can be attributed to the very good solubility of pseudoephedrine HCl in water. Optimization of the coating formulation by changing the nature and concentration of the plasticizer may solve the problem.

  2. Modifying sorbents in controlled release formulations to prevent herbicides pollution

    Energy Technology Data Exchange (ETDEWEB)

    Cespedes, F.F.; Sanchez, M.V.; Garcia, S.P.; Perez, M.F. [University of Almeria, Almeria (Spain). Dept. of Inorganic Chemistry

    2007-10-15

    The herbicides chloridazon and metribuzin, identified as groundwater pollutants, were incorporated in alginate-based granules to obtain controlled release properties. In this research the effect of incorporation of sorbents such as bentonite, anthracite and activated carbon in alginate basic formulation were not only studied on encapsulation efficiency but also on the release rate of herbicides which was studied using water release kinetic tests. In addition, sorption studies of herbicides with bentonite, anthracite and activated carbon were made. The kinetic experiments of chloridazon and metribuzin release in water have shown that the release rate is higher in metribuzin systems than in those prepared with chloridazon, which has lower water solubility. Besides, it can be deduced that the use of sorbents reduces the release rate of the chloridazon and metribuzin in comparison to the technical product and to the alginate formulation without sorbents. The highest decrease in release rate corresponds to the formulations prepared with activated carbon as a sorbent. The water uptake, permeability, and time taken for 50% of the active ingredient to be released into water, were calculated to compare the formulations. On the basis of a parameter of an empirical equation used to fit the herbicide release data, the release of chloridazon and metribuzin from the various formulations into water is controlled by a diffusion mechanism.

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

    Science.gov (United States)

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

    2014-01-22

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

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

    Directory of Open Access Journals (Sweden)

    Ali Kadivar

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2014-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Karin Goebel

    2013-06-01

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

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

    Science.gov (United States)

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

    2015-10-16

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

  9. Investigation of excipient type and level on drug release from controlled release tablets containing HPMC.

    Science.gov (United States)

    Williams, Robert O; Reynolds, Thomas D; Cabelka, Tim D; Sykora, Matthew A; Mahaguna, Vorapann

    2002-05-01

    The purpose of this study was to investigate the influence of excipient type and level on the release of alprazolam formulated in controlled release matrix tablets containing hydroxypropyl methylcellulose (HPMC). Each tablet formulation contained alprazolam, HPMC (Methocel K4MP), excipients, and magnesium stearate. The soluble excipients investigated were lactose monohydrate, sucrose, and dextrose, and the insoluble excipients included dicalcium phosphate dihydrate, dicalcium phosphate anhydrous, and calcium sulfate dihydrate. The similarity factor (f2 factor) was used to compare the dissolution profile of each formulation. The insoluble excipients, especially dicalcium phosphate dihydrate, caused the drug to be released at a slower rate and to a lesser extent than the soluble excipients. Soluble excipients created a more permeable hydrated gel layer for drug release, increased the porosity resulting in faster diffusion of drug, and increased the rate of tablet erosion. Use of binary mixtures of lactose monohydrate and dicalcium phosphate dihydrate produced release profiles of intermediate duration. Rapid drug dissolution was obtained when only 9.1% w/w of lactose monohydrate was present in the tablet formulation. Only when the dicalcium phosphate dihydrate level was sufficiently high (36.5% w/w) was the release rate and extent decreased. It was demonstrated that the type and level of excipient influenced the rate and extent of drug release from controlled release tablets containing HPMC. The release mechanism of alprazolam from each tablet formulation was described by either the Hixson-Crowell cube root kinetics equation or Peppas's equation. However, the different excipient types investigated did not influence the release mechanism of alprazolam from the final tablets.

  10. Phenobarbital loaded microemulsion: development, kinetic release and quality control

    Directory of Open Access Journals (Sweden)

    Kayo Alves Figueiredo

    Full Text Available ABSTRACT This study aimed to obtain and characterize a microemulsion (ME containing phenobarbital (PB. The PB was incorporated in the proportion of 5% and 10% in a microemulsion system containing Labrasol(r, ethanol, isopropyl myristate and purified water. The physicochemical characterization was performed and the primary stability of the ME was evaluated. An analytical method was developed using spectrophotometry in UV = 242 nm. The kinetics of the in vitro release (Franz model of the ME and the emulsion (EM containing PB was evaluated. The incorporation of PB into ME at concentrations of 5 and 10% did not change pH and resistance to centrifugation. There was an increase in particle size, a decrease of conductivity and a change in the refractive index in relation to placebo ME. The ME remained stable in preliminary stability tests. The analytical method proved to be specific, linear, precise, accurate and robust. Regarding the kinetics of the in vitro release, ME obtained an in vitro release profile greater than the EM containing PB. Thus, the obtained ME has a potential for future transdermal application, being able to compose a drug delivery system for the treatment of epilepsy.

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

    OpenAIRE

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

    2012-01-01

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

  12. Controlled Release of Imidacloprid from Poly Styrene-Diacetone - Nanoformulation

    Science.gov (United States)

    Qian, Kun; Guo, Yanzhen; He, Lin

    2012-01-01

    Imidacloprid is a neonicotinoids insecticide, which is important for the cash crops such as tomato, rape and so on. The conventional formulation does not only increase the loss of pesticide but also leads to environmental pollution. Controlled-release formulations of pesticide are highly desirable not only for attaining the most effective utilization of the pesticide, but also for reducing environmental pollution. Pesticide imidacloprid was incorporated in poly (styrene-diacetone crylamide)-based formulation to obtain controlled release properties, and the imidacloprid nanocontrolled release formulation was characterized by infrared (IR) and field emission scanning electron microscope (FESEM). Factors related to loading efficiency, swelling and release behaviors of the formulation were investigated. It showed that the loading efficiency could reach about 40% (w/w). The values for the diffusion exponent "n" were in the range of 0.31-0.58, which indicated that the release of imidacloprid was diffusion-controlled. The time taken for 50% of the active ingredient to be released into water, T50, was also calculated for the comparison of formulations in different conditions. The results showed that the formulation with higher temperature and more diacetone crylamide had lower value of T50, which means a quicker release of the active ingredient. This study highlighted some pieces of evidence that improved pesticide incorporation and slower release were linked to potential interactions between the pesticide and the polymer.

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

    Directory of Open Access Journals (Sweden)

    Gilberto Goissis

    2009-03-01

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

  14. Nutrients Release from a Novel Gel-Based Slow/Controlled Release Fertilizer

    OpenAIRE

    Ding, H.; Zhang, Y. S.; Li, W. H.; Zheng, X. Z.; Wang, M. K.; Tang, L. N.; Chen, D. L.

    2016-01-01

    A novel gel-based slow/controlled release fertilizer (G-CRF) was developed, which was produced by combining various natural, seminatural, and/or synthetic organic macromolecule materials and natural inorganic mineral with conventional NPK fertilizers. Its nutrient release characteristics were studied to compare with conventional fertilizers through the soil column leaching method. The influences of soil factors, including temperature, pH, water, and nutrient contents in the G-CRF on nutrient ...

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

    Directory of Open Access Journals (Sweden)

    Oster Henrik

    2008-03-01

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

  16. 28 CFR 541.68 - Release from controlled housing status.

    Science.gov (United States)

    2010-07-01

    ... and staff members, which demonstrate that the inmate is able to function in a less restrictive... institution guidelines and Bureau of Prisons rules and policy. (b) An inmate released from a controlled...

  17. Progress of nano-controlled releasing system on ophthalmologic administration

    Directory of Open Access Journals (Sweden)

    Shu-Rong Wang

    2015-12-01

    Full Text Available The ophthalmic application of nanometer materials are mainly concentrated on controlled releasing systems. Due to the unique properties of nanometer materials,it has great advantages in carrying ophthalmic drugs compared with the conventional method, mainly in higher bioavailability and fewer side effects. As a result, nano-controlled releasing system has good application prospect in ophthalmology. At present, a variety of different types of nano-controlled releasing systems have been used to enhance the efficiency of the ophthalmic drugs, including nanomicelle, nanoparticles, nanosuspensions, liposomes,dendrimers, etc. In this paper, the research progress as well as the application of nano-controlled releasing system on ophthalmologic administration is reviewed.

  18. Encapsulated Urea-Kaolinite Nanocomposite for Controlled Release Fertilizer Formulations

    National Research Council Canada - National Science Library

    Sempeho, Siafu Ibahati; Kim, Hee Taik; Mubofu, Egid; Pogrebnoi, Alexander; Shao, Godlisten; Hilonga, Askwar

    2015-01-01

    Urea controlled release fertilizer (CRF) was prepared via kaolinite intercalation followed by gum arabic encapsulation in an attempt to reduce its severe losses associated with dissolution, hydrolysis, and diffusion...

  19. 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.

  20. Bioinspired Heparin Nanosponge Prepared by Photo-crosslinking for Controlled Release of Growth Factors

    DEFF Research Database (Denmark)

    Choi, Won Il; Sahu, Abhishek; Vilos, Cristian

    2017-01-01

    Growth factors have great therapeutic potential for various disease therapy and tissue engineering applications. However, their clinical efficacy is hampered by low bioavailability, rapid degradation in vivo and non-specific biodistribution. Nanoparticle based delivery systems are being evaluated...... factor binding ability. Four different growth factors, bFGF, VEGF, BMP-2, and HGF were successfully encapsulated into Hep-NS. In vitro studies showed sustained release of all the growth factors for almost 60 days and the rate of release was directly dependent on the amount of heparin in Hep......-NS. The released growth factors retained their bioactivity as assessed by a cell proliferation assay. This heparin nanosponge is therefore a promising nanocarrier for the loading and controlled release of growth factors....

  1. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1989-01-01

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

  3. Okra (Hibiscus esculentus) gum-alginate blend mucoadhesive beads for controlled glibenclamide release.

    Science.gov (United States)

    Sinha, Priyanka; Ubaidulla, U; Nayak, Amit Kumar

    2015-01-01

    The utility of isolated okra (Hibiscus esculentus) gum (OG) was evaluated as a potential sustained drug release polymer-blends with sodium alginate in the development of controlled glibenclamide release ionically-gelled beads for oral use. OG was isolated from okra fruits and its solubility, pH, viscosity and moisture content were studied. Glibenclamide-loaded OG-alginate blend beads were prepared using CaCl2 as cross-linking agent through ionic-gelation technique. These ionically gelled beads showed drug entrapment efficiency of 64.19 ± 2.02 to 91.86 ± 3.24%. The bead sizes were within 1.12 ± 0.11 to 1.28 ± 0.15 mm. These glibenclamide-loaded OG-alginate blend beads exhibited sustained in vitro drug release over a prolonged period of 8 h. The in vitro drug release from these OG-alginate beads were followed controlled-release (zero-order) pattern with super case-II transport mechanism. The beads were also characterized by SEM and FTIR. The swelling and degradation of these beads was influenced by the pH of the test medium. These beads also exhibited good mucoadhesivity with goat intestinal mucosa.

  4. Nanoporous Silicified Phospholipids and Application to Controlled Glycolic Acid Release

    Directory of Open Access Journals (Sweden)

    Kang SangHwa

    2008-01-01

    Full Text Available Abstract This work demonstrates the synthesis and characterization of novel nanoporous silicified phospholipid bilayers assembled inorganic powders. The materials are obtained by silicification process with silica precursor at the hydrophilic region of phospholipid bilayers. This process involves the co-assembly of a chemically active phospholipids bilayer within the ordered porosity of a silica matrix and holds promise as a novel application for controlled drug release or drug containers with a high level of specificity and throughput. The controlled release application of the synthesized materials was achieved to glycolic acid, and obtained a zero-order release pattern due to the nanoporosity.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-08-01

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

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

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Avadi

    2016-06-01

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

  7. [Study on self-microemulsifying membrane controlled-release drop pill of hawthorn leaves flavonoids].

    Science.gov (United States)

    Wang, Jin-Xuan; Huang, Hong-Zhang; Li, Ning; Gao, Chong-Kai

    2014-03-01

    To prepare the hawthorn leaves flavonoids self-microemulsifying membrane controlled-release coated drop pill, and to study its release rate in vitro and pharmacokinetics study in vivo. In order to improve the dissolution of hawthorn leaves flavonoids, self-microemulsifying technology was used to prepare the hawthorn leaves flavonoids self-microemulsion. Hawthorn leaves flavonoids self-microemulsifying drop pill was prepared with the PEG 6000. Studies were made on the in vitro release of flavonoids from hawthorn leaves self-micro-emulsifying membrane-moderated coated drop pills and the in vivo pharmacokinetic in rats. The prescription of flavonoids from hawthorn leaves self-micro-emulsifying drop pills was 0.25 g of flavonoids from hawthorn leaves, 0.25 g of iodophenyl maleimide, 0.375 g of polyethylene glycol 400, 0.375 g of cremophor RH 40 and 2 g of polyethylene glycol 6000. The optimized prescription was 4 g of ethyl cellulose 20, 0.64 g of polyethylene glycol 400, 1.8 g of diethyl phthalate, and the weight of coating materials increased by 3.5%. Flavonoids from hawthorn leaves self-micro-emulsifying membrane-moderated coated drop pills complied with the design of sustained-release in 12 h in terms of in vitro release and in vivo pharmacokinetic parameters in rats, and its bioavailability was 2.47 times of quick-release drop pills. Slightly soluble flavonoids from hawthorn leaves could be made into sustained-release preparations by the self-micro-emulsifying and coating technology.

  8. Assembly of bio-nanoparticles for double controlled drug release.

    Directory of Open Access Journals (Sweden)

    Wei Huang

    Full Text Available A critical limiting factor of chemotherapy is the unacceptably high toxicity. The use of nanoparticle based drug carriers has significantly reduced the side effects and facilitated the delivery of drugs. Source of the remaining side effect includes (1 the broad final in vivo distribution of the administrated nanoparticles, and (2 strong basal drug release from nanoparticles before they could reach the tumor. Despite the advances in pH-triggered release, undesirable basal drug release has been a constant challenge under in vivo conditions. In this study, functionalized single walled carbon nanohorn supported immunoliposomes were assembled for paclitaxel delivery. The immunoliposomes were formulated with polyethylene glycol, thermal stable and pH sensitive phospholipids. Each nanohorn was found to be encapsulated within one immunoliposome. Results showed a highly pH dependent release of paclitaxel in the presence of serum at body temperature with minimal basal release under physiological conditions. Upon acidification, paclitaxel was released at a steady rate over 30 days with a cumulative release of 90% of the loaded drug. The drug release results proved our hypothesized double controlled release mechanism from the nanoparticles. Other results showed the nanoparticles have doubled loading capacity compared to that of traditional liposomes and higher affinity to breast cancer cells overexpressing Her2 receptors. Internalized nanoparticles were found in lysosomes.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Sanja Petrović

    2017-12-01

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

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

    Science.gov (United States)

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

    2010-04-01

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

  12. Stimuli-Responsive Materials for Controlled Release Applications

    KAUST Repository

    Li, Song

    2015-04-01

    The controlled release of therapeutics has been one of the major challenges for scientists and engineers during the past three decades. To address this outstanding problem, the design and fabrication of stimuli-responsive materials are pursued to guarantee the controlled release of cargo at a specific time and with an accurate amount. Upon applying different stimuli such as light, magnetic field, heat, pH change, enzymes or redox, functional materials change their physicochemical properties through physical transformation or chemical reactions, allowing the release of payload agents on demand. This dissertation studied three stimuli-responsive membrane systems for controlled release from films of macro sizes to microcapsules of nano sizes. The first membrane system is a polymeric composite film which can decrease and sustain diffusion upon light irradiation. The photo-response of membranes is based on the photoreaction of cinnamic derivatives. The second one is composite membrane which can improve diffusion upon heating. The thermo-response of membranes comes from the volume phase transition ability of hydrogels. The third one is microcapsule which can release encapsulated agents upon light irradiation. The photo-response of capsules results from the photoreaction of nitrobenzyl derivatives. The study on these membrane systems reveals that stimuli-responsive release can be achieved by utilizing different functional materials on either macro or micro level. Based on the abundant family of smart materials, designing and fabricating stimuli-responsive systems shall lead to various advanced release processes on demand for biomedical applications.

  13. Controlled release of tocopherols from polymer blend films

    Science.gov (United States)

    Obinata, Noe

    Controlled release packaging has great potential to increase storage stability of foods by releasing active compounds into foods continuously over time. However, a major limitation in development of this technology is the inability to control the release and provide rates useful for long term storage of foods. Better understanding of the factors affecting active compound release is needed to overcome this limitation. The objective of this research was to investigate the relationship between polymer composition, polymer processing method, polymer morphology, and release properties of active compounds, and to provide proof of principle that compound release is controlled by film morphology. A natural antioxidant, tocopherol was used as a model active compound because it is natural, effective, heat stable, and soluble in most packaging polymers. Polymer blend films were produced from combination of linear low density polyethylene (LLDPE) and high density polyethylene (HDPE), polypropylene (PP), or polystyrene (PS) with 3000 ppm mixed tocopherols using conventional blending method and innovative blending method, smart blending with a novel mixer using chaotic advection. Film morphologies were visualized with scanning electron microscopy (SEM). Release of tocopherols into 95% ethanol as a food simulant was measured by UV/Visible spectrophotometry or HPLC, and diffusivity of tocopherols in the polymers was estimated from this data. Polymer composition (blend proportions) and processing methods have major effects on film morphology. Four different types of morphologies, dispersed, co-continuous, fiber, and multilayer structures were developed by either conventional extrusion or smart blending. With smart blending of fixed polymer compositions, different morphologies were progressively developed with fixed polymer composition as the number of rod rotations increased, providing a way to separate effects of polymer composition and morphology. The different morphologies

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

    Science.gov (United States)

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

    2007-04-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

  16. Studies on controlled release effervescent osmotic pump tablets from Traditional Chinese Medicine Compound Recipe.

    Science.gov (United States)

    Li, Xiao-Dong; Pan, Wei-San; Nie, Shu-Fang; Wu, Li-Jun

    2004-05-18

    A controlled release effervescent osmotic pump tablet (EOPT) of Traditional Chinese Medicine Compound Recipe (TCMCR), named Fuzilizhong prescription which includes acidic drugs consisted of many known and unknown effective components and has been used for several thousands years, was successfully prepared with sodium chloride, sodium hydrogen carbonate and hydroxypropylmethylcellulose(HPMC) as osmotic agents. Since the osmotic pressure in EOPT with sodium chloride and sodium hydrogen carbonate increased greatly, which was induced mostly by gas carbon dioxide generating from the reaction of sodium hydrogen carbonate and the acidic drugs in TCMCR after the fluid being imbibed into the compartment through the semipermeable membrane and the in vitro accumulative dissolution percent from prescription 3 was up to 96.6% at 14 hour, the problem that water insoluble drugs can not to be elementary osmotic pump tablet for its low dissolution rate was solved in the paper. On the basis of prescription 3, the drug in effervescent osmotic pump tablet was released controllably after HPMC was selected as retarder and has a good in-vitro-in-vivo correlation(IVIVC, r=0.9550). Threrfore, it could be concluded that the formulation of TCMCR is appropriate to being made into EOPT, which improves acidic drugs composed of soluble and poorly soluble components release more greatly and controllably. From the point of this, water insoluble drugs can be designed to elementary osmotic pump tablet for more complete dissolution release.

  17. Nutrients Release from a Novel Gel-Based Slow/Controlled Release Fertilizer

    Directory of Open Access Journals (Sweden)

    H. Ding

    2016-01-01

    Full Text Available A novel gel-based slow/controlled release fertilizer (G-CRF was developed, which was produced by combining various natural, seminatural, and/or synthetic organic macromolecule materials and natural inorganic mineral with conventional NPK fertilizers. Its nutrient release characteristics were studied to compare with conventional fertilizers through the soil column leaching method. The influences of soil factors, including temperature, pH, water, and nutrient contents in the G-CRF on nutrient release, were also investigated through soil-water incubation method. These results indicated that the G-CRF had better effect on controlling release of N, P, and K nutrients, and the effect was more efficient when soil-water content was lower than 45% (w/w, temperature was below 35°C, and soil pH was in the range from weak acid to neutral. In addition, considering the effect of controlling nutrient release and cost of the materials in the G-CRF, it is recommended that the most feasible NPK nutrient contents in the G-CRF ranged from 30 to 35%.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-07-25

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

  19. Mucoadhesive controlled release microcapsules of indomethacin: optimization and stability study.

    Science.gov (United States)

    Ibrahim, Hany M; Ahmed, Tarek A; Lila, Ahmed E A; Samy, Ahmed M; Kaseem, Ala A; Nutan, Mohammad T H

    2010-01-01

    The aim of this project was to develop and optimize indomethacin microcapsules composed of multiple mucoadhesive polymers for high drug entrapment, good mucoadhesiveness and drug release in a controlled fashion over a longer period of time. Microcapsules containing sodium alginate, sodium carboxymethylcellulose, methylcellulose, Carbopol 934 and hydroxypropyl methylcellulose were prepared by orifice-ionic gelation method. The effects of composition of microcapsules on drug entrapment efficacy, drug release and mucoadhesive character were determined by mixture statistical design. Most formulations exhibited good mucoadhesive property in everted intestinal sac test. Drug entrapment efficiency (68-94%) was dependent on the type of polymers. Drug release (92-100%) extended over 12 h. The optimized formulation resulted in drug entrapment efficiency of 89.3%, drug release of 94.8% and mucoadhesiveness of 30.4%. All formulations were stable for more than 1.5 years. The optimized mucoadhesive microcapsules are promising for controlled delivery of indomethacin with twice a day oral administration.

  20. Magnetic molecularly imprinted polymer for aspirin recognition and controlled release

    Science.gov (United States)

    Kan, Xianwen; Geng, Zhirong; Zhao, Yao; Wang, Zhilin; Zhu, Jun-Jie

    2009-04-01

    Core-shell structural magnetic molecularly imprinted polymers (magnetic MIPs) with combined properties of molecular recognition and controlled release were prepared and characterized. Magnetic MIPs were synthesized by the co-polymerization of methacrylic acid (MAA) and trimethylolpropane trimethacrylate (TRIM) around aspirin (ASP) at the surface of double-bond-functionalized Fe3O4 nanoparticles in chloroform. The obtained spherical magnetic MIPs with diameters of about 500 nm had obvious superparamagnetism and could be separated quickly by an external magnetic field. Binding experiments were carried out to evaluate the properties of magnetic MIPs and magnetic non-molecularly imprinted polymers (magnetic NIPs). The results demonstrated that the magnetic MIPs had high adsorption capacity and selectivity to ASP. Moreover, release profiles and release rate of ASP from the ASP-loaded magnetic MIPs indicated that the magnetic MIPs also had potential applications in drug controlled release.

  1. Design and characterization of controlled release tablet of metoprolol

    Directory of Open Access Journals (Sweden)

    Gautam Singhvi

    2012-01-01

    Full Text Available Metoprolol succinate is a selective beta-adrenergic receptor blocker useful in treatment of hypertension, angina and heart failure. The purpose of the present work was to design and evaluate controlled release matrix type tablet of Metoprolo succinate using HPMC K15M and Eudragit (RLPO and RSPO as a matrix forming agents. Effect of various polymer alone and combinations were studied in pH 1.2 buffer using USP type II paddle at 50 rpm. HPMC was used to form firm gel with Eudragit polymer. Formulation with Equal proportion (1:1 of Eudragit RSPO and RLPO showed optimum drug release t50 =7 hrs and t100 =16 hrs indicate optimum permeability for drug release from matrix. The drug release mechanism was predominantly found to be Non-Fickian diffusion controlled.

  2. Magnetic molecularly imprinted polymer for aspirin recognition and controlled release

    Energy Technology Data Exchange (ETDEWEB)

    Kan Xianwen; Geng Zhirong; Zhao Yao; Wang Zhilin; Zhu Junjie [State Key Laboratory of Coordination Chemistry, MOE Key Lab of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, 22 Hankou Road, Nanjing 210093 (China)], E-mail: wangzl@nju.edu.cn, E-mail: jjzhu@nju.edu.cn

    2009-04-22

    Core-shell structural magnetic molecularly imprinted polymers (magnetic MIPs) with combined properties of molecular recognition and controlled release were prepared and characterized. Magnetic MIPs were synthesized by the co-polymerization of methacrylic acid (MAA) and trimethylolpropane trimethacrylate (TRIM) around aspirin (ASP) at the surface of double-bond-functionalized Fe{sub 3}O{sub 4} nanoparticles in chloroform. The obtained spherical magnetic MIPs with diameters of about 500 nm had obvious superparamagnetism and could be separated quickly by an external magnetic field. Binding experiments were carried out to evaluate the properties of magnetic MIPs and magnetic non-molecularly imprinted polymers (magnetic NIPs). The results demonstrated that the magnetic MIPs had high adsorption capacity and selectivity to ASP. Moreover, release profiles and release rate of ASP from the ASP-loaded magnetic MIPs indicated that the magnetic MIPs also had potential applications in drug controlled release.

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

    Science.gov (United States)

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

    2013-04-01

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

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

    Science.gov (United States)

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

    2010-08-01

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

  5. 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

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

    Science.gov (United States)

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

    2014-06-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-04-15

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

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

    Science.gov (United States)

    Benoit-Marand, Marianne; O'Donnell, Patricio

    2008-09-01

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

  9. FERLENT - a controlled release fertilizer produced from a polymer material

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2011-07-01

    The possibility to use release controlled fertilizers in the agriculture of the tropical countries is more important than in the agriculture of the countries of the template regions. In this context, this work purpose the development of a new Fertilizer of Controlled Release named FERLENT, which was obtained starting from a polymeric material, under controlled conditions which allowed to corroborate the adjustment of the synthesis parameters under the modulate of nutrients liberation. It was characterized by, Scanning Microscopy Electron (SEM), Thermogravimetric analysis (TGA), Nuclear Magnetic Resonance (NMR) and infrared spectroscopy (FTIR). (author)

  10. Chemical analysis of substrates with controlled release fertilizer

    NARCIS (Netherlands)

    Kreij, de C.

    2004-01-01

    Water-soluble fertilizer added to media containing controlled release fertilizer cannot be analysed with the 1:1.5 volume water extract, because the latter increases the element content in the extract. During storage and stirring or mixing the substrate with the extractant, part of the controlled

  11. Controlled release fertilizer improves quality of container longleaf pine seedlings

    Science.gov (United States)

    R. Kasten Dumroese; Jeff Parkhurst; James P. Barnett

    2005-01-01

    In an operational trial, increasing the amount of nitrogen (N) applied to container longleaf pine seedlings by incorporating controlled release fertilizer (CRF) into the media improved seedling growth and quality. Compared with control seedlings that received 40 mg N, seedlings receiving 66 mg N through CRF supplemented with liquid fertilizer had needles that were 4 in...

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

    Directory of Open Access Journals (Sweden)

    Daniela N.B. Felipucci

    2011-10-01

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

  13. Photo-inducible crosslinked nanoassemblies for pH-controlled drug release.

    Science.gov (United States)

    Dickerson, Matthew; Winquist, Nickolas; Bae, Younsoo

    2014-05-01

    To control drug release from block copolymer nanoassemblies by variation in the degree of photo-crosslinking and inclusion of acid sensitive linkers. Poly(ethylene glycol)-poly(aspartate-hydrazide-cinnamate) (PEG-CNM) block copolymers were prepared and conjugated with a model drug, doxorubicin (DOX), through acid sensitive hydrazone linkers. The block copolymers formed photo-inducible, self-assembled nanoassemblies (piSNAs), which were used to produce photo-inducible crosslinked nanoassemblies (piCNAs) through UV crosslinking. The nanoassemblies were characterized to determine particle size, surface charge, pH- and crosslinking-dependent DOX release, in vitro cytotoxicity, and intracellular uptake as a function of photo-crosslinking degree. Nanoassemblies with varying photo-crosslinking degrees were successfully prepared while retaining particle size and surface charge. Photo-crosslinking caused no noticeable change in DOX release from the nanoassemblies at pH 7.4, but the DOX-loaded nanoassemblies modulated drug release as a function of crosslinking at pH 6.0. The nanoassemblies showed similar cytotoxicity regardless of crosslinking degrees, presumably due to the low cellular uptake and cell nucleus drug accumulation. Photo-crosslinking is useful to control drug release from pH-sensitive block copolymer nanoassemblies as a function of crosslinking without altering the particle properties, and thus providing unique tools to investigate the pharmaceutical effects of drug release on cellular response.

  14. Antimicrobial beeswax coated polylactide films with silver control release capacity.

    Science.gov (United States)

    Martínez-Abad, Antonio; Lagarón, Jose Maria; Ocio, María Jose

    2014-03-17

    Although the application of silver based antimicrobial systems is a widespread technology, its implementation in areas such as food packaging is still challenging. The present paper describes the fabrication of poly(lactic acid) (PLA) coated with beeswax with controlled release properties for sustained antimicrobial performance. Release of silver ions from the polymers was monitored voltammetrically under various conditions (surface contact, immersion in various liquid media and at different pH values) throughout at least 7days. A higher release was noted with decreasing pH while surface release was much slower than the release when immersed in liquid medium. While uncoated films demonstrated a high burst release which in some instances implied surpassing some current migration restrictions (<0.05mg/kg food), the addition of a beeswax layer allowed a sustained release of the antimicrobial compound. Increasing the thickness of the beeswax layer resulted in an increase in the water barrier properties of the films while reducing the relatively constant values of sustained release. Antimicrobial performance was correlated with the release of silver ions, indicating threshold concentrations for biocide action of <6μg/L and 9-14μg/L for surface contact and in liquid media, respectively. Either by surface contact or by immersion in growth medium or vegetable soup, the coated films displayed a strong bactericidal effect against Salmonella enterica. The application of this functional barrier thus offers the possibility of tuning the release profiles of the films to suit a specific application and puts forth the possible suitability of these materials for food packaging or other migration sensitive applications. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. A combined chitosan/nano-size hydroxyapatite system for the controlled release of icariin.

    Science.gov (United States)

    Fan, Junjun; Bi, Long; Wu, Tao; Cao, Liangguo; Wang, Dexin; Nan, Kaihui; Chen, Jingdi; Jin, Dan; Jiang, Shan; Pei, Guoxian

    2012-02-01

    Icariin, a plant-derived flavonol glycoside, has been proved as an osteoinductive agent for bone regeneration. For this reason, we developed an icariin-loaded chitosan/nano-sized hydroxyapatite (IC-CS/HA) system which controls the release kinetics of icariin to enhance bone repairing. First, by Fourier transform infrared spectroscopy, we found that icariin was stable in the system developed without undergoing any chemical changes. On the other hand, X-ray diffraction, scanning electron microscopy and mechanical test revealed that the introduction of icariin did not remarkably change the phase, morphology, porosity and mechanical strength of the CS/HA composite. Then the hydrolytic degradation and drug release kinetics in vitro were investigated by incubation in phosphate buffered saline solution. The results indicated that the icariin was released in a temporally controlled manner and the release kinetics could be governed by degradation of both chitosan and hydroxyapatite matrix. Finally the in vitro bioactivity assay revealed that the loaded icariin was biologically active as evidenced by stimulation of bone marrow derived stroma cell alkaline phosphatase activity and formation of mineralized nodules. This successful IC-CS/HA system offers a new delivery method of osteoinductive agents and a useful scaffold design for bone regeneration.

  16. Chitosan-Genipin Microspheres for the Controlled Release of Drugs: Clarithromycin, Tramadol and Heparin

    Directory of Open Access Journals (Sweden)

    Ruth Harris

    2010-05-01

    Full Text Available The aim of this study was to first evaluate whether the chitosan hydrochloride-genipin crosslinking reaction is influenced by factors such as time, and polymer/genipin concentration, and second, to develop crosslinked drug loaded microspheres to improve the control over drug release. Once the crosslinking process was characterized as a function of the factors mentioned above, drug loaded hydrochloride chitosan microspheres with different degrees of crosslinking were obtained. Microspheres were characterized in terms of size, morphology, drug content, surface charge and capacity to control in vitro drug release. Clarithromycin, tramadol hydrochloride, and low molecular weight heparin (LMWH were used as model drugs. The obtained particles were spherical, positively charged, with a diameter of 1–10 μm. X-Ray diffraction showed that there was an interaction of genipin and each drug with chitosan in the microspheres. In relation to the release profiles, a higher degree of crosslinking led to more control of drug release in the case of clarithromycin and tramadol. For these drugs, optimal release profiles were obtained for microspheres crosslinked with 1 mM genipin at 50 ºC for 5 h and with 5 mM genipin at 50 ºC for 5 h, respectively. In LMWH microspheres, the best release profile corresponded to 0.5 mM genipin, 50 ºC, 5 h. In conclusion, genipin showed to be eligible as a chemical-crosslinking agent delaying the outflow of drugs from the microspheres. However, more studies in vitro and in vivo must be carried out to determine adequate crosslinking conditions for different drugs.

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

    Directory of Open Access Journals (Sweden)

    Bronckers Antonius LJJ

    2006-02-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-02-15

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

  19. Controlling pesticide release via structuring agropolymer and nanoclays based materials.

    Science.gov (United States)

    Chevillard, Anne; Angellier-Coussy, Hélène; Guillard, Valérie; Gontard, Nathalie; Gastaldi, Emmanuelle

    2012-02-29

    The potential use of nanoclays for modulating transfer properties of active agents in bio-sourced polymers was explored. For this purpose, new pesticide formulations were designed by combining wheat gluten, ethofumesate (model pesticide) and three montmorillonites (MMT) using a bi-vis extrusion process. Controlled release properties, evaluated through release experiments in water, were discussed in relation to the material formulations and their resulting structure. Partition coefficients were calculated from experimental data and diffusivity values were identified with a Fick's second law mechanistic model. The effect of temperature on release pattern was also evaluated and the activation energy of diffusion was determined. Ethofumesate release was slowed down for all wheat gluten based-formulations as compared to the commercial product. This slow release effect was increased in the presence of hydrophobic MMTs, due to a higher affinity for ethofumesate than for wheat gluten. Contrarily, hydrophilic MMT, displaying a greater affinity for wheat gluten than for ethofumesate seemed ineffective to slow down its release despite the tortuous pathway achieved through a well-exfoliated structure. To conclude, the release mechanisms would be rather governed by pesticide/MMT interactions than MMT/polymer matrix in the case of a hydrophobic pesticide such as ethofumesate and a hydrophilic matrix such as wheat gluten. Copyright © 2011 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    Esmaeili, Akbar; Asgari, Azadeh

    2015-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Malte Scholz

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

  2. Evaluation of microwave assisted grafted sago starch as controlled release polymeric carrier.

    Science.gov (United States)

    Singh, Akhilesh Vikram; Nath, Lila Kanta

    2013-09-01

    In the present investigation an attempt has been made to develop a new co-polymeric material for controlled release tablet formulations. The acrylamide grafting was successfully performed on the backbone of sago starch. The modified starch was tested for acute toxicity and drug-excipient compatibility study. The grafted material was used in making of controlled release tablets of lamivudine. The formulations were evaluated for physical characteristics such as hardness, friability, %drug content and weight variations. The in vitro release study showed that the optimized formulation exhibited highest correlation (R) value in case of Higuchi model and the release mechanism of the optimized formulation predominantly exhibited combination of diffusion and erosion process. There was a significant difference in the pharmacokinetic parameters (T(max), C(max), AUC, V(d), T(1/2) and MDT) of the optimized formulation as compared to the marketed conventional tablet Lamivir(®) was observed. The pharmacokinetics parameters were showed controlled pattern and better bioavailability. The optimized formulation exhibited good stability and release profile at the accelerated stability conditions. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Self-assembled polyelectrolyte complexes films as efficient compression coating layers for controlled-releasing tablets.

    Science.gov (United States)

    Li, Wenyan; Huo, Mengmeng; Sen Chaudhuri, Arka; Yang, Chen; Cao, Dazhong; Wu, Zhenghong; Qi, Xiaole

    2017-05-01

    Currently, polysaccharide-based hydrogels are widely studied macromolecular networks to modify drug dissolution from controlled-releasing matrix tablets. Among them, polyelectrolyte complexes (PEC) films consisted of chitosan (CS) and sodium alginate (SA) could be obtained via spontaneously assembling under physiological gastrointestinal environment. Here, we utilized these self-assembled PEC films as an efficient coating materials to develop controlled-released matrix tablets through compression coating process, with paracetamol (APAP) as model drug. The constitutive and morphology characteristic studies on these PEC films illustrated that the mixture of CS and SA with the weight ratio of 1:1 would be an promising outer layer for compression-coating tablets. In addition, the in vitro drug releasing behavior experiments demonstrated that the optimized compression coating tablets displayed satisfied zero-order drug releasing profits. Furthermore, the in vivo pharmacokinetic studies of these APAP loaded compression-coated tablets in New Zealand rabbits gave that the T max (12.32 ± 1.05 h) was significantly prolonged (p tablets (Jinfuning ® ) after oral administration. These studies suggest that the compression-coated tablets with self-assembled PEC film as coating outer layer may be a promising strategy for peroral controlled release delivery system of water soluble drugs.

  4. Method and apparatus for controlling accidental releases of tritium

    Science.gov (United States)

    Galloway, Terry R. [Berkeley, CA

    1980-04-01

    An improvement in a tritium control system based on a catalytic oxidation reactor wherein accidental releases of tritium into room air are controlled by flooding the catalytic oxidation reactor with hydrogen when the tritium concentration in the room air exceeds a specified limit. The sudden flooding with hydrogen heats the catalyst to a high temperature within seconds, thereby greatly increasing the catalytic oxidation rate of tritium to tritiated water vapor. Thus, the catalyst is heated only when needed. In addition to the heating effect, the hydrogen flow also swamps the tritium and further reduces the tritium release.

  5. Controlled-release nanoencapsulating microcapsules to combat inflammatory diseases

    Directory of Open Access Journals (Sweden)

    Baek JS

    2017-06-01

    Full Text Available Jong-Suep Baek,1 Eng Wan Yeo,1 Yin Hao Lee,2 Nguan Soon Tan,2 Say Chye Joachim Loo1,3 1School of Materials Science and Engineering, Nanyang Technological University, Singapore; 2School of Biological Sciences, Nanyang Technological University, Singapore; 3Singapore Centre on Environmental Life Sciences Engineering (SCELSE, Nanyang Technological University, Singapore Abstract: The World Health Organization (WHO has reported that globally 235 million people suffer from chronic and other inflammatory diseases. The short half-lives of nonsteroidal anti-inflammatory drugs (NSAIDs and their notoriety in causing gastrointestinal discomforts, warrants these drugs to be released in a controlled and sustained manner. Although polymeric particles have been widely used for drug delivery, there are few reports that showcase their ability in encapsulating and sustaining the release of NSAIDs. In this paper, polymeric nanoencapsulating microcapsules loaded with NSAIDs were fabricated using solid/water/oil/water emulsion solvent evaporation method. Two NSAIDs, ibuprofen and naproxen, were first pre-loaded into nanoparticles and then encapsulated into a larger hollow microcapsule that contained the third NSAID, celecoxib. A high encapsulation efficiency (% of these NSAIDs was achieved and a sustained release (up to 30 days of these drugs in phosphate-buffered saline was observed. Then, a gastrointestinal drug – cimetidine (CIM – was co-loaded with the NSAIDs. This floating delivery system exhibited excellent buoyancy (~88% up to 24 h in simulated gastric fluid. It also allowed a sequential release of the drugs, whereby an immediate release of CIM followed by NSAIDs was observed. Drug release of the NSAIDs observed Fickian diffusion mechanism, whereas CIM observed non-Fickian diffusion. Therefore, this delivery system is a promising platform to control the delivery of NSAIDs to combat inflammatory diseases, thereby protecting against possible gastrointestinal

  6. Controlled Release of Multiple Therapeutics from Silicone Hydrogel Contact Lenses

    Science.gov (United States)

    White, Charles J.; DiPasquale, Stephen A.; Byrne, Mark E.

    2016-01-01

    Purpose The majority of contact lens wearers experience a significant level of ocular discomfort associated with lens wear, often within hours of wear, related to dry lenses, inflammation, protein adhesion to the lens surface, etc. Application of controlled drug release techniques has focused on the incorporation and/or release of a single comfort molecule from a lens including high molecular weight comfort agents or pharmaceutical agents. Previous studies have sought to mitigate the occurrence of only single propagators of discomfort. Clinical studies with eye drop solutions have shown that a mixture of diverse comfort agents selected to address multiple propagators of discomfort provide the greatest and longest lasting sensations of comfort for the patient. In this paper, multiple propagators of discomfort are addressed through the simultaneous release of four molecules from a novel contact lens to ensure high level of lens wear comfort. Methods Silicone hydrogel contact lenses were engineered via molecular imprinting strategies to simultaneously release up to four template molecules including hydropropyl methylcellulose (HPMC), trehalose, ibuprofen, and prednisolone. Results By adjusting the ratio of functional monomer to comfort molecule, a high level of control was demonstrated over the release rate. HPMC, trehalose, ibuprofen, and prednisolone were released at therapeutically relevant concentrations with varying rates from a single lens. Conclusions The results indicate use as daily disposable lenses for single day release or extended-wear lenses with multiple day release. Imprinted lenses are expected to lead to higher efficacy for patients compared to topical eye drops by improving compliance and mitigating concentration peaks and valleys associated with multiple drops. PMID:26945177

  7. Use of hydrophilic and hydrophobic polymers for the development of controlled release tizanidine matrix tablets

    Directory of Open Access Journals (Sweden)

    Tariq Ali

    2014-12-01

    Full Text Available The aim of the present study was to develop tizanidine controlled release matrix. Formulations were designed using central composite method with the help of design expert version 7.0 software. Avicel pH 101 in the range of 14-50% was used as a filler, while HPMC K4M and K100M in the range of 25-55%, Ethylcellulose 10 ST and 10FP in the range of 15 - 45% and Kollidon SR in the range of 25-60% were used as controlled release agents in designing different formulations. Various physical parameters including powder flow for blends and weight variation, thickness, hardness, friability, disintegration time and in-vitro release were tested for tablets. Assay of tablets were also performed as specified in USP 35 NF 32. Physical parameters of both powder blend and compressed tablets such as compressibility index, angle of repose, weight variation, thickness, hardness, friability, disintegration time and assay were evaluated and found to be satisfactory for formulations K4M2, K4M3, K4M9, K100M2, K100M3, K100M9, E10FP2, E10FP9, KSR2, KSR3 & KSR9. In vitro dissolution study was conducted in 900 ml of 0.1N HCl, phosphate buffer pH 4.5 and 6.8 medium using USP Apparatus II. In vitro release profiles indicated that formulations prepared with Ethocel 10 standard were unable to control the release of drug while formulations K4M2, K100M9, E10FP2 & KSR2 having polymer content ranging from 40-55% showed a controlled drug release pattern in the above mentioned medium. Zero-order drug release kinetics was observed for formulations K4M2, K100M9, E10FP2 & KSR2. Similarity test (f2 results for K4M2, E10FP2 & KSR2 were found to be comparable with reference formulation K100M9. Response Surface plots were also prepared for evaluating the effect of independent variable on the responses. Stability study was performed as per ICH guidelines and the calculated shelf life was 24-30 months for formulation K4M2, K100M9 and E10FP2.

  8. On-off switch-controlled doxorubicin release from thermo- and pH-responsive coated bimagnetic nanocarriers

    Science.gov (United States)

    Hammad, Mohaned; Nica, Valentin; Hempelmann, Rolf

    2016-08-01

    A switch-controlled drug release system is designed by coating of core/shell bimagnetic nanoparticles with a pH- and thermo-responsive polymer shell, which can be used as hyperthermic agent, drug carrier, and for controlled release. Doxorubicin is loaded onto the surface of the last coating layer, and a high loading efficiency of 90.5 % is obtained. The nanocarriers are characterized by FTIR, dynamic light scattering, Zeta potential, TEM, In vitro hyperthermia, and vibrating sample magnetometry. The core/shell magnetic nanoparticles (Zn0.4Co0.6Fe2O4@Zn0.4Mn0.6Fe2O4) exhibit a superparamagnetic behavior with a saturation magnetization around 45.6 emu/g and a high specific absorption rate of up to 360 W/g. The in vitro drug release experiments confirm that only a small amount of doxorubicin is released at body temperature and physiological pH, whereas a high drug release is obtained at acidic tumor pH under hyperthermia conditions (43 °C). The functionalized core/shell bimagnetic nanocarriers facilitate controllable release of doxorubicin as an effect of induced thermo- and pH-responsiveness of the polymer when are subjected to a high-frequency alternating magnetic field at acidic pH; thereby the drug release rate is controlled using on-off cycles of the applied field.

  9. Role of nitric oxide in control of prolactin release by the adenohypophysis.

    Science.gov (United States)

    Duvilanski, B H; Zambruno, C; Seilicovich, A; Pisera, D; Lasaga, M; Diaz, M C; Belova, N; Rettori, V; McCann, S M

    1995-01-01

    Nitric oxide synthase-containing cells were visualized in the anterior pituitary gland by immunocytochemistry. Consequently, we began an evaluation of the possible role of NO in the control of anterior pituitary function. Prolactin is normally under inhibitory hypothalamic control, and in vitro the gland secretes large quantities of the hormone. When hemipituitaries were incubated for 30 min in the presence of sodium nitroprusside, a releaser of NO, prolactin release was inhibited. This suppression was completely blocked by the scavenger of NO, hemoglobin. Analogs of arginine, such as NG-monomethyl-L-arginine (NMMA, where NG is the terminal guanidino nitrogen) and nitroarginine methyl ester, inhibit NO synthase. Incubation of hemipituitaries with either of these compounds significantly increased prolactin release. Since in other tissues most of the actions of NO are mediated by activation of soluble guanylate cyclase with the formation of cyclic GMP, we evaluated the effects of cyclic GMP on prolactin release. Cyclic GMP (10 mM) produced an approximately 40% reduction in prolactin release. Prolactin release in vivo and in vitro can be stimulated by several peptides, which include vasoactive intestinal polypeptide and substance P. Consequently, we evaluated the possible role of NO in these stimulations by incubating the glands in the presence of either of these peptides alone or in combination with NMMA. In the case of vasoactive intestinal polypeptide, the significant stimulation of prolactin release was augmented by NMMA to give an additive effect. In the case of substance P, there was a smaller but significant release of prolactin that was not significantly augmented by NMMA. We conclude that NO has little effect on the stimulatory action of these two peptides on prolactin release. Dopamine (0.1 microM), an inhibitor of prolactin release, reduced prolactin release, and this inhibitory action was significantly blocked by either hemoglobin (20 micrograms/ml) or

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

    Science.gov (United States)

    Shah, Kifayat Ullah; Khan, Gul Majid

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Kifayat Ullah Shah

    2012-01-01

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

  12. Magnetic hydrogel nanocomposites for remote controlled pulsatile drug release.

    Science.gov (United States)

    Satarkar, Nitin S; Hilt, J Zach

    2008-09-24

    Hydrogel nanocomposites are novel macromolecular biomaterials that promise to impact various applications in medical and pharmaceutical fields. In this paper, magnetic nanocomposites of temperature responsive hydrogels were used to illustrate remote controlled (RC) drug delivery. A high frequency alternating magnetic field (AMF) was used to trigger the on-demand pulsatile drug release from the nanocomposites. Nanocomposites were synthesized by incorporation of superparamagnetic Fe(3)O(4) particles in negative temperature sensitive poly (N-isopropylacrylamide) hydrogels. Pulses of AMF were applied to the nanocomposites and the kinetics of collapse and recovery were characterized. Application of AMF resulted in uniform heating within the nanocomposites leading to accelerated collapse and squeezing out large amounts of imbibed drug (release at a faster rate). Remote controlled pulsatile drug release was characterized for different drugs as well as for different ON-OFF durations of the AMF.

  13. Magnetic Compression of Polyelectrolyte Microcapsules for Controlled Release.

    Science.gov (United States)

    Hu, Yanan; Liu, Chuanyong; Li, Dongzhi; Long, Yue; Song, Kai; Tung, Chen-Ho

    2015-10-20

    In this study, microcapsules with a magnetic particle as the core and polyelectrolyte multilayers as the shell were fabricated. The cavity of the microcapsules was created by etching the SiO2 layer, which was first coated on the magnetic core particle, and the size of the cavity can be adjusted by the thickness of the SiO2 layer. This magnetically responsive microcapsule deforms upon application of a constant magnetic field and results in the release of the core content, and the release velocity could be controlled by the strength of the magnetic field. This release mechanism is proactive and repeatable, combined with its localized and remote controllability; it can be a powerful tool for delivering medical agents on site.

  14. Optimization of primaquine diphosphate tablet formulation for controlled drug release using the mixture experimental design.

    Science.gov (United States)

    Duque, Marcelo Dutra; Kreidel, Rogério Nepomuceno; Taqueda, Maria Elena Santos; Baby, André Rolim; Kaneko, Telma Mary; Velasco, Maria Valéria Robles; Consiglieri, Vladi Olga

    2013-01-01

    A tablet formulation based on hydrophilic matrix with a controlled drug release was developed, and the effect of polymer concentrations on the release of primaquine diphosphate was evaluated. To achieve this purpose, a 20-run, four-factor with multiple constraints on the proportions of the components was employed to obtain tablet compositions. Drug release was determined by an in vitro dissolution study in phosphate buffer solution at pH 6.8. The polynomial fitted functions described the behavior of the mixture on simplex coordinate systems to study the effects of each factor (polymer) on tablet characteristics. Based on the response surface methodology, a tablet composition was optimized with the purpose of obtaining a primaquine diphosphate release closer to a zero order kinetic. This formulation released 85.22% of the drug for 8 h and its kinetic was studied regarding to Korsmeyer-Peppas model, (Adj-R(2) = 0.99295) which has confirmed that both diffusion and erosion were related to the mechanism of the drug release. The data from the optimized formulation were very close to the predictions from statistical analysis, demonstrating that mixture experimental design could be used to optimize primaquine diphosphate dissolution from hidroxypropylmethyl cellulose and polyethylene glycol matrix tablets.

  15. Controlled release of cytokines using silk-biomaterials for macrophage polarization.

    Science.gov (United States)

    Reeves, Andrew R D; Spiller, Kara L; Freytes, Donald O; Vunjak-Novakovic, Gordana; Kaplan, David L

    2015-12-01

    Polarization of macrophages into an inflammatory (M1) or anti-inflammatory (M2) phenotype is important for clearing pathogens and wound repair, however chronic activation of either type of macrophage has been implicated in several diseases. Methods to locally control the polarization of macrophages is of great interest for biomedical implants and tissue engineering. To that end, silk protein was used to form biopolymer films that release either IFN-γ or IL-4 to control the polarization of macrophages. Modulation of the solubility of the silk films through regulation of β-sheet (crystalline) content enabled a short-term release (4-8 h) of either cytokine, with smaller amounts released out to 24 h. Altering the solubility of the films was accomplished by varying the time that the films were exposed to water vapor. The released IFN-γ or IL-4 induced polarization of THP-1 derived macrophages into the M1 or M2 phenotypes, respectively. The silk biomaterials were able to release enough IFN-γ or IL-4 to repolarize the macrophage from M1 to M2 and vice versa, demonstrating the well-established plasticity of macrophages. High β-sheet content films that are not soluble and do not release the trapped cytokines were also able to polarize macrophages that adhered to the surface through degradation of the silk protein. Chemically conjugating IFN-γ to silk films through disulfide bonds allowed for longer-term release to 10 days. The release of covalently attached IFN-γ from the films was also able to polarize M1 macrophages in vitro. Thus, the strategy described here offers new approaches to utilizing biomaterials for directing the polarization of macrophages. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2013-06-14

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

  17. Blend Hydrogel Microspheres of Carboxymethyl Chitosan and Gelatin for the Controlled Release of 5-Fluorouracil

    Directory of Open Access Journals (Sweden)

    Vanarchi Rajini Kanth

    2017-03-01

    Full Text Available Carboxymethyl chitosan (CMCS was synthesized and blended with gelatin (GE to prepare hydrogel microspheres by w/o emulsion cross-linking in the presence of glutaraldehyde (GA, which acted as a cross-linker. 5-Fluorouracil (5-FU was encapsulated to investigate its controlled release (CR characteristics in acidic (pH 1.2 and alkaline (pH 7.4 buffer media. The microspheres which formed were spherical in nature, with smooth surfaces, as judged by the scanning electron microscopy (SEM. Fourier transform infrared spectroscopy (FTIR confirmed the carboxymethylation of CS and the chemical stability of 5-FU in the formulations. Differential scanning calorimetry (DSC and X-ray diffraction (XRD confirmed the physical state and molecular level dispersion of 5-FU. Equilibrium swelling of microspheres was performed in water, in order to understand the water uptake properties. The in vitro release of 5-FU was extended up to 12 h in pH 7.4 phosphate buffer, revealing an encapsulation efficiency of 72%. The effects of blend composition, the extent of cross-linking, and initial drug loading on the in vitro release properties, were investigated. When analyzed through empirical equations, the release data suggested a non-Fickian transport mechanism.

  18. Natural Non-Mulberry Silk Nanoparticles for Potential-Controlled Drug Release.

    Science.gov (United States)

    Wang, Juan; Yin, Zhuping; Xue, Xiang; Kundu, Subhas C; Mo, Xiumei; Lu, Shenzhou

    2016-12-01

    Natural silk protein nanoparticles are a promising biomaterial for drug delivery due to their pleiotropic properties, including biocompatibility, high bioavailability, and biodegradability. Chinese oak tasar Antheraea pernyi silk fibroin (ApF) nanoparticles are easily obtained using cations as reagents under mild conditions. The mild conditions are potentially advantageous for the encapsulation of sensitive drugs and therapeutic molecules. In the present study, silk fibroin protein nanoparticles are loaded with differently-charged small-molecule drugs, such as doxorubicin hydrochloride, ibuprofen, and ibuprofen-Na, by simple absorption based on electrostatic interactions. The structure, morphology and biocompatibility of the silk nanoparticles in vitro are investigated. In vitro release of the drugs from the nanoparticles depends on charge-charge interactions between the drugs and the nanoparticles. The release behavior of the compounds from the nanoparticles demonstrates that positively-charged molecules are released in a more prolonged or sustained manner. Cell viability studies with L929 demonstrated that the ApF nanoparticles significantly promoted cell growth. The results suggest that Chinese oak tasar Antheraea pernyi silk fibroin nanoparticles can be used as an alternative matrix for drug carrying and controlled release in diverse biomedical applications.

  19. Blend Hydrogel Microspheres of Carboxymethyl Chitosan and Gelatin for the Controlled Release of 5-Fluorouracil.

    Science.gov (United States)

    Kanth, Vanarchi Rajini; Kajjari, Praveen B; Madalageri, Priya M; Ravindra, Sakey; Manjeshwar, Lata S; Aminabhavi, Tejraj M

    2017-03-27

    Carboxymethyl chitosan (CMCS) was synthesized and blended with gelatin (GE) to prepare hydrogel microspheres by w/o emulsion cross-linking in the presence of glutaraldehyde (GA), which acted as a cross-linker. 5-Fluorouracil (5-FU) was encapsulated to investigate its controlled release (CR) characteristics in acidic (pH 1.2) and alkaline (pH 7.4) buffer media. The microspheres which formed were spherical in nature, with smooth surfaces, as judged by the scanning electron microscopy (SEM). Fourier transform infrared spectroscopy (FTIR) confirmed the carboxymethylation of CS and the chemical stability of 5-FU in the formulations. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) confirmed the physical state and molecular level dispersion of 5-FU. Equilibrium swelling of microspheres was performed in water, in order to understand the water uptake properties. The in vitro release of 5-FU was extended up to 12 h in pH 7.4 phosphate buffer, revealing an encapsulation efficiency of 72%. The effects of blend composition, the extent of cross-linking, and initial drug loading on the in vitro release properties, were investigated. When analyzed through empirical equations, the release data suggested a non-Fickian transport mechanism.

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

    Directory of Open Access Journals (Sweden)

    V. Raj

    2016-10-01

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

  1. Multiparticulate Drug Delivery Systems for Controlled Release | Dey ...

    African Journals Online (AJOL)

    Pharmaceutical invention and research are increasingly focusing on delivery systems which enhance desirable therapeutic objectives while minimising side effects. Recent trends indicate that multiparticulate drug delivery systems are especially suitable for achieving controlled or delayed release oral formulations with low ...

  2. Application of polymeric nanoparticles for controlled release of ...

    African Journals Online (AJOL)

    The most effectiveness extract was for 0.4% concentration by observing reduction in the eggs mass compared to control group. The nanomaterial proved to be able to anchor and release the insecticide gradually in pH between 5 and 6 regions, which makes it feasible for use in cattle, prolonging the exposure time between ...

  3. Controlled release of diclofenac sodium from pH-responsive ...

    Indian Academy of Sciences (India)

    In this paper, controlled release of diclofenac sodium (DS) from pH-sensitive carrageenan-gpoly(acrylic acid) superabsorbent hydrogels was investigated. The hydrogels were prepared by graft copolymerization of acrylic acid (AA) onto kappa-carrageenan, using ammonium persulfate (APS) as a free radical initiator in the ...

  4. Using Randomized Controlled Trials to Evaluate Interventions for Releasing Prisoners

    Science.gov (United States)

    Pettus-Davis, Carrie; Howard, Matthew Owen; Dunnigan, Allison; Scheyett, Anna M.; Roberts-Lewis, Amelia

    2016-01-01

    Randomized controlled trials (RCTs) are rarely used to evaluate social and behavioral interventions designed for releasing prisoners. Objective: We use a pilot RCT of a social support intervention (Support Matters) as a case example to discuss obstacles and strategies for conducting RCT intervention evaluations that span prison and community…

  5. Rectal absorption of morphine from controlled release suppositories

    NARCIS (Netherlands)

    Moolenaar, Frits; Meyler, Pim; Frijlink, Erik; Jauw, Tjoe Hang; Visser, Jan; Proost, Johannes

    1995-01-01

    The absorption profiles and bioavailability of morphine in human volunteers (n = 13) were described after oral administration of MS Contin tablets and rectal administration of a newly developed controlled release suppository. By manipulating the viscosity of fatty suppository base an entirely

  6. Biopolymers in controlled release devices for agricultural applications.

    Science.gov (United States)

    The use of biopolymers such as starch for agricultural applications including controlled release devices is growing due the environmental benefits. Recently, concerns have grown about the worldwide spread of parasitic mites (Varroa destructor) that infect colonies of honey bees (Apis mellifera L.). ...

  7. Formulation and Pharmacokinetic Evaluation of Controlled-Release ...

    African Journals Online (AJOL)

    Controlled-Release Oxybutynin Tablets in Dogs. Joonho Bae1 and Jin Woo Park2*. 1Amorepacific Corporation R&D Center, 314-1, Bora-dong, Giheung-gu, Yongin-si, Gyeonggi-do, 446-729, 2College of. Pharmacy and Natural Medicine Research Institute, Mokpo National University, 1666 Youngsan-ro, Muan-gun, ...

  8. Improvement of waste release control in French NPP

    Energy Technology Data Exchange (ETDEWEB)

    Samson, T.; Lucquin, E.; Dupin, M. [EDF/GDL (France); Florence, D. [EDF/GENV (France); Grisot, M. [EDF/CNPE Saint Laurent (France)

    2002-07-01

    The new waste release control in French NPP is more restrictive than the old one and needs heavy investment to bring plants to compliance with it. The great evolutions are a chemical follow up on more chemicals with a higher measurement frequency and with lower maximum concentrations and a specific measurement of carbon 14. Regarding radioactive releases, a new counting has been settled and activity of carbon 14 release is now measured and no longer calculated. The evolution of the French regulation leads to develop specific procedures and analytical techniques in chemistry and in radiochemistry (UV spectrometric methods, carbon 14 measurements,..) EDF NPP operators have launched a voluntarist process to reduce their releases since the beginning and before the evolution of the regulation. EDF priorities in terms of environment care lead henceforth to implement a global optimisation of the impact for a better control of releases. The new regulation will help EDF to reach its goals because it covers all the aspects in one administrative document: it is seen as a real simplification and a clarification towards public. In addition, this new regulation fits in with international practices which will allow an easier comparison of results between EDF and foreign NPP. These big environmental concerns lead EDF to create a national dedicated laboratory (LAMEN) in charge of developing specific measurement procedures to be implemented either by NPP or by sub-contractor laboratories. (authors)

  9. Controlled release of ethylene via polymeric films for food packaging

    Science.gov (United States)

    Pisano, Roberto; Bazzano, Marco; Capozzi, Luigi Carlo; Ferri, Ada; Sangermano, Marco

    2015-12-01

    In modern fruit supply chain a common method to trigger ripening is to keep fruits inside special chambers and initiate the ripening process through administration of ethylene. Ethylene is usually administered through cylinders with inadequate control of its final concentration in the chamber. The aim of this study is the development of a new technology to accurately regulate ethylene concentration in the atmosphere where fruits are preserved: a polymeric film, containing an inclusion complex of α-cyclodextrin with ethylene, was developed. The complex was prepared by molecular encapsulation which allows the entrapment of ethylene into the cavity of α-cyclodextrin. After encapsulation, ethylene can be gradually released from the inclusion complex and its release rate can be regulated by temperature and humidity. The inclusion complex was dispersed into a thin polymeric film produced by UV-curing. This method was used because is solvent-free and involves low operating temperature; both conditions are necessary to prevent rapid release of ethylene from the film. The polymeric films were characterized with respect to thermal behaviour, crystalline structure and kinetics of ethylene release, showing that can effectively control the release of ethylene within confined volume.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1990-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Ching-Wen Lou

    2017-11-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

  14. Characterization and in vitro release of cyclosporine-A from poly(D,L-lactide-co-glycolide implants obtained by solvent/extraction evaporation

    Directory of Open Access Journals (Sweden)

    Juliana Barbosa Saliba

    2012-01-01

    Full Text Available Cyclosporine-A-loaded PLGA implants were developed intended for ocular route. Implants were prepared using solvent extraction/evaporation technique followed by casting of the cake into rods in a heated surface. XRD patterns showed that cyclosporine-A was completely incorporated into PLGA. FTIR and DSC results indicated alterations on drug molecular conformation aiming to reach the most stable thermodynamic conformation at polymer/drug interface. Implants provided controlled/sustained in vitro release of the drug. During the first 7 weeks, the drug release was controlled by the diffusion of the cyclosporine-A; and between 7-23 week period, the drug diffusion and degradation of PLGA controlled the drug release.

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

    Directory of Open Access Journals (Sweden)

    Monica Borgatti

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

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

    Science.gov (United States)

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

    2012-07-01

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

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

    Science.gov (United States)

    Yeh, Hsi-Wei; Chen, Da-Ren

    2017-08-07

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

  18. In Vitro And In Vivo Evaluation Of Controlled-Release ...

    African Journals Online (AJOL)

    ... the direct compression method using some selective polymers like carbopol 934(CP 934) and hydroxypropyl methylcellulose (HPMC K4M) in different amounts along with other tablet excipients. The disks were evaluated for thickness uniformity, weight variation, drug content uniformity, hardness, friability and surface pH.

  19. Effect of inclusion complexation of meloxicam with β-cyclodextrin- and β-cyclodextrin-based nanosponges on solubility, in vitro release and stability studies.

    Science.gov (United States)

    Shende, Pravin K; Gaud, R S; Bakal, Ravindra; Patil, Dipmala

    2015-12-01

    The objective of the present work was to develop inclusion complexes of meloxicam with β-cyclodextrin- and β-cyclodextrin-based nanosponges to enhance their solubility and stability and to prolong release using different methods that included physical mixing, kneading and sonication. Particle size, zeta potential, encapsulation efficiency, stability study results, in vitro and in vivo drug release study results, FTIR, DSC and XRPD were used as characterization parameters. SEM (Scanning Electron Microscope) studies revealed that the particle sizes of the inclusion complexes of meloxicam were within the range of 350 ± 5.69-765 ± 13.29 nm. The zeta potentials were sufficiently high to obtain stable formulations. In vitro and in vivo release studies revealed the controlled release of meloxicam from the nanosponges for 24h. The interaction of the meloxicam with the nanosponges was confirmed by FTIR and DSC. A XRPD study revealed that the crystalline nature of meloxicam was changed to an amorphous form due to the complexation with the nanosponges. A stability study revealed that the meloxicam nanosponges were stable. Therefore, β-cyclodextrin-based nanosponges represent a novel approach for the controlled release of meloxicam for anti-inflammatory and analgesic effects. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Yi-Chuan Kau

    2014-09-01

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

  1. Montmorillonite-alginate nanocomposites as a drug delivery system: intercalation and in vitro release of vitamin B1 and vitamin B6.

    Science.gov (United States)

    Kevadiya, Bhavesh D; Joshi, Ghanshyam V; Patel, Hasmukh A; Ingole, Pravin G; Mody, Haresh M; Bajaj, Hari C

    2010-08-01

    Sustained intestinal delivery of thiamine hydrochloride (Vitamin B(1); VB(1)) and pyridoxine hydrochloride (Vitamin B(6); VB(6)) seems to be a feasible alternative to existing therapy. The vitamins (VB(1)/VB(6)) intercalated in montmorillonite (MMT) and intercalated VB(1)/VB(6)-MMT hybrid is further used for synthesis of VB(1)/VB(6)-MMT-alginate nanocomposite beads by gelation method and in vitro release in the intestinal environment. The structure and surface morphology of the synthesized VB(1)/VB(6)-MMT hybrid, VB(1)/VB(6)-alginate and VB(1)/VB(6)-MMT-alginate nanocomposite beads were characterized by XRD, FT-IR, TGA and SEM. In vitro release experiments revealed that the VB(1)/VB(6) releases suddenly from VB(1)/VB(6)-MMT hybrid and is pH dependent. The controlled release of VB(1)/VB(6) from VB(1)/VB(6)-MMT-alginate nanocomposite beads was observed to be controlled as compared to their release from VB(1)/VB(6)-MMT hybrid and VB(1)/VB(6)-alginate beads.

  2. Optogenetic Control of Serotonin and Dopamine Release in Drosophila Larvae

    Science.gov (United States)

    2014-01-01

    Optogenetic control of neurotransmitter release is an elegant method to investigate neurobiological mechanisms with millisecond precision and cell type-specific resolution. Channelrhodopsin-2 (ChR2) can be expressed in specific neurons, and blue light used to activate those neurons. Previously, in Drosophila, neurotransmitter release and uptake have been studied after continuous optical illumination. In this study, we investigated the effects of pulsed optical stimulation trains on serotonin or dopamine release in larval ventral nerve cords. In larvae with ChR2 expressed in serotonergic neurons, low-frequency stimulations produced a distinct, steady-state response while high-frequency patterns were peak shaped. Evoked serotonin release increased with increasing stimulation frequency and then plateaued. The steady-state response and the frequency dependence disappeared after administering the uptake inhibitor fluoxetine, indicating that uptake plays a significant role in regulating the extracellular serotonin concentration. Pulsed stimulations were also used to evoke dopamine release in flies expressing ChR2 in dopaminergic neurons and similar frequency dependence was observed. Release due to pulsed optical stimulations was modeled to determine the uptake kinetics. For serotonin, Vmax was 0.54 ± 0.07 μM/s and Km was 0.61 ± 0.04 μM; and for dopamine, Vmax was 0.12 ± 0.03 μM/s and Km was 0.45 ± 0.13 μM. The amount of serotonin released per stimulation pulse was 4.4 ± 1.0 nM, and the amount of dopamine was 1.6 ± 0.3 nM. Thus, pulsed optical stimulations can be used to mimic neuronal firing patterns and will allow Drosophila to be used as a model system for studying mechanisms underlying neurotransmission. PMID:24849718

  3. Highly Efficient Thermoresponsive Nanocomposite for Controlled Release Applications

    KAUST Repository

    Yassine, Omar

    2016-06-23

    Highly efficient magnetic release from nanocomposite microparticles is shown, which are made of Poly (N-isopropylacrylamide) hydrogel with embedded iron nanowires. A simple microfluidic technique was adopted to fabricate the microparticles with a high control of the nanowire concentration and in a relatively short time compared to chemical synthesis methods. The thermoresponsive microparticles were used for the remotely triggered release of Rhodamine (B). With a magnetic field of only 1 mT and 20 kHz a drug release of 6.5% and 70% was achieved in the continuous and pulsatile modes, respectively. Those release values are similar to the ones commonly obtained using superparamagnetic beads but accomplished with a magnetic field of five orders of magnitude lower power. The high efficiency is a result of the high remanent magnetization of the nanowires, which produce a large torque when exposed to a magnetic field. This causes the nanowires to vibrate, resulting in friction losses and heating. For comparison, microparticles with superparamagnetic beads were also fabricated and tested; while those worked at 73 mT and 600 kHz, no release was observed at the low field conditions. Cytotoxicity assays showed similar and high cell viability for microparticles with nanowires and beads.

  4. Controlled release of 5-fluorouracil from microporous zeolites.

    Science.gov (United States)

    Spanakis, Marios; Bouropoulos, Nikolaos; Theodoropoulos, Dimitrios; Sygellou, Lamprini; Ewart, Sinead; Moschovi, Anastasia Maria; Siokou, Angeliki; Niopas, Ioannis; Kachrimanis, Kyriakos; Nikolakis, Vladimiros; Cox, Paul A; Vizirianakis, Ioannis S; Fatouros, Dimitrios G

    2014-01-01

    Zeolite particles with different pore diameter and particle size were loaded with the model anticancer drug 5-fluorouracil. The loaded zeolites were characterized by means of SEM, XRD, DSC, XPS, N2 physisorption and FT-IR. Higher loading of 5-FU was observed for NaX-FAU than BEA. Release studies were carried out in HCl 0.1N. Release of 5-FU from NaX-FAU showed exponential-type behaviour with the drug fully released within 10 min. In the case of BEA, the kinetics of 5-FU shows a multi-step profile with prolonged release over time. Molecular dynamics simulations showed that diffusion of the drug molecule through the BEA framework is lower than for NaX-FAU due to increased van der Waals interaction between the drug and the framework. The effect of zeolitic particles on the viability of Caco-2 monolayers showed that the NaX-FAU particles cause a reduction of cell viability in a more pronounced way compared with the BEA particles. This article describes zeolite-based nanoparticles in generating time-controlled release of 5-FU from zeolite preparations for anti-cancer therapy. © 2013.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

    Djordjevic, Ljiljana; Primorac, Marija; Stupar, Mirjana

    2005-05-30

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

  7. Mechanism of controlled release kinetics from medical devices

    Directory of Open Access Journals (Sweden)

    A. Raval

    2010-06-01

    Full Text Available Utilization of biodegradable polymers for controlled drug delivery has gained immense attention in the pharmaceutical and medical device industry to administer various drugs, proteins and other bio-molecules both systematically and locally to cure several diseases. The efficacy and toxicity of this local therapeutics depends upon drug release kinetics, which will further decide drug deposition, distribution, and retention at the target site. Drug Eluting Stent (DES presently possesses clinical importance as an alternative to Coronary Artery Bypass Grafting due to the ease of the procedure and comparable safety and efficacy. Many models have been developed to describe the drug delivery from polymeric carriers based on the different mechanisms which control the release phenomenon from DES. Advanced characterization techniques facilitate an understanding of the complexities behind design and related drug release behavior of drug eluting stents, which aids in the development of improved future drug eluting systems. This review discusses different drug release mechanisms, engineering principles, mathematical models and current trends that are proposed for drug-polymer coated medical devices such as cardiovascular stents and different analytical methods currently utilized to probe diverse characteristics of drug eluting devices.

  8. Controlled Release of Agrochemicals Intercalated into Montmorillonite Interlayer Space

    Science.gov (United States)

    2014-01-01

    Periodic application of agrochemicals has led to high cost of production and serious environmental pollution. In this study, the ability of montmorillonite (MMT) clay to act as a controlled release carrier for model agrochemical molecules has been investigated. Urea was loaded into MMT by a simple immersion technique while loading of metalaxyl was achieved by a rotary evaporation method. The successful incorporation of the agrochemicals into the interlayer space of MMT was confirmed by several techniques, such as, significant expansion of the interlayer space, reduction of Barrett-Joyner-Halenda (BJH) pore volumes and Brunauer-Emmett-Teller (BET) surface areas, and appearance of urea and metalaxyl characteristic bands on the Fourier-transform infrared spectra of the urea loaded montmorillonite (UMMT) and metalaxyl loaded montmorillonite (RMMT) complexes. Controlled release of the trapped molecules from the matrix was done in water and in the soil. The results reveal slow and sustained release behaviour for UMMT for a period of 10 days in soil. For a period of 30 days, MMT delayed the release of metalaxyl in soil by more than 6 times. It is evident that MMT could be used to improve the efficiency of urea and metalaxyl delivery in the soil. PMID:24696655

  9. Controlled Release of Agrochemicals Intercalated into Montmorillonite Interlayer Space

    Directory of Open Access Journals (Sweden)

    Harrison Wanyika

    2014-01-01

    Full Text Available Periodic application of agrochemicals has led to high cost of production and serious environmental pollution. In this study, the ability of montmorillonite (MMT clay to act as a controlled release carrier for model agrochemical molecules has been investigated. Urea was loaded into MMT by a simple immersion technique while loading of metalaxyl was achieved by a rotary evaporation method. The successful incorporation of the agrochemicals into the interlayer space of MMT was confirmed by several techniques, such as, significant expansion of the interlayer space, reduction of Barrett-Joyner-Halenda (BJH pore volumes and Brunauer-Emmett-Teller (BET surface areas, and appearance of urea and metalaxyl characteristic bands on the Fourier-transform infrared spectra of the urea loaded montmorillonite (UMMT and metalaxyl loaded montmorillonite (RMMT complexes. Controlled release of the trapped molecules from the matrix was done in water and in the soil. The results reveal slow and sustained release behaviour for UMMT for a period of 10 days in soil. For a period of 30 days, MMT delayed the release of metalaxyl in soil by more than 6 times. It is evident that MMT could be used to improve the efficiency of urea and metalaxyl delivery in the soil.

  10. Thermo-responsive polymer-functionalized mesoporous carbon for controlled drug release

    Energy Technology Data Exchange (ETDEWEB)

    Zhu Shenmin, E-mail: smzhu@sjtu.edu.cn [State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240 (China); Chen Chenxin [State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240 (China); Chen Zhixin [Faculty of Engineering, University of Wollongong, Wollongong, NSW 2522 (Australia); Liu Xinye; Li Yao; Shi Yang; Zhang Di [State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240 (China)

    2011-03-15

    Research highlights: {yields} A responsive drug delivery system based on poly(N-isopropyl acrylamide) (PNIPAM) functionalized ordered mesoporous carbon (CMK-3) is developed. {yields} A combination of surface modification of CMK-3 and in situ internal polymerization of PNIPAM was used. {yields} The system exhibited a pronounced transition at around 20-25 deg. C. - Abstract: A novel responsive drug delivery system based on poly(N-isopropyl acrylamide) (PNIPAM) functionalized ordered mesoporous carbon (CMK-3) is developed. The polymer-functionalized CMK-3 was obtained by a combination of simple surface modification of CMK-3 and in situ internal polymerization of PNIPAM. The formation of the PNIPAM inside the CMK-3 was confirmed by thermal gravimetric analysis, Fourier transform-infrared spectroscopy, scanning and transmission electron microscopy and N{sub 2} adsorption/desorption measurements. Controlled drug release tests through the porous network of the PNIPAM functionalized CMK-3 were carried out by measuring the uptake and release of ibuprofen in vitro. The release profiles exhibited a pronounced transition at around 20-25 deg. C. This thermo-sensitive release property of this delivery system was further confirmed by temperature-variable hydrogen nuclear magnetic resonance analysis. The internal PNIPAM layers acted as a storage gate as well as a release switch in response to the stimuli of environment.

  11. Controlled release for local delivery of drugs: barriers and models.

    Science.gov (United States)

    Weiser, Jennifer R; Saltzman, W Mark

    2014-09-28

    Controlled release systems are an effective means for local drug delivery. In local drug delivery, the major goal is to supply therapeutic levels of a drug agent at a physical site in the body for a prolonged period. A second goal is to reduce systemic toxicities, by avoiding the delivery of agents to non-target tissues remote from the site. Understanding the dynamics of drug transport in the vicinity of a local drug delivery device is helpful in achieving both of these goals. Here, we provide an overview of controlled release systems for local delivery and we review mathematical models of drug transport in tissue, which describe the local penetration of drugs into tissue and illustrate the factors - such as diffusion, convection, and elimination - that control drug dispersion and its ultimate fate. This review highlights the important role of controlled release science in development of reliable methods for local delivery, as well as the barriers to accomplishing effective delivery in the brain, blood vessels, mucosal epithelia, and the skin. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Bajpai AK

    2009-10-01

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

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

    Science.gov (United States)

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

    2014-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Hui A

    2017-09-01

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

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

    Science.gov (United States)

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

    2015-11-01

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

  16. Organoclays for controlled release of the herbicide fenuron.

    Science.gov (United States)

    Hermosin, M C; Calderón, M J; Aguer, J P; Cornejo, J

    2001-09-01

    Organoclays were assayed as matrices in which to associate herbicides, with the aim of decreasing product losses that could give rise to water contamination from agricultural activities. Fenuron was selected as model of a very mobile and highly water-soluble herbicide. Two different organoclays of high (A-HDT) and low (H-C18) reversible fenuron sorption were selected. Herbicide-organoclay complexes were prepared from the two organoclays and with two different fenuron contents (20 and 40 g AI kg-1) and two different mixing times, so as to form a series of weak and strong complexes. The release of fenuron from those complexes into water and water/soil suspensions gave values of T50 (time to release 50% of the fenuron content) ranging from 0.3 min to 2400 h. The total fenuron released in these closed systems ranged from 48 to 80% of the fenuron in the complex. The organoclay type (high or low sorptivity) had the greatest influence on fenuron release, followed by the strong or weak complex, suggesting that herbicide-organoclay interactions are the main factors controlling release. Soil column leaching experiments showed fenuron-organoclay complexes to be effective in reducing the peak herbicide concentration in the leachate to a half (6 microns) or a quarter (3 microns) of that obtained from the free technical compound (12 microns). Herbicide lost through leaching was reduced from 78% for the free technical fenuron to 50-30%, depending on the organoclay used as carrier and the strength of the complex. Bioassay with ryegrass showed that the weak fenuron/H-C18 complex (40 g AI kg-1) gave the same herbicidal activity as technical fenuron. The potential suitability of low-sorptive organoclays for conferring slow-release properties on the fenuron complex has been demonstrated.

  17. Development and characterization of solid dispersion-microsphere controlled release system for poorly water-soluble drug.

    Science.gov (United States)

    Malipeddi, Venkata Ramana; Dua, Kamal; Awasthi, Rajendra

    2016-10-01

    The present study aimed to improve solubility and prolong the release duration of a poorly soluble drug using a combination of two different types of formulations (solid dispersion and microspheres). The solid dispersions were prepared by fusion method using urea and mannitol as hydrophilic carriers. Microspheres were prepared by solvent evaporation method using Eudragit L-100 (EL100) and Eudragit RS PO (ERS) as rate-controlling polymers. Flurbiprofen (FBP)-urea (1:2) solid dispersion and microspheres of FBP-EL-100-ERS (1:0.25:0.75) were used for the development of controlled release formulation by mixing them in different proportions. The FBP-containing formulations were evaluated for percentage yield, drug content, morphology, in vitro release, and in vivo anti-inflammatory activity. The best selected formulation was further evaluated for the controlled and improved effects. SEM photomicrograph confirmed the spherical shape of microspheres and with particle size in the range of 73.5-85.4 μm. In vitro release of FBP from controlled release formulations indicated that the formulation containing solid dispersion:microspheres (1:0.5) yielded prolonged effect up to 10 h. The release kinetics followed zero-order, and the mechanism of drug release was found to be diffusion rate controlled. This formulation had shown better inhibition of edema of rat paw up to 16 h and identified as a suitable product for controlled delivery of FBP. In conclusion, the concept of using a binary mixture of solid dispersion and microspheres can be used for other drugs that exhibit a poor solubility in stomach pH and a faster release in intestinal pH.

  18. Nutritional effects of folic acid controlled release from mesoporous materials

    OpenAIRE

    Barat, José; Pérez-Esteve, Édgar; Bernardos,Andrea; Martínez-Mañez, Ramón

    2011-01-01

    [EN] Folic acid deficiency causes serious disorders in humans and supplementation has numerous health benefits. However, there is initial evidence that suggest a negative impact of an increased exposure to folic with respect to certain developmental and degenerative disorders. In this line, controlled release of folic acid by using mesoporous silica materials, MCM-41, has been studied as an alternative to direct supplementation. For this purpose, various mesoporous solids MCM-41 loaded with f...

  19. Encapsulation and Controlled Release of Pharmaceuticals with Biodegradable Hyperbranched Polyesters

    OpenAIRE

    Mallepally, Rajendar Reddy

    2009-01-01

    The main aim of this work is to prepare enzyme triggered controlled release systems based on hyperbranched polyesters. Attempts to encapsulate drugs with the synthetic polymers often require the use of organic solvents, which is an obstacle for pharmaceutical applications. In this work a solvent free method, called melt dispersion, is used for this purpose. This method is based on the emulsification of the polymer melt and is firstly applied to hyperbranched polymers. The investigated drug su...

  20. Encapsulated Urea-Kaolinite Nanocomposite for Controlled Release Fertilizer Formulations

    OpenAIRE

    Siafu Ibahati Sempeho; Hee Taik Kim; Egid Mubofu; Alexander Pogrebnoi; Godlisten Shao; Askwar Hilonga

    2015-01-01

    Urea controlled release fertilizer (CRF) was prepared via kaolinite intercalation followed by gum arabic encapsulation in an attempt to reduce its severe losses associated with dissolution, hydrolysis, and diffusion. Following the beneficiation, the nonkaolinite fraction decreased from 39.58% to 0.36% whereas the kaolinite fraction increased from 60.42% to 99.64%. The X-ray diffractions showed that kaolinite was a major phase with FCC Bravais crystal lattice with particle sizes ranging betwee...

  1. Controlled Release of Doxorubicin from Doxorubicin/γ-Polyglutamic Acid Ionic Complex

    Directory of Open Access Journals (Sweden)

    Bhavik Manocha

    2010-01-01

    Full Text Available Formation of drug/polymer complexes through ionic interactions has proven to be very effective for the controlled release of drugs. The stability of such drug/polymer ionic complexes can be greatly influenced by solution pH and ionic strength. The aim of the current work was to evaluate the potential of γ-polyglutamic acid (γ-PGA as a carrier for the anticancer drug, Doxorubicin (DOX. We investigated the formation of ionic complexes between γ-PGA and DOX using scanning electron microscopy, spectroscopy, thermal analysis, and X-ray diffraction. Our studies demonstrate that DOX specifically interacts with γ-PGA forming random colloidal aggregates and results in almost 100% complexation efficiency. In vitro drug release studies illustrated that these complexes were relatively stable at neutral pH but dissociates slowly under acidic pH environments, facilitating a pH-triggered release of DOX from the complex. Hydrolytic degradation of γ-PGA and DOX/γ-PGA complex was also evaluated in physiological buffer. In conclusion, these studies clearly showed the feasibility of γ-PGA to associate cationic drug such as DOX and that is may serve as a new drug carrier for the controlled release of DOX in malignant tissues.

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

    Science.gov (United States)

    Wang, Xiang; Wang, Gen; Zhang, Ying

    2017-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Praveen Kumar Gaur

    2014-01-01

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

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

    Science.gov (United States)

    Harsha, Sree

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Gagganapalli Santhoshi Reddy

    2014-01-01

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

  6. Understanding controlled drug release from mesoporous silicates: theory and experiment.

    Science.gov (United States)

    Ukmar, T; Maver, U; Planinšek, O; Kaučič, V; Gaberšček, M; Godec, A

    2011-11-07

    Based on the results of carefully designed experiments upgraded with appropriate theoretical modeling, we present clear evidence that the release curves from mesoporous materials are significantly affected by drug-matrix interactions. In experimental curves, these interactions are manifested as a non-convergence at long times and an inverse dependence of release kinetics on pore size. Neither of these phenomena is expected in non-interacting systems. Although both phenomena have, rather sporadically, been observed in previous research, they have not been explained in terms of a general and consistent theoretical model. The concept is demonstrated on a model drug indomethacin embedded into SBA-15 and MCM-41 porous silicates. The experimental release curves agree exceptionally well with theoretical predictions in the case of significant drug-wall attractions. The latter are described using a 2D Fokker-Planck equation. One could say that the interactions affect the relative cross-section of pores where the local flux has a non-vanishing axial component and in turn control the effective transfer of drug into bulk solution. Finally, we identify the critical parameters determining the pore size dependence of release kinetics and construct a dynamic phase diagram of the various resulting transport regimes. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Encapsulated Urea-Kaolinite Nanocomposite for Controlled Release Fertilizer Formulations

    Directory of Open Access Journals (Sweden)

    Siafu Ibahati Sempeho

    2015-01-01

    Full Text Available Urea controlled release fertilizer (CRF was prepared via kaolinite intercalation followed by gum arabic encapsulation in an attempt to reduce its severe losses associated with dissolution, hydrolysis, and diffusion. Following the beneficiation, the nonkaolinite fraction decreased from 39.58% to 0.36% whereas the kaolinite fraction increased from 60.42% to 99.64%. The X-ray diffractions showed that kaolinite was a major phase with FCC Bravais crystal lattice with particle sizes ranging between 14.6 nm and 92.5 nm. The particle size varied with intercalation ratios with methanol intercalated kaolinite > DMSO-kaolinite > urea-kaolinite (KPDMU. Following intercalation, SEM analysis revealed a change of order from thick compact overlapping euhedral pseudohexagonal platelets to irregular booklets which later transformed to vermiform morphology and dispersed euhedral pseudohexagonal platelets. Besides, dispersed euhedral pseudohexagonal platelets were seen to coexist with blocky-vermicular booklets. In addition, a unique brain-form agglomeration which transformed into roundish particles mart was observed after encapsulation. The nanocomposites decomposed between 48 and 600°C. Release profiles showed that 100% of urea was released in 97 hours from KPDMU while 87% was released in 150 hours from the encapsulated nanocomposite. The findings established that it is possible to use Pugu kaolinite and gum arabic biopolymer to prepare urea CRF formulations.

  8. Controlled release of vancomycin from cross-linked gelatine.

    Science.gov (United States)

    Tigani, Domenico; Zolezzi, Carola; Trentani, Federico; Ragaini, Alessandro; Iafisco, Michele; Manara, Silvia; Palazzo, Barbara; Roveri, Norberto

    2008-03-01

    This paper explores the possibility of using biodegradable cross-linked gelatines as antibiotic devices for a long-term elution (80 days). Capillary electrophoresis (CE) has been utilized to evaluate the mass percentage of vancomycin and gelatine contemporary released from differently cross-linked vancomycin loaded gelatine samples in an elution time ranging from 24 to 1920 h. While the solubilization kinetic of gelatine samples differently cross-linked can be very close described by the simplified Higuchi model, the vancomycin release kinetic is contemporary governed by both the Fickian diffusion process trough the gelatine matrix network and the dissolution process of the matrix due to its degradation. Comparing the antibiotic eluting kinetics from gelatine at diverse cross-linking degree we observed that the degradation of the proteic matrix appears to have a minor influence in the drug release control. Vancomycin released from all the gelatine partially cross-linked samples results active against Staphylococcus aureus and Streptococcus faecalis which represent the most pathogens commonly isolated in orthopaedic infections. Vancomycin overcomes the minimum inhibitory concentration for both the bacteria in the whole range of elution time. Cross-linked gelatine devices appear to represent a useful biodegradable delivery system for local anti-infective therapy in arthoplasty.

  9. Silk fibroin/polyacrylamide semi-interpenetrating network hydrogels for controlled drug release.

    Science.gov (United States)

    Mandal, Biman B; Kapoor, Sonia; Kundu, Subhas C

    2009-05-01

    The present study describes a semi-interpenetrating network hydrogel fabricated using silk fibroin/polyacrylamide for controlled drug delivery applications. Hydrogels were synthesized using varied ratios of silk fibroin/acrylamide mixtures crosslinked by N,N'-Methylenebisacrylamide. Fourier-Transform Infrared analysis was performed suggesting beta sheet transition of silk fibroin with hydrogels. Scanning electron microscopy revealed microporous surface with maximum pore size of 50+/-11 microm. Rheological properties along with swellability, degradation, sol fraction estimation, equilibrium water content and swelling kinetics were evaluated. Compressive strength of 241.9+/-5.5 kPa was observed suggesting mechanically stronger gels. MTT assay showed biocompatibility and absence of deleterious effects of hydrogel on cell viability and functionality. In vitro release studies using two model compounds i.e. trypan blue dye and FITC-inulin reveal their sustained release from the fabricated hydrogel constructs.

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

    Science.gov (United States)

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

    2016-07-01

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

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

    Science.gov (United States)

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

    2013-10-01

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

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

    Science.gov (United States)

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

    2013-05-01

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

  13. Sol-gel Derived Warfarin - Silica Composites for Controlled Drug Release.

    Science.gov (United States)

    Dolinina, Ekaterina S; Parfenyuk, Elena V

    2017-01-01

    Warfarin, commonly used anticoagulant in clinic, has serious shortcomings due to its unsatisfactory pharmacodynamics. One of the efficient ways for the improvement of pharmacological and consumer properties of drugs is the development of optimal drug delivery systems. The aim of this work is to synthesize novel warfarin - silica composites and to study in vitro the drug release kinetics to obtain the composites with controlled release. The composites of warfarin with unmodified (UMS) and mercaptopropyl modified silica (MPMS) were synthesized by sol-gel method. The composite formation was confirmed by FTIR spectra. The concentrations of warfarin released to media with pH 1.6, 6.8 and 7.4 were measured using UV spectroscopy. The drug release profiles from the solid composites were described by a series of kinetic models which includes zero order kinetics, first order kinetics, the modified Korsmeyer-Peppas model and Hixson-Crowell model. The synthesized sol-gel composites have different kinetic behavior in the studied media. In contrast to the warfarin composite with unmodified silica, the drug release from the composite with mercaptopropyl modified silica follows zero order kinetics for 24 h irrespective to the release medium pH due to mixed mechanism (duffusion + degradation and/or disintegration of silica matrix). The obtained results showed that warfarin - silica sol-gel composites have a potential application for the development of novel oral formulation of the drug with controlled delivery. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Controlled release of NELL-1 protein from chitosan/hydroxyapatite-modified TCP particles.

    Science.gov (United States)

    Zhang, Yulong; Dong, Rui; Park, Yujin; Bohner, Marc; Zhang, Xinli; Ting, Kang; Soo, Chia; Wu, Benjamin M

    2016-09-10

    NEL-like molecule-1 (NELL-1) is a novel osteogenic protein that showing high specificity to osteochondral cells. It was widely used in bone regeneration research by loading onto carriers such as tricalcium phosphate (TCP) particles. However, there has been little research on protein controlled release from this material and its potential application. In this study, TCP was first modified with a hydroxyapatite coating followed by a chitosan coating to prepare chitosan/hydroxyapatite-coated TCP particles (Chi/HA-TCP). The preparation was characterized by SEM, EDX, FTIR, XRD, FM and Zeta potential measurements. The NELL-1 loaded Chi/HA-TCP particles and the release kinetics were investigated in vitro. It was observed that the Chi/HA-TCP particles prepared with the 0.3% (wt/wt) chitosan solution were able to successfully control the release of NELL-1 and maintain a slow, steady release for up to 28 days. Furthermore, more than 78% of the loaded protein's bioactivity was preserved in Chi/HA-TCP particles over the period of the investigation, which was significantly higher than that of the protein released from hydroxyapatite coated TCP (HA-TCP) particles. Collectively, this study suggests that the osteogenic protein NELL-1 showed a sustained release pattern after being encapsulated into the modified Chi/HA-TCP particles, and the NELL-1 integrated composite of Chi/HA-TCP showed a potential to function as a protein delivery carrier and as an improved bone matrix for use in bone regeneration research. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2017-09-04

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

  16. Biological control in vitro of Phytophtora megakarya , the causal ...

    African Journals Online (AJOL)

    Biological control in vitro of Phytophtora megakarya , the causal organism of black-pod disease of cocoa ( Theobroma cacao L.) ... Trichoderma harzianum and Trichoderma Koningii were isolated and tested for their ability to inhibit growth of P. megakarya on Potato Dextrose Agar (PDA). In-vitro screening was carried out ...

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

    Science.gov (United States)

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

    2016-06-01

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

  18. Chitosan Hydrogels for Chondroitin Sulphate Controlled Release: An Analytical Characterization

    Directory of Open Access Journals (Sweden)

    Annalisa Bianchera

    2014-01-01

    Full Text Available This paper provides an analytical characterization of chitosan scaffolds obtained by freeze-gelation toward the uptake and the controlled release of chondroitin sulphate (CS, as cartilage repair agent, under different pH conditions. Scanning electron microscopy (SEM, attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR, and liquid chromatography-UV spectrophotometry (LC-UV techniques were exploited to obtain qualitative and quantitative descriptions of polymer and drug behaviour in the biomaterial. As for morphology, SEM analysis allowed the evaluation of scaffold porosity in terms of pore size and distribution both at the surface (Feret diameter 58±19 μm and on the cross section (Feret diameter 106±51 μm. LC and ATR-FTIR evidenced a pH-dependent CS loading and release behaviour, strongly highlighting the role of electrostatic forces on chitosan/chondroitin sulphate interactions.

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

    OpenAIRE

    Oksana Megasari

    2007-01-01

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

  20. Controlled release of ibuprofen by meso–macroporous silica

    Energy Technology Data Exchange (ETDEWEB)

    Santamaría, E., E-mail: esthersantamaria@ub.edu; Maestro, A.; Porras, M.; Gutiérrez, J.M.; González, C.

    2014-02-15

    Structured meso–macroporous silica was successfully synthesized from an O/W emulsion using decane as a dispersed phase. Sodium silicate solution, which acts as a silica source and a poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide) (EO{sub 19}PO{sub 39}EO{sub 19}) denoted as P84 was used in order to stabilize the emulsion and as a mesopore template. The materials obtained were characterized through transmission electron microscopy (TEM), scanning electron microscopy (SEM), small-angle X-ray diffraction scattering (SAXS) and nitrogen adsorption–desorption isotherms. Ibuprofen (IBU) was selected as the model drug and loaded into ordered meso–macroporous materials. The effect of the materials’ properties on IBU drug loading and release was studied. The results showed that the loading of IBU increases as the macropore presence in the material is increased. The IBU adsorption process followed the Langmuir adsorption isotherm. A two-step release process, consisting of an initial fast release and then a slower release was observed. Macropores enhanced the adsorption capacity of the material; this was probably due to the fact that they allowed the drug to access internal pores. When only mesopores were present, ibuprofen was probably adsorbed on the mesopores close to the surface. Moreover, the more macropore present in the material, the slower the release behaviour observed, as the ibuprofen adsorbed in the internal pores had to diffuse along the macropore channels up to the surface of the material. The material obtained from a highly concentrated emulsion was functionalized with amino groups using two methods, the post-grafting mechanism and the co-condensation mechanism. Both routes improve IBU adsorption in the material and show good behaviour as a controlled drug delivery system. - Graphical abstract: Ibuprofen release profiles for the materials obtained from samples P84{sub m}eso (black diamonds), P84{sub 2}0% (white squares), P84{sub 5

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

    Science.gov (United States)

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

    2017-02-01

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

  2. Effectiveness of myofascial release: systematic review of randomized controlled trials.

    Science.gov (United States)

    Ajimsha, M S; Al-Mudahka, Noora R; Al-Madzhar, J A

    2015-01-01

    Myofascial release (MFR) is a form of manual therapy that involves the application of a low load, long duration stretch to the myofascial complex, intended to restore optimal length, decrease pain, and improve function. Anecdotal evidence shows great promise for MFR as a treatment for various conditions. However, research to support the anecdotal evidence is lacking. To critically analyze published randomized controlled trials (RCTs) to determine the effectiveness of MFR as a treatment option for different conditions. Electronic databases: MEDLINE, CINAHL, Academic Search Premier, Cochrane library, and Physiotherapy Evidence Database (PEDro), with key words myofascial release and myofascial release therapy. No date limitations were applied to the searches. Articles were selected based upon the use of the term myofascial release in the abstract or key words. The final selection was made by applying the inclusion and exclusion criteria to the full text. Studies were included if they were English-language, peer-reviewed RCTs on MFR for various conditions and pain. Data collected were number of participants, condition being treated, treatment used, control group, outcome measures and results. Studies were analyzed using the PEDro scale and the Center for Evidence-Based Medicine's Levels of Evidence scale. The literature regarding the effectiveness of MFR was mixed in both quality and results. Although the quality of the RCT studies varied greatly, the result of the studies was encouraging, particularly with the recently published studies. MFR is emerging as a strategy with a solid evidence base and tremendous potential. The studies in this review may help as a respectable base for the future trials. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    OpenAIRE

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

    2014-01-01

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

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

    Science.gov (United States)

    Salama, Ahmed

    2017-12-07

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

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

    NARCIS (Netherlands)

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

    2006-01-01

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

  7. Multilayer laminar co-extrudate as a novel controlled release dosage form.

    Science.gov (United States)

    Müllers, Katrin C; Wahl, Martin A; Pinto, João F

    2013-07-16

    Design of a new dosage form manufactured by laminar extrusion for oral administration of drugs. Different mixtures of materials (microcrystalline cellulose [MCC], hydroxypropyl methylcellulose [HPMC], lactose [LAC], dicalcium phosphate [DCP], coumarin [COU], propranolol hydrochloride [PRO], water [W]) were prepared prior to laminar extrusion. Mono, bi and tri layer extrudates were manufactured and evaluated for extrudability, drying, water uptake and swelling ability and in vitro characterization of the drug release. Good quality extrudates were manufactured with higher HPMC molecular weight and fraction in formulation at an extrusion rate of 400 mm/min and slow drying (forced air stream), otherwise surface roughness, thickness in-homogeneity, bending and shark skin were present in the extrudates. Swelling of extrudates was dependent on HPMC fraction and molecular weight (60% up to 90% weight gain for low and high polymer chains, respectively) and the presence of either MCC or DCP. The release of drug was dependent on its solubility (PRO>COU), the fraction of HPMC (low>high fractions), the type of diluent (DCP>MCC) and number of layers (1>2>3 layers). By designing the number and type of layers, dosage forms with well-defined release-kinetics can be tailored. The study has shown the ability of the technology of extrusion to manufacture a controlled release dosage form in a continuous fashion. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Novel nanocomposite biomaterials with controlled copper/calcium release capability for bone tissue engineering multifunctional scaffolds.

    Science.gov (United States)

    Cattalini, J P; Hoppe, A; Pishbin, F; Roether, J; Boccaccini, A R; Lucangioli, S; Mouriño, V

    2015-09-06

    This work aimed to develop novel composite biomaterials for bone tissue engineering (BTE) made of bioactive glass nanoparticles (Nbg) and alginate cross-linked with Cu(2+) or Ca(2+) (AlgNbgCu, AlgNbgCa, respectively). Two-dimensional scaffolds were prepared and the nanocomposite biomaterials were characterized in terms of morphology, mechanical strength, bioactivity, biodegradability, swelling capacity, release profile of the cross-linking cations and angiogenic properties. It was found that both Cu(2+) and Ca(2+) are released in a controlled and sustained manner with no burst release observed. Finally, in vitro results indicated that the bioactive ions released from both nanocomposite biomaterials were able to stimulate the differentiation of rat bone marrow-derived mesenchymal stem cells towards the osteogenic lineage. In addition, the typical endothelial cell property of forming tubes in Matrigel was observed for human umbilical vein endothelial cells when in contact with the novel biomaterials, particularly AlgNbgCu, which indicates their angiogenic properties. Hence, novel nanocomposite biomaterials made of Nbg and alginate cross-linked with Cu(2+) or Ca(2+) were developed with potential applications for preparation of multifunctional scaffolds for BTE. © 2015 The Author(s).

  9. β-Cyclodextrin grafted polypyrrole magnetic nanocomposites toward the targeted delivery and controlled release of doxorubicin

    Science.gov (United States)

    Hong, Shasha; Li, Zengbo; Li, Chenzhong; Dong, Chuan; Shuang, Shaomin

    2018-01-01

    The Fe3O4@PPy-HA-β-CD nanocomposites as the novel nanocarrier were prepared by grafting ethylenediamine derivative of​ β-​CD to the surface of polypyrrole-coated magnetic nanoparticles (Fe3O4@PPy) via using hyaluronan (HA) as the intermediate linker. HA was also the efficient target ligand for CD44. The as-prepared drug carrier was characterized by TEM, TGA, XRD, and VSM and used for the delivery of doxorubicin hydrochloride (DOX) with the high loading content of 447 mg/g. The multilayer Freundlich isotherm model was found to be a good fit for the loading of the drug carrier for DOX. Significant NIR-triggered release of DOX was observed in a weak acidic pH. And the release data in vitro was well described using the Retiger-Pepper kinetic model. Furthermore, MTT assay and confocal microscopy against Hep-G2 cells clearly illustrated that the drug carrier had no associated cytotoxicity and could easily enter the cells. The release and accumulation of DOX were observed in the cell nuclei. Thus, the DOX-loaded drug carrier killed the cancer cells efficaciously and minimized adverse side effects due to its target effect. These results suggested the as-prepared drug carrier would be of great potential for the controlled release and targeted delivery of DOX.

  10. Controlled Release of Antibiotics From Vitamin E-Loaded Silicone-Hydrogel Contact Lenses.

    Science.gov (United States)

    Paradiso, Patrizia; Serro, Ana Paula; Saramago, Benilde; Colaço, Rogério; Chauhan, Anuj

    2016-03-01

    Symptoms of bacterial and fungal keratitis are typically treated through the frequent application of antibiotic and antifungal eye drops. The high frequency of half hourly or hourly eye drop administration required to treat these indications is tedious and could reduce compliance. Here, we combine in vitro experiments with a mathematical model to develop therapeutic soft contact lenses to cure keratitis by extended release of suitable drugs. We specifically focus on increasing the release duration of levofloxacin and chlorhexidine from 1-DAY ACUVUE(®) TrueEye™ and ACUVUE OASYS(®) contact lenses by incorporating vitamin E diffusion barriers. Results show that 20% of vitamin E loading in the contact lens increases the release duration of levofloxacin to 100 h and 50 h from 1-DAY ACUVUE(®) TrueEye™ and ACUVUE OASYS(®), respectively, which is a 3- and 6-fold increase, respectively, for the 2 lenses. For chlorhexidine, the increase is 2.5- and 10-fold, for the TrueEye™ and OASYS(®), respectively, to 130 h and 170 h. The mass of drug loaded in the lenses can be controlled to achieve a daily release comparable to the commonly prescribed eye drop therapy. The vitamin E-loaded lenses retain all critical properties for in vivo use. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  11. Biomimetic synthesized nanoporous silica@poly(ethyleneimine)s xerogel as drug carrier: characteristics and controlled release effect.

    Science.gov (United States)

    Li, Jing; Xu, Lu; Liu, Hongzhuo; Wang, Yan; Wang, Qifang; Chen, Hongtao; Pan, Weisan; Li, Sanming

    2014-06-05

    The purpose of this study was to prepare and characterize nanoporous silica@poly(ethyleneimine)s (NS@P) xerogel and methanol modified NS@P xerogel synthesized with biomimetic method, and investigate controlled release behavior of propranolol hydrochloride (PNH) loaded carrier materials in vitro and in vivo. Preparation was conducted at ambient conditions, and NS@P xerogel as well as PNH loaded NS@P xerogel were characterized using Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and differential scanning calorimeter (DSC). Investigations on morphology and porous characteristics of NS@P xerogel and methanol modified NS@P xerogel were evaluated with scanning electron microscopy (SEM), transmission electron microscopy (TEM) and nitrogen adsorption. The results showed that the order of morphology compactness was NS@P xerogel>25%NS@P xerogel>75%NS@P xerogel because PEIs scaffold ability for silica condensation and forming hydrogen bond weakened with increasing volume ratio of methanol modification. Moreover, SBET decreased and uniformity of pore size distribution was interrupted after methanol modification. PNH loaded carrier materials displayed controlled release, and release effect was related with pore size of materials and PEIs scaffold ability. In vivo pharmacokinetic study demonstrated that release of PNH was delayed due to the PNH incorporated inside carrier materials and controlled release effect was in accordance with in vitro results. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Improved antimicrobial property and controlled drug release kinetics of silver sulfadiazine loaded ordered mesoporous silica

    National Research Council Canada - National Science Library

    Jangra, Suman; Devi, Sunita; Tomer, Vijay K; Chhokar, Vinod; Duhan, Surender

    2016-01-01

    The present study deals with the loading of silver sulfadiazine into ordered mesoporous silica material by post-impregnation method and its effect on the in vitro release kinetics and antimicrobial property of the drug...

  13. Controlled release of metronidazole from composite poly-ε-caprolactone/alginate (PCL/alginate) rings for dental implants.

    Science.gov (United States)

    Lan, Shih-Feng; Kehinde, Timilehin; Zhang, Xiangming; Khajotia, Sharukh; Schmidtke, David W; Starly, Binil

    2013-06-01

    Dental implants provide support for dental crowns and bridges by serving as abutments for the replacement of missing teeth. To prevent bacterial accumulation and growth at the site of implantation, solutions such as systemic antibiotics and localized delivery of bactericidal agents are often employed. The objective of this study was to demonstrate a novel method of controlled localized delivery of antibacterial agents to an implant site using a biodegradable custom fabricated ring. The study involved incorporating a model antibacterial agent (metronidazole) into custom designed poly-ε-caprolactone/alginate (PCL/alginate) composite rings to produce the intended controlled release profile. The rings can be designed to fit around the body of any root form dental implants of various diameters, shapes and sizes. In vitro release studies indicate that pure (100%) alginate rings exhibited an expected burst release of metronidazole in the first few hours, whereas Alginate/PCL composite rings produced a medium burst release followed by a sustained release for a period greater than 4 weeks. By varying the PCL/alginate weight ratios, we have shown that we can control the amount of antibacterial agents released to provide the minimal inhibitory concentration (MIC) needed for adequate protection. The fabricated composite rings have achieved a 50% antibacterial agent release profile over the first 48 h and the remaining amount slowly released over the remainder of the study period. The PCL/alginate agent release characteristic fits the Ritger-Peppas model indicating a diffusion-based mechanism during the 30-day study period. The developed system demonstrates a controllable drug release profile and the potential for the ring to inhibit bacterial biofilm growth for the prevention of diseases such as peri-implantitis resulting from bacterial infection at the implant site. Copyright © 2013 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2013-10-01

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

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

    Science.gov (United States)

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

    2012-04-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

  17. Controlled release of bioactive PDGF-AA from a hydrogel/nanoparticle composite.

    Science.gov (United States)

    Elliott Donaghue, Irja; Shoichet, Molly S

    2015-10-01

    Polymer excipients, such as low molar mass poly(ethylene glycol) (PEG), have shown contradictory effects on protein stability when co-encapsulated in polymeric nanoparticles. To gain further insight into these effects, platelet-derived growth factor (PDGF-AA) was encapsulated in polymeric nanoparticles with vs. without PEG. PDGF-AA is a particularly compelling protein, as it has been demonstrated to promote cell survival and induce the oligodendrocyte differentiation of neural stem/progenitor cells (NSPCs) both in vitro and in vivo. Here we show, for the first time, the controlled release of bioactive PDGF-AA from an injectable nanoparticle/hydrogel drug delivery system (DDS). PDGF-AA was encapsulated, with high efficiency, in poly(lactide-co-glycolide) nanoparticles, and its release from the drug delivery system was followed over 21 d. Interestingly, the co-encapsulation of low molecular weight poly(ethylene glycol) increased the PDGF-AA loading but, unexpectedly, accelerated the aggregation of PDGF-AA, resulting in reduced activity and detection by enzyme-linked immunosorbent assay (ELISA). In the absence of PEG, released PDGF-AA remained bioactive as demonstrated with NSPC oligodendrocyte differentiation, similar to positive controls, and significantly different from untreated controls. This work presents a novel delivery method for differentiation factors, such as PDGF-AA, and provides insights into the contradictory effects reported in the literature of excipients, such as PEG, on the loading and release of proteins from polymeric nanoparticles. Previously, the polymer poly(ethylene glycol) (PEG) has been used in many biomaterials applications, from surface coatings to the encapsulation of proteins. In this work, we demonstrate that, unexpectedly, low molecular weight PEG has a deleterious effect on the release of the encapsulated protein platelet-derived growth factor AA (PDGF-AA). We also demonstrate release of bioactive PDGF-AA (in the absence of PEG

  18. In vitro effect of low intensity laser on the cytotoxicity produced by substances released by bleaching gel

    Directory of Open Access Journals (Sweden)

    Caroline Maria Gomes Dantas

    2010-12-01

    Full Text Available This in vitro study aimed to analyze the effect of different parameters of phototherapy with low intensity laser on the viability of human dental pulp fibroblasts under the effect of substances released by bleaching gel. Cells were seeded into 96 wells plates (1 x 10³ cells/well and placed in contact with culture medium conditioned by a 35 % hydrogen peroxide bleaching gel for 40 minutes, simulating the clinical condition of the in-office bleaching treatment. Cells cultured in ideal growth conditions served as positive control group (PC, and the cells grown in conditioned medium and non-irradiated served as negative control group (NC. Cells grown in conditioned medium were submitted to a single irradiation with a diode laser (40 mW, 0.04 cm² emitting at visible red (660 nm; RL or near infrared (780 nm; NIR using punctual technique, in contact mode and energy densities of 4, 6 or 10 J/cm². The cell viability was analyzed through the MTT reduction assay immediately and 24 hours after the irradiation. The data was compared by ANOVA followed by the Tukey's test (p < 0.05. The cell viability increased significantly in 24 hours within each group. The PC presented cell viability significantly higher than NC in both experimental times. Only the NIR/10 J/cm² group presented cell viability similar to that of PC in 24 hours. The phototherapy with low intensity laser in defined parameters is able to compensate the cytotoxic effects of substances released by 35 % hydrogen peroxide bleaching gel.

  19. A comparative study on long-term MTX controlled release from intercalated nanocomposites for nanomedicine applications.

    Science.gov (United States)

    Alexa, Iuliana Florentina; Pastravanu, Cristina Giorgiana; Ignat, Maria; Popovici, Evelini

    2013-06-01

    The feasibility of some mesoporous materials such as SBA-15 and MCM-41 silica, LDH (layered double hydroxide) (Mg3Al-NO3) and MC (mesoporous carbon) have been comparatively evaluated for oral drug delivery applications, in order to broaden the range of matrices and implicitly to develop the class of drug delivery systems based on diffusion mechanism. As well known, methotrexate (MTX) is used widely to treat various neoplastic diseases such as acute lymphoblast leukemia, lymphoma and solid cancers and autoimmune diseases such as psoriasis and rheumatoid arthritis. The commercially available formulations of this drug have disadvantages due to the traditional release process that occurs in the body. Thus, this work is focused on the long-term controlled MTX delivery because this one could eliminate over or underdosing, could maintain drug levels in desired range, could increase patient compliance and prevent the side effects. Therefore, the mesoporous materials are used and efficient MTX-delivery systems, based on above-mentioned mesoporous materials, are successfully prepared by intercalation. The obtained drug carriers were tested in the controlled MTX-drug release process and the influence of the pore morphology and geometry on MTX release profiles was extensively studied comparatively. The prepared MTX delivery systems were characterized by FTIR and UV-vis spectroscopy, N2 sorption measurements. Then, the data obtained from the in vitro release studies have been analyzed, and in order to evaluate the MTX-release mechanism and kinetics, the Korsmeyer-Peppas equation has been applied. Copyright © 2013 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Cirley Quintero

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

  1. Enhanced legumain-recognition and NIR controlled released of cisplatin-indocyanine nanosphere against gastric carcinoma.

    Science.gov (United States)

    Shi, Tianyi; Gu, Lianshuai; Sun, Yu; Wang, Senlin; You, Chaoqun; Zhang, Xiangyang; Zhu, Jin; Sun, Baiwang

    2017-01-05

    Cisplatin-therapy has faced limitations in the gastric cancer therapy. To settle the bottleneck, enhanced specificity and controlled-release property are choosen. We synthesize cisplatin and indocyanine green (ICG) loaded PLGA-(DSPE-PEG2000) nanoparticles, which is abbreviated as CINPs. And we conjugate the Gly-Cys-Gly-Ala-Ala-Asn-Leu (GCGAANL) heptapeptide upon the surface of CINPs, the product is abbreviated as ACINPs. ACINPs with nearly 110nm exhibit good monodispersity and size stability. The EE (efficiency of encapsulation) and LE (loading of encapsulation) of cisplatin loaded into ACINPs are optimized as 29.81% and 3.88%. MGC803 cells overexpressing the legumain and MKN28 cells, which negatively express the legumain as well as the normal stomach cells, are selected. In vitro studies have suggested ACINPs, compared with CINPs, could be recognized by MGC803 cells and efficiently killed the cancer cells, while be harmless to MKN28 cells, which indicates the specificity and safety of ACINPs. Under irradiation of 808nm NIR irradiation, ICG loaded in ACINPs could rapidly transform the light to heat up to 60℃. Nanoparticles compared with non-irraditaion group could be quickly disrupted and release the cisplatin which could enhance the controlled-release ability. Hence, the ACINPs exhibit great potential in avoiding the side effects and enhancing the therapy ability of cisplatin. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Improved antimicrobial property and controlled drug release kinetics of silver sulfadiazine loaded ordered mesoporous silica

    Directory of Open Access Journals (Sweden)

    Suman Jangra

    2016-09-01

    Full Text Available The present study deals with the loading of silver sulfadiazine into ordered mesoporous silica material by post-impregnation method and its effect on the in vitro release kinetics and antimicrobial property of the drug. The formulated SBA-15 silica material with rope-like morphology and SBA-15-silver sulfadiazine (SBA-AgSD were characterized by UV–visible spectrophotometer, small and wide-angle powder X-ray diffraction (PXRD, field emission scanning electron microscope (FESEM and high resolution transmission electron microscope (HRTEM. Thermo-gravimetric analysis of SBA-AgSD revealed a high loading amount of 52.87%. Nitrogen adsorption–desorption analysis confirmed the drug entrapment into host material by revealing a reduced surface area (214 m2/g and pore diameter (6.7 nm of the SBA-AgSD. The controlled release of silver sulfadiazine drug from the mesoporous silica to simulated gastric, intestinal and body fluids was evaluated. The Korsmeyer–Peppas model fits the drug release data with the non-Fickian diffusion model and zero order kinetics of SBA-AgSD. The antibacterial performance of the SBA-AgSD was evaluated with respect to Staphylococcus aureus, Bacillus subtilis and Pseudomonas aeruginosa. The controlled drug delivery of the SBA-AgSD revealed improved antibacterial activity, thus endorsing its applicability in effective wound dressing.

  3. AnIn-vitroInvestigation of Swelling Controlled Delivery of Insulin from Egg Albumin Nanocarriers.

    Science.gov (United States)

    Mahobia, Swati; Bajpai, Jaya; Bajpai, Anil Kumar

    2016-01-01

    The aim of the present work was to prepare and characterize biopolymer nanocarriers and evaluate their suitability in possible oral delivery of insulin. The egg albumin biopolymer was used to prepare nanoparticles which were further characterized by Fourier transformed Infrared spectroscopy (FTIR), transmission electron microscopy (TEM), scanning electron microscopy (SEM), zeta potential, Dynamic Light scattering (DLS) and cytotoxicity. From the characterization studies the size of the nanoparticles washemoly found to lie in the range 20-80 nm with surface charge of -23 mV and also offering extremely fair biocompatibility.. The in-vitro biocompatibility of the prepared nanocarriers was judged by BSA adsorption test and haemolysis assay. The in vitro release kinetics of the insulin loaded nanoparticles was studied in phosphate buffer saline (PBS) solution, and the influence of various factors such as pH, temperature and simulated physiological fluids was studied on the controlled release of insulin.

  4. Electrospun fibers of acid-labile biodegradable polymers containing ortho ester groups for controlled release of paracetamol.

    Science.gov (United States)

    Qi, Mingbo; Li, Xiaohong; Yang, Ye; Zhou, Shaobing

    2008-10-01

    The local delivery and controllable release profiles make electrospun ultrafine fibers as potential implantable drug carriers and functional coatings of medical devices. There are few attempts to form acid-labile electrospun fibers, whose release behaviors respond to the local environment and fiber characteristics. In the current study a novel strategy was presented to synthesize biodegradable pH-sensitive polymers containing ortho ester groups. The acid-labile segments were synthesized through reacting 3,9-dimethylene-2,4,8,10-tetraoxaspiro [5.5] undecane with 1,10-decanediol or poly(ethylene glycol), which were further copolymerized with D,L-lactide to obtain triblock copolymers. Biodegradable acid-labile polymers were electrospun with the encapsulation of paracetamol as a model drug. In vitro release study showed that the total amount of drug released from acid-labile polymeric fibers was accelerated after incubation into acid buffer solutions, and the amount of initial burst release and sustained release rate were significantly higher for matrix polymers with hydrophilic acid-labile segments. In vitro degradation study indicated that the electrospun fibers containing acid-labile segments were stable in neutral buffer solution, but the molecular weight reduction of matrix polymers, the morphological changes and mass loss of fibrous mats were significantly enhanced under acid circumstances.

  5. Modeling controlled nutrient release from a population of polymer coated fertilizers: statistically based model for diffusion release.

    Science.gov (United States)

    Shaviv, Avi; Raban, Smadar; Zaidel, Elina

    2003-05-15

    A statistically based model for describing the release from a population of polymer coated controlled release fertilizer (CRF) granules by the diffusion mechanism was constructed. The model is based on a mathematical-mechanistic description of the release from a single granule of a coated CRF accounting for its complex and nonlinear nature. The large variation within populations of coated CRFs poses the need for a statistically based approach to integrate over the release from the individual granules within a given population for which the distribution and range of granule radii and coating thickness are known. The model was constructed and verified using experimentally determined parameters and release curves of polymer-coated CRFs. A sensitivity analysis indicated the importance of water permeability in controlling the lag period and that of solute permeability in governing the rate of linear release and the total duration of the release. Increasing the mean values of normally distributed granule radii or coating thickness, increases the lag period and the period of linear release. The variation of radii and coating thickness, within realistic ranges, affects the release only when the standard deviation is very large or when water permeability is reduced without affecting solute permeability. The model provides an effective tool for designing and improving agronomic and environmental effectiveness of polymer-coated CRFs.

  6. Comparative evaluation of polymersome versus micelle structures as vehicles for the controlled release of drugs

    Energy Technology Data Exchange (ETDEWEB)

    Alibolandi, Mona [Mashhad University of Medical Sciences, Biotechnology Research Center, School of Pharmacy (Iran, Islamic Republic of); Ramezani, Mohammad; Abnous, Khalil [Mashhad University of Medical Sciences, Pharmaceutical Research Center, School of Pharmacy (Iran, Islamic Republic of); Sadeghi, Fatemeh, E-mail: sadeghif@mums.ac.ir [Mashhad University of Medical Sciences, Targeted Drug Delivery Research Center, School of Pharmacy (Iran, Islamic Republic of); Hadizadeh, Farzin, E-mail: hadizadehf@mums.ac.ir [Mashhad University of Medical Sciences, Biotechnology Research Center, School of Pharmacy (Iran, Islamic Republic of)

    2015-02-15

    Di-block copolymers composed of two biocompatible polymers, poly(ethylene glycol) and poly(d,l-lactide), were synthesized by ring-opening polymerization for the preparation of doxorubicin-loaded self-assembled nanostructures, including polymeric vesicles (polymersomes) and micelles. The capability and stability of the nanostructures prepared for the controlled release of DOX are discussed in this paper. The in vitro drug release at 37 °C was evaluated up to 6 days at pH 7.4 and 5.5 and in the presence of 50 % FBS. The cellular uptake and cytotoxicity effect of both formulations were also evaluated in the MCF-7 cell line. The SEM and AFM images confirmed the hollow spherical structure of the polymersomes and the solid round structures of the micelles. The TEM results also revealed the uniformity in size and shape of the drug-loaded micelle and polymersome nanostructures. The DOX-loaded micelles and polymersomes presented efficient anticancer performance, as verified by flow cytometry and MTT assay tests. The most important finding of this study is that the prepared nanopolymersomes presented significant increases in the doxorubicin encapsulation efficiency and the stability of the formulation in comparison with the micelle formulation. In vitro studies revealed that polymersomes may be stable in the blood circulation and meet the requirements for an effective drug delivery system.

  7. Synthesis and characterisation of chitosan crosslinked-β-cyclodextrin grafted silylated magnetic nanoparticles for controlled release of Indomethacin

    Energy Technology Data Exchange (ETDEWEB)

    Anirudhan, T.S., E-mail: tsani@rediffmail.com; Dilu, D.; Sandeep, S.

    2013-10-15

    In this work, a novel hydrogel, chitosan crosslinked β-cyclodextrin grafted silylated magnetic nanoparticle (CTSCD-g-SilylMNP) was synthesised as a drug delivery system onto which Indomethacin (IND) drug was loaded. Characterisation of the drug delivery system was carried out by Tunnelling electron microscopy, Scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction analysis, Dynamic light scattering and a Vibrating sample magnetometer. Swelling behaviour, in vitro drug release kinetics, and encapsulation efficiency of CTSCD-g-SilylMNP were studied. Swelling behaviour varied according to pH. In vitro release studies revealed that CTSCD-g-SilylMNP demonstrated a swelling and diffusion controlled release. Dependence of pH was also studied. Encapsulation efficiency (EE) at different percentages of drug loadings was studied. The results collectively suggest that the hydrogel has promising application in the field of controlled drug release. The biodegradability also adds to the advantage. - Highlights: • A novel hydrogel chitosan crosslinked β-cyclodextrin grafted silylated magnetic nanoparticles (CTS–CD-g-SilylMNP) were synthesised. • Chitosan would increase the biocompatibility and swellability of the material. • Indomethacin drug was loaded onto CTS–CD-g-SilylMNP. • The swelling behaviour,drug release and encapsulation efficiency of the hydrogel were studied. • CTS–CD-g-SilylMNP can be used as a promising drug delivery system.

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

    Science.gov (United States)

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

    2016-01-01

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

  9. Controlled release of estradiol solubilized in carbopol/surfactant aggregates.

    Science.gov (United States)

    Barreiro-Iglesias, Rafael; Alvarez-Lorenzo, Carmen; Concheiro, Angel

    2003-12-12

    The potential of carbopol/surfactant dispersions as solubilizing and controlled release systems of estradiol (a poorly water-soluble drug) was evaluated. The solubilization of estradiol in the dispersions of Carbopol 934 (0.25%) and Pluronic F-127, Tween 80, sodium dodecylsulfate (SDS), or benzalkonium chloride (BkCl) was assessed, by differential scanning calorimetry (DSC) of films obtained by desiccation, as a decrease in estradiol melting temperature and enthalpy. The amounts of estradiol solubilized in carbopol/SDS and carbopol/Tween 80 aqueous dispersions were considerably greater (solubilization capacity: 1.3 and 9 times greater) than in the surfactant alone solutions and up to 100 times greater than in water. High aggregates/water equilibrium partition coefficients of estradiol in carbopol/SDS (1768 M(-1)) and carbopol/Tween 80 (14114 M(-1)) dispersions were found. Carbopol/(1%) SDS/(25 mg/dl) estradiol and carbopol/(0.1%) Tween 80/(5 mg/dl) estradiol dispersions had a pH of around 4, were easy flowing, and showed sustained release for at least 1 week. Estradiol diffusion coefficients were greater when the receptor medium was 0.3-1.0% SDS solution than when it was iso-osmotic NaCl solution or pH 7.5 phosphate buffer. At this pH, a viscoelastic gel is formed on the donor side of the membrane and the drug diffusion slowed down. When the receptor medium contains a surfactant, estradiol release seems to happen as a direct exchange between the carbopol/surfactant aggregates and the receptor surfactant micelles. If no surfactant is in the receptor fluid, estradiol/surfactant complexes migrate towards the receptor. Despite the low viscosity of these dispersions, estradiol diffusion coefficients were in the same order of magnitude as those obtained with a commercially available neutralized ethanol/water carbopol gel of estradiol (60 mg/dl). When the receptor medium had no surfactant, the low affinity of estradiol for water prevented drug diffusion from the

  10. Controlling Hazardous Releases while Protecting Passengers in Civil Infrastructure Systems

    Science.gov (United States)

    Rimer, Sara P.; Katopodes, Nikolaos D.

    2015-11-01

    The threat of accidental or deliberate toxic chemicals released into public spaces is a significant concern to public safety, and the real-time detection and mitigation of such hazardous contaminants has the potential to minimize harm and save lives. Furthermore, the safe evacuation of occupants during such a catastrophe is of utmost importance. This research develops a comprehensive means to address such scenarios, through both the sensing and control of contaminants, and the modeling of and potential communication to occupants as they evacuate. A computational fluid dynamics model is developed of a simplified public space characterized by a long conduit (e.g. airport terminal) with unidirectional ambient flow that is capable of detecting and mitigating the hazardous contaminant (via boundary ports) over several time horizons using model predictive control optimization. Additionally, a physical prototype is built to test the real-time feasibility of this computational flow control model. The prototype is a blower wind-tunnel with an elongated test section with the capability of sensing (via digital camera) an injected `contaminant' (propylene glycol smoke), and then mitigating that contaminant using actuators (compressed air operated vacuum nozzles) which are operated by a set of pressure regulators and a programmable controller. Finally, an agent-based model is developed to simulate ``agents'' (i.e. building occupants) as they evacuate a public space, and is coupled with the computational flow control model such that agents must interact with a dynamic, threatening environment. NSF-CMMI #0856438.

  11. Thermal post-treatment alters nutrient release from a controlled-release fertilizer coated with a waterborne polymer

    OpenAIRE

    Zhou, Zijun; Du, Changwen; Li, Ting; Shen, Yazhen; Zhou, Jianmin

    2015-01-01

    Controlled-release fertilizers (CRF) use a controlled-release technology to enhance the nutrient use efficiency of crops. Many factors affect the release of nutrients from the waterborne polymer-coated CRF, but the effects of thermal post-treatments remain unclear. In this study, a waterborne polyacrylate-coated CRF was post-treated at different temperatures (30 °C, 60 °C, and 80 °C) and durations (2, 4, 8, 12, and 24 h) after being developed in the Wurster fluidized bed. To characterize the ...

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

    Science.gov (United States)

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

    2015-06-01

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

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

    Science.gov (United States)

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

    1999-01-01

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

  14. Enhancing Vascularization through the Controlled Release of Platelet-Derived Growth Factor-BB.

    Science.gov (United States)

    Minardi, Silvia; Pandolfi, Laura; Taraballi, Francesca; Wang, Xin; De Rosa, Enrica; Mills, Zachary D; Liu, Xuewu; Ferrari, Mauro; Tasciotti, Ennio

    2017-05-03

    Using delivery systems to control the in vivo release of growth factors (GFs) for tissue engineering applications is extremely desirable as the clinical use of GFs is limited by their fast in vivo turnover. Hence, the development of effective platforms that are able to finely control the release of GFs in vivo remains a challenge. Herein, we investigated the ability of multiscale microspheres, composed by a nanostructured silicon multistage vector (MSV) core and a poly(dl-lactide-co-glycolide) acid (PLGA) forming outer shell (PLGA-MSV), to release functional platelet-derived growth factor-BB (PDGF-BB) to induce in vivo localized neovascularization. The in vitro release of PDGF-BB was assessed by enzyme-linked immunosorbent assay (ELISA) over 2 weeks and showed a sustained, zero-order release kinetics. The ability to promote in vivo localized neovascularization was investigated in a subcutaneous injection model in BALB/c mice and followed by intravital microscopy up to 2 weeks. Fully functional newly formed vessels were found within the area where PLGA-MSVs were localized and covered 3.0 ± 0.9 and 19 ± 5.1% at 7 and 14 days, respectively, showing a 6-fold increase in 1 week. The distribution of CD31 + and α-SMA + cells was detected by immunofluorescence on harvested tissues. CD31 was significantly more expressed (4-fold increase) compared to the untreated control. Finally, the level of up-regulation of angiogenesis-associated genes (Vegfa, Vwf, and Col3a1) was assessed by q-PCR, resulting in a significantly higher expression where PLGA-MSVs were localized (Vegfa: 2.32 ± 0.50 at 7 days and 4.37 ± 0.75 at 14 days; Vwf: 4.13 ± 0.82 and 7.74 ± 0.91; Col3a1: 5.43 ± 0.37 and 6.66 ± 0.89). Altogether, our data supported the conclusion that the localized delivery of PDGF-BB from PLGA-MSVs induced the localized de novo formation of fully functional vessels in vivo. With this study, we demonstrated that PLGA-MSV holds promise for accomplishing the controlled

  15. Self-Emulsifying Granules and Pellets: Composition and Formation Mechanisms for Instant or Controlled Release

    Directory of Open Access Journals (Sweden)

    Ioannis Nikolakakis

    2017-11-01

    Full Text Available Many articles have been published in the last two decades demonstrating improvement in the dissolution and absorption of low solubility drugs when formulated into self-emulsifying drug delivery systems (SEDDS. Several such pharmaceutical products have appeared in the market for medium dose (Neoral® for Cyclsoprin A, Kaletra® for Lopinavir and Ritonavir, or low dose medications (Rocaltrol® for Calcitriol and Avodart® for Dutasteride. However, these are in the form of viscous liquids or semisolid presentations, characterized by the disadvantages of high production cost, stability problems and the requirement of large quantities of surfactants. Solid SEDDS (S-SEDDS, as coarse powders, granules or pellets, besides solubility improvement, can be filled easily into capsules or processed into tablets providing a handy dosage form with instant release, which can be further developed into controlled release by mixing with suitable polymers or coating with polymeric films. In this review, the materials used for the preparation of S-SEDDS, their properties and role in the formulations are detailed. Factors affecting the physical characteristics, mechanical properties of S-SEDDS as well as their in vitro release and in vivo absorption are discussed. The mechanisms involved in the formation of instant and sustained release self-emulsifying granules or pellets are elucidated. Relationships are demonstrated between the characteristics of S-SEDDS units (size, shape, mechanical properties, re-emulsification ability, drug migration and drug release and the properties of the submicron emulsions used as massing liquids, with the aim to further elucidate the formation mechanisms. The influence of the composition of the powdered ingredients forming the granule or pellet on the properties of S-SEDDS is also examined. Examples of formulations of S-SEDDS that have been reported in the literature in the last thirteen years (2004–2017 are presented.

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

    Science.gov (United States)

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

    2004-11-01

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

  17. Halloysite Nanotubes: Controlled Access and Release by Smart Gates.

    Science.gov (United States)

    Cavallaro, Giuseppe; Danilushkina, Anna A; Evtugyn, Vladimir G; Lazzara, Giuseppe; Milioto, Stefana; Parisi, Filippo; Rozhina, Elvira V; Fakhrullin, Rawil F

    2017-07-28

    Hollow halloysite nanotubes have been used as nanocontainers for loading and for the triggered release of calcium hydroxide for paper preservation. A strategy for placing end-stoppers into the tubular nanocontainer is proposed and the sustained release from the cavity is reported. The incorporation of Ca(OH)₂ into the nanotube lumen, as demonstrated using transmission electron microscopy (TEM) imaging and Energy Dispersive X-ray (EDX) mapping, retards the carbonatation, delaying the reaction with CO₂ gas. This effect can be further controlled by placing the end-stoppers. The obtained material is tested for paper deacidification. We prove that adding halloysite filled with Ca(OH)₂ to paper can reduce the impact of acid exposure on both the mechanical performance and pH alteration. The end-stoppers have a double effect: they preserve the calcium hydroxide from carbonation, and they prevent from the formation of highly basic pH and trigger the response to acid exposure minimizing the pH drop-down. These features are promising for a composite nanoadditive in the smart protection of cellulose-based materials.

  18. Properties and controlled release of chitosan microencapsulated limonene oil

    Directory of Open Access Journals (Sweden)

    Jefferson M. Souza

    Full Text Available Chitosan microcapsules containing limonene essential oil as active ingredient were prepared by coacervation using three different concentrations of NaOH (0.50, 1.00, 1.45 wt% and fixed concentrations of chitosan and surfactant of 0.50 wt%. The produced microcapsules were fully characterized in their morphology and chemical composition, and the kinetic release analysis of the active ingredient was evaluated after deposition in a non-woven cellulose fabric. The concentration of 1.00 and 1.45 wt% clearly show the best results in terms of dimension and shape of the microcapsules as well as in the volatility results. However, at the concentration of 1 wt% a higher number of microcapsules were produced as confirmed by FTIR and EDS analysis. Free microcapsules are spherical in size with disperse diameters between 2 and 12 μm. Immobilized microcapsules showed sizes from 4 to 7 μm, a rough surface and loss of spherical shape with pore formation in the chitosan walls. SEM analysis confirms that at higher NaOH concentrations, the larger the size of the microcapsules. This technique shows that by tuning NaOH concentration it is possible to efficiently control the release rate of encapsulated active agents demonstrating great potential as insect repellent for textiles.

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

    Science.gov (United States)

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

    2017-05-01

    Tissue engineering (particularly for the case of load-bearing cardiovascular and connective tissues) requires the ability to promote the production and accumulation of extracellular matrix (ECM) components (e.g., collagen, glycosaminoglycan and elastin). Although different approaches have been attempted in order to enhance ECM accumulation in tissue engineered constructs, studies of underlying signalling mechanisms that influence ECM deposition and degradation during tissue remodelling and regeneration in multi-cellular culture systems have been limited. The current study investigated vascular smooth muscle cell (VSMC)-monocyte co-culture systems using different VSMC:monocyte ratios, within a degradable polyurethane scaffold, to assess their influence on ECM generation and degradation processes, and to elucidate relevant signalling molecules involved in this in vitro vascular tissue engineering system. It was found that a desired release profile of growth factors (e.g. insulin growth factor-1 (IGF-1)) and hydrolytic proteases (e.g. matrix-metalloproteinases 2, 9, 13 and 14 (MMP2, MMP9, MMP13 and MMP14)), could be achieved in co-culture systems, yielding an accumulation of ECM (specifically for 2:1 and 4:1 VSMC:monocyte culture systems). This study has significant implications for the tissue engineering field (including vascular tissue engineering), not only because it identified important cytokines and proteases that control ECM accumulation/degradation within synthetic tissue engineering scaffolds, but also because the established culture systems could be applied to improve the development of different types of tissue constructs. Sufficient extracellular matrix accumulation within cardiovascular and connective tissue engineered constructs is a prerequisite for their appropriate function in vivo. This study established co-culture systems with tissue specific cells (vascular smooth muscle cells (VSMCs)) and defined ratios of immune cells (monocytes) to investigate

  20. Control of drug release through the in situ assembly of stimuli-responsive ordered mesoporous silica with magnetic particles.

    Science.gov (United States)

    Zhu, Shenmin; Zhou, Zhengyang; Zhang, Di

    2007-12-03

    A site-selective controlled delivery system for controlled drug release is fabricated through the in situ assembly of stimuli-responsive ordered SBA-15 and magnetic particles. This approach is based on the formation of ordered mesoporous silica with magnetic particles formed from Fe(CO)5 via the surfactant-template sol-gel method and control of transport through polymerization of N-isopropyl acrylamide inside the pores. Hydrophobic Fe(CO)5 acts as a swelling agent as well as being the source of the magnetic particles. The obtained system demonstrates a high pore diameter (7.1 nm) and pore volume (0.41 cm(3) g(-1)), which improves drug storage for relatively large molecules. Controlled drug release through the porous network is demonstrated by measuring the uptake and release of ibuprofen (IBU). The delivery system displays a high IBU storage capacity of 71.5 wt %, which is almost twice as large as the highest value based on SBA-15 ever reported. In vitro testing of IBU loading and release exhibits a pronounced transition at around 32 degrees C, indicating a typical thermosensitive controlled release.

  1. Iron/dextran sulfate multilayered microcapsules for controlled release of 10-hydroxycamptothecin.

    Science.gov (United States)

    Guo, Shenglei; Zheng, Jian; Dong, Jing; Guo, Na; Jing, Lijia; Yue, Xiuli; Yan, Xiufeng; Wang, Yang; Dai, Zhifei

    2011-10-01

    Stable 10-hydroxycamptothecin (HCPT) microcrystals with a length of about 5-10μm and a ζ-potential of -38.5mV were produced by pH-induced reprecipitation in presence of a stabilizer hydroxypropylmethylcellulose. Sequential layer growth was achieved by the layer-by-layer (LbL) assembly of Fe(3+) and dextran sulfate (DS) on the surface of HCPT microcrystals via both electrostatic interaction and chemical complexation process. The satisfactory drug loading content (67.2±0.82%) as well as high encapsulation efficiency (60.56±0.82%) for four bilayers of Fe(3+)/DS coating was achieved. Both in vitro and in vivo release study revealed that the release time increased as the number of deposited Fe(3+)/DS bilayers increased. These results indicated that such iron-polysaccharide multilayered microcapsules can be a promising approach for the construction of an effective controlled release delivery system of HCPT as well as other drugs with potential cytotoxicity or short half-life time. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Folic acid conjugated magnetic drug delivery system for controlled release of doxorubicin

    Energy Technology Data Exchange (ETDEWEB)

    Andhariya, Nidhi, E-mail: nidhiandhariya@gmail.com [Thapar University, School of Physics and Materials Science (India); Upadhyay, Ramesh [Charotar University of Science and Technology, P.D. Patel Institute of Applied Sciences (India); Mehta, Rasbindu [Maharaja Krishnakumarsinhji Bhavnagar University, Department of Physics (India); Chudasama, Bhupendra, E-mail: bnchudasama@gmail.com [Thapar University, School of Physics and Materials Science (India)

    2013-01-15

    Targeting tumors by means of their vascular endothelium is a promising strategy, which utilizes targets that are easily accessible, stable, and do not develop resistance against therapeutic agents. Folate receptor is a highly specific tumor marker, frequently over expressed in cancer tumors. In the present study, an active drug delivery system, which can effectively target cancer cells by means of folate receptor-mediated endocytosis, have ability to escape from opsonization and capability of magnetic targeting to withstand the drag force of the body fluid have been designed and synthesized. The core of the drug delivery system is of mono-domain magnetic particles of magnetite. Magnetite nanoparticles are shielded with PEG, which prevents their phagocytosis by reticuloendothelial system. These PEG shielded magnetite nanoparticles are further decorated with an antitumor receptor-folic acid and loaded with an antineoplastic agent doxorubicin. An in vitro drug loading and release kinetics study reveals that the drug delivery system can take 52 % of drug load and can release doxorubicin over a sustained period of 7 days. The control and sustained release over a period of several days may find its practical utilities in chemotherapy where frequent dosing is not possible.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Wendy Leticia Guerra-Ponce

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

  5. Premature luteinization during gonadotropin-releasing hormone antagonist cycles and its relationship with in vitro fertilization outcome.

    Science.gov (United States)

    Bosch, Ernesto; Valencia, Iván; Escudero, Ernesto; Crespo, Juana; Simón, Carlos; Remohí, José; Pellicer, Antonio

    2003-12-01

    To determine the prevalence and the effect of premature luteinization in GnRH antagonist IVF-ET cycles. Prospective observational study. In vitro fertilization-embryo transfer (IVF-ET) program at the Instituto Valenciano de Infertilidad. Eighty-one infertile patients undergoing controlled ovarian hyperstimulation with gonadotropins and GnRH antagonist for IVF-ET. Gonadotropin-releasing hormone (GnRH) antagonist was administered from stimulation day 6. Serum P, E(2), and LH were determined on the day of hCG administration. Cycles were grouped according to serum P level on the day of hCG administration ( or =1.2 ng/mL). Clinical pregnancy and implantation rates were determined. The incidence of premature luteinization was 38.3%. Total recombinant FSH dose and stimulation days differed significantly between the groups. Pregnancy rate (25.8% vs. 54.0%) and implantation rate (13.8% vs. 32.0%) were significantly lower in the premature luteinization group. Premature luteinization during GnRH antagonist IVF-ET cycles is a frequent event that is associated with lower pregnancy and implantation rates. Progesterone elevations are not related to serum LH levels and may reflect the mature granulosa cell response to high FSH exposure.

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

    Directory of Open Access Journals (Sweden)

    Schubert Jochen

    2008-11-01

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

  7. WE-AB-BRA-03: Non-Invasive Controlled Release from Implantable Hydrogel Scaffolds Using Ultrasound

    Energy Technology Data Exchange (ETDEWEB)

    Moncion, A; Kripfgans, O.D; Putnam, A.J; Frances chi, R.T; Fabiilli, M.L [University of Michigan, Ann Arbor, MI (United States)

    2016-06-15

    Purpose: To control release of a model payload in acoustically responsive scaffolds (ARSs) using focused ultrasound (FUS). Methods: Fluorescently-labeled dextran (10 kDa) was encapsulated in sonosensitive perfluorocarbon (C{sub 6}F{sub 14} or C{sub 5}F{sub 12}) double emulsions (mean diameter: 2.9±0.1 µm). For in vitro release studies, 0.5 mL ARSs (10 mg/mL fibrin, 1% (v/v) emulsion) were polymerized in 24 well plates and covered with 0.5 mL medium. Starting one day after polymerization, ARSs were exposed to FUS (2.5 MHz, Pr = 8 MPa, 13 cycles, 100 Hz PRF) for 2 min daily. The amount of dextran released into the media was quantified. For in vivo studies, 0.25 mL ARSs were prepared as described previously and injected subcutaneously in the lower back of BALB/c mice. After polymerization, a subset of the implanted ARSs were exposed to FUS (as previously described). Animals were imaged longitudinally using a fluorescence imaging system to quantify the amount of dextran released from the ARSs. Results: In vitro: Over 6 days, +FUS displayed an 8.2-fold increase in dextran release compared to −FUS (−FUS: 2.7±0.6%; +FUS: 22.2±3.0%) for C{sub 6}F{sub 14} ARSs, and a 6.7-fold increase (−FUS: 5.0±0.8%; +FUS: 38.5±1.6%) for C{sub 5}F{sub 12}:C{sub 6}F{sub 14} ARSs. In vivo: +FUS displayed statistically greater dextran release compared to −FUS one day after implantation for C{sub 5}F{sub 12}:C{sub 6}F{sub 14} ARSs (−FUS: 55.1±1.5%; +FUS: 74.1±2.2%) and three days after implantation for C{sub 6}F{sub 14} ARSs (−FUS: 1.4±6.5%; +FUS: 30.4±5.4%). Conclusion: FUS enables non-invasive control of payload release from an ARS, which could benefit growth factor delivery for tissue regeneration. ARS are versatile due to their tunability (i.e. stiffness, emulsion composition, FUS pressure, FUS frequency, etc.) and can be modified to for optimal payload release. Future work will optimize ARS formulations for in vivo use to minimize payload release in the absence of

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

    Science.gov (United States)

    Donnelly, D F

    1993-05-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

  10. In vitro immunomodulation of a whole blood IFN-γ release assay enhances T cell responses in subjects with latent tuberculosis infection.

    Directory of Open Access Journals (Sweden)

    Rajiv L Gaur

    Full Text Available Activation of innate immunity via pathogen recognition receptors (PRR modulates adaptive immune responses. PRR ligands are being exploited as vaccine adjuvants and as therapeutics, but their utility in diagnostics has not been explored. Interferon-gamma (IFN-γ release assays (IGRAs are functional T cell assays used to diagnose latent tuberculosis infection (LTBI; however, novel approaches are needed to improve their sensitivity.In vitro immunomodulation of a whole blood IGRA (QuantiFERON®-TB GOLD In-Tube with Toll-like receptor agonists poly(I:C, LPS, and imiquimod was performed on blood from subjects with LTBI and negative controls.In vitro immunomodulation significantly enhanced the response of T cells stimulated with M. tuberculosis antigens from subjects with LTBI but not from uninfected controls. Immunomodulation of IGRA revealed T cell responses in subjects with LTBI whose T cells otherwise do not respond to in vitro stimulation with antigens alone. Similar to their in vivo functions, addition of poly(I:C and LPS to whole blood induced secretion of inflammatory cytokines and IFN-α and enhanced the surface expression of antigen presenting and costimulatory molecules on antigen presenting cells.In vitro immunomodulation of whole blood IGRA may be an effective strategy for enhancing the sensitivity of T cells for diagnosis of LTBI.

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

    DEFF Research Database (Denmark)

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

    2005-01-01

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

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

    Science.gov (United States)

    Rajesh, A Michael; Popat, Kiritkumar Mangaldas

    2017-02-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    OpenAIRE

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

    2017-01-01

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

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

    Science.gov (United States)

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

    1989-04-01

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

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

    OpenAIRE

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

    2017-01-01

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

  17. Design and evaluation of novel barrier layer technologies for controlling venlafaxine hydrochloride release from tablet dosage form.

    Science.gov (United States)

    Malewar, Nikhil; Avachat, Makarand; Kulkarni, Shirish; Pokharkar, Varsha

    2015-01-01

    Venlafaxine Hydrochloride (VH) is a highly soluble and highly permeable antidepressant compound. Thus controlling VH release from tablet dosage form over a prolonged period is a challenge. The objective of this work was to study the effect of various barrier layer formulation compositions, its orientations and manufacturing technology on release profile of highly soluble VH. Different barrier compositions and orientations were established on the same extended release formulations of VH using compression as well as film coating technologies. Barrier effectiveness in reducing the VH release was verified through in vitro dissolution studies. The "belly band" portion of the tablets was successfully oriented in different ways to develop bilayer as well as trilayer tablets. The compression technology had substantially reduced the VH release up to 16% in various compositions and orientation as compared to core tablet. The film coating technology had reduced the VH release up to 14% effectively; thereby shifting the dissolution curve to downside. The explored "belly band" portion of the tablets had reduced the VH release substantially. These innovatively created different barrier orientation technologies hold the great promise of commercialization in future.

  18. Controlled release gelatin hydrogels and lyophilisates with potential application as ocular inserts

    Energy Technology Data Exchange (ETDEWEB)

    Natu, Madalina V [Department of Chemical Engineering, University of Coimbra, Polo II, Pinhal de Marrocos, 3030-290 Coimbra (Portugal); Sardinha, Jose P [Department of Chemical Engineering, University of Coimbra, Polo II, Pinhal de Marrocos, 3030-290 Coimbra (Portugal); Correia, IlIdio J [Centro de Investigacao em Ciencias da Saude, Faculdade de Ciencias da Saude, Universidade da Beira Interior, Covilha (Portugal); Gil, M H [Department of Chemical Engineering, University of Coimbra, Polo II, Pinhal de Marrocos, 3030-290 Coimbra (Portugal)

    2007-12-15

    Hydrogels and lyophilisates were obtained by chemical crosslinking of gelatin using N-hydroxysuccinimide and N, N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride. The systems were characterized with respect to the degree of crosslinking, morphology, water uptake, in vitro drug release and biocompatibility studies. Pilocarpine hydrochloride, a drug for the treatment of glaucoma, was loaded by soaking in an aqueous solution containing the drug. In vitro, the released drug percentage varied between 29.2% and 99.2% in 8 h of study. The release data were fitted to the Korsmeyer-Peppas equation to calculate the release exponent, which indicated anomalous transport for the release of pilocarpine. The corneal endothelial cell culture tests indicated that the prepared biomaterials are not cytotoxic.

  19. The design of controlled-release formulations resistant to alcohol-induced dose dumping--a review.

    Science.gov (United States)

    Jedinger, N; Khinast, J; Roblegg, E

    2014-07-01

    The concomitant intake of alcoholic beverages together with oral controlled-release opioid formulations poses a serious safety concern since alcohol has the potential to alter the release rate controlling mechanism of the dosage form which may result in an uncontrolled and immediate drug release. This effect, known as alcohol-induced dose dumping, has drawn attention of the regulatory authorities. Thus, the Food and Drug Administration (FDA) recommends that in vitro drug release studies of controlled-release dosage forms containing drugs with narrow therapeutic range should be conducted in ethanolic media up to 40%. So far, only a limited number of robust dosage forms that withstand the impact of alcohol are available and the development of such dosage forms is still a challenge. This review deals with the physico-chemical key factors which have to be considered for the preparation of alcohol-resistant controlling dosage forms. Furthermore, appropriate matrix systems and promising technological strategies, which are suitable to prevent alcohol-induced dose dumping, are discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Fluoride uptake in human teeth from fluoride-releasing restorative material in vivo and in vitro: two-dimensional mapping by EPMA-WDX.

    Science.gov (United States)

    Yamamoto, H; Iwami, Y; Unezaki, T; Tomii, Y; Ebisu, S

    2001-01-01

    Class V cavities were prepared in the upper and lower left second premolars from an individual under infiltration anesthesia. The cavities were filled with fluoride- releasing resin (TF). One month later, the teeth were extracted. As a control (in vitro), the upper and lower right second premolars were extracted at the time of the cavity preparation in vivo. Immediately after extraction, class V cavities were prepared and filled with TF, and immersed in normal saline solution for 1 month at 37 degrees C. All four premolars were bisected longitudinally and the fluoride uptake around the cavity wall on the cut surface was measured using an electron probe microanalyzer-wavelength dispersive X-ray method. The fluoride uptake was given in the form of a two-dimensional map. Comparison of the observed values of each corresponding part of the tooth in vivo and in vitro revealed no characteristic differences. The maps were quite analogous as a whole.

  1. Factors controlling alkalisalt deposition in recovery boiler- release mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    McKeough, P.; Kylloenen, H.; Kurkela, M. [VTT Energy, Espoo (Finland). Process Technology Group

    1996-12-01

    As part of a cooperative effort to develop a model to describe the behaviour of inorganic compounds in kraft recovery boilers, an experimental investigation of the release of sulphur during black liquor pyrolysis has been undertaken. Previous to these studies, the mechanisms of sulphur release and the reasons for the observed effects of process conditions on sulphur release were very poorly understood. On the basis of the experimental results, the main reactions leading to sulphur release have been elucidated with a fair degree of certainty. Logical explanations for the variations of sulphur release with temperature and with liquor solids content have been proposed. The influence of pressure has been investigated in order to gain insights into the effects of mass transfer on the sulphur-release rate. In the near future, the research will be aimed at generating the kinetic data necessary for modelling the release of sulphur in the recovery furnace. (author)

  2. Reaction-Multi Diffusion Model for Nutrient Release and Autocatalytic Degradation of PLA-Coated Controlled-Release Fertilizer

    Directory of Open Access Journals (Sweden)

    Sayed Ameenuddin Irfan

    2017-03-01

    Full Text Available A mathematical model for the reaction-diffusion equation is developed to describe the nutrient release profiles and degradation of poly(lactic acid (PLA-coated controlled-release fertilizer. A multi-diffusion model that consists of coupled partial differential equations is used to study the diffusion and chemical reaction (autocatalytic degradation simultaneously. The model is solved using an analytical-numerical method. Firstly, the model equation is transformed using the Laplace transformation as the Laplace transform cannot be inverted analytically. Numerical inversion of the Laplace transform is used by employing the Zakian method. The solution is useful in predicting the nutrient release profiles at various diffusivity, concentration of extraction medium, and reaction rates. It also helps in explaining the transformation of autocatalytic concentration in the coating material for various reaction rates, times of reaction, and reaction-multi diffusion. The solution is also applicable to the other biodegradable polymer-coated controlled-release fertilizers.

  3. Controlled release of silyl ether camptothecin from thiol-ene click chemistry-functionalized mesoporous silica nanoparticles.

    Science.gov (United States)

    Yan, Yue; Fu, Jie; Wang, Tianfu; Lu, Xiuyang

    2017-03-15

    As efficient drug carriers, stimuli-responsive mesoporous silica nanoparticles are at the forefront of research on drug delivery systems. An acid-responsive system based on silyl ether has been applied to deliver a hybrid prodrug. Thiol-ene click chemistry has been successfully utilized for tethering this prodrug to mesoporous silica nanoparticles. Here, by altering the steric bulk of the substituent on the silicon atom, the release rate of a model drug, camptothecin, was controlled. The synthesized drug delivery system was investigated by analytical methods to confirm the functionalization and conjugation of the mesoporous silica nanoparticles. Herein, trimethyl silyl ether and triethyl silyl ether were selected to regulate the release rate. Under normal plasma conditions (pH 7.4), both types of camptothecin-loaded mesoporous silica nanoparticles (i.e., MSN-Me-CPT and MSN-Et-CPT) did not release the model drug. However, under in vitro acidic conditions (pH 4.0), based on a comparison of the release rates, camptothecin was released from MSN-Me-CPT more rapidly than from MSN-Et-CPT. To determine the biocompatibility of the modified mesoporous silica nanoparticles and the in vivo camptothecin uptake behavior, MTT assays with cancer cells and confocal microscopy observations were conducted, with positive results. These functionalized nanoparticles could be useful in clinical treatments requiring controlled drug release. As the release rate of drug from drug-carrier plays important role in therapy effects, trimethyl silyl ether (TMS) and triethyl silyl ether (TES) were selected as acid-sensitive silanes to control the release rates of model drugs conjugated from MSNs by thiol-ene click chemistry. The kinetic profiles of TMS and TES materials have been studied. At pH 4.0, the release of camptothecin from MSN-Et-CPT occurred after 2h, whereas MSN-Me-CPT showed immediate drug release. The results showed that silyl ether could be used to control release rates of drugs from

  4. Controlled release studies of antimalarial 1, 3, 5-trisubstituted-2-pyrazolines from biocompatible chitosan-heparin Layer-by-Layer (LbL) self assembled thin films.

    Science.gov (United States)

    Bhalerao, Uma M; Valiveti, Aditya Kapil; Acharya, Jyotiranjan; Halve, Anand K; Kaushik, Mahabir Parshad

    2015-01-01

    Herein we report the in-vitro controlled release properties of 1, 3, 5-trisubstituted-2-pyrazolines through Layer-by-Layer (LbL) self assembled thin films fabricated from chitosan and heparin sodium salt as biocompatible polyelectrolytes. This study was carried out as a preliminary step towards the applicability of LbL technique in prophylactic drug delivery of antimalarial drugs. The growth of LbL self assembly was monitored by UV-Visible spectrophotometry and Quartz Crystal Microbalance (QCM). The loading as well as in-vitro release studies (in phosphate buffer saline at pH 7.4) were carried out using UV-Visible spectroscopy. Three compounds having good antimalarial activity were tested and the release rate was found inversely proportional to the hydrophobicity of the drug. Pzln-4 has shown best release among all the three compounds (up to 780 min) followed by Pzln-5 and Pzln-8. The release trend was that of a fast release up to first 2 h followed by a steady release. Kinetic fitting of the data confirmed the process of drug release followed a pseudo second order kinetics (R(2)≥0.99). A large value of rate constant (k) revealed a faster release. Pzln-4 has shown smallest value of k corresponding to slowest release among all the three compounds. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Feasibility of optimizing trimetazidine dihydrochloride release from controlled porosity

    Directory of Open Access Journals (Sweden)

    Basant A. Habib

    2014-05-01

    Full Text Available The aim of this study was to develop and optimize Trimetazidine dihydrochloride (TM controlled porosity osmotic pump (CPOP tablets of directly compressed cores. A 23 full factorial design was used to study the influence of three factors namely: PEG400 (10% and 25% based on coating polymer weight, coating level (10% and 20% of tablet core weight and hole diameter (0 “no hole” and 1 mm. Other variables such as tablet cores, coating mixture of ethylcellulose (4% and dibutylphthalate (2% in 95% ethanol and pan coating conditions were kept constant. The responses studied (Yi were cumulative percentage released after 2 h (Q%2h, 6 h (Q%6h, 12 h (Q%12h and regression coefficient of release data fitted to zero order equation (RSQzero, for Y1, Y2, Y3, and Y4, respectively. Polynomial equations were used to study the influence of different factors on each response individually. Response surface methodology and multiple response optimization were used to search for an optimized formula. Response variables for the optimized formula were restricted to 10% ⩽ Y1 ⩽ 20%, 40% ⩽ Y2 ⩽ 60%, 80% ⩽ Y3 ⩽ 100%, and Y4 > 0.9. The statistical analysis of the results revealed that PEG400 had positive effects on Q%2h, Q%6h and Q%12h, hole diameter had positive effects on all responses and coating level had positive effect on Q%6h, Q%12h and negative effect on RSQzero. Full three factor interaction (3FI equations were used for representation of all responses except Q%2h which was represented by reduced (3FI equation. Upon exploring the experimental space, no formula in the tested range could satisfy the required constraints. Thus, direct compression of TM cores was not suitable for formation of CPOP tablets. Preliminary trials of CPOP tablets with wet granulated cores were promising with an intact membrane for 12 h and high RSQzero. Further improvement of these formulations to optimize TM release will be done in further studies.

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

    Science.gov (United States)

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

    1999-02-01

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

  7. Novel iron-polysaccharide multilayered microcapsules for controlled insulin release.

    Science.gov (United States)

    Zheng, Jian; Yue, Xiuli; Dai, Zhifei; Wang, Yang; Liu, Shaoqin; Yan, Xiufeng

    2009-06-01

    Iron-polysaccharide complexes have been extensively used for the treatment of iron-deficiency anemia without side-effects. In this study, insulin-loaded microcapsules were prepared via layer-by-layer deposition of oppositely charged Fe(3+) and dextran sulfate (DS) onto the surface of insulin microparticles. Fe(3+) was combined with DS via both electrostatic interaction and chemical complexation process, leading to the formation of a stable complex of Fe(3+)/DS. Subsequently, protamine was used as the outermost layer of the insulin-loaded microcapsules to facilitate nuclear delivery. The sufficient charge reversal with successive deposition cycles and successful fabrication of hollow microcapsules provided strong evidence for the growth of (Fe(3+)/DS)(n) multilayer on the surface of microparticles. The experiments showed that the microcapsules successfully entrapped insulin with encapsulation efficiency of 70.56+/-0.97% and drug loading content of 46.15+/-0.97%. It was found that the release time and hypoglycemic effect increased as the number of deposited bilayers increased. The insulin-loaded microcapsules significantly improved glucose tolerance from 2 h (free insulin) to even 12 h (insulin-loaded microcapsules with 10 bilayers). Moreover, the microcapsules with protamine as the outermost layer displayed a prolonged and stable glucose-lowering profile over a period of over 6 h compared with Fe(3+) as the outermost layer. These findings indicate that such microcapsules can be a promising approach for the construction of an effective controlled release delivery system of insulin as well as other proteins with short half-life time.

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

    Directory of Open Access Journals (Sweden)

    Edward R. Bastow

    2012-02-01

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

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

    DEFF Research Database (Denmark)

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

    1994-01-01

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

  10. Factors controlling phosphorus release from sediments in coastal archipelago areas.

    Science.gov (United States)

    Puttonen, Irma; Kohonen, Tuula; Mattila, Johanna

    2016-07-15

    In coastal archipelago areas of the northern Baltic Sea, significantly higher phosphate concentrations (6.0±4.5μmol/l, mean±SD) were measured in water samples close to the sediment surface compared with those from 1m above the seafloor (1.6±2.0μmol/l). The results indicated notable phosphate release from sediments under the bottom water oxygen concentrations of up to 250μmol/l, especially in areas that had experienced recent temporal fluctuation between oxic and hypoxic/anoxic conditions. No single factor alone was found to control the elevated PO4-P concentrations in the near-bottom water. In addition to the oxygen in the water, the contents of potentially mobile phosphorus fractions, grain-size, the organic content at the sediment surface, and the water depth were all important factors controlling the internal loading of phosphorus. The complexity of this process needs to be accounted for in assessments of the internal loading of phosphorus and in potential mitigation plans. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. {delta}-FeOOH: a superparamagnetic material for controlled heat release under AC magnetic field

    Energy Technology Data Exchange (ETDEWEB)

    Chagas, Poliane; Candido da Silva, Adilson [ICEx, Universidade Federal de Minas Gerais, Departamento de Quimica (Brazil); Caetano Passamani, Edson [Universidade Federal do Espirito Santo, Departamento de Fisica (Brazil); Ardisson, Jose Domingos [Centro de Desenvolvimento da Tecnologia Nuclear (Brazil); Alves de Oliveira, Luiz Carlos [ICEx, Universidade Federal de Minas Gerais, Departamento de Quimica (Brazil); Domingos Fabris, Jose [Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM) (Brazil); Paniago, Roberto M. [ICEx, Universidade Federal de Minas Gerais, Departamento de Fisica (Brazil); Monteiro, Douglas Santos; Pereira, Marcio Cesar, E-mail: mcpqui@gmail.com [Instituto de Ciencia, Engenharia e Tecnologia, UFVJM (Brazil)

    2013-04-15

    Experimental evidences on its in vitro use reveal that {delta}-FeOOH is a material that release-controlled amount of heat if placed under an AC magnetic field. {delta}-FeOOH nanoparticles were prepared by precipitating Fe(OH){sub 2} in alkaline solution followed by fast oxidation with H{sub 2}O{sub 2}. XRD and {sup 57}Fe Moessbauer spectroscopy data confirmed that {delta}-FeOOH is indeed the only iron-bearing compound in the produced sample. TEM images evidence that the averaged particle sizes for this {delta}-FeOOH sample is 23 nm. Magnetization measurements indicate that these {delta}-FeOOH particles behave superparamagnetically at 300 K; its saturation magnetization was found to be 13.2 emu g{sup -1}; the coercivity and the remnant magnetization were zero at 300 K. The specific absorption rate values at 225 kHz were 2.1, 6.2, and 34.2 W g{sup -1}, under 38, 64, and 112 mT, respectively. The release rate of heat can be directly controlled by changing the mass of {delta}-FeOOH nanoparticles. In view of these findings, the so-prepared {delta}-FeOOH is a real alternative to be further tested as a material for medical practices in therapies involving magnetic hyperthermia as in clinical oncology.

  12. Controlled release system for ametryn using polymer microspheres: Preparation, characterization and release kinetics in water

    Energy Technology Data Exchange (ETDEWEB)

    Grillo, Renato [Department of Environmental Engineering, UNESP - Univ Estadual Paulista, Avenida Tres de Marco, no 511, CEP 18087-180 Sorocaba, SP (Brazil); Department of Biochemistry, Institute of Biology, UNICAMP, Cidade Universitaria Zeferino Vaz, s/n, Campinas, SP (Brazil); Pereira, Anderson do Espirito Santo [Department of Biochemistry, Institute of Biology, UNICAMP, Cidade Universitaria Zeferino Vaz, s/n, Campinas, SP (Brazil); Department of Biotechnology, University of Sorocaba, Sorocaba, SP (Brazil); Ferreira Silva de Melo, Nathalie [Department of Environmental Engineering, UNESP - Univ Estadual Paulista, Avenida Tres de Marco, no 511, CEP 18087-180 Sorocaba, SP (Brazil); Department of Biochemistry, Institute of Biology, UNICAMP, Cidade Universitaria Zeferino Vaz, s/n, Campinas, SP (Brazil); Porto, Raquel Martins; Feitosa, Leandro Oliveira [Department of Biotechnology, University of Sorocaba, Sorocaba, SP (Brazil); Tonello, Paulo Sergio [Department of Environmental Engineering, UNESP - Univ Estadual Paulista, Avenida Tres de Marco, no 511, CEP 18087-180 Sorocaba, SP (Brazil); Dias Filho, Newton L. [Department of Physics and Chemistry, UNESP - Univ Estadual Paulista, Ilha Solteira, SP (Brazil); Rosa, Andre Henrique [Department of Environmental Engineering, UNESP - Univ Estadual Paulista, Avenida Tres de Marco, no 511, CEP 18087-180 Sorocaba, SP (Brazil); Lima, Renata [Department of Biotechnology, University of Sorocaba, Sorocaba, SP (Brazil); Fraceto, Leonardo Fernandes, E-mail: leonardo@sorocaba.unesp.br [Department of Environmental Engineering, UNESP - Univ Estadual Paulista, Avenida Tres de Marco, no 511, CEP 18087-180 Sorocaba, SP (Brazil); Department of Biochemistry, Institute of Biology, UNICAMP, Cidade Universitaria Zeferino Vaz, s/n, Campinas, SP (Brazil)

    2011-02-28

    The purpose of this work was to develop a modified release system for the herbicide ametryn by encapsulating the active substance in biodegradable polymer microparticles produced using the polymers poly(hydroxybutyrate) (PHB) or poly(hydroxybutyrate-valerate) (PHBV), in order to both improve the herbicidal action and reduce environmental toxicity. PHB or PHBV microparticles containing ametryn were prepared and the efficiencies of herbicide association and loading were evaluated, presenting similar values of approximately 40%. The microparticles were characterized by scanning electron microscopy (SEM), which showed that the average sizes of the PHB and PHBV microparticles were 5.92 {+-} 0.74 {mu}m and 5.63 {+-} 0.68 {mu}m, respectively. The ametryn release profile was modified when it was encapsulated in the microparticles, with slower and more sustained release compared to the release profile of pure ametryn. When ametryn was associated with the PHB and PHBV microparticles, the amount of herbicide released in the same period of time was significantly reduced, declining to 75% and 87%, respectively. For both types of microparticle (PHB and PHBV) the release of ametryn was by diffusion processes due to anomalous transport (governed by diffusion and relaxation of the polymer chains), which did not follow Fick's laws of diffusion. The results presented in this paper are promising, in view of the successful encapsulation of ametryn in PHB or PHBV polymer microparticles, and indications that this system may help reduce the impacts caused by the herbicide, making it an environmentally safer alternative.

  13. Interaction between fed and gastric media (ensure Plus) and different hypromellose based caffeine controlled release tablets; comparison and mechanistic study of caffeine release in fed and fasted media versus water using USP dissolution apparatus 3

    DEFF Research Database (Denmark)

    Franek, Frans; Holm, Per; Larsen, Frank

    2014-01-01

    and fasted gastro-intestinal dissolution conditions. The effect of tablet reciprocation rate (dip speed) in dissolution media (10 and 15 dips per minute) and media (water, fed and fasted) on caffeine release rate from – and erosion rate of – 100, 4000 and 15,000 mPa s HPMC viscosity tablets was investigated....... Using fasted media instead of water slightly decreases caffeine release from 100 and 4000 mPa s HPMC viscosity tablets as well as erosion rates, while 15,000 mPa s tablets remain unaffected. Fed compared to fasted media decreases caffeine release rate, and the food effect is greater for the 100 mPa s......The aim of the study was to investigate caffeine release in fed and fasted state media from three controlled release matrix tablets containing different HPMC viscosity grades. The biorelevant in vitro dissolution methods utilize the USP 3 dissolution apparatus and biorelevant media to simulate fed...

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

    Science.gov (United States)

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

    2001-09-01

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

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

    Science.gov (United States)

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

    2003-08-01

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

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

    DEFF Research Database (Denmark)

    Baumbach, L; Skøtt, O

    1986-01-01

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

  17. Conductive polymers for controlled release and treatment of central nervous system injury

    Science.gov (United States)

    Saigal, Rajiv

    [(D,L-lactide-co-glycolide)-co-polyethylene glycol] (PLGA-PEG) nanoparticles and then demonstrated scalable incorporation and controlled release. In a functional application, electronically-controlled release of minocycline nanoparticles was used to rescue primary spinal cord neurons from an excitotoxic environment in vitro. This approach offers a wide range of therapeutic possibilities, especially for treating traumatic lesions of the central nervous system. Finally, we explored use of conductive polymers for directed differentiation of progenitor cells. Retinal progenitors were seeded on custom polypyrrole cell culture devices and subjected to a biomimetic pattern of electrical stimulation. Stimulated cells showed phenotypic changes, increased neurite outgrowth, increased immunocytochemical expression of cone rod homeobox (CRX) and protein kinase C (PK-C), and decreased expression of glial fibrillary acidic protein (GFAP). Biomimetic stimulation thus led cells towards early photoreceptor and bipolar cell fates, and away from an astrocytic cell fate. Electrical stimulation via a conductive polymer offers a novel approach for directing differentiation of progenitor cells.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1985-08-01

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

  19. In vitro control of Alternaria citri using antifungal potentials of ...

    African Journals Online (AJOL)

    In vitro control of Alternaria citri using antifungal potentials of Trichoderma species. Asma Murtaza, Shazia Shafique, Tehmina Anjum, Sobiya Shafique. Abstract. The antifungal potential of five species of Trichoderma viz., Trichoderma viride, Trichoderma aureoviride, Trichoderma reesei, Trichoderma koningii and ...

  20. PH-triggered micellar membrane for controlled release microchips

    KAUST Repository

    Yang, Xiaoqiang

    2011-01-01

    A pH-responsive membrane based on polystyrene-b-poly(4-vinylpyridine) (PS-b-P4VP) block copolymer was developed on a model glass microchip as a promising controlled polymer delivery system. The PS-b-P4VP copolymer assembles into spherical and/or worm-like micelles with styrene block cores and pyridine coronas in selective solvents. The self-assembled worm-like morphology exhibited pH-responsive behaviour due to the protonation of the P4VP block at low pH and it\\'s deprotonation at high pH and thus constituting a switchable "off/on" system. Doxorubicin (Dox) was used as cargo to test the PS-b-P4VP membrane. Luminescence experiments indicated that the membrane was able to store Dox molecules within its micellar structure at neutral pH and then release them as soon as the pH was raised to 8.0. The performance of the cast membrane was predictable and most importantly reproducible. The physiochemical and biological properties were also investigated carefully in terms of morphology, cell viability and cell uptake. This journal is © The Royal Society of Chemistry.

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

    Science.gov (United States)

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

    2013-08-15

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

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

    Science.gov (United States)

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

    2014-11-01

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

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

    Science.gov (United States)

    Anirudhan, T S; Parvathy, J

    2014-06-01

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

  4. Once-Daily, Controlled-Release Tramadol and Sustained-Release Diclofenac Relieve Chronic Pain due to Osteoarthritis: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    André D Beaulieu

    2008-01-01

    Full Text Available OBJECTIVE: The present study was a randomized, parallel, double-blind comparison between controlled-release (CR tramadol and sustained-release (SR diclofenac in patients with chronic pain due to osteoarthritis of the hips and/or knees.

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

    Science.gov (United States)

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

    2011-06-01

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

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

    Science.gov (United States)

    Tarafder, Solaiman; Bose, Susmita

    2014-07-09

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

  7. Patrón de liberación de flúor in vitro en sellantes fluorados de resina In vitro fluoride-release profile of fluoridated resin-based sealants

    Directory of Open Access Journals (Sweden)

    S Gómez

    2011-12-01

    Full Text Available Objetivo: Comparar in vitro la cantidad de fluoruros liberados por los principales sellantes de puntos y fisuras basados en resina comercialmente disponibles en Latinoamérica. Material y Métodos: Se evaluó la liberación de fluoruros in vitro en tres sellantes fluorados de puntos y fisuras: Helioseal F (HF, Fissurit F (FF, Clinpro (CF y Delton (D, sin flúor como control. Se utilizaron 28 discos de 12 mm de diámetro y 2 mm de espesor (n=7 por grupo. Las muestras fueron almacenadas en 5 ml de agua ultra de-ionizada con pH neutro a 37º C por 93 días. La liberación de fluoruros fue medida mediante un electrodo iónico selectivo a los 1, 2, 3, 8, 15, 28 y 93 días. Los datos fueron analizados con el test ANOVA y Tukey (pAim: To compare in vitro the amount of fluoride released from the main pit and fissure sealant resin-based on commercially available in Latin America. Materials and Methods: Twenty-eight samples of 12 x 2 mm were made from three commercial fluoridated resin-based sealants: Helioseal F (HF, Fissurit F (FF, Clinpro (CF and without fluoride Delton (D, as a control. Samples were stored in 5 ml of deionized water at 37° C and neutral pH. Fluoride releases were measured at 1, 2, 3, 8, 15, 28 and 93 days with an ion-selective electrode. Data were analyzed using ANOVA and one-way and Tukey (p0.05. Conclusion: The fluoride-release profile is similar for the fluoridated resin-based sealants under study: a high release during the first two days and afterwards, a very slow release. These results can explain the lack of differences in caries rate between fluoridated and non-fluoridated resin-based sealants observed in clinical trials.

  8. Optimization of preparation conditions of poly(ε-caprolactone microspheres for controlled release of carbamazepine

    Directory of Open Access Journals (Sweden)

    Pepić Dragana S.

    2010-01-01

    drug crystals. The encapsulation efficiency and the release behavior of the carbamazepine were examined using high performance liquid chromatography-ultraviolet spectroscopy (HPLC-UV. The drug encapsulation efficiencies were in the range from 69 to 81%, and were increasing with the increase of the amount of carbamazepine in both series. In vitro release experiments were carried out in the phosphate buffer solution (pH 7 at 37ºC. The release rate was influenced by the microspheres size and morphology. The larger microspheres released more carbamazepine (85-95% compared to the small ones (50-65% for the same period. This behavior was attributed to the different drug distribution in the PCL matrix. Different mathematical models were used to describe drug release kinetics. It was concluded that the mechanism of the carbamazepine release from the microspheres was diffusion-controlled, independent on the type of microspheres. The kinetic parameters showed that the release of carbamazepine was slower from the smaller microspheres, probably as a result of more even distribution of the drug in the polymer matrix.

  9. Exploring polyvinylpyrrolidone in the engineering of large porous PLGA microparticles via single emulsion method with tunable sustained release in the lung: In vitro and in vivo characterization.

    Science.gov (United States)

    Ni, Rui; Muenster, Uwe; Zhao, Jing; Zhang, Lan; Becker-Pelster, Eva-Maria; Rosenbruch, Martin; Mao, Shirui

    2017-03-10

    Sustained pulmonary drug delivery is regarded as an effective strategy for local treatment of chronic lung diseases. Despite of the progress made so far, there remains a need for respirable drug loaded porous microparticles, where porosity of the microparticles can be readily engineered during the preparation process, with tunable sustained drug release upon lung deposition. In this work, polyvinyl pyrrolidone (PVP) was used as a novel porogen to engineer PLGA-based large porous particles (LPPs) using single emulsion method, with fine tuning of the porosity, sustained drug release both in vitro and in vivo. Using cinaciguat as the model drug, influence of PVP content and PLGA type on the properties of the LPPs was characterized, including geometric particle size, drug encapsulation efficiency, tap density, theoretical and experimental aerodynamic particle size, specific surface area, morphology, and in vitro drug release. Solid state of cinaciguat in the LPPs was studied based on DSC and X-ray analysis. LPPs retention in the rat lung was carried out using bronchoalveolar lavage fluid method. Raw 264.7 macrophage cells were used for LPPs uptake study. Pharmacodynamic study was performed in mini-pigs in a well-established model of pulmonary arterial hypertension (thromboxane challenge). It was demonstrated that porosity of the LPPs is tunable via porogen content variation. Cinaciguat can be released from the LPP in a controlled manner for over 168h. Significant reduction of macrophage phagocytosis was presented for LPPs. Furthermore, LPPs was found to have extended retention time (~36h) in the rat lung and accordingly, sustained pharmacodynamics effect was achieved in mini-pig model. Taken together, our results demonstrated that this simple PLGA based LPPs engineering using single emulsion method with PVP as porogen may find extensive application for the pulmonary delivery of hydrophobic drugs to realize tunable sustained effect with good safety profile. Copyright

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

    Science.gov (United States)

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

    2008-12-01

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

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

    Science.gov (United States)

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

    2010-06-01

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

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

    Science.gov (United States)

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

    2014-11-01

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

  13. Controlled-release NPK fertilizer encapsulated by polymeric membranes.

    Science.gov (United States)

    Jarosiewicz, Anna; Tomaszewska, Maria

    2003-01-15

    The commercial granular fertilizer NPK6-20-30 was coated using polysulfone (PSF), polyacrylonitrile (PAN), and cellulose acetate (CA). The coatings were formed from the polymer solutions by the phase inversion technique. Measurements of the thickness and porosity of the prepared coatings and a microphotographic observation of the coatings were performed. The physical properties of the coatings influence the release rate of macronutrients which are present in the core of the coated fertilizer. In the case of PAN coating with 60.45% porosity, prepared from a 16% polymer solution, 100% of NH(4)(+) and P(2)O(5) was released after 4 h of test and 99.7% of K(+) after 5 h of test, whereas in the case of coating with 48.8% porosity, 31.8% of NH(4)(+), 16.7% of P(2)O(5), and 11.6% of K(+) was released after 5 h. In all experiments, different selectivities of the coatings in terms of the release of components were observed. The release of potassium through the coatings made of PSF and PAN was the slowest. The same tendency was observed for the release of nitrogen through a coating of CA. The release of fertilizer active components was the slowest in the case of PSF. The lowest porosity coating was prepared from the 18% PSF solution.

  14. Development and characterization of multiple emulsions for controlled release of Trichilia catigua (Catuaba) extract.

    Science.gov (United States)

    Lonni, Audrey Alesandra Stinghen Garcia; Munhoz, Vanessa Marquito; Lopes, Gisely Cristiny; Longhini, Renata; Borghi-Pangoni, Fernanda Belincanta; Dos Santos, Rafaela Said; Junqueira, Mariana Volpato; Natali, Maria Raquel Marçal; Leite-Mello, Eneri; Guimaraes, Francine Baesso; Baesso, Mauro Luciano; Scarminio, Ieda Spacino; Bruschi, Marcos Luciano; Mello, João Carlos Palazzo de

    2016-12-01

    Considering the antioxidant activity of the Trichilia catigua extract (TCE), the aim of the current study was to develop and characterize W/O/W multiple emulsions containing different vegetable oils as a platform to deliver a TCE. The extract displayed antioxidant activity (IC50) of 4.59 µg/mL and total phenol content (TPC) of 50.84%. Formulations were prepared by the phase-inversion emulsification method and analyzed for morphological appearance, pH, conductivity, droplet size and distribution, content of active, rheological properties, in vitro release, skin permeation, and stability. Formulations prepared with canola oil were selected and displayed regular morphology, mean diameter 2.77 µm (without TCE), 3.07 µm with 0.5% and 3.23 µm with 1.0% TCE. Rheometry (flow) showed pseudoplastic behavior with minimal thixotropy for both systems. TCE could be released from emulsions containing 1.0% and 0.5% TCE in a controlled manner for 16 and 23 h, respectively. The emulsions allowed good retention of TCE in the skin (stratum corneum, epidermis, and dermis). In a 180-d assessment of accelerated chemical stability, TPC was more reduced for the emulsions at 40 °C; other parameters remained stable. Multiple emulsions containing TCE were developed, exhibited good characteristics, and may be considered for future investigations as anti-aging formulations for the skin.

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

    Science.gov (United States)

    Swamy, Bala Yerri; Yun, Yeoung-Sang

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Shende N

    2008-01-01

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

  17. In vitro evaluation of novel polymer-coated magnetic nanoparticles for controlled drug delivery.

    Science.gov (United States)

    Rahimi, Maham; Wadajkar, Aniket; Subramanian, Khaushik; Yousef, Monet; Cui, Weina; Hsieh, Jer-Tsong; Nguyen, Kytai Truong

    2010-10-01

    Previously uncharacterized poly(N-isopropylacrylamide-acrylamide-allylamine)-coated magnetic nanoparticles (MNPs) were synthesized using silane-coated MNPs as a template for radical polymerization of N-isopropylacrylamide, acrylamide, and allylamine. Properties of these nanoparticles such as size, biocompatibility, drug loading efficiency, and drug release kinetics were evaluated in vitro for targeted and controlled drug delivery. Spherical core-shell nanoparticles with a diameter of 100 nm showed significantly lower systemic toxicity than did bare MNPs, as well as doxorubicin encapsulation efficiency of 72%, and significantly higher doxorubicin release at 41°C compared with 37°C, demonstrating their temperature sensitivity. Released drugs were also active in destroying prostate cancer cells (JHU31). Furthermore, the nanoparticle uptake by JHU31 cells was dependent on dose and incubation time, reaching saturation at 500 μg/mL and 4 hours, respectively. In addition, magnetic resonance imaging capabilities of the particles were observed using agarose platforms containing cells incubated with nanoparticles. Future work includes investigation of targeting capability and effectiveness of these nanoparticles in vivo using animal models. In this paper, previously uncharacterized magnetic nanoparticles were synthesized using silane-coated MNPs as a template for radical polymerization of N-isopropylacrylamide, acrylamide, and allylamine. Various properties of these nanoparticles were evaluated in vitro for targeted drug delivery. Copyright © 2010 Elsevier Inc. All rights reserved.

  18. Materials for Pharmaceutical Dosage Forms: Molecular Pharmaceutics and Controlled Release Drug Delivery Aspects

    Directory of Open Access Journals (Sweden)

    Patrick P. DeLuca

    2010-09-01

    Full Text Available Controlled release delivery is available for many routes of administration and offers many advantages (as microparticles and nanoparticles over immediate release delivery. These advantages include reduced dosing frequency, better therapeutic control, fewer side effects, and, consequently, these dosage forms are well accepted by patients. Advances in polymer material science, particle engineering design, manufacture, and nanotechnology have led the way to the introduction of several marketed controlled release products and several more are in pre-clinical and clinical development.

  19. Materials for pharmaceutical dosage forms: molecular pharmaceutics and controlled release drug delivery aspects.

    Science.gov (United States)

    Mansour, Heidi M; Sohn, Minji; Al-Ghananeem, Abeer; Deluca, Patrick P

    2010-09-15

    Controlled release delivery is available for many routes of administration and offers many advantages (as microparticles and nanoparticles) over immediate release delivery. These advantages include reduced dosing frequency, better therapeutic control, fewer side effects, and, consequently, these dosage forms are well accepted by patients. Advances in polymer material science, particle engineering design, manufacture, and nanotechnology have led the way to the introduction of several marketed controlled release products and several more are in pre-clinical and clinical development.

  20. Effects of Controlled Release Fertilizer on the Flag Leaves Senescence in Dry-land Wheat

    OpenAIRE

    Dandan Liu; Yan Shi

    2013-01-01

    In order to select a reasonable controlled release fertilizer application method to slow down the senescence of flag leaf in dry-land wheat. The effects of controlled release fertilizer on soluble protein content, MDA content, the Catalase (CAT) activity, the Superoxide Dismutase (SOD) activity on the flag leaves senescence in dry-land wheat had been studied in the open field with the variety wheat Jimai22. The results indicated that, the combination application of controlled release fertiliz...

  1. Remotely Triggered Scaffolds for Controlled Release of Pharmaceuticals

    Directory of Open Access Journals (Sweden)

    Clare Hoskins

    2013-04-01

    Full Text Available Fe3O4-Au hybrid nanoparticles (HNPs have shown increasing potential for biomedical applications such as image guided stimuli responsive drug delivery. Incorporation of the unique properties of HNPs into thermally responsive scaffolds holds great potential for future biomedical applications. Here we successfully fabricated smart scaffolds based on thermo-responsive poly(N-isopropylacrylamide (pNiPAM. Nanoparticles providing localized trigger of heating when irradiated with a short laser burst were found to give rise to remote control of bulk polymer shrinkage. Gold-coated iron oxide nanoparticles were synthesized using wet chemical precipitation methods followed by electrochemical coating. After subsequent functionalization of particles with allyl methyl sulfide, mercaptodecane, cysteamine and poly(ethylene glycol thiol to enhance stability, detailed biological safety was determined using live/dead staining and cell membrane integrity studies through lactate dehydrogenase (LDH quantification. The PEG coated HNPs did not show significant cytotoxic effect or adverse cellular response on exposure to 7F2 cells (p < 0.05 and were carried forward for scaffold incorporation. The pNiPAM-HNP composite scaffolds were investigated for their potential as thermally triggered systems using a Q-switched Nd:YAG laser. These studies show that incorporation of HNPs resulted in scaffold deformation after very short irradiation times (seconds due to internal structural heating. Our data highlights the potential of these hybrid-scaffold constructs for exploitation in drug delivery, using methylene blue as a model drug being released during remote structural change of the scaffold.

  2. Controlled release from stimuli-sensitive microgel capsules

    Science.gov (United States)

    Masoud, Hassan; Alexeev, Alexander

    2011-10-01

    We introduce a mesoscale computational model for responsive gels, i.e. chemically cross-linked polymer networks immersed in Newtonian fluids, and use it to probe the release of nanoparticles from hollow microgel capsules that swell and deswell in response to external stimuli. Our model explicitly describes the transport of nanoparticles in swelling/deswelling polymer networks with complex geometries and associated fluid flows. Our simulations reveal that responsive microcapsules can be effectively utilized for steady and pulsatile release of encapsulated solutes. Steady, diffusive release of nanoparticle takes place from swollen gel capsules, whereas capsule deswelling cause burst-like discharge of solutes driven by a flow from the shrinking capsule interior. We demonstrate that this hydrodynamic release can be regulated by introducing rigid microscopic rods inside the capsule. Our calculations indicate that the rods stretch the deswelling membrane and promote the formation of large pores in the shell, which allow massive flow-driven release of nanoparticles. Thus, our findings unveil a new approach for regulating the release from stimulus responsive micro-carriers that will be especially useful for designing new drug delivery systems.

  3. Control of oxygen release from peroxides using polymers.

    Science.gov (United States)

    Steg, Hilde; Buizer, Arina T; Woudstra, Willem; Veldhuizen, Albert G; Bulstra, Sjoerd K; Grijpma, Dirk W; Kuijer, Roel

    2015-07-01

    An important limitation in cell therapy for the regeneration of tissue is the initial lack of oxygen. After implantation of large 3D cell-seeded structures, cells die rather than contribute to tissue regenerating. Here we've tested oxygen-releasing materials to improve cell survival and growth after implantation. Calcium peroxide (CaO2) in a polymer matrix was used as source of oxygen. Two polymers were tested in order to slow down and extend the period of oxygen release, poly(D,L-lactic acid) and poly(lactic-co-glycolic acid). Compared to CaO2 particles, both releasing systems showed an initially higher and shorter oxygen release. Human mesenchymal stromal cells cultured on casted films of these oxygen-releasing composites required catalase to proliferate, indicating the production of cytotoxic hydrogen peroxide as intermediate. Poly(D,L-lactic acid) and poly(lactic-co-glycolic acid) are less suited for slowly oxygen-releasing materials. Catalase was able to reduce the cytotoxic effect of H2O2.

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

    Science.gov (United States)

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

    1998-01-01

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

  5. In situ green synthesis of antimicrobial carboxymethyl chitosan-nanosilver hybrids with controlled silver release.

    Science.gov (United States)

    Huang, Siqi; Yu, Zhiming; Zhang, Yang; Qi, Chusheng; Zhang, Shifeng

    2017-01-01

    In order to fabricate antimicrobial carboxymethyl chitosan-nanosilver (CMC-Ag) hybrids with controlled silver release, this study demonstrated comparable formation via three synthetic protocols: 1) carboxymethyl chitosan (CMC) and glucose (adding glucose after AgNO3), 2) CMC and glucose (adding glucose before AgNO3), and 3) CMC only. Under principles of green chemistry, the synthesis was conducted in an aqueous medium exposed to microwave irradiation for 10 minutes with nontoxic chemicals. The structure and formation mechanisms of the three CMC-Ag hybrids were explored using X-ray diffraction, ultraviolet-visible spectroscopy, transmission electron microscopy, and Fourier-transform infrared analyses. Additionally, antimicrobial activity and in vitro silver release of the three synthesized hybrids were investigated in detail. The results revealed that a large number of stable, uniform, and small silver nanoparticles (AgNPs) were synthesized in situ on CMC chains via protocol 1. AgNPs were well dispersed with narrow size distribution in the range of 6-20 nm, with mean diameter only 12.22±2.57 nm. The addition of glucose resulted in greater AgNP synthesis. The order of addition of glucose and AgNO3 significantly affected particle size and size distribution of AgNPs. Compared to CMC alone and commercially available AgNPs, the antimicrobial activities of three hybrids were significantly improved. Of the three hybrids, CMC-Ag1 synthesized via protocol 1 exhibited better antimicrobial activity than CMC-Ag2 and CMC-Ag3, and showed more effective inhibition of Staphylococcus aureus than Escherichia coli. Due to strong coordination and electrostatic interactions between CMC and silver and good steric protection provided by CMC, CMC-Ag1 displayed stable and continuous silver release and better performance in retaining silver for prolonged periods than CMC-Ag2 and CMC-Ag3.

  6. PDMS embedded microneedles as a controlled release system for the eye.

    Science.gov (United States)

    Mahadevan, Geetha; Sheardown, Heather; Selvaganapathy, Ponnambalam

    2013-07-01

    To demonstrate intraocular drug delivery using a novel device fabricated by embedding hollow glass microneedles within a soft and flexible poly (dimethylsiloxane) (PDMS) substrate for ease of device insertion into the eye. Hollow glass microneedles (5 µm ID tips), fabricated using standard glass drawing techniques, were assembled into a photolithographically micropatterned PDMS substrate. The microneedles were fluidically coupled to a drug reservoir through a 300 µm microchannel to test for in vitro release of 6-aminoquinolone (144 Da) and Rose Bengal (1044 Da). Intravitreal delivery in ex vivo bovine eyes was also studied. The microneedles penetrated UV-crosslinked collagen and excised bovine sclera without breaking or delaminating from the PDMS matrix. A total of 45 ng of 6-aminoquinolone and 16 µg of Rose Bengal was released into buffered saline over a 20-min infusion at a delivery rate of 50 µL/min. Microinjection of Rose Bengal for 8 h into ex vivo bovine vitreous resulted in a total mass accumulation of 0.0202 mg into both phases of the vitreous humor and to the uveal face of the sclera without clogging of the internal needle microchannel. PDMS-embedded microneedles offer an integrated method of drug targeting to the intraocular tissues using a less invasive and less painful approach when compared with macroscale hypodermic needles. The release rates from the microneedles were controllable on demand using a syringe pump and were independent of the properties of the drugs tested. The device demonstrated a new hybrid approach of coupling rigid microneedles strong enough to penetrate the tough, fibrous sclera with a soft and pliable PDMS substrate that could conform to the contours of the eye.

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

    Directory of Open Access Journals (Sweden)

    Atul Jain

    2017-03-01

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

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

    Science.gov (United States)

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

    2013-06-05

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

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

    DEFF Research Database (Denmark)

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

    2001-01-01

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

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

    OpenAIRE

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

    2015-01-01

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

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

    DEFF Research Database (Denmark)

    Guo, Wenjia; Quan, Peng; Fang, Liang

    2015-01-01

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

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

    Science.gov (United States)

    Tiwari, S; Nandlal, B

    2012-01-01

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

  13. Development of functional fibrous matrices for the controlled release of basic fibroblast growth factor to improve therapeutic angiogenesis.

    Science.gov (United States)

    Kim, Min Sup; Bhang, Suk-Ho; Yang, Hee Seok; Rim, Nae Gyune; Jun, Indong; Kim, Sun I; Kim, Byung-Soo; Shin, Heungsoo

    2010-10-01

    In this study, novel fibrous matrices were developed as a depot to store and liberate growth factors in a controlled manner. Specifically, heparin was covalently conjugated onto the surface of fibrous matrices (composites of poly[caprolactone] and gelatin crosslinked with genipin), and basic fibroblast growth factor (bFGF) was then reversibly immobilized. The immobilization of bFGF was controlled as a function of the amount of conjugated heparin. The sustained release of bFGF from the fibrous matrices was successfully achieved over 4 weeks whereas physical adsorption of bFGF released quickly. The bFGF released from the fibrous matrices significantly enhanced in vitro proliferation of human umbilical vein endothelial cells. From the in vivo study, the group implanted with a higher amount of immobilized bFGF significantly facilitated neo-blood vessel formation as compared with other implantation groups. These results indicate that the sustained release of bFGF is important for the formation of blood vessels and that our fibrous matrices could be useful for regulation of tissue damage requiring angiogenesis. Further, our system can be combined with other growth factors with heparin binding domains, representing a facile depot for spatiotemporal control over the delivery of bioactive molecules in regenerative medicine.

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

    Science.gov (United States)

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

    2009-03-01

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

  15. Influence of formulation and process variables on in vitro release of theophylline from directly-compressed Eudragit matrix tablets.

    Science.gov (United States)

    Ceballos, A; Cirri, M; Maestrelli, F; Corti, G; Mura, P

    2005-01-01

    Extended-release theophylline (TP) matrix tablets were prepared by direct compression of drug and different pH-dependent (Eudragit L100, S100 and L100-55) and pH-independent (Eudragit RLPO and RSPO) polymer combinations. The influence of varying the polymer/polymer (w/w) ratio and the drug incorporation method (simple blend or solid dispersion) was also evaluated. Drug release, monitored using the Through Flow Cell system, markedly depended on both the kind of Eudragit polymer combinations used and their relative content in the matrix. Maintaining a constant 1:1 (w/w) drug/polymers ratio, the selection of appropriate mixtures of pH-dependent and pH-independent polymers enabled achievement of a suitable control of TP release. In particular, matrices with a 0.7:0.3 w/w mixture of Eudragit L100-Eudragit RLPO showed highly reproducible drug release profiles, with an almost zero-order kinetic, and allowed 100% released drug after 360 min. As for the effect of the drug incorporation method, simple blending was better than the solid dispersion technique, which not only did not improve the release data reproducibility, but also caused, unexpectedly, a marked slowing down in drug release rate.

  16. Factors controlling alkali salt deposition in recovery boilers. Release mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    McKeough, P.; Kurkela, M.; Kylloenen, H.; Tapola, E. [VTT Energy, Espoo (Finland). Process Technology Group

    1997-10-01

    The research was part of an ongoing cooperative research effort aimed at developing a model to describe the behaviour of inorganic compounds in kraft recovery boilers. During 1996 experimental investigations of sulphur release were continued. Experiments at elevated pressures and employing larger particle sizes were performed in order to gain information about mass transfer effects. The first experiments yielding data on the rates of the sulphur-release reactions were performed. This data will be used as the basis of a drop model for sulphur release being developed in cooperation with another research group. The other part of the work during 1996 explored the possibility of using chemical equilibrium calculations to predict the release of sodium, potassium and chlorine in the recovery furnace. The approach is essentially different from that employed in earlier studies in that the effects of fume formation are taken into account. So far, the predictions of the chemical equilibrium release model have, in no way, conflicted with field measurements. (orig.)

  17. Desktop 3D printing of controlled release pharmaceutical bilayer tablets.

    Science.gov (United States)

    Khaled, Shaban A; Burley, Jonathan C; Alexander, Morgan R; Roberts, Clive J

    2014-01-30

    Three dimensional (3D) printing was used as a novel medicine formulation technique for production of viable tablets capable of satisfying regulatory tests and matching the release of standard commercial tablets. Hydroxypropyl methylcellulose (HPMC 2208) (Methocel™ K100M Premium) and poly(acrylic acid) (PAA) (Carbopol(®) 974P NF) were used as a hydrophilic matrix for a sustained release (SR) layer. Hypromellose(®) (HPMC 2910) was used as a binder while microcrystalline cellulose (MCC) (Pharmacel(®) 102) and sodium starch glycolate (SSG) (Primojel(®)) were used as disintegrants for an immediate release (IR) layer. Commercial guaifenesin bi-layer tablets (GBT) were used as a model drug (Mucinex(®)) for this study. There was a favourable comparison of release of the active guaifenesin from the printed hydrophilic matrix compared with the commercially available GBT. The printed formulations were also evaluated for physical and mechanical properties such as weight variation, friability, hardness and thickness as a comparison to the commercial tablet and were within acceptable range as defined by the international standards stated in the United States Pharmacopoeia (USP). All formulations (standard tablets and 3D printed tablets) showed Korsmeyer-Peppas n values between 0.27 and 0.44 which indicates Fickian diffusion drug release through a hydrated HPMC gel layer. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Mesenchymal stem cells modulate release of matrix proteins from tendon surfaces in vitro: a potential beneficial therapeutic effect.

    Science.gov (United States)

    Garvican, Elaine R; Dudhia, Jayesh; Alves, Ana-Liz; Clements, Lucy E; Plessis, Francois Du; Smith, Roger K W

    2014-05-01

    Injury of tendons contained within a synovial environment, such as joint, bursa or tendon sheath, frequently fails to heal and releases matrix proteins into the synovial fluid, driving inflammation. This study investigated the effectiveness of cells to seal tendon surfaces and provoke matrix synthesis as a possible effective injectable therapy. Equine flexor tendon explants were cultured overnight in suspensions of bone marrow and synovium-derived mesenchymal stems cells and, as controls, two sources of fibroblasts, derived from tendon and skin, which adhered to the explants. Release of the most abundant tendon extracellular matrix proteins into the media was assayed, along with specific matrix proteins synthesis by real-time PCR. Release of extracellular matrix proteins was influenced by the coating cell type. Fibroblasts from skin and tendon appeared less capable of preventing the release of matrix proteins than mesenchymal stems cells. The source of cell is an important consideration for cell therapy.

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

    Science.gov (United States)

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

    2015-03-06

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Nangalama, A.W.

    1989-01-01

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

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

    Science.gov (United States)

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

    2017-05-19

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

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

    Directory of Open Access Journals (Sweden)

    Geethi Pamunuwa

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Susan D’Souza

    2014-01-01

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

  4. Controlling benthic release of phosphorus in different Baltic Sea scales

    DEFF Research Database (Denmark)

    Pitkänen, Heikki; Bendtsen, Jørgen; Hansen, Jørgen L. S.

    The general aim of the PROPPEN project was to study whether it is possible to counteract near-bottom anoxia and excess benthic nutrient release ("internal loading") in the Baltic Sea by artificial oxygenation in cost-efficient and socio-economically beneficial ways. Two pilot sites were selected...... to counteract anoxia and benthic release of nutrients in coastal marine conditions in the Baltic Sea. The project undertook monitoring of the pilot tests, modelling of effects at different scales, risk management, cost effectiveness and cost benefit analysis....

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

    Directory of Open Access Journals (Sweden)

    Giovana Carolina Bazzo

    2012-12-01

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

  6. Synthesis and applications of polyacrylamide grafted agar as a matrix for controlled drug release of 5-ASA.

    Science.gov (United States)

    Usha Rani, G; Konreddy, Ananda Kumar; Mishra, Sumit; Sen, Gautam

    2014-04-01

    Agar has been modified by microwave assisted grafting with acrylamide monomer, resulting in poly acrylamide grafted agar (Ag-g-PAM). The synthesized grades of Ag-g-PAM were characterized by standard physico-chemical characterization techniques (FTIR spectroscopy, elemental analysis, scanning electron microscopy (SEM)) to ascertain the intended grafting. The synthesized graft copolymer (Ag-g-PAM) has been investigated (in vitro) for controlled and colon targeted release of 5-amino salicylic acid (5-ASA). Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Fabrication and Evaluation of Multilayer Nanofiber-Hydrogel Meshes with a Controlled Release Property

    Directory of Open Access Journals (Sweden)

    Rigumula Wu

    2015-07-01

    Full Text Available Controlled release drug delivery systems enable the sustained release of bioactive molecules, and increase bioavailability over an extended length of time. Biocompatible and biodegradable materials such as polycaprolactone (PCL nanofibers and alginate hydrogel play a significant role in designing controlled release systems. Prolonged release of bioactive molecules is observed when these polymer materials are used as matrices independently. However, there has not been a report in the literature that shows how different molecules are released at various rates over time. The goal of this study is to demonstrate a novel drug delivery system that has a property of releasing designated drugs at various rates over a defined length of time. We fabricated multilayer nanofiber-hydrogel meshes using electrospun PCL nanofiber and alginate hydrogel, and evaluated their controlled release properties. The multilayer meshes are composed of sandwiched layers of alternating PCL nanofibers and alginate hydrogel. Adenosine triphosphate (ATP, encapsulated in the designated hydrogel layers, is used as a mock drug for the release study. The exposed top layer of the meshes demonstrates a dramatically higher burst release and shorter release time compared to the deeper layers. Such properties of the different layers within the meshes can be employed to achieve the release of multiple drugs at different rates over a specified length of time.

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

    Science.gov (United States)

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

    2006-01-01

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

  9. Control of oxygen release from peroxides using polymers

    NARCIS (Netherlands)

    Steg, Hilde; Buizer, Arina T.; Woudstra, Willem; Veldhuizen, Albert G.; Bulstra, Sjoerd K.; Grijpma, Dirk W.; Kuijer, Roel

    An important limitation in cell therapy for the regeneration of tissue is the initial lack of oxygen. After implantation of large 3D cell-seeded structures, cells die rather than contribute to tissue regenerating. Here we've tested oxygen-releasing materials to improve cell survival and growth after

  10. Control of oxygen release from peroxides using polymers

    NARCIS (Netherlands)

    Steg, Hilde; Buizer, A.T.; Woudstra, W.; Veldhuizen, A.G.; Bulstra, S.K.; Grijpma, Dirk W.; Kuijer, R.

    2015-01-01

    An important limitation in cell therapy for the regeneration of tissue is the initial lack of oxygen. After implantation of large 3D cell-seeded structures, cells die rather than contribute to tissue regenerating. Here we’ve tested oxygen-releasing materials to improve cell survival and growth after

  11. Controlled Release Formulation of Indomethacin Prepared With Bee ...

    African Journals Online (AJOL)

    Erah

    2010-12-27

    Dec 27, 2010 ... toothpaste and dental floss, and as a health- food/dietary supplement in various dosage forms - tablets, capsules, ampoules and syrups [3]. The United ..... by diffusion and that erosion contributes negligibly. F13 formulation showed an optimal drug release properties as it closely approximated zero order.

  12. Controlled Release Formulation of Indomethacin Prepared With Bee ...

    African Journals Online (AJOL)

    Purpose: To prepare and evaluate new sustained release formulations of indomethacin based on extracts of propolis (bee glue). Methods: Standardization of propolis (bee glue) extracts was performed by high performance liquid chromatography (HPLC) and determination of the values of fat and fixed oils. Several ...

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

    Directory of Open Access Journals (Sweden)

    Cristhian J. Yarce

    2017-01-01

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

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

    Science.gov (United States)

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

    2017-01-24

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

  15. Comparative evaluation of fluoride release and recharge of pre-reacted glass ionomer composite and nano-ionomeric glass ionomer with daily fluoride exposure: an in vitro study.

    Science.gov (United States)

    Mungara, Jayanthi; Philip, John; Joseph, Elizabeth; Rajendran, Sakthivel; Elangovan, Arun; Selvaraju, Girija

    2013-01-01

    This in vitro study was designed to investigate the effects of daily fluoride exposures on fluoride release and recharge by prereacted glass ionomer (PRG) composite and nano-ionomeric glass ionomer. Seventy-two specimens (36 of each material) were prepared and by placing the restorative materials into Teflon mold. Each specimen was subjected to one of three daily treatments (n = 12): (1) No fluoride treatment (control); (2) application of a fluoride dentifrice (1,000 ppm) once daily; and (3) the same regimen as (2), plus immersion in a 0.05% sodium fluoride (NaF) mouth rinse (225 ppm) immediately following the dentifrice application. Specimens were suspended in a storage vial containing 10 ml demineralizing solution for 6 h and transferred to a new test tube containing 10 ml remineralizing solution for 18 h. Fluoride treatments of the specimens were completed every day prior to their immersion in the demineralizing solution. Media solutions were buffered with equal volumes of total ionic strength adjustment buffer (TISAB) II; fluoride levels were measured using a digital ion analyzer and fluoride electrode throughout the 21 day duration of the experiment. Nano-ionomeric glass ionomer showed a better amount of fluoride release than PRG composite irrespective of the fluoride treatment supplementation (P recharge ability for both the materials when compared to their respective control groups. The fluoride recharge for both materials did not show any sustained pattern of release. Nano-ionomeric glass ionomer demonstrated a greater ability to release and recharge compared with that of PRG composite.

  16. Concerning Workload Control and Order Release : The Pre-Shop Pool Sequencing Decision

    NARCIS (Netherlands)

    Thürer, Matthias; Land, Martin J.; Stevenson, Mark; Fredendall, Lawrence D.; Godinho Filho, Moacir

    2015-01-01

    Every production planning concept that incorporates controlled order release will initially withhold jobs from the shop floor and create a pre-shop pool. Order release is a key component of the Workload Control concept that aims to maintain work-in-process within limits while ensuring due dates are

  17. 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

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

    Directory of Open Access Journals (Sweden)

    Seidel Petra

    2012-10-01

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

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

    Science.gov (United States)

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

    2012-10-04

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

  20. Synthetic geopolymers for controlled delivery of oxycodone: adjustable and nanostructured porosity enables tunable and sustained drug release.

    Science.gov (United States)

    Forsgren, Johan; Pedersen, Christian; Strømme, Maria; Engqvist, Håkan

    2011-03-15

    In this article we for the first time present a fully synthetic mesoporous geopolymer drug carrier for controlled release of opioids. Nanoparticulate precursor powders with different Al/Si-ratios were synthesized by a sol-gel route and used in the preparation of different geopolymers, which could be structurally tailored by adjusting the Al/Si-ratio and the curing temperatures. In particular, it was shown that the pore sizes of the geopolymers decreased with increasing Al/Si ratio and that completely mesoporous geopolymers could be produced from precursor particles with the Al/Si ratio 2:1. The mesoporosity was shown to be associated with a sustained and linear in vitro release profile of the opioid oxycodone. A clinically relevant release period of about 12 h was obtained by adjusting the size of the pellets. The easily fabricated and tunable geopolymers presented in this study constitute a novel approach in the development of controlled release formulations, not only for opioids, but whenever the clinical indication is best treated with a constant supply of drugs and when the mechanical stability of the delivery vehicle is crucial.

  1. Dissolution of copper mineral phases in biological fluids and the controlled release of copper ions from mineralized alginate hydrogels.

    Science.gov (United States)

    Bassett, David C; Madzovska, Ivana; Beckwith, Kai S; Melø, Thor Bernt; Obradovic, Bojana; Sikorski, Pawel

    2014-12-29

    Here we investigate the dissolution behaviour of copper minerals contained within biocompatible alginate hydrogels. Copper has a number of biological effects and has most recently been evaluated as an alternative to expensive and controversial growth factors for applications in tissue engineering. Precise control and sustained release of copper ions are important due to a narrow therapeutic window of this potentially toxic ion, and alginate would appear to be a good material of choice for this purpose. We found that aqueously insoluble copper minerals could be precipitated during gelling within or mixed into alginate hydrogels in the form of microbeads prior to gelling to serve as depots of copper. These minerals were found to be soluble in a variety of biological fluids relevant to in vitro and in vivo investigations, and the alginate carrier served as a barrier to diffusion of these ions and therefore offered control over the rate and duration of release (Cu(2+) release rates observed between 10-750 µMol g(-1) h(-1) and duration for up to 32 d). Copper mineral and copper mineralized alginate microbeads were characterized using powder x-ray diffraction, FTIR, thermogravimetric analysis and scanning electron microscopy. Dissolution kinetics were studied based on measurements of copper ion concentrations using colourimetric methods. In addition we characterized the complexes formed between released copper ions and biological fluids by electron paramagnetic spectroscopy which offers an insight into the behaviour of these materials in the body.

  2. Synthetic Geopolymers for Controlled Delivery of Oxycodone: Adjustable and Nanostructured Porosity Enables Tunable and Sustained Drug Release

    Science.gov (United States)

    Forsgren, Johan; Pedersen, Christian; Strømme, Maria; Engqvist, Håkan

    2011-01-01

    In this article we for the first time present a fully synthetic mesoporous geopolymer drug carrier for controlled release of opioids. Nanoparticulate precursor powders with different Al/Si-ratios were synthesized by a sol-gel route and used in the preparation of different geopolymers, which could be structurally tailored by adjusting the Al/Si-ratio and the curing temperatures. In particular, it was shown that the pore sizes of the geopolymers decreased with increasing Al/Si ratio and that completely mesoporous geopolymers could be produced from precursor particles with the Al/Si ratio 2∶1. The mesoporosity was shown to be associated with a sustained and linear in vitro release profile of the opioid oxycodone. A clinically relevant release period of about 12 h was obtained by adjusting the size of the pellets. The easily fabricated and tunable geopolymers presented in this study constitute a novel approach in the development of controlled release formulations, not only for opioids, but whenever the clinical indication is best treated with a constant supply of drugs and when the mechanical stability of the delivery vehicle is crucial. PMID:21423616

  3. Synthetic geopolymers for controlled delivery of oxycodone: adjustable and nanostructured porosity enables tunable and sustained drug release.

    Directory of Open Access Journals (Sweden)

    Johan Forsgren

    Full Text Available In this article we for the first time present a fully synthetic mesoporous geopolymer drug carrier for controlled release of opioids. Nanoparticulate precursor powders with different Al/Si-ratios were synthesized by a sol-gel route and used in the preparation of different geopolymers, which could be structurally tailored by adjusting the Al/Si-ratio and the curing temperatures. In particular, it was shown that the pore sizes of the geopolymers decreased with increasing Al/Si ratio and that completely mesoporous geopolymers could be produced from precursor particles with the Al/Si ratio 2:1. The mesoporosity was shown to be associated with a sustained and linear in vitro release profile of the opioid oxycodone. A clinically relevant release period of about 12 h was obtained by adjusting the size of the pellets. The easily fabricated and tunable geopolymers presented in this study constitute a novel approach in the development of controlled release formulations, not only for opioids, but whenever the clinical indication is best treated with a constant supply of drugs and when the mechanical stability of the delivery vehicle is crucial.

  4. Poly(N-methacryloyl glycine)/nanocellulose composites as pH-sensitive systems for controlled release of diclofenac.

    Science.gov (United States)

    Saïdi, Louise; Vilela, Carla; Oliveira, Helena; Silvestre, Armando J D; Freire, Carmen S R

    2017-08-01

    The present study reports the development of non-cytotoxic and pH-sensitive nanostructured membranes consisting of a polymer with amino acid pending moieties and bacterial nanocellulose (BC). The nanocomposites were prepared through a simple methodology under green reaction conditions. The obtained materials display good thermal stability (up to 200°C), viscoelastic (storage modulus>700MPa) and mechanical (Young's modulus=3.5-4.9GPa) properties, together with high water uptake capacity. The results of the in vitro MTT assay showed that the nanocomposites are non-cytotoxic to HaCaT cells for 72h. The in vitro release profile of diclofenac sodium salt (DCF) from the nanocomposites into simulated body fluids at different pH values demonstrates the pH-responsive behaviour of these materials. Besides, DCF is mainly retained in the nanocomposites at pH 2.1 and released at pH 7.4, revealing their potential for the controlled release of DCF in dermal as well as in oral drug delivery applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Development of a Controlled Release of Salicylic Acid Loaded Stearic Acid-Oleic Acid Nanoparticles in Cream for Topical Delivery

    Directory of Open Access Journals (Sweden)

    J. O. Woo

    2014-01-01

    Full Text Available Lipid nanoparticles are colloidal carrier systems that have extensively been investigated for controlled drug delivery, cosmetic and pharmaceutical applications. In this work, a cost effective stearic acid-oleic acid nanoparticles (SONs with high loading of salicylic acid, was prepared by melt emulsification method combined with ultrasonication technique. The physicochemical properties, thermal analysis and encapsulation efficiency of SONs were studied. TEM micrographs revealed that incorporation of oleic acid induces the formation of elongated spherical particles. This observation is in agreement with particle size analysis which also showed that the mean particle size of SONs varied with the amount of OA in the mixture but with no effect on their zeta potential values. Differential scanning calorimetry analysis showed that the SONs prepared in this method have lower crystallinity as compared to pure stearic acid. Different amount of oleic acid incorporated gave different degree of perturbation to the crystalline matrix of SONs and hence resulted in lower degrees of crystallinity, thereby improving their encapsulation efficiencies. The optimized SON was further incorporated in cream and its in vitro release study showed a gradual release for 24 hours, denoting the incorporation of salicylic acid in solid matrix of SON and prolonging the in vitro release.

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

    Indian Academy of Sciences (India)

    WINTEC

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

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

    African Journals Online (AJOL)

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

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

    African Journals Online (AJOL)

    HP

    2013-07-15

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

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

    Directory of Open Access Journals (Sweden)

    Delmo Santiago Vaitsman

    2009-01-01

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

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

    DEFF Research Database (Denmark)

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

    1986-01-01

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

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

    Science.gov (United States)

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

    2012-07-01

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

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

    Science.gov (United States)

    Coulson, James; Thompson, John Paul

    2010-02-01

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

  13. Gastrin release: Antrum microdialysis reveals a complex neural control

    DEFF Research Database (Denmark)

    Ericsson, P; Håkanson, R; Rehfeld, Jens F.

    2010-01-01

    in serum regardless of the prandial state. The rats were conscious during microdialysis except when subjected to electrical vagal stimulation. Acid blockade (omeprazole treatment of freely fed rats for 4 days), or bilateral sectioning of the abdominal vagal trunks (fasted, 3 days post-op.), raised...... the gastrin concentration in blood as well as microdialysate. The high gastrin concentration following omeprazole treatment was not affected by vagotomy. Vagal excitation stimulated the G cells: electrical vagal stimulation and pylorus ligation (fasted rats) raised the gastrin concentration transiently...... microdialysate gastrin concentration in omeprazole-treated rats by 65%. We conclude that activated gastrin release, unlike basal gastrin release, is highly dependent on a neural input: 1) Vagal excitation has a transient stimulating effect on the G cells. The transient nature of the response suggests...

  14. Gastrin release: Antrum microdialysis reveals a complex neural control

    DEFF Research Database (Denmark)

    Ericsson, P; Håkanson, R; Rehfeld, Jens F.

    2010-01-01

    We used microdialysis to monitor local gastrin release in response to food, acid blockade and acute vagal excitation. For the first time, gastrin release has been monitored continuously in intact conscious rats in a physiologically relevant experimental setting in a fashion that minimizes...... confounding systemic effects. Microdialysis probes were placed in the submucosa on either side of the antrum, 3 days before the experiments. The concentration of gastrin in the antral submucosal compartment was about 20 times higher than in the microdialysate and estimated to be 5-10 times higher than...... the gastrin concentration in blood as well as microdialysate. The high gastrin concentration following omeprazole treatment was not affected by vagotomy. Vagal excitation stimulated the G cells: electrical vagal stimulation and pylorus ligation (fasted rats) raised the gastrin concentration transiently...

  15. Controlled drug release on amine functionalized spherical MCM-41

    Science.gov (United States)

    Szegedi, Agnes; Popova, Margarita; Goshev, Ivan; Klébert, Szilvia; Mihály, Judit

    2012-10-01

    MCM-41 silica with spherical morphology and small particle sizes (100 nm) was synthesized and modified by post-synthesis method with different amounts of 3-aminopropyltriethoxysilane (APTES). A comparative study of the adsorption and release of a model drug, ibuprofen, was carried out. The modified and drug loaded mesoporous materials were characterized by XRD, TEM, N2 physisorption, elemental analysis, thermal analysis and FT-IR spectroscopy. A new method was developed for the quantitative determination of amino groups in surface modified mesoporous materials by the ninhydrin reaction. Good correlation was found between the amino content of the MCM-41 materials determined by the ninhydrin method and their ibuprofen adsorption capacity. Amino modification resulted in high degree of ibuprofen loading and slow release rate in comparison to the parent non-modified MCM-41.

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

    Directory of Open Access Journals (Sweden)

    Maria Bastianini

    2017-07-01

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

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

    Science.gov (United States)

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

    2012-09-28

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

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

    Science.gov (United States)

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

    2013-03-01

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

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

    Science.gov (United States)

    Lamprecht, Guenther

    2009-10-01

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

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

    African Journals Online (AJOL)

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

  1. 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

  2. Photonic hydrogel beads for controlled release of risedronate

    Science.gov (United States)

    Khajuria, Deepak K.; Roy Mahapatra, D.

    2014-03-01

    pH-sensitive photonic composite hydrogel beads composed of sodium alginate and risedronate sodium (SA/RIS) was prepared crosslinked by Ca2+ owing to the ionic gelation of SA. The structure and surface morphology of the composite hydrogel beads were characterized by SEM. pH-sensitivity of these composite hydrogels beads and the release behaviors of drug from them were investigated. The results showed that the composite hydrogel beads had good pH-sensitivity. The drug loading and encapsulation efficiency were 27.7% and 92% for RIS, respectively. The cumulative release ratios of RIS from the composite hydrogel beads were 2.47% in pH 2.1 solution and 83 % in pH 6.8 solutions within 24 h, respectively. However, the cumulative release ratio of RIS in pH 7.4 solution reached 91% within 7 h. It is proposed that the novel photonic SA/RIS composite hydrogel bead could possess the potential of an increased intestinal absorption and fewer adverse effects of RIS. The pH and salt response of photonic hydrogel bead, as well as the encapsulation of macromolecules, are promising for applications in biomedicine and biotechnology.

  3. Controlled drug release on amine functionalized spherical MCM-41

    Energy Technology Data Exchange (ETDEWEB)

    Szegedi, Agnes, E-mail: szegedi@chemres.hu [Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, 1025 Budapest, Pusztaszeri ut 59-67 (Hungary); Popova, Margarita; Goshev, Ivan [Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Sofia (Bulgaria); Klebert, Szilvia [Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, 1025 Budapest, Pusztaszeri ut 59-67 (Hungary); Mihaly, Judit [Institute of Molecular Pharmacology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, 1025 Budapest, Pusztaszeri ut 59-67 (Hungary)

    2012-10-15

    MCM-41 silica with spherical morphology and small particle sizes (100 nm) was synthesized and modified by post-synthesis method with different amounts of 3-aminopropyltriethoxysilane (APTES). A comparative study of the adsorption and release of a model drug, ibuprofen, was carried out. The modified and drug loaded mesoporous materials were characterized by XRD, TEM, N{sub 2} physisorption, elemental analysis, thermal analysis and FT-IR spectroscopy. A new method was developed for the quantitative determination of amino groups in surface modified mesoporous materials by the ninhydrin reaction. Good correlation was found between the amino content of the MCM-41 materials determined by the ninhydrin method and their ibuprofen adsorption capacity. Amino modification resulted in high degree of ibuprofen loading and slow release rate in comparison to the parent non-modified MCM-41. - Graphical abstract: Determination of surface amino groups by ninhidrin method. Highlights: Black-Right-Pointing-Pointer Spherical MCM-41 modified by different amounts of APTES was studied. Black-Right-Pointing-Pointer Ibuprofen (IBU) adsorption and release characteristics was tested. Black-Right-Pointing-Pointer The ninhydrin reaction was used for the quantitative determination of amino groups. Black-Right-Pointing-Pointer Stoichiometric amount of APTES is enough for totally covering the surface with amino groups. Black-Right-Pointing-Pointer Good correlation was found between the amino content and IBU adsorption capacity.

  4. Electrospun biodegradable nanofiber nonwovens for controlled release of proteins.

    Science.gov (United States)

    Maretschek, Sascha; Greiner, Andreas; Kissel, Thomas

    2008-04-21

    Electrospinning of emulsions composed of an organic poly(l-lactide) solution and an aqueous protein solution yielded protein containing nanofiber nonwovens (NNs) having a mean fiber diameter of approximately 350 nm. Cytochrome C was chosen as a hydrophilic model protein for encapsulation. SEM imaging and gas adsorption measurements were carried out to determine morphology and surface characteristics of the different nanofiber nonwovens. Transmission electron microscopy was used to clarify the localization of the protein within the NN. PLLA NNs exhibited a highly hydrophobic surface which led to a slow wetting. It was shown that the protein release was dependent on the surface tension of the release medium. Electrospinning of emulsions consisting of an organic solution of PLLA and an aqueous solution of hydrophilic polymers yielded fibers composed of a polymer blend. The resulting NNs exhibited a less hydrophobic surface, which gave us the opportunity to tailor the release profile via this technology. Furthermore it was investigated how the addition of different amounts of hydrophilic polymer to the aqueous phase influenced the morphology of the resulting NNs.

  5. Controlled release of ibuprofen using Mg Al LDH nano carrier

    Science.gov (United States)

    Dasgupta, Sudip

    2017-08-01

    In the present study, NSAID (non-steroidal anti-inflammatory drugs) such as ibuprofen in anionic form has been intercalated in-situ into the interlayer space of Mg Al LDH nanoparticle during co-precipitation of hydroxides. LDH nanohybrids are characterized by XRD, FTIR and UV spectroscopy. Mg1-xAlx(NO3)x(OH)2.nH2O nanoparticles were synthesized using co-precipitation method from an aqueous solution of Mg(NO3)2.6H2O and Al(NO3)3.9H2O. Ibuprofen was intercalated in inter layer space of Mg-Al LDH during coprecipitation of drug LDH conjugate in nitrogen atmosphere. The nanopowders synthesised were in the size range between 25 to 90 nm with an average particle size of 55 nm. XRD analysis proved that there is an increase in d003 spacing from 7.89 Å for pristine LDH to 14.71 Å for ibuprofen intercalated LDH due to the intercalation of bigger ibuprofen molecule in the interlayer space of LDH. FTIR analysis showed hydroxyl and carbonyl stretching of ibuprofen in LDH-IBU sample confirming the intercalation of ibuprofen in the interlayer structure of LDH. The drug release study in phosphate buffer solution at pH 7.4 using UV-Vis spectroscopy demonstrated that 50 % drug molecules were released in 15 hours and more than 85 % release was achieved after 36 hours.

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

    Science.gov (United States)

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

    2016-01-01

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

  7. Hydroxypropyl methylcellulose-based controlled release dosage by melt extrusion and 3D printing: Structure and drug release correlation.

    Science.gov (United States)

    Zhang, Jiaxiang; Yang, Weiwei; Vo, Anh Q; Feng, Xin; Ye, Xingyou; Kim, Dong Wuk; Repka, Michael A

    2017-12-01

    The objective of this study was to develop a new approach for fabrication of zero order release of active pharmaceutical ingredients (APIs) using hot-melt extrusion (HME) and 3D printing technology to generate tablets with specific 3D structures. By correlating the geometry of the 3D printed tablets with their dissolution and drug release rates, mathematical models that have been developed to describe drug release mechanisms were also studied. Acetaminophen was used as a model drug, and Benecel™ hydroxypropyl methylcellulose (HPMC) E5 and Soluplus(®) were used to formulate nine fuse depositional 3D-printed tablets with different inner core fill densities and outside shell thicknesses. This work reports the successful fabricatio