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Sample records for vitro release studies

  1. 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.

  2. 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 ...

  3. 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...

  4. 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.

  5. 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 ...

  6. 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...

  7. 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...

  8. 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 ...

  9. 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 ...

  10. 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.

  11. 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

  12. 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.

  13. 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 ...

  14. 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.

  15. 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.

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    Xiangyang Xie

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

  18. 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.

  19. 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.

  20. 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...

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. [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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    Hernawan Hernawan

    2013-12-01

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

  15. 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.

  16. 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.

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

    Indian Academy of Sciences (India)

    WINTEC

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

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

    Directory of Open Access Journals (Sweden)

    Bajpai AK

    2009-10-01

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

  19. In vitro 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...

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

    Science.gov (United States)

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

    2017-11-10

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

  1. 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.

  2. 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.

  3. 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.

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

    Science.gov (United States)

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

    2017-09-01

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

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    Praveen Kumar Gaur

    2014-12-01

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

  7. 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.

  8. 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 ...

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

    OpenAIRE

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

    2012-01-01

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

  10. 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.

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

    Science.gov (United States)

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

    2013-06-03

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

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

    Directory of Open Access Journals (Sweden)

    Hatem Fessi

    2013-06-01

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

  13. 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.

  14. Leptin amplifies the action of thyrotropin-releasing hormone in the solitary nucleus: an in vitro calcium imaging study.

    Science.gov (United States)

    Rogers, Richard C; McDougal, David H; Hermann, Gerlinda E

    2011-04-18

    Leptin exerts a powerful permissive influence on neurogenic thermogenesis. During starvation and an absence of leptin, animals cannot produce thermogenic reactions to cold stress. However, thermogenesis is rescued by restoring leptin. We have previously observed a highly cooperative interaction between leptin and thyrotropin-releasing hormone [TRH] to activate hindbrain-generated thermogenic responses (Hermann et al., 2006). In vivo physiological studies (Rogers et al., 2009) suggested that the thermogenic impact of TRH in the hindbrain is amplified by the action of leptin through a leptin receptor-mediated production of phosphoinositol-trisphosphate [PIP3]. In turn, PIP3 can activate a tyrosine kinase whose target is the Src-SH2 regulatory site on the phospholipase C [PLC] complex. The TRH receptor signals through the PLC complex. Our immunohistochemical studies (Barnes et al., 2010) suggest that this transduction interaction between leptin and TRH occurs within neurons of the solitary nucleus [NST], though this interaction had not been verified. The present in vitro live cell calcium imaging study shows that while medial NST neurons are rarely activated by leptin alone, leptin pre-treatment significantly augments NST neurons' responsiveness to TRH. This leptin-mediated priming of NST neurons was uncoupled by pre-treatment with the phosphoinositide 3-kinase [PI3K] inhibitor [wortmannin], the phospholipase C inhibitor [U73122] and the Src-SH2 antagonist [PP2]. TTX did not eliminate the synergistic response of the agonists, thus the sensitization cannot be attributed to pre-synaptic mechanisms. It seems likely that NST neurons are involved in the leptin-mediated increase in BAT temperature by sensitizing the TRH-PLC-IP3-calcium release mechanism. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Withania somnifera aqueous extract facilitates the expression and release of GnRH: In vitro and in vivo study.

    Science.gov (United States)

    Kataria, Hardeep; Gupta, Muskan; Lakhman, Sukhwinder; Kaur, Gurcharan

    2015-10-01

    Ashwagandha (Withania somnifera) has a long history in traditional medicines as an aphrodisiac. It has been known to influence sexual behaviour in animal models but mechanism of action is still unknown. The present study was aimed to investigate the mechanisms by which Ashwagandha extract exert its gonadotropic activities. Due to the complexity of neuroendocrine pathways, there are limited in vitro models available despite the strong demand for such systems to study and predict neuroendocrine effects of chemicals or natural products. Immortalized rat hypothalamic GnV-3 cell line was investigated as a model to screen for neuroendocrine effects of Ashwagandha extract. GnV-3 cells were cultured under different media conditions and evaluated after treatment with Ashwagandha water extract, for GnRH expression and release by immunostaining and ELISA respectively. These cells acquired differentiated morphology, characteristic shape displayed by preoptic GnRH neurons in vivo. In addition, GnV-3 cells exhibited upregulation of plasticity related polysialylated neural cell adhesion molecule (PSA-NCAM) and mature dendrite marker microtubule associated protein (MAP2) as well as GnRH expression and release. Chloroform fraction of the extract proved to exhibit all the bioactive properties as it induced differentiation and upregulated GnRH and MAP2 expression in GnV-3 cells, similar to Ashwagandha extract. Withanone and Withaferin A were found to be present in ASH-WEX and chloroform fraction while Withanone came out to be the major constituent of chloroform fraction. The preliminary in vivo studies in adult male animals showed that ASH-WEX was able to upregulate the GnRH levels although non-significantly. Taken together, this data demonstrate significant morphological and physiological changes in GnV-3 cells after treatment with Ashwagandha extract and may suggest the potential beneficial effects of Ashwagandha on reproductive functions in vivo. Copyright © 2015 Elsevier Ltd

  16. A comparative in vitro study on fluoride release and water sorption of different flowable esthetic restorative materials

    OpenAIRE

    Harhash, Asmaa Youssif; ElSayad, Iman Ibrahim; Zaghloul, Ahmad G. S.

    2017-01-01

    Objectives: The objective of the study was to evaluate fluoride release and water sorption of three flowable esthetic restorative materials: a giomer, a fluoride-releasing resin composite, and a nonfluoridated resin composite. Materials and Methods: Ten samples from a giomer, a fluoride releasing nano-hybrid, and a nonfluoridated nano-hybrid composite were prepared and immersed in deionized water. Fluoride measurements were done using an ion-specific electrode attached to a microprocessor-bas...

  17. 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.

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

    Science.gov (United States)

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

    2016-04-01

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

  19. Protein release from hippocampus in vitro.

    Science.gov (United States)

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

    1984-07-02

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

  20. 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.

  1. In vitro solubility, dissolution and permeability studies combined with semi-mechanistic modeling to investigate the intestinal absorption of desvenlafaxine from an immediate- and extended release formulation

    DEFF Research Database (Denmark)

    Franek, F; Jarlfors, A; Larsen, F.

    2015-01-01

    (ERF). Semi-mechanistic models of desvenlafaxine were built (using SimCyp®) by combining in vitro data on dissolution and permeation (mechanistic part of model) with clinical data (obtained from literature) on distribution and clearance (non-mechanistic part of model). The model predictions...... for desvenlafaxine absorption (i.e. intestinal dissolution or permeation) is not fully clarified. The aim of this study was to investigate whether dissolution and/or intestinal permeability rate-limit desvenlafaxine absorption from an immediate-release formulation (IRF) and Pristiq®, an extended release formulation...... of desvenlafaxine pharmacokinetics after IRF and ERF administration were compared with published clinical data from 14 trials. Desvenlafaxine in vivo dissolution from the IRF and ERF was predicted from in vitro solubility studies and biorelevant dissolution studies (using the USP3 dissolution apparatus...

  2. Assessment of Ions released from Three Types of Orthodontic Brackets immersed in Different Mouthwashes: An in vitro Study.

    Science.gov (United States)

    Nahidh, Mohammed; Garma, Noor Mh; Jasim, Esraa S

    2018-01-01

    Herbs are used widely in medicine. The purpose of the present study was to assess the ion release from gold-plated orthodontic bracket compared with other stainless steel brackets, and based on the findings of the study, the orthodontists can choose the most biocompatible brackets and mouthwashes useful in the clinical practice. A total of 150 orthodontic brackets from Orthotechnology™ Company, USA (50 stainless steel one-piece brackets, 50 stainless steel two-piece brackets, and 50 gold brackets) were immersed in four mouthwashes in addition to distilled water. Ten of each type of brackets in every media were immersed under 37°C for 45 days. Ions released in these mouthwashes were measured, and comparisons among different bracket types and among various mouthwashes were done by one-way analysis of variance (ANOVA) and then with Games-Howell tests. Increased amounts of ions released in herbal mouth-washes were recorded in gold and two-piece brackets in comparison with one-piece stainless steel brackets. Herbal mouthwashes must be used with caution as they showed an increased amount of ions released in comparison with chlorhexidine. One-piece stainless steel bracket system is the most compatible bracket type, as they released the least amount of ions. One-piece stainless steel brackets are better than two-piece brackets in terms of ions released.

  3. 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.

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

    Science.gov (United States)

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

    2005-04-01

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

  5. Evaluation and comparison of quantity and pattern of fluoride release from orthodontic adhesives: an in vitro study.

    Science.gov (United States)

    Regalla, Ravindra Reddy; Jadav, Chandulal; Babu, Devatha Ashok; Sriram, Roopa Rani S; Sriram, Sanjay Krishna; Kattimani, Vivekanand S

    2014-01-01

    Orthodontic treatment has gained popularity since beginning of era of dentistry. Now a day, everyone is conscious about their appearance, smile and function. During orthodontic treatment use of brackets and adhesives are common. The bonding of brackets will cause demineralization which requires the fluoridation. So the study has been under- taken to analyze the pattern of fluoride release by commercially available adhesive bonding material for the prevention of demineralization. To evaluate and compare the clinical significance of quantity and pattern of fluoride release from three commercially available adhesives. To assess the pattern of fluoride release and quantity, to reduce the decalcification of enamel around orthodontic brackets and bands during treatment and to prevent further use of topical fluoride both office and self-use agents for prevention of demineralization/for remineralization. The comparison of quantity and pattern of fluoride release study involved commercially available bonding adhesives. They are: Group I--resin reinforced glass Ionomer light cure material (OrthoLC), Group II--fluoride releasing composite resin material (Excel) and Group III--conventional composite (Relay-a-bond) evaluated on 78 freshly extracted premolar teeth divided into three groups consisting 26 specimens in each group. The prepared specimens were stored in artificial saliva at 37°C in an incubator for subsequent fluoride analysis using ORION ion selective electrode coupled with ionalyzer 901. Fluoride analysis made at 24 hours intervals for first 3 consecutive days and thereafter at the end of 10th, 17th, 24th and 31st day of bonding. The data obtained were tabulated and interpreted by statistical analysis using 't' test and one-way analysis of variance (ANOVA). The quantity of fluoride release in groups I and II was significant even at the end of 31st day. The one-way AVOVA showed intra and inter group significance in the quantity of fluoride release. But group III

  6. 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 ...

  7. Potential Use of Polyvinyl Acetate-Polyvinylpyrrolidone Mixture for the Development of Atenolol Sustained Release Matrix Tablets: Optimization of Formulation through in Vitro-in Vivo Assessment Study.

    Science.gov (United States)

    Owayez, Ali Saeed; Abd El-Ghany, Galal Mahmoud; Abu Hashim, Irhan Ibrahim

    2017-01-01

    The objective of this study was to develop sustained release matrix tablets of atenolol (AT) using different concentrations of polyvinyl acetate-polyvinylpyrrolidone mixture (KSR) (20, 30, or 40%) with various types of fillers such as spray dried lactose (SP.D.L), avicel pH 101 (AV), and emcompress (EMS). The physical characteristics of the prepared tablets were evaluated. Characterization of the optimized formulation was performed using Fourier transform (FT)-IR spectroscopy and differential scanning calorimetry (DSC). Moreover, the in vitro release profiles of AT formulations were investigated in different pH dissolution media. Drug release kinetics and mechanisms were also determined. The results revealed that there was no potential incompatibility of the drug with the polymer. The release profiles of AT were affected by the concentration of KSR, fillers used, and pH of the dissolution media. The drug release kinetic from most of the formulations obeyed Higuchi diffusion model. The selected formulae were investigated for their stability by storage at 30 and 40°C with atmospheric humidity and 75% relative humidity (RH), respectively. The results demonstrated that no change in the physicochemical properties of the tablets stored at 30°C/atmospheric RH in comparison with some changes at 40°C/75% RH. Finally, the in vivo study provided an evidence that the optimized AT tablet containing 40% KSR and SP.D.L exhibited prominent higher oral bioavailability and more efficient sustained-release effect than the drug alone or the commercial tablet product. It is noteworthy that KSR could be considered as a promising useful release retardant for the production of AT sustained release matrix tablets.

  8. 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

  9. Sustained release of antibiotic complexed by multivalent ion: in vitro and in vivo study for the treatment of peritonitis.

    Science.gov (United States)

    Na, Seung Yeon; Oh, Se Heang; Kim, Tae Ho; Yoon, Jin A; Lee, In Soo; Lee, Jin Ho

    2014-12-10

    The main aims of this study are (i) the development of an antibiotic complexed with multivalent ion, which can allow sustained release of the antibiotic without any additional matrix or difficult process and (ii) the feasibility study of the ion-complexed antibiotic as a therapeutic technique for peritonitis treatment. An ion-complexed antibiotic is prepared by simple mixing of two aqueous solutions containing an ionized (water-soluble) drug (tetracycline) and a multivalent counter ionic compound. The ion-complexed antibiotic shows a continuous release of the antibiotic up to 21 days, and thus prolonged anti-bacterial effect by gradual ionic exchange between the multivalent ions in the complex and same-charged monovalent ions in surrounding medium. From the in vivo animal study using a cecum perforated peritonitis mouse model, the ion-complexed antibiotic group shows sufficient anti-bacterial effect and thus effectively treat the peritonitis because of the extermination of the contaminated enteric bacteria in the peritoneum during wound healing of injury cecum (by the sustained release of antibiotic from the ion complex). These results suggest that the ion-complexed antibiotic system may be promising for the effective treatment of the peritonitis caused by frequent gastrointestinal defect in clinical fields. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. 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.

  11. About the effect of eye blinking on drug release from pHEMA-based hydrogels: an in vitro study.

    Science.gov (United States)

    Galante, R; Paradiso, P; Moutinho, M G; Fernandes, A I; Mata, J L G; Matos, A P A; Colaço, R; Saramago, B; Serro, A P

    2015-01-01

    The development of new ophthalmic drug delivery systems capable of increasing the residence time of drugs in the eye and improve its bioavailability relatively to eyedrops has been object of intense research in recent years. Several studies have shown that drug-loaded therapeutic soft contact lenses (SCLs) constitute a promising approach, with several potential advantages as compared with collyria. The main objective of this work is to study the effect of repetitive load and friction cycles caused by the eye blinking, on the drug release from hydrogels used in SCLs which, as far as we know, was never investigated before. Two poly-2-hydroxyethylmethacrylate-based hydrogels, pHEMA-T and pHEMA-UV, were used as model materials. Levofloxaxin was chosen as model drug. The hydrogels were fully characterized in what concerns structural and physicochemical properties. pHEMA-UV revealed some superficial porosity and a lower short-range order than pHEMA-T. We observe that the load and friction cycles enhanced the drug release from pHEMA-UV hydrogels. The application of a simple mathematical model, which takes into account the drug dilution caused by the tear flow, showed that the enhancement of the drug release caused by blinking on this hydrogel may be relevant in in vivo conditions. Conversely, the more sustained drug release from pHEMA-T is not affected by load and friction cycles. The conclusion is that, depending on the physicochemical and microstructural characteristics of the hydrogels, blinking is a factor that may affect the amount of drug delivered to the eye by SCLs and should thus be considered.

  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. Green synthesis of Si-incorporated hydroxyapatite using sodium metasilicate as silicon precursor and in vitro antibiotic release studies.

    Science.gov (United States)

    Abinaya Sindu, P; Kolanthai, Elayaraja; Suganthi, R V; Thanigai Arul, K; Manikandan, E; Catalani, Luiz H; Narayana Kalkura, S

    2017-10-01

    The aim of the current study is to synthesize nanosized silicon incorporated HAp (Si-HAP) using sodium metasilicate as the silicon source. The sol-gel derived samples were further subjected to microwave irradiation. Incorporation of Si into HAp did not alter the HAp phase, as confirmed by the X-ray diffraction analysis (XRD). Moreover, variation in the lattice parameters of the Si-incorporated HAp indicates that Si is substituted into the HAp lattice. The decrease in the intensity of the peaks attributed to hydroxyl groups, which appeared in the FTIR and Raman spectra of Si-HAp, further confirms the Si substitution in HAp lattices. The silicon incorporation enhanced the nanorods length by 70%, when compared to that of pure HAp. Microwave irradiation improved the crystallinity of Si-HAp when compared to as-synthesized Si-HAp samples. As-synthesized Si-incorporated HAp sample showed an intense blue emission under UV excitation. Microwave irradiation reduced the intensity of blue emission and exhibited red shift due to the reduction of defects in the Si-HAp crystal. The morphological change from rod to spherical and ribbon-like forms was observed with an increase in silicon content. Further, Si-HAp exhibited better bioactivity and low dissolution rate. Initially there was a burst release of amoxicillin from all the samples, subsequently it followed a sustained release. The microwave-irradiated HAp showed extended period of sustained release than that of as-synthesized HAp and Si-HAp. Similarly, the microwave-irradiated Si-incorporated samples exhibited prolonged drug release, as compared to that of the as-synthesized samples. Hence, Si-HAp is rapidly synthesized by a simple and cost effective method without inducing any additional phases, as compared to the conventional sintering process. This study provides a new insight into the rapid green synthesis of Si-HAp. Si-HAp could emerge as a promising material for the bone tissue replacement and as a drug delivery system

  14. 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...

  15. Effects of coating layer and release medium on release profile from coated capsules with Eudragit FS 30D: an in vitro and in vivo study.

    Science.gov (United States)

    Moghimipour, Eskandar; Rezaei, Mohsen; Kouchak, Maryam; Fatahiasl, Jafar; Angali, Kambiz Ahmadi; Ramezani, Zahra; Amini, Mohsen; Dorkoosh, Farid Abedin; Handali, Somayeh

    2018-05-01

    The aim of the present research was to evaluate the impact of coating layers on release profile from enteric coated dosage forms. Capsules were coated with Eudragit FS 30D using dipping method. The drug profile was evaluated in both phosphate buffer and Hank's solutions. Utilization X-ray imaging, gastrointestinal transmission of enteric coated capsules was traced in rats. According to the results, no release of the drug was found at pH 1.2, and the extent of release drug in pH 6.8 medium was decreased by adding the coating layers. The results indicated single-layer coated capsules in phosphate buffer were significantly higher than that in Hank's solution. However, no significant difference was observed from capsules with three coating layers in two different dissolution media. X-ray imaging showed that enteric coated capsules were intact in the stomach and in the small intestine, while disintegrated in the colon.

  16. Quantitative assessment of fluoride release and recharge ability of different restorative materials in different media: an in vitro study.

    Science.gov (United States)

    Jingarwar, Mahesh M; Pathak, Anuradha; Bajwa, Navroop Kaur; Sidhu, Haridarshan Singh

    2014-12-01

    To measure fluoride release and recharge ability of restorative materials in deionised water, artificial saliva and lactic acid. Pellets were prepared from GC2, Ketac N100 and Beautifil II. Each pellets were individually immersed in 10 ml deionised water, artificial saliva or lactic acid as per respective subgroup for 24 h and then elutes were collected. Specimens were reimmersed in respective container. Fluoride released was analysed after 24 h, 7(th) and 15(th) day. On 15(th) day all specimens were exposed to 1.23% APF gel and fluoride release in respective solution was measured on 16(th), 22(nd), 30(th) day. Fluoride release was more after 24 h for all materials in all media then decrease gradually. GC2 shows more fluoride release than Ketac N100 at 24 hours and on 7(th) day but onwards Ketac N100 released significantly more fluoride. Beautifil II showed least fluoride release at all measured intervals in all media. Order of fluoride release in media was lactic acid > deionised water > artificial saliva for all materials. GICs are smart material which release more fluoride when environment become more acidic and also show tendency to recharge which helps clinically in caries risk children.

  17. In vitro release studies on drugs suspended in non-polar media I. Release of sodium chloride from suspensions in liquid paraffin

    NARCIS (Netherlands)

    Crommelin, D.J.A.; Blaey, C.J. de

    The release of a readily water-soluble substance (sodium chloride) from a liquid paraffin phase to an underlying water phase was investigated as a function of particle size (10–50 μm) and concentration (up to 10% m/m). Transport of the suspended particles to the interface by sedimentation was the

  18. In vitro release studies on drugs suspended in non-polar media II. The release of paracetamol and chloramphenicol from suspensions in liquid paraffin

    NARCIS (Netherlands)

    Crommelin, D.J.A.; Blaey, C.J. de

    The release of paracetamol and chloramphenicol (water solubility 13 and 3.6 mg · g−1, respectively), suspended in liquid paraffin, to an underlying aqueous layer was investigated as a function of particle size (10–60 μm), concentration (0.5–6% m/m) and the presence of additives (DOSS-Na:

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

    Science.gov (United States)

    Gomes, Maria João; Martins, Susana; Ferreira, Domingos; Segundo, Marcela A; Reis, Salette

    2014-01-01

    Alopecia is a dermatological disorder, commonly known as hair loss, which affects up to half of the Caucasian male population by middle age, and almost all (95%) Caucasian men by old age. Considering that alopecia affects so many people and that there is currently no scientifically proven treatment with few side effects, new drug-delivery systems able to improve alopecia therapy are urgently required. With this purpose in mind, the present study aimed to develop lipid nanoparticles (nanostructured lipid carriers) with the ability to incorporate and deliver anti-alopecia active compounds (minoxidil and finasteride) into the dermis and hair follicles. Lipid nanoparticles, prepared by ultrasonication method, showed mean particle sizes around 200 nm, which is sufficient for reaching the dermis and hair follicles, and zeta potential values around −30 mV, which indicates good physical stability. Over 28 days of storage, no significant variations in these parameters were observed, which indicates that all nanoformulations are stable in storage over that period. Cryo-scanning electron microscope measurements showed that all the lipid nanoparticles exhibited a spherical shape and a smooth surface regardless of their composition. Differential scanning calorimetry studies allowed the determination of phase transition temperatures and confirmed the recrystallization of the lipid nanoparticles (recrystallization index between 11% and 86%). A high loading efficiency was achieved for finasteride (between 70% and 90%), while less than 30% was achieved for minoxidil nanoparticles, over 28 days. Controlled release assays in physiological conditions demonstrated that nanoparticles loaded with minoxidil yielded a prolonged release, as desired. Penetration assays through pig ear skin demonstrated that nanoparticles loaded with minoxidil and finasteride had low levels of penetration. These results suggest that the proposed novel formulation presents several good characteristics

  20. Activity-Dependent Adenosine Release May Be Linked to Activation of Na+-K+ ATPase: An In Vitro Rat Study

    Science.gov (United States)

    Sims, Robert Edward; Dale, Nicholas

    2014-01-01

    In the brain, extracellular adenosine increases as a result of neuronal activity. The mechanisms by which this occurs are only incompletely understood. Here we investigate the hypothesis that the Na+ influxes associated with neuronal signalling activate the Na+-K+ ATPase which, by consuming ATP, generates intracellular adenosine that is then released via transporters. By measuring adenosine release directly with microelectrode biosensors, we have demonstrated that AMPA-receptor evoked adenosine release in basal forebrain and cortex depends on extracellular Na+. We have simultaneously imaged intracellular Na+ and measured adenosine release. The accumulation of intracellular Na+ during AMPA receptor activation preceded adenosine release by some 90 s. By removing extracellular Ca2+, and thus preventing indiscriminate neuronal activation, we used ouabain to test the role of the Na+-K+ ATPase in the release of adenosine. Under conditions which caused a Na+ influx, brief applications of ouabain increased the accumulation of intracellular Na+ but conversely rapidly reduced extracellular adenosine levels. In addition, ouabain greatly reduced the amount of adenosine released during application of AMPA. Our data therefore suggest that activity of the Na+-K+ ATPase is directly linked to the efflux of adenosine and could provide a universal mechanism that couples adenosine release to neuronal activity. The Na+-K+ ATPase-dependent adenosine efflux is likely to provide adenosine-mediated activity-dependent negative feedback that will be important in many diverse functional contexts including the regulation of sleep. PMID:24489921

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

    Energy Technology Data Exchange (ETDEWEB)

    Gallo, Annemarie; Mani, Gopinath, E-mail: Gopinath.Mani@usd.edu

    2013-08-15

    Most drug-eluting stents currently available are coated with anti-proliferative drugs on both abluminal (toward blood vessel wall) and luminal (toward lumen) surfaces to prevent neointimal hyperplasia. While the abluminal delivery of anti-proliferative drugs is useful for controlling neointimal hyperplasia, the luminal delivery of such drugs impairs or prevents endothelialization which causes late stent thrombosis. This research is focused on developing a bidirectional dual drug-eluting stent to co-deliver an anti-proliferative agent (paclitaxel – PAT) and an endothelial cell promoting agent (nitric oxide – NO) from abluminal and luminal surfaces of the stent, respectively. Phosphonoacetic acid, a polymer-free drug delivery platform, was initially coated on the stents. Then, the PAT and NO donor drugs were co-coated on the abluminal and luminal stent surfaces, respectively. The co-coating of drugs was collectively confirmed by the surface characterization techniques such as Fourier transform infrared spectroscopy, scanning electron microscopy (SEM), 3D optical surface profilometry, and contact angle goniometry. SEM showed that the integrity of the co-coating of drugs was maintained without delamination or cracks formation occurring during the stent expansion experiments. In vitro drug release studies showed that the PAT was released from the abluminal stent surfaces in a biphasic manner, which is an initial burst followed by a slow and sustained release. The NO was burst released from the luminal stent surfaces. Thus, this study demonstrated the co-delivery of PAT and NO from abluminal and luminal stent surfaces, respectively. The stent developed in this study has potential applications in inhibiting neointimal hyperplasia as well as encouraging luminal endothelialization to prevent late stent thrombosis.

  2. 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.

  3. 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.

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

    Science.gov (United States)

    Policianova, Olivia; Brus, Jiri; Hruby, Martin; Urbanova, Martina

    2014-07-22

    Abstract Due to their high versatility and diverse excipient options, solid dispersions (SDs) are an elegant choice for the formulation of active pharmaceutical ingredients with inconvenient solubility. Four distinct types of polymers with different physicochemical properties [polyvinylpyrrolidone, poly[N-(2-hydroxypropyl)-metacrylamide], poly(2-ethyl-2-oxazoline), and polyethylene glycol] and variable molecular weights were compared to investigate the influence of the polymer matrix on drug release. To probe the extent of intercomponent interactions, acetylsalicylic acid (ASA) was used as a model active substance. Controlled drug release was demonstrated for all four types of polymer-ASA SDs created by the freeze-drying method. While the polyethylene glycol-ASA SD exhibited an increased dissolution rate, the other polymer-ASA systems exhibited significantly reduced drug dissolution kinetics compared to free ASA. Furthermore, in contrast to physical mixtures, the prepared SDs all exhibited zero-order dissolution kinetics for ASA. The dissolution rate was strongly dependent on the molecular weight of the polymer. These results demonstrate that the type of SD may be controlled by the chemical constitutions of the polymers and that appropriate selection of the molecular weight of the polymer matrix enables finely tuned drug release over a wide range of dissolution rates.

  5. 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.

  6. Pharmacokinetics of Abamectin/Levamisole Combination in a Medium Chain Mono and Diglyceride-Based Vehicle and an In Vitro Release and In Vitro In Vivo Correlation Study for Levamisole.

    Science.gov (United States)

    Sari, Peyami; Sun, Jianguo; Razzak, Majid; Tucker, Ian G

    2017-05-01

    A combination of lipophilic and hydrophilic drugs in a single solution is a challenge due to their different physicochemical properties. In vitro and in vivo release studies are useful to optimize this solution. The in vitro (Franz diffusion cell) release rate of levamisole phosphate from an isotropic vehicle of medium chain mono and diglycerides (MCMDG) was significantly slower than the release from water. The injectable solution of the isotropic MCMDG-based system was prepared with 13.65% of levamisole phosphate and 0.5% of abamectin. Two milliliters/50 kg (0.04 ml/kg) was injected subcutaneously into five healthy adult sheep. None of the animals showed the signs of inflammation at injection site. Both drugs were assayed using validated HPLC methods. The absorption rates for levamisole (0.71 ± 0.32 h -1 ) and abamectin (0.24 ± 0.08 day -1 ) from the MCMDG-based formulation were considerably slower than those of other studies conducted on the commercial products. The t max was delayed for levamisole (2.20 ± 0.45 h) and abamectin (4.20 ± 1.64 days) compared with those in published studies. Longer MRT values for levamisole (6.14 ± 1.14 h) and abamectin (8.80 ± 1.39 days) were found in this study compared to those reported. A correlation was observed between in vivo fraction absorbed and in vitro fraction released for levamisole phosphate in the MCMDG-based formulation. The injection vehicle of isotropic MCMDG-based system delayed the subcutaneous absorption of levamisole phosphate and abamectin compared to the commercial subcutaneous injection products for levamisole and abamectin. Notably, this isotropic MCMDG-based vehicle system is prepared with a combination of two drugs with different physicochemical properties.

  7. Bisphenol A Alters β-hCG and MIF Release by Human Placenta: An In Vitro Study to Understand the Role of Endometrial Cells

    Directory of Open Access Journals (Sweden)

    C. Mannelli

    2014-01-01

    Full Text Available A proper fetomaternal immune-endocrine cross-talk in pregnancy is fundamental for reproductive success. This might be unbalanced by exposure to environmental chemicals, such as bisphenol A (BPA. As fetoplacental contamination with BPA originates from the maternal compartment, this study investigated the role of the endometrium in BPA effects on the placenta. To this end, in vitro decidualized stromal cells were exposed to BPA 1 nM, and their conditioned medium (diluted 1 : 2 was used on chorionic villous explants from human placenta. Parallel cultures of placental explants were directly exposed to 0.5 nM BPA while, control cultures were exposed to the vehicle (EtOH 0.1%. After 24–48 h, culture medium from BPA-treated and control cultures was assayed for concentration of hormone human Chorionic Gonadotropin (β-hCG and cytokine Macrophage Migration Inhibitory Factor (MIF. The results showed that direct exposure to BPA stimulated the release of both MIF and β-hCG. These effects were abolished/diminished in placental cultures exposed to endometrial cell-conditioned medium. GM-MS analysis revealed that endometrial cells retain BPA, thus reducing the availability of this chemical for the placenta. The data obtained highlight the importance of in vitro models including the maternal component in reproducing the effects of environmental chemicals on human fetus/placenta.

  8. [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.

  9. Preparation and characterization of chitosan-Polyethylene glycol-polyvinylpyrrolidone-coated superparamagnetic iron oxide nanoparticles as carrier system: Drug loading and in vitro drug release study.

    Science.gov (United States)

    Prabha, G; Raj, V

    2016-05-01

    In the present research work, the anticancer drug "curcumin" is loaded with Chitosan (CS)-polyethylene glycol (PEG)-polyvinylpyrrolidone (PVP) (CS-PEG-PVP) polymer nanocomposites coated with superparamagnetic iron oxide (Fe3 O4 ) nanoparticles. The system can be used for targeted and controlled drug delivery of anticancer drugs with reduced side effects and greater efficiency. The prepared nanoparticles were characterized by Fourier transmission infrared spectroscopy (FTIR), vibrating sample magnetometry (VSM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Curcumin drug-loaded Fe3 O4 -CS, Fe3 O4 -CS- PEG and Fe3 O4 -CS-PEG-PVP nanoparticles exhibited the mean particle size in the range of 183 - 390 nm with a zeta potential value of 26 mV-41 mV as measured using Malvern Zetasizer. The encapsulation efficiency, loading capacity and in-vitro drug release behaviour of curcumin drug-loaded Fe3 O4 -CS, Fe3 O4 -CS-PEG, and Fe3 O4 -CS-PEG-PVP nanoparticles were studied using UV spectrophotometer. Besides, the cytotoxicity of the prepared nanoparticles using MTT assay was also studied. The curcumin drug release was examined at different pH medium (4.5 and 7.4) and temperature (37°C and 45°C), and it was proved that the drug release depends upon the pH medium and temperature in addition to the nature of matrix. © 2016 Wiley Periodicals, Inc.

  10. Polymorphism in Commercial Sources of Fusidic Acid: A Comparative Study of the In Vitro Release Characteristics of Forms I and III from a Marketed Pharmaceutical Cream

    Directory of Open Access Journals (Sweden)

    Jonathan Byrne

    2017-01-01

    Full Text Available A comparison of the polymorphic forms of 3 commercial sources of fusidic acid using FTIR and XRPD techniques has been performed in this study. It has been demonstrated that polymorphic Forms I and III are currently available on the commercial market. The influence of the observed polymorphism on the stability of the drug substance in bulk form has been investigated through stability and stress testing according to current ICH guidelines. Significant differences were detected between commercial sources with regard to the stability of the bulk substance under photolytic and humidity stress conditions. When properly packaged in an inert atmosphere, fusidic acid from all 3 manufacturers showed a comparable stability. The effects of the observed polymorphic differences on the intrinsic dissolution rate of the drug substance and its in vitro release from the marketed drug product Fusicutan® plus Betamethasone cream have been investigated. Results indicated that the release rate of the drug substance is similar for polymorphic Forms I and III, allowing both forms to be used during manufacture without affecting the safety or efficacy of the drug product.

  11. In vitro uptake and release studies of ocular pharmaceutical agents by silicon-containing and p-HEMA hydrogel contact lens materials.

    Science.gov (United States)

    Karlgard, C C S; Wong, N S; Jones, L W; Moresoli, C

    2003-05-12

    The in vitro uptake and release behaviour of cromolyn sodium, ketotifen fumarate, ketorolac tromethamine and dexamethasone sodium phosphate with silicon-containing (lotrafilcon and balafilcon) and p-HEMA-containing (etafilcon, alphafilcon, polymacon, vifilcon and omafilcon) hydrogel contact lenses indicated that both drug and material affected the uptake and release behaviour. Rapid uptake and release (within 50 min) was observed for all drugs except ketotifen fumarate which was more gradual taking approximately 5h. Furthermore, the maximum uptake differed significantly between drugs and materials. The highest average uptake (7879+/-684 microg/lens) was cromolyn sodium and the lowest average uptake (67+/-13 microg/lens) was dexamethasone sodium phosphate. Partial release of the drug taken up was observed for all drugs except dexamethasone sodium phosphate where no release was detected. Sustained release was demonstrated only by ketotifen fumarate. Drug uptake/release appeared to be a function of lens material ionicity, water and silicon content. The silicon-containing materials released less drug than the p-HEMA-containing materials. The lotrafilcon material demonstrated less interactions with the drugs than the balafilcon material which can be explained by their different bulk composition and surface treatment.

  12. Evaluation of metal ion release from Ti6Al4V and Co-Cr-Mo casting alloys: in vivo and in vitro study.

    Science.gov (United States)

    El Sawy, Amal A; Shaarawy, Mohammed A

    2014-02-01

    The aim of this study was to evaluate the amount of ions released from Ti6Al4V and Co-Cr-Mo alloys both in vivo and in vitro. Twenty-one discs of each alloy were constructed and divided into seven groups. Three specimens from each group were immersed in a buffered saline solution over a period of 1, 3, 5, 7, 14, 21, and 28 days. Twenty-eight participants were also included in the study, where the study group consisted of 14 mandibular partially edentulous patients, and the control group consisted of 14 volunteers. The study group was further divided into two equal groups: the first group received removable partial dentures (RPDs) constructed from Co-Cr-Mo alloy, while the second group received RPDs constructed from Ti6Al4V alloy. Saliva samples were collected from each participant over the same study period. The conditioning media and saliva samples were analyzed using a spectrophotometer. One-way ANOVA and Tukey tests were used for statistical analysis (p Ti6Al4V alloys were higher in the buffered saline solutions than in the studied saliva samples and control groups; however, these amounts were still within the physiological limit of trace elements in the human body. © 2013 by the American College of Prosthodontists.

  13. 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.

  14. 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...

  15. Poloxamer-based binary hydrogels for delivering tramadol hydrochloride: sol-gel transition studies, dissolution-release kinetics, in vitro toxicity, and pharmacological evaluation

    Science.gov (United States)

    dos Santos, Ana Claudia Mendonça; Akkari, Alessandra Cristina Santos; Ferreira, Iasmin Rosanne Silva; Maruyama, Cintia Rodrigues; Pascoli, Monica; Guilherme, Viviane Aparecida; de Paula, Eneida; Fraceto, Leonardo Fernandes; de Lima, Renata; Melo, Patrícia da Silva; de Araujo, Daniele Ribeiro

    2015-01-01

    In this work, poloxamer (PL)-based binary hydrogels, composed of PL 407 and PL 188, were studied with regard to the physicochemical aspects of sol-gel transition and pharmaceutical formulation issues such as dissolution-release profiles. In particular, we evaluated the cytotoxicity, genotoxicity, and in vivo pharmacological performance of PL 407 and PL 407–PL 188 hydrogels containing tramadol (TR) to analyze its potential treatment of acute pain. Drug–micelle interaction studies showed the formation of PL 407–PL 188 binary systems and the drug partitioning into the micelles. Characterization of the sol-gel transition phase showed an increase on enthalpy variation values that were induced by the presence of TR hydrochloride within the PL 407 or PL 407–PL 188 systems. Hydrogel dissolution occurred rapidly, with approximately 30%–45% of the gel dissolved, reaching ~80%–90% up to 24 hours. For in vitro release assays, formulations followed the diffusion Higuchi model and lower Krel values were observed for PL 407 (20%, Krel =112.9±10.6 μg·h−1/2) and its binary systems PL 407–PL 188 (25%–5% and 25%–10%, Krel =80.8±6.1 and 103.4±8.3 μg·h−1/2, respectively) in relation to TR solution (Krel =417.9±47.5 μg·h−1/2, P72 hours) pointed to PL-based hydrogels as a potential treatment, by subcutaneous injection, for acute pain. PMID:25848258

  16. Comparative study of in vitro release and mucoadhesivity of gastric compacts composed of multiple unit system/bilayered discs using direct compression of metformin hydrochloride.

    Science.gov (United States)

    Jelvehgari, Mitra; Zakeri-Milani, Parvin; Khonsari, Fatemeh

    2014-01-01

    Metformin is an oral anti-diabetic drug in the biguanide class. The goal of this study was to develop gastric-retentive MH discs in order to prolong the retention of drug in gastric mucosa. Two groups of metformin hydrochloride (MH) mucoadhesive gastroretentive discs were prepared: (a) bilayered discs prepared by direct compression of powders containing polymers as Carbopol 934P (CP, mucoadhesive polymer) and ethylcellulose (EC, rotardant polymer), (b) multiple unit system (microparticle) discs prepared by the emulsification, solvent evaporation, and compression technique from microparticles using polymers CP and EC. Gastric-mucoadhesive compacts were evaluated by investigating their release pattern, swelling capacity, mucoadhesion property, surface pH, and in vitro gastro-retentive time. Discs formulation was subjected to disintegration and dissolution tests by placing in 0.1 M hydrochloric acid for 8 h. The production yield showed F2 microparticles of 98.80%, mean particle size of 933.25 µm and loading efficiency of 98.44%. The results showed that prepared microparticle discs had slower release than bilayered discs (p>0.05). The bilayered discs exhibited very good percentage of mucoadhesion. The results also showed a significant higher retention of mucoadhesive bilayered discs in upper gastrointestinal tract (F´1, 1:2 ratio of CP:EC). Histopathological studies revealed no gastric mucosal damage. Mucoadhesive multiple unit system/bilayered discs interact with mucus of gastrointestinal tract and are considered to be localized or trapped at the adhesive site by retaining a dosage form at the site of action as well as improving in the intimacy of contact with underlying absorptive membrane to achieve a better therapeutic performance of anti-diabetic drug.

  17. Comparative study of in vitro release and mucoadhesivity of gastric-compacts composed of multiple unit system/bilayered discs using direct compression of metformin hydrochloride

    Directory of Open Access Journals (Sweden)

    Mitra Jelvehgari

    2014-03-01

    Full Text Available Introduction: Metformin is an oral anti-diabetic drug in the biguanide class. The goal of this study was to develop gastric-retentive MH discs in order to prolong the retention of drug in gastric mucosa.Methods:Two groups of metformin hydrochloride (MH mucoadhesive gastroretentive discs were prepared: (a bilayered discs prepared by direct compression of powders containing polymers as Carbopol 934P (CP, mucoadhesive polymer and ethylcellulose (EC, rotardant polymer, (b multiple unit system (microparticle discs prepared by the emulsification, solvent evaporation, and compression technique from microparticles using polymers CP and EC. Gastric-mucoadhesive compacts were evaluated by investigating their release pattern, swelling capacity, mucoadhesion property, surface pH, and in vitro gastro-retentive time. Discs formulation was subjected to disintegration and dissolution tests by placing in 0.1 M hydrochloric acid for 8 h. Results: The production yield showed F2 microparticles of 98.80%, mean particle size of 933.25 µm and loading efficiency of 98.44%. The results showed that prepared microparticle discs had slower release than bilayered discs (p>0.05. The bilayered discs exhibited very good percentage of mucoadhesion. The results also showed a significant higher retention of mucoadhesive bilayered discs in upper gastrointestinal tract (F´1, 1:2 ratio of CP:EC. Histopathological studies revealed no gastric mucosal damage.Conclusion: Mucoadhesive multiple unit system/bilayered discs interact with mucus of gastrointestinal tract and are considered to be localized or trapped at the adhesive site by retaining a dosage form at the site of action as well as improving in the intimacy of contact with underlying absorptive membrane to achieve a better therapeutic performance of anti-diabetic drug.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    with few side effects, new drug-delivery systems able to improve alopecia therapy are urgently required. With this purpose in mind, the present study aimed to develop lipid nanoparticles (nanostructured lipid carriers) with the ability to incorporate and deliver anti-alopecia active compounds (minoxidil...

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

    Directory of Open Access Journals (Sweden)

    Xinyang Yu

    2012-11-01

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

  20. Formulation Development and Release Studies of Indomethacin Suppositories

    OpenAIRE

    Sah, M. L.; Saini, T. R.

    2008-01-01

    Indomethacin suppositories were prepared by using water-soluble and oil soluble suppository bases, and evaluated for in vitro release by USP I and modified continuous flow through bead bed apparatus. Effect of the Tween 80 (1% and 5%) was further studied on in vitro release of the medicament. Release rate was good in water-soluble suppositories bases in comparison to oil soluble suppositories bases. Release was found to be greater in modified continuous flow through bead bed...

  1. Comparative study of transfersomes, liposomes, and niosomes for topical delivery of 5-fluorouracil to skin cancer cells: preparation, characterization, in-vitro release, and cytotoxicity analysis.

    Science.gov (United States)

    Alvi, Iqrar Ali; Madan, Jitender; Kaushik, Dinesh; Sardana, Satish; Pandey, Ravi Shankar; Ali, Asgar

    2011-09-01

    Topical 5-fluorouracil (5-FU) is used for the treatment of actinic keratosis and nonmelanoma skin cancer. Unfortunately, 5-FU per se shows a poor percutaneous permeation, thus reducing its anticancer effectiveness after topical administration. Therefore, we have constructed transfersomes, liposomes, and niosomes of 5-FU for topical applications in this investigation. Transfersomes were prepared by the solvent evaporation method, whereas liposomes and niosomes were constructed by reverse-phase evaporation method. The nanovesicles were characterized for particle size, shape, zeta potential, viscosity, entrapment efficiency, deformability, in-vitro permeation release, and kinetics and retention. Cytotoxicity study was carried out on HaCaT cells. Transfersomes (153.2 ± 10.3 nm), liposomes (120.3 ± 9.8 nm), and niosomes (250.4 ± 8.6 nm) were produced with a maximum entrapment efficiency of 82.4 ± 4.8, 45.4 ± 3.3, and 43.4 ± 3.2%, respectively. Moreover, transmission electron microscopy and atomic force microscopy assure the smooth and spherical shape of nanovesicles. Skin permeation and retention showed better permeability and retention than the nonvesiculized dosage form. The IC50 value of transfersomes (1.02 μmol/l), liposomes (6.83 μmol/l), and niosomes (9.91 μmol/l) was found to be far less than 5-FU (15.89 μmol/l) at 72 h. 5-FU-loaded transfersomes were found to be most cytotoxic on the HaCaT cell line in comparison with liposomes and niosomes. We concluded that vesiculization of 5-FU not only improves the topical delivery, but also enhances the cytotoxic effect of 5-FU. We have presented here a viable formulation of 5-FU for the management of actinic keratosis and nonmelanoma skin carcinoma.

  2. In vitro drug release studies of polymeric freeze-dried wafers and solvent-cast films using paracetamol as a model soluble drug.

    Science.gov (United States)

    Boateng, Joshua S; Matthews, Kerr H; Auffret, Anthony D; Humphrey, Mike J; Stevens, Howard N; Eccleston, Gillian M

    2009-08-13

    Drug dissolution and release characteristics from freeze-dried wafers and solvent-cast films prepared from sodium carboxymethylcellulose (CMC) have been investigated to determine the mechanisms of drug release from the two systems. The formulations were prepared by freeze-drying (wafers) or drying in air (films), the hydrated gel of the polymer containing paracetamol as a model soluble drug. Scanning electron microscopy (SEM) was used to examine differences between the physical structure of the wafers and films. Dissolution studies were performed using an exchange cell and drug release was measured by UV spectroscopy at 242 nm. The effects of drug loading, polymer content and amount of glycerol (films) on the release characteristics of paracetamol were investigated. The release profiles of paracetamol from the wafers and films were also compared. A digital camera was used to observe the times to complete hydration and dissolution of the wafers containing different amounts of CMC and how that impacts on drug release rates. Both formulations showed sustained type drug release that was modelled by the Korsmeyer-Peppas equation. Changes in the concentration of drug and glycerol (films) did not significantly alter the rate of drug release while increasing polymer content significantly decreased the rate of drug release from both formulations. The results show that the rate of paracetamol release was faster from the wafers than the corresponding films due to differences in their physical structures. The wafers which formed a porous network, hydrated faster than the more dense and continuous, (non-porous) sheet-like structure of the films.

  3. Lecithin-based microemulsions for targeted delivery of ceramide AP into the stratum corneum: formulation, characterizations, and in vitro release and penetration studies.

    Science.gov (United States)

    Sahle, Fitsum F; Metz, Hendrik; Wohlrab, Johannes; Neubert, Reinhard H H

    2013-02-01

    To improve the solubility and penetration of Ceramide AP (CER [AP]) into the stratum corneum that potentially restores the barrier function of aged and affected skin. CER [AP] microemulsions (MEs) were formulated using lecithin, Miglyol® 812 (miglyol) and water-1,2 pentandiol (PeG) mixture as amphiphilic, oily and hydrophilic components, respectively. The nanostructure of the MEs was revealed using electrical conductivity, differential scanning calorimeter (DSC) and electron paramagnetic resonance (EPR) techniques. Photon correlation spectroscopy (PCS) was used to measure the sizes and shape of ME droplets. The release and penetration of the CER into the stratum corneum was investigated in vitro using a multi-layer membrane model. The MEs exhibited excellent thermodynamic stability (>2 years) and loading capacity (0.5% CER [AP]). The pseudo-ternary phase diagrams of the MEs were obtained and PCS results showed that the droplets are spherical in shape and bigger in size. In vitro investigations showed that the MEs exhibited excellent rate and extent of release and penetration. Stable lecithin-based CER [AP] MEs that significantly enhance the solubility and penetration of CER [AP] into the stratum corneum were developed. The MEs also have better properties than the previously reported polyglycerol fatty acid surfactant-based CER [AP] MEs.

  4. Optimization (Central Composite Design and Validation of HPLC Method for Investigation of Emtricitabine Loaded Poly(lactic-co-glycolic acid Nanoparticles: In Vitro Drug Release and In Vivo Pharmacokinetic Studies

    Directory of Open Access Journals (Sweden)

    Gurinder Singh

    2014-01-01

    Full Text Available The objective of the current study is to develop nanoparticles (NPs drug delivery system of emtricitabine solely using poly(lactic-co-glycolic acid (PLGA and evaluate its in vitro and in vivo release performance by systematically optimized HPLC method using Formulation by Design (FbD. NPs were evaluated for in vitro release and in vivo absorption study. The desired chromatographic separation was achieved on a Phenomenex C18 (250 mm × 4.6 mm I.D., 5 μm column, under isocratic conditions using UV detection at 280 nm. The optimized mobile phase consisted of a mixture of 40 mM phosphate dihydrogen phosphate buffer (pH 6.8, methanol, and 2% acetonitrile in a ratio of (83 : 15 : 2, v/v/v at a flow rate of 1 mL/min. The linear regression analysis for the calibration curves showed a good linear correlation over the concentration range 0.040–2.0 μg/mL, with retention time of 4.39 min. An average encapsulation efficiency of 74.34% was obtained for NPs. In vitro studies showed zero-order release and about 95% drug being released within 15 days in PBS (pH 7.4. In conclusion, the proposed optimized method was successfully applied for the determination of in vitro and in vivo release studies of emtricitabine NPs.

  5. An in vitro-in vivo correlation study for nifedipine immediate release capsules administered with water, alcoholic and non-alcoholic beverages: Impact of in vitro dissolution media and hydrodynamics.

    Science.gov (United States)

    Mercuri, A; Fares, R; Bresciani, M; Fotaki, N

    2016-02-29

    The impact of hydrodynamics and media composition on nifedipine dissolution profile from IR (immediate release) soft capsules was investigated using dissolution apparatus USP1, USP2, USP3 and USP4 (United State Pharmacopoeia). Media composition was varied in terms of pH and content, to mimic the dosage form intake with water or non-alcoholic beverages (orange juice) and alcoholic beverages (orange juice/ethanol mixture (47% v/v)). Through construction of in vitro-in vivo correlations (IVIVC) with corresponding in vivo data from the literature, it was possible to evaluate the in vitro conditions that are likely to simulate the in vivo formulation behaviour. Both linear and nonlinear correlations were obtained depending on experimental set-ups. Testing of 20mg nifedipine capsules in FaSSGFst (Fasted State Simulated Gastric Fluid pH 1.6; water administration) produced IVIVC with the USP3 (after time scaling) and USP4 apparatus. IVIVC were obtained for USP2, USP3 and USP4 in FaSSGFoj (Fasted State Simulated Gastric Fluid pH 3.4; orange juice administration). Linear and nonlinear correlations were obtained with the USP1, USP2 and USP3 apparatus when testing the capsules in FaSSGFoj/EtOH (orange juice/ethanol administration). This study highlighted that selection of physiologically relevant dissolution set-ups is critical for predicting the in vivo impact of formulations co-administration with water, non-alcoholic and alcoholic beverages. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Comparative evaluation of the calcium release from mineral trioxide aggregate and its mixture with glass ionomer cement in different proportions and time intervals – An in vitro study

    Directory of Open Access Journals (Sweden)

    Surbhi Sawhney

    2015-10-01

    Conclusions: Adding GIC to improve the setting time and handling properties of the MTA powder can be detrimental to the calcium-releasing ability of the resultant mixture, depending on the proportion of GIC added. Adding MTA and GIC at a proportion of 2:1 by volume did not impact calcium release from the mixture. These findings should be verified through further clinical studies.

  7. 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

  8. Comparison of antibacterial activity of three fluorides- and zinc-releasing commercial glass ionomer cements on strains of mutans streptococci: an in vitro study.

    Science.gov (United States)

    Shashibhushan, K K; Basappa, N; Subba Reddy, V V

    2008-01-01

    The purpose of present study was to investigate the antibacterial activity of three commercially available fluoride- and zinc-releasing glass ionomer cements on strains of mutans streptococci. Three glass ionomers (Fuji II Conventional, Fuji II Light Cure, and Fuji IX) were used. The antibacterial effect of glass ionomer cements were estimated by anaerobically growing mutans streptococci on a selective medium by inoculating human saliva and measuring the inhibition zones around the glass ionomer discs on the medium. Fluoride and zinc release were measured and compared with the antibacterial activity. The results, when statistically analyzed, showed a direct correlation between fluoride release and antibacterial activity, but there was no correlation between zinc release and antibacterial activity.

  9. 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.

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

    Science.gov (United States)

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

    2017-09-01

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

  11. 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.

  12. An In-Vitro Study on the Release of Fluoride from Two Restorative Materials and Their Rechargeability after Exposure to Daily 1000 ppm Fluoride

    Directory of Open Access Journals (Sweden)

    A. Kowsari

    2005-09-01

    Full Text Available Statement of Problem: Since the fluoride releases from materials with the property of releasing fluoride are decreasing gradually, it seems that probably the material rechargeability is more important than their long-term fluoride release.Purpose: the objective of this study was to asses the fluoride release and rechargeability of 2 types of fluoride releasing restorative materials, a resin modified glass ionomer(Vitremer and a compomer (Compoglass F, after exposure to daily NaF solutionscontaining 1000 ppm F, for 1 minute.Materials and Methods: Twelve discs ( 8 mm ×2 mm of each of the materials were fabricated, and divided into 2 groups (test and control. All discs were stored in 4 mL artificial saliva at 37°C. In group 1 (N=6, the specimens were immersed in artificialsaliva which was changed daily for 25 days. In group 2 (N=6, in addition to receiving the same treatment as group 1, the specimens were immersed in NaF solution (1000ppm F, ph=6.9 for 1 minute before daily saliva change. A potentiometer was used to determine the amount of fluoride released on days 1, 2, 3, 5, 10, 15, 20 and 25, after the daily saliva change, in all study groups. Data were analyzed by the t-student test after confirmation of the equality of variances by Leven’s test.Results: Both materials continued releasing fluoride throughout the whole study period. For each material, the release was highest on day one. During the first 3 days,glass ionomer released significantly higher amounts of fluoride as compared to compomer (p0.05. After exposure to NaF solution, none of the materials showed statistically significant rechargeability (p>0.05 and the amount of fluoride-releasecontinued to drop during the study period in similar patterns for both the test and the control groups.Conclusion: It may be concluded that rechargeability of glass ionomer and compomer,using daily neutral fluoride mouth rinses and toothpastes does not occur in reliable amounts.

  13. A comparative study to evaluate the effect of fluoride releasing sealant cured by visible light, argon laers, and light emitting diode curing units: An in vitro study

    Directory of Open Access Journals (Sweden)

    Das U

    2009-09-01

    Full Text Available In Pediatric Dentistry, the use of pit and fissure sealant is one of the essential forms of prevention. Pit and fissure caries may be substantially decreased by obliteration of these developmental defects in occlusal, buccal and lingual surfaces with resin based dental sealants. Visible light-curing units, or LCUs, are an integral part of modern adhesive dentistry" They are used to cure resin based composite restoration materials, resin modified glass-ionomer and pit and fissure sealants, as well as to bond orthodontic teeth. Most recently, the argon laser has been approved for initiating the setting reaction with visible light cured-resins. Argon curing of resin materials has been show to enhance the physical properties and degree of polymerization of the resin, while reducing the polymerization time by 75 percent. The study is undertaken considering the inadequate research reports of regarding the comparison of curing ability using argon laser. LEDs and visible light as well as the resistant towards caries activity of the preventive fluoride releasing pit and fissure sealant cured by above mentioned curing units.

  14. Photoacoustic methods for in vitro study of kinetics progesterone release from the biodegradation of polyhydroxybutyrate/polycaprolactone used as intravaginal devices

    Energy Technology Data Exchange (ETDEWEB)

    Souza Filho, N. E. [Universidade Estadual de Maringá, Departamento de Física, Grupo de Estudos dos Fenômenos Fototérmicos-GEFF/DFI/UEM, Av. Colombo 5790, Maringá-PR (Brazil); Universidade Federal de Santa Maria, Departamento de Eng. Acústica, Av. Roraima 1000, CEP 97105–900, Santa Maria-RS (Brazil); Mariucci, V. V. G.; Dias, G. S.; Szpak, W.; Medina, A. N.; Baesso, M. L.; Bento, A. C. [Universidade Estadual de Maringá, Departamento de Física, Grupo de Estudos dos Fenômenos Fototérmicos-GEFF/DFI/UEM, Av. Colombo 5790, Maringá-PR (Brazil); Miguez, P. H. P.; Madureira, E. H. [Universidade de São Paulo, Departamento de Reprodução Animal–VRA/USP, Av. Prof. Dr. Orlando Marques Paiva 87, São Paulo–SP (Brazil)

    2013-09-30

    Intravaginal devices composed of polyhydroxybutyrate/polycaprolactone blends incorporating progesterone were used over eight days in crossbred cow ovariectomized, and then analyzed with photoacoustic methods, measuring the absorption spectra, thermal diffusivity, and inspecting its degradation by means of scanning electron microscopy. The characteristic time found for progesterone release was TR ∼ 53 h, and the typical time found for biodegradation was TB ∼ 30 h. Morphological analysis complements the study showing that release of progesterone and biodegradation of the blend occurs on sample surface.

  15. 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.

  16. Critical quality attributes, in vitro release and correlated in vitro skin permeation-in vivo tape stripping collective data for demonstrating therapeutic (non)equivalence of topical semisolids: A case study of "ready-to-use" vehicles.

    Science.gov (United States)

    Ilić, Tanja; Pantelić, Ivana; Lunter, Dominique; Đorđević, Sanela; Marković, Bojan; Ranković, Dragana; Daniels, Rolf; Savić, Snežana

    2017-08-07

    This work aimed to prove the ability of "ready-to-use" topical vehicles based on alkyl polyglucoside-mixed emulsifier (with/without co-solvent modifications) to replace the conventionally used pharmacopoeial bases (e.g., non-ionic hydrophilic cream) in compounding practice. For this purpose, considering the regulatory efforts to establish alternative, scientifically valid methods for evaluating therapeutic equivalence of topical semisolids, we performed a comparative assessment of microstructure, selected critical quality attributes (CQAs) and in vitro/in vivo product performances, by utilizing aceclofenac as a model drug. The differences in composition between investigated samples have imposed remarkable variances in monitored CQAs (particularly in the amount of aceclofenac dissolved, rheological properties and water distribution mode), reflecting the distinct differences in microstructure formed, as partially observed by polarization microscopy and confocal Raman spectral imaging. Although not fully indicative of the in vivo performances, in vitro release data (vertical diffusion vs. immersion cells) proved the microstructure peculiarities, asserting the rheological properties as decisive factor for obtained liberation profiles. Contrary, in vitro permeation results obtained using pig ear epidermis correlated well with in vivo dermatopharmacokinetic data and distinguished unequivocally between tested formulations, emphasizing the importance of skin/vehicle interactions. In summary, suggested multi-faceted approach can provide adequate proof on topical semisolids therapeutic equivalence or lack thereof. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. 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 ...

  18. Angiotensin II and angiotensin-(1-7 decrease sFlt1 release in normal but not preeclamptic chorionic villi: an in vitro study

    Directory of Open Access Journals (Sweden)

    Moorefield Cheryl

    2010-11-01

    Full Text Available Abstract Background During preeclampsia, placental angiogenesis is impaired. Factors released from the placenta including vascular endothelial growth factor (VEGF, placental growth factor (PLGF, soluble VEGF receptor 1 (sFlt1, and soluble endoglin (sEng are regulatory molecules of placental development and function. While the renin angiotensin system has been shown to regulate angiogenic factors in other research fields, these mechanisms have not been extensively studied during pregnancy. Methods We evaluated the effects of angiotensin II (Ang II and angiotensin-(1-7 [Ang-(1-7] on the release of VEGF, PLGF, sFlt1, and sEng from placental chorionic villi (CV. CV were collected from nulliparous third-trimester normotensive and preeclamptic subjects. CV were incubated for 0, 2, 4, and 16 hours with or without Ang II (1 nM and 1 microM or Ang-(1-7 (1 nM and 1 microM. The release of VEGF, PLGF, sFlt1, sEng, lactate dehydrogenase (LDH, and human placenta lactogen (HPL was measured by ELISA. Results The release of sFlt1, PLGF, sEng from normal and preeclamptic CV increased over time. Release of sFlt1 and sEng was significantly higher from preeclamptic CV. VEGF was below the detectable level of the assay in normal and preeclamptic CV. After 2 hours, sFlt1 release from normal CV was significantly inhibited with Ang II (1 nM and 1 microM and Ang-(1-7 (1 nM and 1 microM. There was a time-dependent increase in HPL indicating that the CV were functioning normally. Conclusions Our study demonstrates a critical inhibitory role of angiotensin peptides on sFlt1 in normal pregnancy. Loss of this regulation in preeclampsia may allow sFlt1 to increase resulting in anti-angiogenesis and end organ damage in the mother.

  19. In vitro study of the role of thrombin in platelet rich plasma (PRP) preparation: utility for gel formation and impact in growth factors release

    Science.gov (United States)

    Huber, Stephany Cares; Cunha Júnior, José Luiz Rosenberis; Montalvão, Silmara; da Silva, Letícia Queiroz; Paffaro, Aline Urban; da Silva, Francesca Aparecida Ramos; Rodrigues, Bruno Lima; Lana, José Fabio Santos Duarte; Annichino-Bizzacchi, Joyce Maria

    2016-01-01

    Introduction: The use of PRP has been studied for different fields, with promising results in regenerative medicine. Until now, there is no study in the literature evaluating thrombin levels in serum, used as autologous thrombin preparation. Therefore, in the present study we evaluated the role played by different thrombin concentrations in PRP and the impact in the release of growth factors. Also, different activators for PRP gel formation were evaluated. Methods: Thrombin levels were measured in different autologous preparations: serum, L-PRP (PRP rich in leukocytes) and T-PRP (thrombin produced through PRP added calcium gluconate). L-PRP was prepared according to the literature, with platelets and leukocytes being quantified. The effect of autologous thrombin associated or not with calcium in PRP gel was determined by measuring the time of gel formation. The relationship between thrombin concentration and release of growth factors was determined by growth factors (PDGF-AA, VEGF and EGF) multiplex analysis. Results: A similar concentration of thrombin was observed in serum, L-PRP and T-PRP (8.13 nM, 8.63 nM and 7.56 nM, respectively) with a high variation between individuals (CV%: 35.07, 43 and 58.42, respectively). T-PRP and serum with calcium chloride showed similar results in time to promote gel formation. The increase of thrombin concentrations (2.66, 8 and 24 nM) did not promote an increase in growth factor release. Conclusions: The technique of using serum as a thrombin source proved to be the most efficient and reproducible for promoting PRP gel formation, with some advantages when compared to other activation methods, as this technique is easier and quicker with no need of consuming part of PRP. Noteworthy, PRP activation using different thrombin concentrations did not promote a higher release of growth factors, appearing not to be necessary when PRP is used as a suspension. PMID:27397996

  20. 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.

  1. In vitro study of soil arsenic release by human gut microbiota and its intestinal absorption by Caco-2 cells.

    Science.gov (United States)

    Yin, Naiyi; Cai, Xiaolin; Du, Huili; Zhang, Zhennan; Li, Zejiao; Chen, Xiaochen; Sun, Guoxin; Cui, Yanshan

    2017-02-01

    Arsenic (As) speciation is essential in assessing health risks from As-contaminated soil. Release of soil-bound arsenic, As transformation by human gut microbiota, and the subsequent intestinal absorption of soil As metabolites were evaluated. A colon microbial community in a dynamic human gut model and the intestinal epithelial cell line Caco-2 were cultured. Arsenic speciation analysis and absorption of different As species were undertaken. In this study, soil As release (3.7-581.2 mg kg-1) was observed in the colon. Arsenic in the colon digests was transformed more quickly than that in the soil solid phase. X-ray absorption near-edge spectroscopy (XANES) analysis showed that 44.2-97.6% of arsenite [As(III)] generated due to arsenate [As(V)] reduction was in the soil solid phase after the colon phase. We observed a high degree of cellular absorption of soil As metabolites, exhibiting that the intestinal absorption of monomethylarsonic acid and As(III) (33.6% and 30.2% resp.) was slightly higher than that of dimethylarsinic acid and As(V) (25.1% and 21.7% resp.). Our findings demonstrate that human gut microbiota can directly release soil-bound arsenic, particularly As-bearing amorphous Fe/Al-oxides. Determining As transformation and intestinal absorption simultaneously will result in an accurate risk assessment of human health with soil As exposures. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Tablets compressed with gastric floating pellets coated with acrylic resin for gastro retention and sustained release of famotidine: in-vitro and in-vivo study.

    Science.gov (United States)

    Qi, Xiaole; Jiang, Yingchun; Zhang, Huiting; Wu, Zhenghong

    2015-04-01

    The aim of this study was to prepare a disintegrating gastric floating tablet composed of floating pellets coated with acrylic resin to prolong the gastric residence time and increase the oral bioavailability of famotidine. The gastric floating pellets containing famotidine, stearyl alcohol and microcrystalline cellulose (1 : 10 : 1) were prepared by extrusion-spheronization process and coated with acrylic resin, then compressed into tablets with Avicel PH 301 pellets and cross-linked polyvinylpyrrolidone. The coating weight, volume ratio of Eudragit RL30 D and RS30 D and solid content of coating fluid were optimized by Box-Behnken design. In 0.1 M HCl, tablets can immediately disintegrate into pellets which can remain floating and sustained drug releasing over 12 h. The AUC0-∞ of famotidine gastric floating pellets (7776.52 ± 1065.93 h ng/ml) administered into rats was significantly higher than that of marketed rapid release tablets Xingfading® (Xingyi, Shanghai, China) (4166.23 ± 312.43 h ng/ml), while the relative bioavailability was 187.01 ± 22.81%. The experimental results indicated that the optimized formulation did offer a new gastro retention and sustained release approach to enhance the oral absorption of famotidine. © 2014 Royal Pharmaceutical Society.

  3. 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

  4. 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...

  5. Engineering of mesoporous silica nanoparticles for release of ginsenoside CK and Rh2 to enhance their anticancer and anti-inflammatory efficacy: in vitro studies

    Science.gov (United States)

    Singh, Priyanka; Singh, Hina; Castro-Aceituno, Verónica; Ahn, Sungeun; Kim, Yeon Ju; Farh, Mohamed El-Agamy; Yang, Deok Chun

    2017-07-01

    The current study highlights the fabrication of drug delivery system by utilizing 200 nm mesoporous silica nanoparticles (MSNPs) with 4-nm pore size, as a carrier system for delivery ginsenoside compound K (CK) and Rh2 to enhance their efficacy. The two pharmacologically imperative ginsenosides, CK and Rh2, were loaded to the MSNPs to prepare MSNPs-CK and MSNPs-Rh2, respectively. A fluorescein isothiocyanate (FITC) fluorescent dye was combined in the MSNPs carrier system, in order to trace the cellular uptake of ginsenoside-loaded nanoparticles for in vitro studies. Following purification, the so-prepared MSNPs-CK-FITC and MSNPs-Rh2-FITC were characterized by several analytical techniques, which includes, high-pressure liquid chromatography (HPLC), 1H NMR, field emission transmission electron microscopy (FE-TEM), Fourier transform infrared spectroscopy (FT-IR), x-ray diffraction (XRD), thermogravimetric analysis (TGA), and dynamic light scattering (DLS). In vitro cytotoxicity assay in HaCaT skin cells, A549 lung cancer cells, HepG2 liver carcinoma cells, and HT-29 colon cancer cell lines were tested for MSNPs-CK-FITC and MSNPs-Rh2-FITC. The results demonstrate the excellent biocompatibility of nanoparticles in normal cell lines (HaCaT skin cells) and anticancer efficacy in all the tested cancer cell lines at 10-μM concentration. Additionally, the in vitro anti-inflammatory behavior of MSNPs-CK-FITC and MSNPs-Rh2-FITC were checked in RAW264.7 (murine macrophage) cell lines. The outcomes showed higher anti-inflammatory efficacy of MSNPs-CK-FITC and MSNPs-Rh2-FITC as compared to standard ginsenosides CK and Rh2 in RAW264.7 cell lines. Thus, with 200 nm MSNPs carrier system for the delivery ginsenosides CK and Rh2, a high amount of loading and increasing in vitro pharmacological efficacies of ginsenosides were realized. This study may provide useful insights for designing and improving the applicability of MSNPs for ginsenoside delivery.

  6. Characterization, inclusion mode, phase-solubility and in vitro release studies of inclusion binary complexes with cyclodextrins and meglumine using sulfamerazine as model drug.

    Science.gov (United States)

    Aloisio, Carolina; Gomes de Oliveira, Anselmo; Longhi, Marcela

    2014-07-01

    In order to investigate the effect on the aqueous solubility and release rate of sulfamerazine (SMR) as model drug, inclusion complexes with β-cyclodextrin (βCD), methyl-β-cyclodextrin (MβCD) and hydroxypropyl-β-cyclodextrin (HPβCD) and a binary system with meglumine (MEG) were developed. The formation of 1:1 inclusion complexes of SMR with the CDs and a SMR:MEG binary system in solution and in solid state was revealed by phase solubility studies (PSS), nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FT-IR), thermal analysis and X-Ray diffractometry (XRD) studies. The CDs solubilization of SMR could be improved by ionization of the drug molecule through pH adjustments. The higher apparent stability constants of SMR:CDs complexes were obtained in pH 2.00, demonstrating that CDs present more affinity for the unionized drug. The best approach for SMR solubility enhancement results from the combination of MEG and pH adjustment, with a 34-fold increment and a Smax of 54.8 mg/ml. The permeability of the drug was reduced due to the presence of βCD, MβCD, HPβCD and MEG when used as solubilizers. The study then suggests interesting applications of CD or MEG complexes for modulating the release rate of SMR through semipermeable membranes.

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

    Science.gov (United States)

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

    2015-01-01

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

  8. Radioactive waste study released

    Science.gov (United States)

    Dowhaluk, Bohdan

    A National Research Council (NRC) panel has concluded that the technology for safely storing radioactive waste is ready for confirmation in a test facility. At the same time, the panel proposed safety standards that are more stringent than standards currently proposed by some government agencies. The report, Study of the Isolation System for the Geologic Disposal of Radioactive Wastes, was funded by the Department of Energy as part of its effort to comply with a Congressional mandate to open a national radioactive waste storage facility by the end of the century.The Waste Isolation Panel of the NRC's Board on Radioactive Waste Management did not choose a specific site for the first U.S. repository because the state of current technology does not allow the U.S. to design, construct, and safely operate a full-fledged site. However, the panel's chairman, Thomas H. Pigford, of the University of California at Berkeley, believes that the goal established by Congress can be met.

  9. 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.

  10. In-vitro/in-vivo studies of the biodegradable poly-(D,L-lactide-co-glycolide) microspheres of a novel luteinizing hormone-releasing hormone antagonist for prostate cancer treatment.

    Science.gov (United States)

    Du, Lina; Mei, Xingguo; Wang, Chenyun; Li, Xin; Zhang, Fucheng; Jin, Yiguang

    2011-03-01

    The introduction of luteinizing hormone-releasing hormone (LHRH) analogs and their antagonists is revolutionizing the treatment of prostate cancer. In this study, poly(D,L-lactideco-glycolide) (PLGA) microspheres containing a highly potent LHRH antagonist (LXT-101) of interest in the indication of prostate cancer were evaluated on release mechanisms in vitro and biological performance in vivo. LXT-101 microspheres were prepared by the water/oil/water double emulsion method and the solid/oil/oil method. The results showed that the mechanism of LXT-101 releasing from PLGA 14,000 microspheres was the cooperation of drug diffusion and polymer degradation. This clarified the relationship between the microsphere characterization and hormone level in vivo. The larger microspheres (33 μm) could inhibit the testosterone level to castration for a longer time (35 days) than the smaller microspheres (15 μm, 14 days). The formulation containing the hydrophilic additive (polyethylene glycol 6000) could suppress the testosterone level to castration for a longer time (> 35 days) than the formulation without polyethylene glycol (14 days). The appearance of testis, vesicular seminalis, and prostates changed after treatment. The weights of sexual organs decreased significantly. The in-vivo release of the LXT-101 PLGA 14,000 microspheres curve showed that in-vivo release started immediately after day 1 (22.7%) and was rapid during the first 5 days (40.2% release). The LXT-101 microspheres could be a promising drug delivery system candidate to treat sex hormone-dependent tumors and other related disorders.

  11. 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

  12. 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.

  13. 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.

  14. N-Methyl-d-aspartate Modulation of Nucleus Accumbens Dopamine Release by Metabotropic Glutamate Receptors: Fast Cyclic Voltammetry Studies in Rat Brain Slices in Vitro.

    Science.gov (United States)

    Yavas, Ersin; Young, Andrew M J

    2017-02-15

    The N-methyl-d-aspartate (NMDA) receptor antagonist, phencyclidine, induces behavioral changes in rodents mimicking symptoms of schizophrenia, possibly mediated through dysregulation of glutamatergic control of mesolimbic dopamine release. We tested the hypothesis that NMDA receptor activation modulates accumbens dopamine release, and that phencyclidine pretreatment altered this modulation. NMDA caused a receptor-specific, dose-dependent decrease in electrically stimulated dopamine release in nucleus accumbens brain slices. This decrease was unaffected by picrotoxin, making it unlikely to be mediated through GABAergic neurones, but was decreased by the metabotropic glutamate receptor antagonist, (RS)-α-methyl-4-sulfonophenylglycine, indicating that NMDA activates mechanisms controlled by these receptors to decrease stimulated dopamine release. The effect of NMDA was unchanged by in vivo pretreatment with phencyclidine (twice daily for 5 days), with a washout period of at least 7 days before experimentation, which supports the hypothesis that there is no enduring direct effect of PCP at NMDA receptors after this pretreatment procedure. We propose that NMDA depression of accumbal dopamine release is mediated by metabotropic glutamate receptors located pre- or perisynaptically, and suggest that NMDA evoked increased extrasynaptic spillover of glutamate is sufficient to activate these receptors that, in turn, inhibit dopamine release. Furthermore, we suggest that enduring functional changes brought about by subchronic phencyclidine pretreatment, modeling deficits in schizophrenia, are downstream effects consequent on chronic blockade of NMDA receptors, rather than direct effects on NMDA receptors themselves.

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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) ...

  10. 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

  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. In Vitro Sustained Release Study of Gallic Acid Coated with Magnetite-PEG and Magnetite-PVA for Drug Delivery System

    Directory of Open Access Journals (Sweden)

    Dena Dorniani

    2014-01-01

    Full Text Available The efficacy of two nanocarriers polyethylene glycol and polyvinyl alcohol magnetic nanoparticles coated with gallic acid (GA was accomplished via X-ray diffraction, infrared spectroscopy, magnetic measurements, thermal analysis, and TEM. X-ray diffraction and TEM results showed that Fe3O4 nanoparticles were pure iron oxide having spherical shape with the average diameter of 9 nm, compared with 31 nm and 35 nm after coating with polyethylene glycol-GA (FPEGG and polyvinyl alcohol-GA (FPVAG, respectively. Thermogravimetric analyses proved that after coating the thermal stability was markedly enhanced. Magnetic measurements and Fourier transform infrared (FTIR revealed that superparamagnetic iron oxide nanoparticles could be successfully coated with two polymers (PEG and PVA and gallic acid as an active drug. Release behavior of gallic acid from two nanocomposites showed that FPEGG and FPVAG nanocomposites were found to be sustained and governed by pseudo-second-order kinetics. Anticancer activity of the two nanocomposites shows that the FPEGG demonstrated higher anticancer effect on the breast cancer cell lines in almost all concentrations tested compared to FPVAG.

  13. 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.

  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. 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.

  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. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. The combination of ultrasound with antibiotics released from bone cement decreases the viability of planktonic and biofilm bacteria : an in vitro study with clinical strains

    NARCIS (Netherlands)

    Ensing, Geert T.; Neut, Danielle; Horn, Jim R. van; van der Mei, Henny C.; Busscher, Henk J.

    2006-01-01

    Objectives: Antibiotic-loaded bone cements are used for the permanent fixation of joint prostheses. Antibiotic-loaded cements significantly decrease the incidence of infection. The objective of this study was to investigate whether the viability of bacteria derived from patients with a

  3. Discrepancies between the skin test and IgE antibody assays: study of histamine release, complement activation in vitro, and occurrence of allergen-specific IgG

    NARCIS (Netherlands)

    van der Zee, J. S.; de Groot, H.; van Swieten, P.; Jansen, H. M.; Aalberse, R. C.

    1988-01-01

    Intracutaneous skin tests (STs) and RAST with the common allergens, grass pollen, house dust mite, and cat dander, were performed on 660 adult patients. In 117 patients (18%), we found 140 discordances (7%) in a total number of 1980 ST and RAST combinations. In agreement with studies in the

  4. Use of spray-cooling technology for development of microencapsulated capsicum oleoresin for the growing pig as an alternative to in-feed antibiotics: a study of release using in vitro models.

    Science.gov (United States)

    Meunier, J-P; Cardot, J-M; Manzanilla, E G; Wysshaar, M; Alric, M

    2007-10-01

    The aim of this study was to develop sustained release microspheres of capsicum oleoresin as an alternative to in-feed additives. Two spray-cooling technologies, a fluidized air bed using a spray nozzle system and a vibrating nozzle system placed on top of a cooling tower, were used to microencapsulate 20% of capsicum oleoresin in a hydrogenated, rapeseed oil matrix. Microencapsulation was intended to reduce the irritating effect of capsicum oleoresin and to control its release kinetics during consumption by the animal. Particles produced by the fluidized air bed process (batch F1) ranged from 180 to 1,000 microm in size. The impact of particle size on release of capsaicin, the main active compound of capsicum oleoresin, was studied after sieving batch F1 to obtain 4 formulations: F1a (180 to 250 microm), F1b (250 to 500 microm), F1c (500 to 710 microm), and F1d (710 to 1,000 microm). The vibrating nozzle system can produce a monodispersive particle size distribution. In this study, particles of 500 to 710 microm were made (batch F2). The release kinetics of the formulations was estimated in a flow-through cell dissolution apparatus (CFC). The time to achieve a 90% dissolution value (T90%) of capsaicin for subbatches of F1 increased with the increase in particle size (P < 0.05), with the greatest value of 165.5 +/- 13.2 min for F1d. The kinetics of dissolution of F2 was slower than all F1 subbatches, with a T90% of 422.7 +/- 30.0 min. Nevertheless, because CFC systems are ill suited for experiments with solid feed and thus limit their predictive values, follow-up studies were performed on F1c and F2 using an in vitro dynamic model that simulated more closely the digestive environment. For both formulations a lower quantity of capsaicin dialyzed was recorded under fed condition vs. fasting condition with 46.9% +/- 1.0 vs. 74.7% +/- 2.7 for F1c and 32.4% +/- 1.4 vs. 44.2% +/- 2.6 for F2, respectively. This suggests a possible interaction between capsaicin and the

  5. Comparative study of in vitro release and mucoadhesivity of gastric compacts composed of multiple unit system/bilayered discs using direct compression of metformin hydrochloride

    OpenAIRE

    Jelvehgari, Mitra; Zakeri-Milani, Parvin; Khonsari, Fatemeh

    2014-01-01

    Introduction: Metformin is an oral anti-diabetic drug in the biguanide class. The goal of this study was to develop gastric-retentive MH discs in order to prolong the retention of drug in gastric mucosa. Methods: Two groups of metformin hydrochloride (MH) mucoadhesive gastroretentive discs were prepared: (a) bilayered discs prepared by direct compression of powders containing polymers as Carbopol 934P (CP, mucoadhesive polymer) and ethylcellulose (EC, rotardant polymer), (b) multiple unit sys...

  6. Comparative study of in vitro release and mucoadhesivity of gastric-compacts composed of multiple unit system/bilayered discs using direct compression of metformin hydrochloride

    OpenAIRE

    Mitra Jelvehgari; Parvin Zakeri-Milani; Fatemeh Khonsari

    2014-01-01

    Introduction: Metformin is an oral anti-diabetic drug in the biguanide class. The goal of this study was to develop gastric-retentive MH discs in order to prolong the retention of drug in gastric mucosa.Methods:Two groups of metformin hydrochloride (MH) mucoadhesive gastroretentive discs were prepared: (a) bilayered discs prepared by direct compression of powders containing polymers as Carbopol 934P (CP, mucoadhesive polymer) and ethylcellulose (EC, rotardant polymer), (b) multiple ...

  7. 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.

  8. An in vitro study of the antifungal activity of Trichoderma virens 7b and a profile of its non-polar antifungal components released against Ganoderma boninense.

    Science.gov (United States)

    Angel, Lee Pei Lee; Yusof, Mohd Termizi; Ismail, Intan Safinar; Ping, Bonnie Tay Yen; Mohamed Azni, Intan Nur Ainni; Kamarudin, Norman Hj; Sundram, Shamala

    2016-11-01

    Ganoderma boninense is the causal agent of a devastating disease affecting oil palm in Southeast Asian countries. Basal stem rot (BSR) disease slowly rots the base of palms, which radically reduces productive lifespan of this lucrative crop. Previous reports have indicated the successful use of Trichoderma as biological control agent (BCA) against G. boninense and isolate T. virens 7b was selected based on its initial screening. This study attempts to decipher the mechanisms responsible for the inhibition of G. boninense by identifying and characterizing the chemical compounds as well as the physical mechanisms by T. virens 7b. Hexane extract of the isolate gave 62.60% ± 6.41 inhibition against G. boninense and observation under scanning electron microscope (SEM) detected severe mycelial deformation of the pathogen at the region of inhibition. Similar mycelia deformation of G. boninense was observed with a fungicide treatment, Benlate ® indicating comparable fungicidal effect by T. virens 7b. Fraction 4 and 5 of hexane active fractions through preparative thin layer chromatography (P-TLC) was identified giving the best inhibition of the pathogen. These fractions comprised of ketones, alcohols, aldehydes, lactones, sesquiterpenes, monoterpenes, sulphides, and free fatty acids profiled through gas chromatography mass spectrometry detector (GC/MSD). A novel antifungal compound discovery of phenylethyl alcohol (PEA) by T. virens 7b is reported through this study. T. virens 7b also proved to be an active siderophore producer through chrome azurol S (CAS) agar assay. The study demonstrated the possible mechanisms involved and responsible in the successful inhibition of G. boninense.

  9. 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.

  10. 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.

  11. Estudo de sistemas acrílicos bioadesivos para liberação sustentada in vitro de fluoreto Study of bioadhesive acrylic systems for in vitro sustained release of fluoride

    Directory of Open Access Journals (Sweden)

    Elza Helena Guimarães LARA

    1998-07-01

    Full Text Available Os autores desenvolveram dispositivos de liberação programada de fluoreto para aplicação intrabucal. O princípio ativo usado foi o fluoreto de sódio, que era associado à mistura de polimetilmetacrilato e hidroxietilmetacrilato, resinas acrílicas que formavam o sistema. Como produto acabado, os dispositivos tiveram comportamento adequado com relação à liberação de fluoreto e ao período de permanência na cavidade bucal, já que se mantiveram por um tempo relativamente elevado na boca (10 dias, liberando continuamente pequenas quantidades do agente terapêutico. Como forma de aplicação medicamentosa, estes dispositivos oferecem uma soma de vantagens, sendo a principal delas o fornecimento do princípio terapêutico no local correto (no alvo e a manutenção constante dele neste local em concentração eficiente e segura. O desenvolvimento desses dispositivos abre campo para novas terapias.The authors developed sustained fluoride release devices for intraoral application. The drug used, sodium fluoride, was associated to a mixture of polimethylmetacrilate and hydroxiethylmetacrilate, acrylic resins that formed the systems. The finished product presented an adequate behavior in terms of fluoride release and period of time in the oral cavity, as it remained in the mouth for a relatively long time (10 days, continuously liberating small quantities of the drug. These devices have several advantages concerning about drug dosage, mainly by supplying the drug to the right place (target, and maintaining it continuously in the site in an efficient and safe concentration. The development of these devices is the beginning of a field of new therapies.

  12. Studies on renin release in vitro

    DEFF Research Database (Denmark)

    Skøtt, O

    1989-01-01

    with an increase in intracellular pH. 5) Results with the monovalent cation ionophores nigericin and monensin, are similar to those obtained with weak permeable bases, and suggest that their effects are due to swelling and alkalinization of acidic cellular organelles. 6) A decrease in the extracellular calcium...

  13. 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.

  14. 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®..

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

    Science.gov (United States)

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

    1999-07-01

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

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    Ching-Wen Lou

    2017-11-01

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

  19. 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.

  20. 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.

  1. 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...

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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 ...

  9. 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.

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

    Science.gov (United States)

    Tang, Yu; Singh, Jagdish

    2008-06-05

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

  11. 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.

  12. 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...

  13. 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.

  14. 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.

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

    Directory of Open Access Journals (Sweden)

    Ikrima Khalid

    2014-09-01

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

  16. 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

  17. 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.

  18. In vitro permeation studies of diclofenac diethylamine from newly ...

    African Journals Online (AJOL)

    The study was designed to investigate the feasibility of developing a transdermal drug dosage form of diclofenac diethylamine (DDA). The in vitro release and diffusion characteristics of DDA from two dermatological oleogel bases were studied using full thickness skin from the abdominal hairless surface of rabbit, as the ...

  19. 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...

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

    DEFF Research Database (Denmark)

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

    1994-01-01

    Fast-scan cyclic voltammetry with carbon fibre microelectrodes was used to detect endogenous dopamine (DA) and 5-hydroxytryptamine (5-HT) release from three distinct regions of guinea-pig mid-brain in vitro: rostral and caudal substantia nigra (SN) and the ventral tegmental area (VTA). Previous...... 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...

  1. 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

  2. Programmed subcellular release to study the dynamics of cell detachment

    Science.gov (United States)

    Wildt, Bridget

    Cell detachment is central to a broad range of physio-pathological changes however there are no quantitative methods to study this process. Here we report programmed subcellular release, a method for spatially and temporally controlled cellular detachment and present the first quantitative results of the detachment dynamics of 3T3 fibroblasts at the subcellular level. Programmed subcellular release is an in vitro technique designed to trigger the detachment of distinct parts of a single cell from a patterned substrate with both spatial and temporal control. Subcellular release is achieved by plating cells on an array of patterned gold electrodes created by standard microfabrication techniques. The electrodes are biochemically functionalized with an adhesion-promoting RGD peptide sequence that is attached to the gold electrode via a thiol linkage. Each electrode is electrically isolated so that a subcellular section of a single cell spanning multiple electrodes can be released independently. Upon application of a voltage pulse to a single electrode, RGD-thiol molecules on an individual electrode undergo rapid electrochemical desorption that leads to subsequent cell contraction. The dynamics of cell contraction are found to have characteristic induction and contraction times. This thesis presents the first molecular inhibition studies conducted using programmed subcellular release verifying that this technique can be used to study complex signaling pathways critical to cell motility. Molecular level dynamics of focal adhesion proteins and actin stress fibers provide some insight into the complexities associated with triggered cell detachment. In addition to subcellular release, the programmed release of alkanethiols provides a tool for to study the spatially and temporally controlled release of small molecules or particles from individually addressable gold electrodes. Here we report on experiments which determine the dynamics of programmed release using fluorophore

  3. [Study on sustained release preparations of Epimedium component].

    Science.gov (United States)

    Yan, Hong-mei; Ding, Dong-mei; Zhang, Zhen-hai; Sun, E; Song, Jie; Jia, Xiao-bin

    2015-04-01

    The formulation for sustained release tablet of Epinedium component was selected and the evaluation equation of in vitro release was established. The liquidity of component was improved with the help of colloidal silica aided by spray drying, which would be the main drug in the sustained release tablets. Dissolution was selected as an evaluation index to investigate skeletal material type, fillers, impact porogen, lubricants and other materials on the quality of sustained release tablet. The sustained release tablets were prepared by dry compression. Formulation of sustained release preparations was main drug 35%, HPMC K(4M) 20% and HPMC K(15M) 10% as skeleton material, MCC 31% as filler, PEG6000 2% as porogen and magnesium stearate 2% as lubricant. The sustained release tablets released up to 80% in 8 h. The zero order equation, primary equation and Higuchi equation could simulate the release characteristics of sustained release tablets in vitro, the correlation coefficients r were larger than 0.96. The primary equation was most similar in vitro release characteristics and its correlation coefficient r was 0.9950. The preparation method is simple and the results of formulation selection are reliable. It can be used to guide the production of Epimedium component sustained release preparations.

  4. Repeat dose of gonadotropin-releasing hormone agonist trigger in polycystic ovarian syndrome undergoing In Vitro fertilization cycles provides a better cycle outcome - a proof-of-concept study

    Directory of Open Access Journals (Sweden)

    Krishna Deepika

    2017-01-01

    Full Text Available Objective: Is a single dose of gonadotropin-releasing hormone agonist (GnRHa trigger to induce final oocyte maturation in polycystic ovarian syndrome (PCOS undergoing in vitro fertilization (IVF cycles with GnRH antagonist protocol sufficient to provide optimal oocyte maturity? Design: This is a prospective, randomized, double-blind, proof-of-concept study. Setting: This study was carried out at a tertiary care center. Material and Methods: A total of 125 patients diagnosed with PCOS defined as per the ESHRE/ASRM Rotterdam criteria (2003 undergoing IVF in antagonist protocol were randomized into two groups. Group A: single dose of GnRHa 0.2 mg, 35 h prior to oocyte retrieval, and Group B: 0.2 mg GnRHa 35 h prior to oocyte retrieval + repeat dose of 0.1 mg 12 h following the 1st dose. 12 h post-trigger, luteinizing hormone (LH, progesterone (P4, and follicle-stimulating hormone (FSH values were estimated. Statistical Analysis: Continuous variables were expressed as mean ± standard deviation and categorical variables as proportions where applicable. Independent sample t-test was used for continuous variables which were normally distributed and Mann–Whitney U-test for data not normally distributed. Chi-square test or Fisher's exact test was used for categorical variables where appropriate. Odds ratio (OR with 95% confidence intervals (CIs was calculated. In addition, receiver operating characteristic curve was used to evaluate the post-trigger LH, P4, and FSH values at 12 h as predictors of oocyte maturity. Main Outcome Measures: Primary outcome: maturity rate of the oocytes. Secondary outcomes: oocyte yield, fertilization rate, availability of good quality embryos on day 3, blastocyst conversion, OHSS rates, post-trigger serum LH (IU/L, FSH (IU/L, and P4 (ng/mL levels implantation rate and clinical pregnancy rate. Results: A higher number of mature (metaphase II oocytes were obtained in Group B compared to Group A (OR of 0.47; CI: 0.38–0

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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...

  18. 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.

  19. 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.

  20. 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...

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    Juçara Ribeiro Franca

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

  3. 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...

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

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

    Science.gov (United States)

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

    2004-06-01

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

  14. Studies on aminophenazone and phenobarbital release from suppositories prepared on different bases.

    Science.gov (United States)

    Piasecka, H; Zakrzewski, Z

    1976-01-01

    Employing in the studies in vitro the dynamic system, we investigated aminophenazone (APH) and phenobarbital (PHB) release through semipermeable membrane from suppositories prepared on different bases, namely. Massupol, Oleum Cacao, H-15 Witepsol, Imhausen Suppositorien Masse SB, 1500 polioxyethylene glycol. The rate of APH liberation was highest from Imhausen and lowest from H-15 Witepsol; PHB was released most rapidly from Oleum Cacao, the poorest results being observed in the case of polioxyethylene glycol.

  15. Improvement of penile erection, sperm count and seminal fructose levels in vivo and nitric oxide release in vitro by ayurvedic herbs.

    Science.gov (United States)

    Thakur, M; Thompson, D; Connellan, P; Deseo, M A; Morris, C; Dixit, V K

    2011-08-01

    In the present study, the effect of four Vajikaran Rasayana herbs on penile erection, sperm count, seminal fructose content in vivo and nitric oxide (NO) release in vitro was assessed. Lyophilised aqueous extracts of Asparagus racemosus Willd. (AR), Chlorophytum borivilianum Sant. F. (CB), Curculigo orchioides Gaertn. (CO), and Dactylorhiza hatagirea (D. Don) Soo (DH) were orally administered at 100 mg/kg body weight to Wistar strain male albino rats. Penile erection index and sperm count were determined by visual observation; the seminal fructose concentration was measured spectrophotometrically using resorcinol reagent; and NO release was assessed in a mouse macrophage cell line (RAW264) spectrophotometrically using a commercial Griess reagent kit. Penile erection index, sperm count, seminal fructose concentration and in vitro NO release were the parameters measured. A significant effect on the sperm count, seminal fructose content and penile erection index was observed upon treatment with the extracts. The effect of extracts on inducible NO release in vitro directly correlated with the enhanced erectile function in vivo. The aphrodisiac claims attributed to the four Vajikaran Rasayana herbs were tested and a distinctive effect of all extracts tested was observed, with C. borivilianum showing a highly significant response for all parameters measured in vivo and in vitro. The present study also provides a good correlation between the in vivo improvement of penile erection and in vitro NO releasing activity of the extracts. Increase in seminal fructose levels and sperm count further validates the role of these herbs in improving reproductive function. © 2011 Blackwell Verlag GmbH.

  16. 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

  17. 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.

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  20. Field study of the long-term release of block copolymers from fouling-release coatings

    DEFF Research Database (Denmark)

    Noguer, Albert Camós; Olsen, A.; Hvilsted, Søren

    2017-01-01

    The addition of block copolymers (i.e. oils) is a common technique to enhance the biofouling-resistance properties of poly(dimethylsiloxane) (PDMS)-based fouling-release coatings. These copolymers diffuse from the bulk to the surface of the coating, thus modifying the properties of the surface an...... fouling-release coatings. Finally, the potential of long-term field-studies is discussed, as compared to short-term laboratory experiments usually performed within fouling-release coatings studies....

  1. 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

  2. Sustained-release effervescent floating matrix tablets of baclofen: development, optimization and in vitro-in vivo evaluation in healthy human volunteers.

    Science.gov (United States)

    Gande, S; Rao, Ym

    2011-01-01

    Baclofen, a centrally acting skeletal muscle relaxant, is indicated in the long-term treatment of spasticity. It is difficult to formulate baclofen sustained release dosage forms because its absorption on arrival to colon (or even before) is low or nonexistent. In the present investigation efforts were made to improve the bioavailability of baclofen by increasing the residence time of the drug through sustained-release matrix tablet formulation via gastroretentive mechanism. Tablets were prepared by wet granulation technique. The influence of gas generating and gel forming agents, amount of baclofen and total weight of tablet on physical properties, in vitro buoyancy, floating lag time, drug release, DSC, X-ray studies were investigated. The release mechanisms were explored and explained by applying zero order, first order, Higuchi and Korsmeyer equations. The selected formulations were subjected to stability study for the period of three months. For all formulations, kinetics of drug release from tablet followed Higuchi's square root of time kinetic treatment heralding diffusion as predominant mechanism of drug release. Formulations containing 20 mg and 40 mg (F-1 and F-7) showed similar release profiles. There was no significant change in the selected formulations, when subjected to accelerated stability conditions over a period of three months. X-ray imaging in six healthy human volunteers revealed a mean gastric retention period of 5.50±0.7 hrs for the selected formulation. Stable, sustained release effervescent floating matrix tablets of baclofen could be prepared by wet granulation technique.

  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. 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

  5. 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.

  6. 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.

  7. 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

  8. 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 ...

  9. 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 ...

  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. Biscuits with No Added Sugar Containing Stevia, Coffee Fibre and Fructooligosaccharides Modifies α-Glucosidase Activity and the Release of GLP-1 from HuTu-80 Cells and Serotonin from Caco-2 Cells after In Vitro Digestion.

    Science.gov (United States)

    Martinez-Saez, Nuria; Hochkogler, Christina Maria; Somoza, Veronika; Del Castillo, Maria Dolores

    2017-07-04

    This study assessed the in vitro effects of the bioaccessible food components released during the simulated human digestion of a coffee fibre-containing biscuit (CFB) on α-glucosidase activity, antioxidant capacity and satiety hormones. Digest of CFB presented a significantly (p diabetes-related digestive enzyme, and to improve the release of satiety hormones.

  12. 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 ...

  13. Study on drug release of and biological response to UHMWPE wear debris carrying estradiol

    Energy Technology Data Exchange (ETDEWEB)

    Qu Shuxin, E-mail: qushuxin@swjtu.edu.cn [Key Lab of Advanced Technologies of Materials, Ministry of Education, School of Material Science and Engineering, Southwest Jiaotong University, Chengdu 610031 (China); Liu Aiqin; Liu Xiaomin; Bai Yinlong; Weng Jie [Key Lab of Advanced Technologies of Materials, Ministry of Education, School of Material Science and Engineering, Southwest Jiaotong University, Chengdu 610031 (China)

    2012-12-01

    Highlights: Black-Right-Pointing-Pointer We prepared ultra-high molecular weight polyethylene (UHMWPE) loaded with 17{beta}-estradiol (E2) to treat osteolysis after artificial joint replacement. Black-Right-Pointing-Pointer We investigate the in vitro release of E2 and the cell biological response to UHMWPE-E2 wear debris. Black-Right-Pointing-Pointer The in vitro E2 release included three stages during the release process: initial burst release, celerity release and steady release. Black-Right-Pointing-Pointer The UHMWPE-E2 wear debris could promote the proliferation and ALP activity of osteoblasts and inhibit the expression of IL-6 of osteoblasts. Black-Right-Pointing-Pointer The E2 in UHMWPE-E2 would play a role in the treatment of the osteolysis after artificial hip joint replacement. - Abstract: The aim of this study is to investigate in vitro release of 17{beta}-estradiol (E2), the potential drug to treat osteolysis, and the biological response to ultra-high molecular weight polyethylene loaded with E2 (UHMWPE-E2) wear debris. The osteoblasts (MC3T3-E1) and macrophages (RAW264.7) were co-cultured with UHMWPE-E2 wear debris via inversion culture technique, respectively. MTT, ALP and ELISA assay were employed to evaluate the cell proliferation, ALP activity and the expression of interleukin-6 (IL-6). In vitro E2 release included: initial burst release, celerity release and steady release. The E2 released steadily after 40 d and lasted more than 60 d. The E2 in UHMWPE-E2 wear debris promoted the proliferation and ALP activity of MC3T3-E1 cells at the high debris dosages of 8-10 mg. In particular, the UHMWPE-E2 wear debris inhibited the expression of IL-6 of osteoblasts at all dosages in the present study. RAW264.7 cells cultured with UHMWPE-E2 and UHMWPE wear debris exhibited large sizes about 100 {mu}m in diameter. The small size wear debris presented inside of cells indicated that the wear debris activated the phagocytosis of macrophages. The results indicated

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

    Science.gov (United States)

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

    2014-01-02

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

  15. 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.

  16. 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

  17. 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.

  18. 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

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

    Directory of Open Access Journals (Sweden)

    Carol L. Berkower

    2013-01-01

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

  20. 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

  1. 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

  2. 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

  3. Nanocomposites coated with xyloglucan for drug delivery: In vitro studies.

    Science.gov (United States)

    Ribeiro, C; Arizaga, G G C; Wypych, F; Sierakowski, M-R

    2009-02-09

    Enalaprilate (Enal), an active pharmaceutical component, was intercalated into a layered double hydroxide (Mg/Al-LDH) by an ion exchange reaction. The use of a layered double hydroxide (LDH) to release active drugs is limited by the low pH of the stomach (pH approximately 1.2), in whose condition it is readily dissolved. To overcome this limitation, xyloglucan (XG) extracted from Hymenaea courbaril (jatobá) seeds, Brazilian species, was used to protect the LDH and allow the drug to pass through the gastrointestinal tract. All the materials were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, elemental analyses, transmission electronic microscopy, thermal analyses, and a kinetic study of the in vitro release was monitored by ultraviolet spectroscopy. The resulting hybrid system containing HDL-Enal-XG(3) slowly released the Enal. In an 8-h of test, the system protected 40% (w/v) of the drug. The kinetic profile showed that the drug release was a co-effect behavior, involving dissolution of inorganic material and ion exchange between the intercalated anions in the lamella and those of phosphate in the buffer solution. The nanocomposite coated protection with XG was therefore efficient in obtaining a slow release of Enal.

  4. The differences in Hg content released from high copper amalgam and silverfil argentum restoration into artificial saliva after one week of soaking (in vitro

    Directory of Open Access Journals (Sweden)

    Deriz Rieskanoerbachra Wisuardy

    2008-07-01

    Full Text Available Dental restoration is a treatment in dentistry that very often implemented. One of the restoration materials used is an amalgam. Amalgam has some deficiencies, among others, the presence of free Hg. The purpose of this study was to find out the difference in Hg content released from two different kinds of amalgam, namely, high copper amalgam and silverfil argentum carried out in vitro. This study was carried out on thirty premolar teeth of the maxilla which underwent class one occlusal restoration. The Hg content released was measured using the Atomic Absorption Spectrophotometry (AAS. This was a quasi-experimental study. The study results analyzed using the independent t paired statistical test method indicated that after one week of immersion, the average Hg content released from high copper amalgam restoration was 10,695 ng/mL and from silverfil argentum restoration was 5,602 ng/mL. The conclusion of the study was that there was a difference in Hg content released from high copper amalgam restoration and silverfil argentum restoration. The Hg content released from high copper amalgam restoration was higher than the Hg content released from silverfil argentum restoration.

  5. 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.

  6. Influence of drug property and product design on in vitro-in vivo correlation of complex modified-release dosage forms.

    Science.gov (United States)

    Qiu, Yihong; Li, Xia; Duan, John Z

    2014-02-01

    The present study examines how drug's inherent properties and product design influence the evaluation and applications of in vitro-in vivo correlation (IVIVC) for modified-release (MR) dosage forms consisting of extended-release (ER) and immediate-release (IR) components with bimodal drug release. Three analgesic drugs were used as model compounds, and simulations of in vivo pharmacokinetic profiles were conducted using different release rates of the ER component and various IR percentages. Plasma concentration-time profiles exhibiting a wide range of tmax and maximum observed plasma concentration (Cmax) were obtained from superposition of the simulated IR and ER profiles based on a linear IVIVC. It was found that depending on the drug and dosage form design, direct use of the superposed IR and ER data for IVIVC modeling and prediction may (1) be acceptable within errors, (2) become unreliable and less meaningful because of the confounding effect from the non-negligible IR contribution to Cmax, or (3) be meaningless because of the insensitivity of Cmax to release rate change of the ER component. Therefore, understanding the drug, design and drug release characteristics of the product is essential for assessing the validity, accuracy, and reliability of IVIVC of complex MR products obtained via directly modeling of in vivo data. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

  7. A dissolução in vitro na previsão da absorção oral de fármacos em formas farmacêuticas de liberação modificada Dissolution studies in vitro as a prognostic tool for oral absorption of modified release pharmaceutical dosage forms

    Directory of Open Access Journals (Sweden)

    Rui Manadas

    2002-12-01

    Full Text Available Pretende-se com o presente trabalho abordar os aspectos teóricos e práticos dos estudos de dissolução das formas farmacêuticas sólidas orais de liberação modificada, em três partes. Na primeira parte faz-se referência à classificação, interesse terapêutico e teoria da liberação do fármaco. Na segunda parte abordam-se as teorias de dissolução, os modelos de liberação, os sistemas de dissolução e sua validação, as especificações e critérios de aceitação dos ensaios de dissolução e ainda os fatores condicionantes da dissolução, liberação e absorção. Na terceira parte confrontamse as condições em que são efetuados os ensaios de dissolução com os parâmetros fisiológicos, fazendo referência aos meios de dissolução e composição do lume do trato gastrintestinal e aos modelos hidrodinâmicos.The aim of the present work focused on the theoretical and practical aspects of the dissolution studies of the modified release pharmaceutical dosage forms. This paper was divided in three parts: the first refers to the classification, therapeutic interest and release of the drug; the second part presents the theory of the dissolution process, the models of drug release, dissolution systems and their validation, specifications and acceptance criteria for the dissolution studies and the factors conditioning the dissolution, release and absorption of the drug; the third part discusses the conditions in which the dissolution studies are performed and the physiological parameters making reference to the dissolution media, to the composition of the gastrointestinal tract lumen and to the hydrodynamic models.

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

    Directory of Open Access Journals (Sweden)

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

    2016-10-01

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

  9. Defective synthesis and release of astrocytic thrombospondin-1 mediates the neuronal TDP-43 proteinopathy, resulting in defects in neuronal integrity associated with chronic traumatic encephalopathy: in vitro studies.

    Science.gov (United States)

    Jayakumar, Arumugam Radhakrishnan; Tong, Xiao Y; Shamaladevi, Nagarajarao; Barcelona, Stephanie; Gaidosh, Gabriel; Agarwal, Apeksha; Norenberg, Michael D

    2017-02-01

    Transactivating DNA-binding protein-43 (TDP-43) inclusions and the accumulation of phosphorylated and ubiquitinated tau proteins (p-tau) have been identified in postmortem brain specimens from patients with chronic traumatic encephalopathy (CTE). To examine whether these proteins contribute to the development of CTE, we utilized an in vitro trauma system known to reproduce many of the findings observed in humans and experimental animals with traumatic brain injury. Accordingly, we examined the role of TDP-43 and Tau in an in vitro model of trauma, and determined whether these proteins contribute to the defective neuronal integrity associated with CNS trauma. Single or multiple episodes of trauma to cultured neurons resulted in a time-dependent increase in cytosolic levels of phosphorylated TDP-43 (p-TDP-43). Trauma to cultured neurons also caused an increase in levels of casein kinase 1 epsilon (CK1ε), and ubiquitinated p-TDP-43, along with a decrease in importin-β (all factors known to mediate the "TDP-43 proteinopathy"). Defective neuronal integrity, as evidenced by a reduction in levels of the NR1 subunit of the NMDA receptor, and in PSD95, along with increased levels of phosphorylated tau were also observed. Additionally, increased levels of intra- and extracellular thrombospondin-1 (TSP-1) (a factor known to regulate neuronal integrity) were observed in cultured astrocytes at early stages of trauma, while at later stages decreased levels were identified. The addition of recombinant TSP-1, conditioned media from cultured astrocytes at early stages of trauma, or the CK1ε inhibitor PF4800567 hydrochloride to traumatized cultured neurons reduced levels of p-TDP-43, and reversed the trauma-induced decline in NR1 subunit of the NMDA receptor and PSD95 levels. These findings suggest that a trauma-induced increase in TDP-43 phosphorylation contributes to defective neuronal integrity, and that increasing TSP-1 levels may represent a useful therapeutic approach for

  10. 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.

  11. 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.

  12. 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.

  13. [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.

  14. Assessing the risk of alcohol-induced dose dumping from sustained-release oral dosage forms: in vitro-in silico approach.

    Science.gov (United States)

    Cvijić, Sandra; Aleksić, Ivana; Ibrić, Svetlana; Parojčić, Jelena

    2017-10-29

    Consumption of alcoholic beverages with sustained-release oral dosage forms may pose a risk to patients due to potential alcohol-induced dose dumping (ADD). Regulatory guidances recommend in vitro dissolution testing to identify the risk of ADD, but the question remains whether currently proposed test conditions can be considered biopredictive. The purpose of this study was to evaluate different dissolution setups to assess ADD, and the potential of combined in vitro-in silico approach to predict drug absorption after concomitant alcohol intake for hydrophilic and lipophilic sustained-release tablets containing ibuprofen or diclofenac sodium. According to the obtained results, the impact of ethanol was predominantly governed by the influence on matrix integrity, with the increase in drug solubility being less significant. Hydrophilic matrix tablets were less susceptible to ADD than lipophilic matrices, although the conclusion on formulation ethanol-vulnerability depended on the employed experimental conditions. In silico predictions indicated that the observed changes in drug dissolution would not result in plasma concentrations beyond therapeutic window, but sustained-release characteristics of the formulations might be lost. Overall, the study demonstrated that in vitro-in silico approach may provide insight into the effect of ADD on drug clinical performance, and serve as a tool for ADD risk assessment.

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

    Directory of Open Access Journals (Sweden)

    Ana Cristina Soares Santos Haddad

    2009-12-01

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

  17. Barrier and operational risk analysis of hydrocarbon releases (BORA-Release). Part II: Results from a case study.

    Science.gov (United States)

    Sklet, Snorre; Vinnem, Jan Erik; Aven, Terje

    2006-09-21

    This paper presents results from a case study carried out on an offshore oil and gas production platform with the purpose to apply and test BORA-Release, a method for barrier and operational risk analysis of hydrocarbon releases. A description of the BORA-Release method is given in Part I of the paper. BORA-Release is applied to express the platform specific hydrocarbon release frequencies for three release scenarios for selected systems and activities on the platform. The case study demonstrated that the BORA-Release method is a useful tool for analysing the effect on the release frequency of safety barriers introduced to prevent hydrocarbon releases, and to study the effect on the barrier performance of platform specific conditions of technical, human, operational, and organisational risk influencing factors (RIFs). BORA-Release may also be used to analyse the effect on the release frequency of risk reducing measures.

  18. 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.

  19. 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.

  20. 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

  1. Self-carried curcumin nanoparticles for in vitro and in vivo cancer therapy with real-time monitoring of drug release

    Science.gov (United States)

    Zhang, Jinfeng; Li, Shengliang; An, Fei-Fei; Liu, Juan; Jin, Shubin; Zhang, Jin-Chao; Wang, Paul C.; Zhang, Xiaohong; Lee, Chun-Sing; Liang, Xing-Jie

    2015-08-01

    The use of different nanocarriers for delivering hydrophobic pharmaceutical agents to tumor sites has garnered major attention. Despite the merits of these nanocarriers, further studies are needed to improve their drug loading capacities (which are typically self-carried nanodrug delivery strategies without using inert carriers is highly desirable. In this study, we developed a self-carried curcumin (Cur) nanodrug for highly effective cancer therapy in vitro and in vivo with real-time monitoring of drug release. With a biocompatible C18PMH-PEG functionalization, the Cur nanoparticles (NPs) showed excellent dispersibility and outstanding stability in physiological environments with drug loading capacities >78 wt%. Both confocal microscopy and flow cytometry confirmed the cellular fluorescence ``OFF-ON'' activation and real-time monitoring of the Cur molecule release. In vitro and in vivo experiments clearly show that the therapeutic efficacy of the PEGylated Cur NPs is considerably better than that of free Cur. This self-carried strategy with real-time monitoring of drug release may open a new way for simultaneous cancer therapy and monitoring.The use of different nanocarriers for delivering hydrophobic pharmaceutical agents to tumor sites has garnered major attention. Despite the merits of these nanocarriers, further studies are needed to improve their drug loading capacities (which are typically self-carried nanodrug delivery strategies without using inert carriers is highly desirable. In this study, we developed a self-carried curcumin (Cur) nanodrug for highly effective cancer therapy in vitro and in vivo with real-time monitoring of drug release. With a biocompatible C18PMH-PEG functionalization, the Cur nanoparticles (NPs) showed excellent dispersibility and outstanding stability in physiological environments with drug loading capacities >78 wt%. Both confocal microscopy and flow cytometry confirmed the cellular fluorescence ``OFF-ON'' activation and real

  2. 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)

  3. Generic sustained release tablets of trimetazidine hydrochloride: Preparation and in vitro–in vivo correlation studies

    Directory of Open Access Journals (Sweden)

    Longmei Wang

    2016-06-01

    Full Text Available The aim of the current work was to develop generic sustained-release tablets containing 35 mg trimetazidine dihydrochloride and to establish an in vitro–in vivo correlation that could predict the bioavailability. The marketed sustained release tablet (Vastarel MR used as reference, a sustained-release matrix tablet was prepared using hydroxypropyl methylcellulose (HPMC as matrix by wet granulation and the in vitro dissolution profiles of the self-made tablets were determined in four different dissolution media (0.1 M HCl, pH 4.5 PBS, pH 6.8 PBS and water. A higher similarity between prepared tablets and Vastarel MR was established, with similarity factor (f2 ranging from 60 to 75 in the four media. The in vivo pharmacokinetics was studied in six healthy beagles. Compared with Vastarel MR, the Cmax of self-made tablets was slightly decreased, while the Tmax and MRT0–t were slightly prolonged, but with no significant difference (P > 0.05. The average of relative bioavailability (F was 102.52% based on AUC0–t. For log-transformed AUC0–t and Cmax, the upper confidence limit on the appropriate criterion is <0, indicating these two formulations were population bioequivalent. The in vivo–in vitro correlation coefficient obtained from point-to-point analysis of self-made tablets was 0.9720. In conclusion, the prepared tablets were bioequivalent to the marketed tablets, according to both the in vitro release rate and extent of absorption, and a good in vivo–in vitro correlation was established for the self-made tablets that indicated in vitro dissolution tests could be used as a surrogate for bioavailability studies.

  4. Sustained-release effervescent floating matrix tablets of baclofen: development, optimization and in vitro-in vivo evaluation in healthy human volunteers

    Directory of Open Access Journals (Sweden)

    YM Rao

    2011-07-01

    Full Text Available "n  Background and the purpose of the study: Baclofen, a centrally acting skeletal muscle relaxant, is indicated in the long-term treatment of spasticity. It is difficult to formulate baclofen sustained release dosage forms because its absorption on arrival to colon (or even before is low or nonexistent. In the present investigation efforts were made to improve the bioavailability of baclofen by increasing the residence time of the drug through sustained-release matrix tablet formulation via gastroretentive mechanism. "n  Methods: Tablets were prepared by wet granulation technique. The influence of gas generating and gel forming agents, amount of baclofen and total weight of tablet on physical properties, in vitro buoyancy, floating lag time, drug release, DSC, X-ray studies were investigated. The release mechanisms were explored and explained by applying zero order, first order, Higuchi and Korsmeyer equations. The selected formulations were subjected to stability study for the period of three months. "n  Results: For all formulations, kinetics of drug release from tablet followed Higuchi's square root of time kinetic treatment heralding diffusion as predominant mechanism of drug release. Formulations containing 20 mg and 40 mg (F-1 and F-7 showed similar release profiles. There was no significant change in the selected formulations, when subjected to accelerated stability conditions over a period of three months. X-ray imaging in six healthy human volunteers revealed a mean gastric retention period of 5.50±0.7 hrs for the selected formulation. "n  Conclusion:Stable, sustained release effervescent floating matrix tablets of baclofen could be prepared by wet granulation technique.

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

    Science.gov (United States)

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

    2014-01-01

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

  6. 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...

  7. A Three-Pulse Release Tablet for Amoxicillin: Preparation, Pharmacokinetic Study and Physiologically Based Pharmacokinetic Modeling

    Science.gov (United States)

    Li, Jin; Chai, Hongyu; Li, Yang; Chai, Xuyu; Zhao, Yan; Zhao, Yunfan; Tao, Tao; Xiang, Xiaoqiang

    2016-01-01

    Background Amoxicillin is a commonly used antibiotic which has a short half-life in human. The frequent administration of amoxicillin is often required to keep the plasma drug level in an effective range. The short dosing interval of amoxicillin could also cause some side effects and drug resistance, and impair its therapeutic efficacy and patients’ compliance. Therefore, a three-pulse release tablet of amoxicillin is desired to generate sustained release in vivo, and thus to avoid the above mentioned disadvantages. Methods The pulsatile release tablet consists of three pulsatile components: one immediate-release granule and two delayed release pellets, all containing amoxicillin. The preparation of a pulsatile release tablet of amoxicillin mainly includes wet granulation craft, extrusion/spheronization craft, pellet coating craft, mixing craft, tablet compression craft and film coating craft. Box–Behnken design, Scanning Electron Microscope and in vitro drug release test were used to help the optimization of formulations. A crossover pharmacokinetic study was performed to compare the pharmacokinetic profile of our in-house pulsatile tablet with that of commercial immediate release tablet. The pharmacokinetic profile of this pulse formulation was simulated by physiologically based pharmacokinetic (PBPK) model with the help of Simcyp®. Results and Discussion Single factor experiments identify four important factors of the formulation, namely, coating weight of Eudragit L30 D-55 (X1), coating weight of AQOAT AS-HF (X2), the extrusion screen aperture (X3) and compression forces (X4). The interrelations of the four factors were uncovered by a Box–Behnken design to help to determine the optimal formulation. The immediate-release granule, two delayed release pellets, together with other excipients, namely, Avicel PH 102, colloidal silicon dioxide, polyplasdone and magnesium stearate were mixed, and compressed into tablets, which was subsequently coated with Opadry

  8. A Three-Pulse Release Tablet for Amoxicillin: Preparation, Pharmacokinetic Study and Physiologically Based Pharmacokinetic Modeling.

    Science.gov (United States)

    Li, Jin; Chai, Hongyu; Li, Yang; Chai, Xuyu; Zhao, Yan; Zhao, Yunfan; Tao, Tao; Xiang, Xiaoqiang

    2016-01-01

    Amoxicillin is a commonly used antibiotic which has a short half-life in human. The frequent administration of amoxicillin is often required to keep the plasma drug level in an effective range. The short dosing interval of amoxicillin could also cause some side effects and drug resistance, and impair its therapeutic efficacy and patients' compliance. Therefore, a three-pulse release tablet of amoxicillin is desired to generate sustained release in vivo, and thus to avoid the above mentioned disadvantages. The pulsatile release tablet consists of three pulsatile components: one immediate-release granule and two delayed release pellets, all containing amoxicillin. The preparation of a pulsatile release tablet of amoxicillin mainly includes wet granulation craft, extrusion/spheronization craft, pellet coating craft, mixing craft, tablet compression craft and film coating craft. Box-Behnken design, Scanning Electron Microscope and in vitro drug release test were used to help the optimization of formulations. A crossover pharmacokinetic study was performed to compare the pharmacokinetic profile of our in-house pulsatile tablet with that of commercial immediate release tablet. The pharmacokinetic profile of this pulse formulation was simulated by physiologically based pharmacokinetic (PBPK) model with the help of Simcyp®. Single factor experiments identify four important factors of the formulation, namely, coating weight of Eudragit L30 D-55 (X1), coating weight of AQOAT AS-HF (X2), the extrusion screen aperture (X3) and compression forces (X4). The interrelations of the four factors were uncovered by a Box-Behnken design to help to determine the optimal formulation. The immediate-release granule, two delayed release pellets, together with other excipients, namely, Avicel PH 102, colloidal silicon dioxide, polyplasdone and magnesium stearate were mixed, and compressed into tablets, which was subsequently coated with Opadry® film to produce pulsatile tablet of

  9. 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 ...

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

    Directory of Open Access Journals (Sweden)

    John Rojas

    2011-09-01

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

  11. Release and deployment at Planon: a case study

    NARCIS (Netherlands)

    R.L. Jansen (Remy); G.C. Ballintijn (Gerco); S. Brinkkemper

    2005-01-01

    textabstractThis case study report describes the research results of a case study at Planon into the processes of development, release, and deployment. The research was done to document the release and deployment processes at Planon, to uncover strengths and weaknesses in these processes, and to

  12. Release and Deployment at Planon: A Case Study

    NARCIS (Netherlands)

    Jansen, S.R.L.; Ballintijn, G.; Brinkkemper, S.

    2005-01-01

    This case study report describes the research results of a case study at Planon into the processes of development, release, and deployment. The research was done to document the release and deployment processes at Planon, to uncover strengths and weaknesses in these processes, and to compare

  13. Comparative study of some mechanical and release properties of ...

    African Journals Online (AJOL)

    The mechanical and release properties of paracetamol tablets formulated with cashew gum (CAG), povidone (PVP) and gelatin (GEL) as binders were studied and compared. The parameters studied were tensile strength (TS), brittle fracture index (BFI), friability (F), disintegration time (DT) and percentage drug released ...

  14. 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

  15. A comparative study between release analysis and column flotation

    Energy Technology Data Exchange (ETDEWEB)

    Jorge Pineres; Juan Barraza [Universidad del Valle, Cali (Colombia)

    2007-07-01

    This paper shows the results of a comparative study between release analysis and column flotation of three Colombian coals: Guachinte (South West), Cerrejon (North) and Nech (Midlands). Analysis release was used in order to evaluate the coal potential cleaning in terms of both low ash and high organic recovery of froth. Results from release analysis were compared with those from a column flotation and showed that the froth from Nechi coal had the highest recovery and the lowest ash, followed by Cerrejon and then by Guachinte. Results of release analysis were in agreement with the column flotation. 10 refs., 4 figs., 1 tab.

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

    Science.gov (United States)

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

    2017-11-01

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

  17. [Study on preparation and release mechanism of effervescent osmotic pump tablet of compound Danshen].

    Science.gov (United States)

    Xue, Li'an; Li, Yuanbo; Guo, Dandan; Yin, Jianhua; Liu, Yanchun; Hou, Shixiang

    2009-04-01

    To prepare effervescent osmotic pump tablet (EOPTs) according to the rhythm of coronary heart disease based on efficacy material and the mechanism of compound Danshen and to study the mechanism of drug released of that tablets. Since compound Danshen consist of compounds with polyphenolic groups or carboxyl groups, such as phenolic acids, flavonoids, and triterpenoids that they were acidic. EOPTs were prepared from tablet cores which containing NaHCO3 as effervescent, NaCL and manitol as osmotic agents, HPMC as retarding agents coating with CA membrane. And study the mechanism of drug released according to the change of tablet osmotic pressure. The results of in vitro experiments showed that no difference was observed among the profiles of Danshensu, protocatechuic aldehyde, ginsenoside Rg1, Rb1, notoginsenoside R1 release EOPTs. The drug was completely released from the device with a zero-order release rate over 12 h. EOPTs are Successfully obtained EOPT which the drug is released from the device over 12 h and the release mechanism of EOPTs is explained.

  18. 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.

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    Feng S

    2017-06-01

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

  1. beta-Endorphin release by angiotensin II: studies on the mechanism of action.

    Science.gov (United States)

    Anhut, H; Knepel, W; Holland, A; Meyer, D K

    1982-07-01

    Blood-borne angiotensin II induces release of beta-endorphin-like immunoreactivity (beta-EI) from rat anterior pituitary gland. To study the mechanism of action we investigated in rats the effect of transection of subfornical organ efferent projections on angiotensin-induced beta-EI release in vivo and also the direct action of angiotensin II on beta-EI release from isolated adenohypophyses in vitro. (i) No effect of transection of subfornical organ efferents on the increase in plasma beta-EI following intravenous infusions of angiotensin II was found. (ii) When anterior pituitary quarters were continuously superfused in vitro, angiotensin II (1-10 nM) caused release of beta-EI into the superfusion medium in a dose-dependent manner. The stimulatory effect of angiotensin II (3 nM) was blocked by the receptor antagonist saralasin (300 nM). We conclude that beta-endorphin release by blood-borne angiotensin II, in contrast to other central effects of angiotensin, is not mediated by the subfornical organ; instead a direct action of angiotensin II on the adenohypophysis could be a mechanism of action responsible.

  2. Effect of processing on polyamine content and bioactive peptides released after in vitro gastrointestinal digestion of infant formulas.

    Science.gov (United States)

    Gómez-Gallego, C; Recio, I; Gómez-Gómez, V; Ortuño, I; Bernal, M J; Ros, G; Periago, M J

    2016-02-01

    This study examined the influence of processing on polyamines and peptide release after the digestion of a commercial infant formula designed for children during the first months of life. Polyamine oxidase activity was not suppressed during the manufacturing process, which implicates that polyamine concentrations were reduced over time and during infant formula self-life. In gel electrophoresis, in vitro gastrointestinal digestion of samples with reduced amount of enzymes and time of digestion shows an increase in protein digestibility, reflected in the increase in nonprotein nitrogen after digestion and the disappearance of β-lactoglobulin and α-lactalbumin bands in gel electrophoresis. Depending on the sample, between 22 and 87 peptides were identified after gastrointestinal digestion. A peptide from β-casein f(98-105) with the sequence VKEAMAPK and antioxidant activity appeared in all of the samples. Other peptides with antioxidant, immunomodulatory, and antimicrobial activities were frequently found, which could have an effect on infant health. The present study confirms that the infant formula manufacturing process determines the polyamine content and peptidic profile after digestion of the infant formula. Because compositional dissimilarity between human milk and infant formula in polyamines and proteins could be responsible for some of the differences in health reported between breast-fed and formula-fed children, these changes must be taken into consideration because they may have a great effect on infant nutrition and development. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  3. Sustained release of complexed DNA from films: Study of bioactivity and intracellular tracking.

    Science.gov (United States)

    Mondal, Debasish; Ramgopal, Yamini; Tiwari, Sandeep Kumar; Venkatraman, Subbu S

    2010-09-01

    Sustained DNA delivery from polymeric films provides a means for localized and prolonged gene therapy. However, in the case of bioactive molecules such as plasmid DNA (pDNA), there are limitations on the achievable release profiles as well as on the maintenance of bioactivity over time. In this report, the authors have investigated the bioactivity of the released DNA (naked and complexed with lipofectamine) from polymeric films using in vitro cell transfection of COS-7 cell lines. The polymeric system consists of a biodegradable semicrystalline polymer such as poly(ε-caprolactone) (PCL) with or without blended gelatin. Sustained release of lipoplexes and of pDNA is shown over several days. However, lipoplexes released from pure PCL films show no transfection on day 18, whereas lipoplexes released from PCL-gelatin films continue to transfect cells on day 18 of release. Confocal studies were used to determine the reasons for this difference in transfection efficiency, and it is proposed that association of the lipoplex with gelatin confers protection from degradation in the cytoplasm. The results also showed that the bioactivity of released lipoplexes was superior to that of the naked pDNA. For both naked pDNA and the lipoplexes, the presence of gelatin helped to maintain the bioactivity over several days.

  4. A study on the release mechanism of drugs from hydrophilic partially coated perforated matrices.

    Science.gov (United States)

    Sangalli, Maria Edvige; Maroni, Alessandra; Zema, Lucia; Cerea, Matteo; Conte, Ubaldo; Gazzaniga, Andrea

    2003-09-01

    Partially coated perforated systems (PCPS) based on low-viscosity hydroxypropyl methylcellulose (HPMC) as the polymeric material were formerly designed, prepared and evaluated in terms of in vitro behaviour. These systems proved to afford the pursued linear release with model drugs (metoprolol tartrate and benfluorex) of different solubility. To the aim of exploring the mechanisms concurring in the definition of zero-order kinetics, studies of drug release, polymer dissolution and medium penetration were performed on PCPS and constant release area systems (CRAS). According to the obtained results, PCPS release kinetics has to be mainly attributed to the progressive outward erosion of the core and to the related variation of the release area. The special geometry of the system, in fact, involves a gradual increase in the release surface, which allows the diffusional path lengthening to be offset. By properly selecting the shape and dimensions of the device as well as the physico-chemical characteristics of the hydrophilic polymer, the advantage of a zero-order release kinetics with programmable rate can be achieved.

  5. 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.

  6. 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.

  7. Estonian and Russian Federation amoxicillin formulations: a comparative study of in vitro dissolution.

    Science.gov (United States)

    Bronnikova, O; Matto, V; Meos, A

    2008-06-01

    The in vitro dissolution properties were compared for four different formulations from the Estonian drug market and four from the Russian Federation drug market. Seven of the eight formulations tested released at least 75% or 80% amoxicillin during 30- or 90-min dissolution tests (37 degrees C, purified water, 75 rpm), respectively. One marketed Russian Federation formulation released 74% amoxicillin over a 90-min period. The present study shows that, in general, the in vitro dissolution properties of the Russian Federation amoxicillin formulations are, with some minor exceptions, comparable to those of the Estonian formulations. Copyright 2008 Prous Science, S.A.U. or its licensors. All rights reserved.

  8. 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.

  9. 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.

  10. Effect of Plasticizer Type on Tensile Property and In Vitro Indomethacin Release of Thin Films Based on Low-Methoxyl Pectin

    Directory of Open Access Journals (Sweden)

    Pensak Jantrawut

    2017-07-01

    Full Text Available This study developed the interests of low-methoxyl pectin (LMP together with plasticizers for the preparation of elastic thin films. The effect of different plasticizer types (glycerol: Gly; sorbitol: Sor; propylene glycol: PG; and polyethylene glycol 300: PEG 300 and concentrations (20–40% w/w on mechanical and thermal properties of LMP films as well as on in vitro release of indomethacin were evaluated. Without any plasticizer, a brittle LMP film with low tensile strength and % elongation at break was obtained. Addition of plasticizers from 20% to 40% caused reduction in the tensile strength and Young’s modulus values, whereas percent elongation was increased. Forty percent Gly-plasticized and PG-plasticized films were selected to deliver indomethacin in comparison with non-plasticized film. No significant difference in indomethacin release profiles was displayed between the films. The analysis of indomethacin release model indicated that more than one drug release mechanism from the film formulation was involved and possibly the combination of both diffusion and erosion. Even though indomethacin incorporated in non-plasticized film showed similar release profile, Gly or PG should be added to enhanced film flexibility and decrease film brittleness.

  11. Effects of surface friction treatment on the in vitro release of constituent metals from the biomedical Co–29Cr–6Mo–0.16N alloy

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xiaoyu [Graduate School of Engineering, Tohoku University, Sendai 980-8577 (Japan); Li, Yunping, E-mail: lyping@csu.edu.cn [State Key Lab for Powder Metallurgy, Central South University, Changsha 410083 (China); School of Materials Science and Engineering, Central South University, Changsha (China); Hou, Yuhang [Graduate School of Engineering, Tohoku University, Sendai 980-8577 (Japan); Bian, Huakang; Koizumi, Yuichiro; Chiba, Akihiko [Institute for Materials Research, Tohoku University, Sendai 980-8577 (Japan)

    2016-07-01

    Due to the ignorance by many researchers on the influence of starting microstructure on the metal release of biomedical materials in human body after implant, in this study, the effect of surface friction treatment on the in vitro release of the constituent elements of the biomedical Co–29Cr–6Mo–0.16N (CCM) alloy is investigated for the first time by immersion test in lactic acid solution combined with electron backscatter diffraction, transmission electron microscope, X-ray diffraction, X-ray photoelectron spectroscopy, and inductively coupled plasma atomic emission spectroscopy (ICP-EOS). The results indicate that friction treatment on the as-annealed CCM alloy sample surface leads to a planar strain-induced martensitic transformation (SIMT) on sample surface; this greatly accelerates the release of all the constituent elements and, in particular, that of Co as indicated by the ICP-EOS analysis. This increase can be ascribed to a localized deformation that occurred over the entire sample surface, with the dislocation density being high within the SIMTed phase and low in the alloy matrix. - Highlights: • Immersion test of biomedical CCM alloy in lactic acid solution was conducted. • Surface friction on CCM alloy leads to martensitic transformation. • The friction treatment accelerated the release of all the elements especially Co. • Localized deformation accounts for the accelerated release of elements.

  12. 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.

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

    Science.gov (United States)

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

    2014-12-10

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

  14. 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.

  15. 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.

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

    Science.gov (United States)

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

    2008-12-01

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

  17. 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.

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

    Science.gov (United States)

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

    2008-03-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2015-04-01

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

  1. 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

  2. A comparative study of fluoride release from two different sealants.

    Science.gov (United States)

    Ananda, Shimoga-Raju; Mythri, Halappa

    2014-12-01

    The introduction of fluoride releasing sealants and glass ionomer cements as fissure sealants adds another dimension to prevention of pit and fissure caries. The ability of resin sealants and glass ionomer cements to release fluoride on a long term basis to the sealed enamel and the adjacent unsealed pit and fissure and cuspal incline enamel may allow for further reduction in pit and fissure caries experience for children. Hence, the study was conducted to compare the amount of fluoride release in the plaque after placing fluoride releasing pit and fissure sealants and glass ionomer fissure sealants used in Atraumatic Restorative Treatment (ART) approach. To compare the fluoride release of both the materials at the different time intervals. A total of 60 school going children were included in this study. Before application of the sealants, baseline plaque fluoride levels were estimated from all the study subjects. After application of sealants again the same was estimated at an interval of 24 hour, 9 days, 2 weeks and 4 weeks. The peak plaque fluoride levels were achieved at 24 hours after application of fissure sealants in all the groups. Within the limitation of the study, the present study indicated that fluoride releasing fissure sealants may act as a source of fluoride in plaque which will help in preventing pit and fissure and smooth surface caries in the tooth sealed with fissure sealants. Key words:Plaque fluoride, pit and fissures sealants, dental caries.

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

    Science.gov (United States)

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

    2016-12-01

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

  4. Solid lipid particles for oral delivery of peptide and protein drugs III - the effect of fed state conditions on the in vitro release and degradation of desmopressin

    DEFF Research Database (Denmark)

    Christophersen, Philip C; Vaghela, Dimple; Müllertz, Anette

    2014-01-01

    The effect of food intake on the release and degradation of peptide drugs from solid lipid particles is unknown and was therefore investigated in vitro using different fed state media in a lipolysis model. Desmopressin was used as a model peptide and incorporated into solid lipid particles...... and the protease or desmopressin. Addition of a medium chain triglyceride, trilaurin, in combination with drug-loaded lipid particles diminished the food effect on the TG18 particles, and trilaurin is therefore proposed to be a suitable excipient for reduction of the food effect. Overall, the present study shows...... that strategies to reduce food effect, such as adding trilaurin, for lipid particle formulations should be considered as drug release from such formulations might be influenced by the presence of food in the gastrointestinal tract....

  5. The Effect in Vitro of Ionizing Irradiation and Small Rises in Temperature on the Uptake and Release of Labelled Lipids by the Human Erythrocyte Membrane

    DEFF Research Database (Denmark)

    Hansen, Heinz Johs. Max; Karle, H.; Stender, S.

    1978-01-01

    1. The effect of X-irradiation (50 000 rad) and an increase in temperature from 37 to 42° C on the synthesis, uptake and release of labelled lipids by erythrocytes was studied in plasma incubations in vitro. 2. Both irradiation and a rise in temperature resulted in an enhanced synthesis of [32P......]phosphatidic acid in the erythrocytes. 3. The uptake by the erythrocytes of 14C- and 3H-labelled cholesterol, [14C, 32P]phosphatidylethanolamine and [14C, 32P]phosphatidylcholine from plasma lipoproteins was increased by a rise in temperature but not by irradiation. These labelled lipids were apparently taken up...... in the ratio in which they were found in plasma. They were not released from the erythrocytes in the same manner....

  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. Preparation and in vitro-in vivo evaluation of none gastric resident dipyridamole (DIP) sustained-release pellets with enhanced bioavailability.

    Science.gov (United States)

    Xu, Lishuang; Luo, Yanfei; Feng, Jia; Xu, Ming; Tao, Xiaoguang; He, Haibing; Tang, Xing

    2012-01-17

    The objective of this study was to develop none gastric resident sustained-release pellets loaded with dipyridamole with a high bioavailability. Two different kinds of core pellets, one containing citric acid as a pH-modifier (CAP) and, the other without pH-modifier (NCAP) were prepared by extrusion-spheronization and then coated with mixtures of enteric soluble and insoluble polymers (referred to as CAP(1) and NCAP(1)) or insoluble polymer alone (referred to as CAP(2) and NCAP(2)). The relative bioavailability of the sustained-release pellets was studied in fasted beagle dogs after oral administration using a commercially available immediate release tablet (IRT) as a reference. The in vitro release, in vivo absorption and in vitro-in vivo correlation were also evaluated. Results revealed that the plasma drug concentrations after administration of CAP(2), NCAP(1) and NCAP(2) were undetectable, indicating that the drug release was almost zero from the preparations throughout the gastro-intestinal tract. The C(max), T(max) and AUC((0→24)) of CAP(1) were 0.78 ± 0.23 (μg/ml), 3.80 ± 0.30 (h), and 6.74 ± 0.47 (μg/mlh), respectively. While the corresponding values were 2.23 ± 0.32 (μg/ml), 3.00 ± 0.44 (h) and 9.42 ± 0.69 (μg/mlh) for IRT. The relative bioavailability of CAP(1) was 71.55% compared with IRT. By combined incorporation of a pH-modifier into the core of pellets to modify the inner micro-environment and employing mixtures of enteric soluble and insoluble polymers as a retarding layer, drugs with high solubility in stomach and limited solubility in small intestine, such as DIP, could be successfully formulated as sustained release preparations with no pH-dependence in drug release and enhanced bioavailability. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. 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.

  9. A comparative study of fluoride release from two different sealants

    OpenAIRE

    Ananda, SR.; H Mythri

    2014-01-01

    Objectives: The introduction of fluoride releasing sealants and glass ionomer cements as fissure sealants adds another dimension to prevention of pit and fissure caries. The ability of resin sealants and glass ionomer cements to release fluoride on a long term basis to the sealed enamel and the adjacent unsealed pit and fissure and cuspal in - cline enamel may allow for further reduction in pit and fissure caries experience for children. Hence, the study was conducted to compar...

  10. A comparative study of fluoride release from two different sealants

    OpenAIRE

    Ananda, Shimoga-Raju; Mythri, Halappa

    2014-01-01

    Objectives: The introduction of fluoride releasing sealants and glass ionomer cements as fissure sealants adds another dimension to prevention of pit and fissure caries. The ability of resin sealants and glass ionomer cements to release fluoride on a long term basis to the sealed enamel and the adjacent unsealed pit and fissure and cuspal incline enamel may allow for further reduction in pit and fissure caries experience for children. Hence, the study was conducted to compare the amount of fl...

  11. Wrist immobilization after carpal tunnel release: a prospective study

    OpenAIRE

    Martins Roberto S.; Siqueira Mario G.; Simplício Hougelli

    2006-01-01

    This prospective study evaluates the possible advantages of wrist imobilization after open carpal tunnel release comparing the results of two weeks immobilization and no immobilization. Fifty two patients with idiopathic carpal tunnel syndrome were randomly selected in two groups after open carpal tunnel release. In one group (A, n=26) the patients wore a neutral-position wrist splint continuosly for two weeks. In the other group (B, n=26) no wrist immobilization was used. Clinical assessment...

  12. 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.

  13. Tunable release of clavam from clavam stabilized gold nanoparticles — Design, characterization and antimicrobial study

    Energy Technology Data Exchange (ETDEWEB)

    Manju, V. [Electrodics and Electrocatalysis Division, CSIR-Central Electrochemical Research Institute, Karaikudi, Tamilnadu 630006 (India); Dhandapani, P. [Corrosion Materials and Protection Division, CSIR-Central Electrochemical Research Institute, Karaikudi, Tamilnadu, 630006 (India); Gurusamy Neelavannan, M. [Characterization and Measurement lab, CSIR-Central Electrochemical Research Institute, Karaikudi, Tamilnadu 630006 (India); Maruthamuthu, S. [Corrosion Materials and Protection Division, CSIR-Central Electrochemical Research Institute, Karaikudi, Tamilnadu, 630006 (India); Berchmans, S. [Electrodics and Electrocatalysis Division, CSIR-Central Electrochemical Research Institute, Karaikudi, Tamilnadu 630006 (India); Palaniappan, A., E-mail: palani112@gmail.com [Electrodics and Electrocatalysis Division, CSIR-Central Electrochemical Research Institute, Karaikudi, Tamilnadu 630006 (India)

    2015-04-01

    A facile one-step approach is developed to synthesize highly stable (up to 6 months) gold nanoparticles (GNPs) using Clavam, pharmaceutical form of amoxicillin which contains a mixture of amoxicillin and potassium salt of clavulanic acid, at room temperature (25–30 °C). The clavam stabilized GNPs are characterized using various techniques including UV–Visible, FT-IR spectrophotometry and transmission electron microscopy (TEM). Tunable release of clavam from clavam stabilized GNPs is demonstrated using intracellular concentrations of glutathione (GSH). The process is monitored using an UV–Vis spectroscopy and the amount of clavam released in terms of amoxicillin concentration is quantitatively estimated using reverse phase high performance liquid chromatographic (RP-HPLC) technique. In vitro study reveals that the clavam released from GNPs' surface was found to show a significant enhancement in antibacterial activity against Escherichia coli and the cause of enhancement is addressed. - Graphical abstract: Stable and nearly monodisperse gold nanoparticles (GNPs) are prepared at room temperature (~ 25–30 °C) using clavam; commercial form of amoxicillin antibiotic. Tunable release of clavam from clavam stabilized GNPs is demonstrated by the addition of varying concentrations of glutathione. Interactions between clavam and gold core are investigated in detail. The mechanism of enhanced antimicrobial activity of clavam released from clavam stabilized GNPs is probed. - Highlights: • Gold nanoparticles (GNPs) are prepared without reducing agent using antibiotic clavam{sup TR}. • Our work shed lights on the nature of interaction between the clavam and GNPs. • Sustained release of clavam from clavam stabilized GNPs is demonstrated using glutathione. • Antimicrobial activity of the released clavam is confirmed using various techniques. • Our study suggests that the clavam released from GNPs shows better inhibition of E. coli.

  14. 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.

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

    Directory of Open Access Journals (Sweden)

    Amit Kumar Nayak

    2013-01-01

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

  16. Development of in vitro-in vivo correlation for extended-release niacin after administration of hypromellose-based matrix formulations to healthy volunteers.

    Science.gov (United States)

    Kesisoglou, Filippos; Rossenu, Stefaan; Farrell, Colm; Van Den Heuvel, Michiel; Prohn, Marita; Fitzpatrick, Shaun; De Kam, Pieter-Jan; Vargo, Ryan

    2014-11-01

    Development of in vitro-in vivo correlations (IVIVCs) for extended-release (ER) products is commonly pursued during pharmaceutical development to increase product understanding, set release specifications, and support biowaivers. This manuscript details the development of Level C and Level A IVIVCs for ER formulations of niacin, a highly variable and extensively metabolized compound. Three ER formulations were screened in a cross-over study against immediate-release niacin. A Multiple Level C IVIVC was established for both niacin and its primary metabolite nicotinuric acid (NUA) as well as total niacin metabolites urinary excretion. For NUA, but not for niacin, Level A IVIVC models with acceptable prediction errors were achievable via a modified IVIVC rather than a traditional deconvolution/convolution approach. Hence, this is in contradiction with current regulatory guidelines that suggest that when a Multiple Level C IVIVC is established, Level A models should also be readily achievable. We demonstrate that for a highly variable, highly metabolized compound such as niacin, development of a Level A IVIVC model fully validated according to agency guidelines may be challenging. However, Multiple Level C models are achievable and could be used to guide release specifications and formulation/manufacturing changes. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  17. 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.

  18. Feasibility study of cavitation-induced liposomal doxorubicin release in an AT2 Dunning rat tumor model.

    Science.gov (United States)

    Lafon, Cyril; Somaglino, Lucie; Bouchoux, Guillaume; Mari, Jean Martial; Chesnais, Sabrina; Ngo, Jacqueline; Mestas, Jean-Louis; Fossheim, Sigrid L; Nilssen, Esben A; Chapelon, Jean-Yves

    2012-09-01

    Targeted and triggered release of liposomal drug using heat or ultrasound represents a promising treatment modality able to increase the therapeutic-totoxicity ratio of encapsulated drugs. To study the ability for high-intensity focused ultrasound to induce liposomal drug release mainly by focused inertial cavitation in vitro and in an animal model. A 1 MHz ultrasound setup has been developed for in vitro and in vivo drug release from a specific liposomal doxorubicin formulation at a target cavitation dose. Controlled cavitation at 1 MHz was applied within the tumors 48 hours after liposome injection according to preliminary pharmacokinetic study. A small non-significant therapeutic effect of US-liposomal treatment was observed compared to liposomes alone suggesting no beneficial effect of ultrasound in the current setup. The in vitro study provided a suitable ultrasound setup for delivering a cavitation dose appropriate for safe liposomal drug release. However, when converting to an in vivo model, no therapeutic benefit was observed. This may be due to a number of reasons, one of which may be the difficulty in converting in vitro findings to an in vivo model. In light of these findings, we discuss important design features for future studies.

  19. In vitro toxicology studies of extracellular vesicles.

    Science.gov (United States)

    Maji, Sayantan; Yan, Irene K; Parasramka, Mansi; Mohankumar, Swathi; Matsuda, Akiko; Patel, Tushar

    2017-03-01

    Extracellular vesicles (EVs) are membrane-bound vesicles released from cells into the extracellular environment. There is emerging interest in the use of EVs as potential therapeutic interventions. We sought to evaluate the safety of EVs that may be therapeutically used by performing in vitro toxicological assessments. EVs were obtained from mesenchymal stem cells (MSC-EV) or from bovine milk (BM-EV) by differential ultracentrifugation, and quantitated using nanoparticle tracking analysis. Genotoxic effects, hematological effects, immunological effects and endotoxin production were evaluated at two dose levels. Neither MSC-EVs nor BM-EVs elicited detectable genotoxic effects using either the alkaline comet assay or micronucleus assay. Hemolysis was observed with BM-EVs but not with MSC-EVs. MSC-EVs did not have any significant effect on either spontaneous or collagen-induced platelet aggregation. In contrast, BM-EVs were noted to increase collagen-induced platelet aggregation, even though no spontaneous increase in platelet aggregation was noted. Both types of EVs induced leukocyte proliferation, which was greater with BM-EV. Neither MSC-EVs nor BM-EVs induced HL-60 phagocytosis, although BM-EVs decreased zymosan-induced phagocytosis. Furthermore, neither MSC-EVs nor BM-EVs induced nitric oxide production. Unlike MSC-EVs, BM-EVs tested positive for endotoxin and induced complement activation. There are significant differences in toxicological profiles between MSC-EVs and BM-EVs that may reflect variations in techniques for EV isolation, EV content or cross-species differences. The safety of MSC-EV supports their use for disease therapeutics, whereas detailed safety and toxicological assessment will be necessary before the use of BM-EVs. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  20. In vitro metabolism and permeation studies in rat jejunum

    DEFF Research Database (Denmark)

    Gammelgaard, B; Jensen, K; Steffansen, B

    1999-01-01

    The purpose of these studies was to compare the in vitro absorption of two inorganic chromium(III) compounds: chromium chloride and chromium nitrate, with organic chromium(III)-picolinate; and to investigate if any in vitro metabolism of chromium(VI) takes place. The in vitro metabolism studies...

  1. In vitro fluoride release from a different kind of conventional and resin modified glass-ionomer cements.

    Science.gov (United States)

    Selimović-Dragaš, Mediha; Hasić-Branković, Lajla; Korać, Fehim; Đapo, Nermin; Huseinbegović, Amina; Kobašlija, Sedin; Lekić, Meliha; Hatibović-Kofman, Šahza

    2013-08-01

    Fluoride release is important characteristic of glass-ionomer cements. Quantity of fluoride ions released from the glass-ionomer cements has major importance in definition of their biological activity. The objectives of this study were to define the quantity of fluoride ions released from the experimental glass-ionomer cements and to define the effect of fluoride ions released from the experimental glass-ionomer cements on their cytotoxicity. Concentrations of the fluoride ions released in the evaluated glass-ionomer cements were measured indirectly, by the fluoride-selective WTW, F500 electrode potential, combined with reference R503/D electrode. Statistical analyses of F-ion concentrations released by all glass-ionomers evaluated at two time points, after 8 and after 24 hours, show statistically higher fluoride releases from RMGICs: Vitrebond, Fuji II LC and Fuji Plus, when compared to conventional glass-ionomer cements: Fuji Triage, Fuji IX GP Fast and Ketac Silver, both after 8 and after 24 hours. Correlation coefficient between concentrations of fluoride ion released by evaluated glass-ionomer cements and cytotoxic response of UMR-106 osteoblast cell-line are relatively high, but do not reach levels of biological significance. Correlation between concentrations of fluoride ion released and cytotoxic response of NIH3T3 mouse fibroblast cell line after 8 hours is high, positive and statistically significant for conventional GICs, Fuji Triage and Fuji IX GP Fast, and RMGIC, Fuji II LC. Statistically significant Correlation coefficient between concentrations of fluoride ion released and cytotoxic response of NIH3T3 cell line after 24 hours is defined for RMGIC Fuji II LC only.

  2. 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.

  3. 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.

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

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    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®.

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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.

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

    Science.gov (United States)

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

    2012-09-28

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

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

    Science.gov (United States)

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

    2013-03-01

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

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

    Science.gov (United States)

    Lamprecht, Guenther

    2009-10-01

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

  13. 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.

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

    Science.gov (United States)

    1989-10-31

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

  15. Optimization of in vitro and ex vitro regeneration and micromorphological studies in Basella alba L.

    Science.gov (United States)

    Shekhawat, Mahipal S; Manokari, M

    2016-10-01

    The optimum concentrations of the plant hormones for in vitro regeneration and subsequent effect of auxins on rooting (in vitro and ex vitro) of shoots of Basella alba L. have been investigated in present study. Nodal shoot segments were used as explants to initiate the cultures. The bud breaking from explants was observed within 1 week of incubation on agar gelled Murashige and Skoog's (MS) medium. Multiple axillary shoots (7.30 ± 0.56 shoots per explant) were induced on MS medium supplemented with 2.0 mg/L 6-benzylaminopurine (BAP). The shoots were multiplied (maximum 17.10 ± 0.44 shoots per explant) on the same medium fortified with 0.5 mg/L each of BAP and Kin (Kinetin) +0.1 mg/L IAA. These shoots were excised and rooted in vitro (10.73 ± 0.92 roots per shoot) on half-strength MS medium augmented with 2.0 mg/L indole-3 butyric acid (IBA). Hundred percentage success rates have been achieved by ex vitro rooting of the in vitro regenerated shoots with IBA at 300 mg/L. The in vitro and ex vitro rooted shoots were acclimatized in greenhouse and subsequently transferred to the natural field conditions where 100 % survival rate was reported. The ex vitro rooting method was found more advantageous than in vitro rooting in terms of time, energy and survival percentage of B. alba. A comparative foliar micromorphological study of B. alba was conducted to understand the micromorphological changes in plants while shifting from in vitro to the in vivo conditions in terms of variations in stomatal index, venation pattern and vein density, and the arrangement of crystals. The study could help in understanding the response of in vitro raised plants towards in vivo environment.

  16. Mesenchymal stem cells modulate release of matrix proteins from tendon surfaces in vitro: a potential beneficial therapeutic effect.

    Science.gov (United States)

    Garvican, Elaine R; Dudhia, Jayesh; Alves, Ana-Liz; Clements, Lucy E; Plessis, Francois Du; Smith, Roger K W

    2014-05-01

    Injury of tendons contained within a synovial environment, such as joint, bursa or tendon sheath, frequently fails to heal and releases matrix proteins into the synovial fluid, driving inflammation. This study investigated the effectiveness of cells to seal tendon surfaces and provoke matrix synthesis as a possible effective injectable therapy. Equine flexor tendon explants were cultured overnight in suspensions of bone marrow and synovium-derived mesenchymal stems cells and, as controls, two sources of fibroblasts, derived from tendon and skin, which adhered to the explants. Release of the most abundant tendon extracellular matrix proteins into the media was assayed, along with specific matrix proteins synthesis by real-time PCR. Release of extracellular matrix proteins was influenced by the coating cell type. Fibroblasts from skin and tendon appeared less capable of preventing the release of matrix proteins than mesenchymal stems cells. The source of cell is an important consideration for cell therapy.

  17. In-vitro release pharmacokinetics of amikacin, teicoplanin and polyhexanide in a platelet rich fibrin-layer (PRF-a laboratory evaluation of a modern, autologous wound treatment.

    Directory of Open Access Journals (Sweden)

    Daniela Knafl

    Full Text Available Platelet rich fibrin (PRF is an autologous fibrin glue, produced from patients' blood, which, besides intraoperative use, has applications in the treatment of infected wounds. The combination with antimicrobial agents results in a prolonged antibacterial effect allowing for wound dressing change intervals of seven days even in infected wounds. The aim of this study was to evaluate release kinetics of amikacin, teicoplanin or polyhexanide from a PRF-layer.PRF mixed with teicoplanin, amikacin or polyhexanide was sprayed on a silicon gauze patch and put on a colombia agar with bacteria with known minimal inhibitory concentration (MIC and incubated for 24 hours and afterwards transferred to another agar with the same bacterial strain. Inhibition zones were measured every 24 hours. This was repeated on 7 consecutive days. Antibiotic concentrations were calculated by interpolation.More than 1000 mg/L teicoplanin were released within the first 24 hours and 28.22 mg/L after 168 hours. Amikacin release was above 10,000 mg/L within the first 24 hours and still 120.8 mg/L after 120 hours. A release of polyhexanide could be verified for the first 24 hours only. Consequently teicoplanin and amikacin released from PRF showed antimicrobial in-vitro effects for almost a week, whereas an antimicrobial effect of polyhexanide could only be verified for the first 24 hours.Our Results show that a weekly dressing regimen may be justified in wounds treated with PRF plus amikacin or teicoplanin, since bacteria will be eradicated over a considerable period of time after a single application of PRF.

  18. In-vitro release pharmacokinetics of amikacin, teicoplanin and polyhexanide in a platelet rich fibrin-layer (PRF)-a laboratory evaluation of a modern, autologous wound treatment.

    Science.gov (United States)

    Knafl, Daniela; Thalhammer, Florian; Vossen, Matthias G

    2017-01-01

    Platelet rich fibrin (PRF) is an autologous fibrin glue, produced from patients' blood, which, besides intraoperative use, has applications in the treatment of infected wounds. The combination with antimicrobial agents results in a prolonged antibacterial effect allowing for wound dressing change intervals of seven days even in infected wounds. The aim of this study was to evaluate release kinetics of amikacin, teicoplanin or polyhexanide from a PRF-layer. PRF mixed with teicoplanin, amikacin or polyhexanide was sprayed on a silicon gauze patch and put on a colombia agar with bacteria with known minimal inhibitory concentration (MIC) and incubated for 24 hours and afterwards transferred to another agar with the same bacterial strain. Inhibition zones were measured every 24 hours. This was repeated on 7 consecutive days. Antibiotic concentrations were calculated by interpolation. More than 1000 mg/L teicoplanin were released within the first 24 hours and 28.22 mg/L after 168 hours. Amikacin release was above 10,000 mg/L within the first 24 hours and still 120.8 mg/L after 120 hours. A release of polyhexanide could be verified for the first 24 hours only. Consequently teicoplanin and amikacin released from PRF showed antimicrobial in-vitro effects for almost a week, whereas an antimicrobial effect of polyhexanide could only be verified for the first 24 hours. Our Results show that a weekly dressing regimen may be justified in wounds treated with PRF plus amikacin or teicoplanin, since bacteria will be eradicated over a considerable period of time after a single application of PRF.

  19. Trehalose maintains bioactivity and promotes sustained release of BMP-2 from lyophilized CDHA scaffolds for enhanced osteogenesis in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Jun Zhao

    Full Text Available Calcium phosphate (Ca-P scaffolds have been widely employed as a supportive matrix and delivery system for bone tissue engineering. Previous studies using osteoinductive growth factors loaded Ca-P scaffolds via passive adsorption often experience issues associated with easy inactivation and uncontrolled release. In present study, a new delivery system was fabricated using bone morphogenetic protein-2 (BMP-2 loaded calcium-deficient hydroxyapatite (CDHA scaffold by lyophilization with addition of trehalose. The in vitro osteogenesis effects of this formulation were compared with lyophilized BMP-2/CDHA construct without trehalose and absorbed BMP-2/CDHA constructs with or without trehalose. The release characteristics and alkaline phosphatase (ALP activity analyses showed that addition of trehalose could sufficiently protect BMP-2 bioactivity during lyophilization and achieve sustained BMP-2 release from lyophilized CDHA construct in vitro and in vivo. However, absorbed BMP-2/CDHA constructs with or without trehalose showed similar BMP-2 bioactivity and presented a burst release. Quantitative real-time PCR (RT-qPCR and enzyme-linked immunosorbent assay (ELISA demonstrated that lyophilized BMP-2/CDHA construct with trehalose (lyo-tre-BMP-2 promoted osteogenic differentiation of bone marrow stromal cells (bMSCs significantly and this formulation could preserve over 70% protein bioactivity after 5 weeks storage at 25°C. Micro-computed tomography, histological and fluorescent labeling analyses further demonstrated that lyo-tre-BMP-2 formulation combined with bMSCs led to the most percentage of new bone volume (38.79% ± 5.32% and area (40.71% ± 7.14% as well as the most percentage of fluorochrome stained bone area (alizarin red S: 2.64% ± 0.44%, calcein: 6.08% ± 1.37% and mineral apposition rate (4.13 ± 0.62 µm/day in critical-sized rat cranial defects healing. Biomechanical tests also indicated the maximum stiffness (118.17 ± 15.02 Mpa and

  20. A systematic study of the release of bisphenol A by orthodontic materials and its biological effects.

    Science.gov (United States)

    Halimi, Abdelali; Benyahia, Hicham; Bahije, Loubna; Adli, Hanane; Azeroual, Mohamed-Faouzi; Zaoui, Fatima

    2016-12-01

    Bisphenol A (BPA) is a synthetic chemical substance used as a starting ingredient in the manufacturing process of a number or orthodontic materials. It is a well-known endocrine disruptor with low estrogenic properties. The aim of this investigation is to present a systematic review regarding the issue of bisphenol A release by orthodontic materials and its impact in orthodontics. A systematic analysis was performed by electronic search (between 1936 and 2015) on several data bases. The search was limited by using several specific key-words in two languages, English and French. Two investigators selected the responses, which met the selection criteria. Of the 376 studies found, only 21 met our selection criteria: 11 of these dealt with the release of bisphenol by orthodontic materials and 10 in vitro studies described the effects of BPA leaching from orthodontic materials on human and murine cells. The rate of BPA release was well below the daily tolerable intake (DTI) (50mg/kg/day in 2006, then 50μg/kg/day in 2015) according to the European Food Safety Authority (EFSA). Theoretical exposure to BPA was 11,000 times lower than recommendations. However, other studies have shown the presence of BPA and of monomers released in large quantities at very low doses. The effects of observed BPA varied significantly (toxic and carcinogenic potential) while some studies found no effects at all. The relatively small number of studies dealing with the release of Bisphenol A by orthodontic materials, apart from orthodontic materials and their significant biological effects, has led to the absence of standard protocols and has hindered precise determination of released BPA. Moreover, the lack of coherence between the various methodological approaches and variations in the experimental protocols have resulted in a low level of proof regarding the impact of BPA by orthodontic materials. Through this study, the authors encourage clinicians to observe the following recommendations

  1. 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

  2. Assessment Study: Value of Vocational Training to the Released Felon.

    Science.gov (United States)

    Hall, Robert A.

    A research study looked at the effect of vocational training on the ability of 151 released felons who had successfully completed vocational training and were still under supervision, on parole, within New Hampshire. A literature review on recidivism and vocational education in corrections showed the value of vocational training in reducing…

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

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    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.

  4. Vibrio vulnificus MO6-24/O Lipopolysaccharide Stimulates Superoxide Anion, Thromboxane B2, Matrix Metalloproteinase-9, Cytokine and Chemokine Release by Rat Brain Microglia in Vitro

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    Alejandro M. S. Mayer

    2014-03-01

    Full Text Available Although human exposure to Gram-negative Vibrio vulnificus (V. vulnificus lipopolysaccharide (LPS has been reported to result in septic shock, its impact on the central nervous system’s innate immunity remains undetermined. The purpose of this study was to determine whether V. vulnificus MO6-24/O LPS might activate rat microglia in vitro and stimulate the release of superoxide anion (O2−, a reactive oxygen species known to cause oxidative stress and neuronal injury in vivo. Brain microglia were isolated from neonatal rats, and then treated with either V. vulnificus MO6-24/O LPS or Escherichia coli O26:B6 LPS for 17 hours in vitro. O2− was determined by cytochrome C reduction, and matrix metalloproteinase-2 (MMP-2 and MMP-9 by gelatinase zymography. Generation of cytokines tumor necrosis factor alpha (TNF-α, interleukin-1 alpha (IL-1α, IL-6, and transforming growth factor-beta 1 (TGF-β1, chemokines macrophage inflammatory protein (MIP-1α/chemokine (C-C motif ligand 3 (CCL3, MIP-2/chemokine (C-X-C motif ligand 2 (CXCL2, monocyte chemotactic protein-1 (MCP-1/CCL2, and cytokine-induced neutrophil chemoattractant-2alpha/beta (CINC-2α/β/CXCL3, and brain-derived neurotrophic factor (BDNF, were determined by specific immunoassays. Priming of rat microglia by V. vulnificus MO6-24/O LPS in vitro yielded a bell-shaped dose-response curve for PMA (phorbol 12-myristate 13-acetate-stimulated O2− generation: (1 0.1–1 ng/mL V. vulnificus LPS enhanced O2− generation significantly but with limited inflammatory mediator generation; (2 10–100 ng/mL V. vulnificus LPS maximized O2− generation with concomitant release of thromboxane B2 (TXB2, matrix metalloproteinase-9 (MMP-9, and several cytokines and chemokines; (3 1000–100,000 ng/mL V. vulnificus LPS, with the exception of TXB2, yielded both attenuated O2− production, and a progressive decrease in MMP-9, cytokines and chemokines investigated. Thus concentration-dependent treatment of

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

    Science.gov (United States)

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

    2017-04-30

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

  6. Development of a Physiologically Relevant Population Pharmacokinetic in Vitro-in Vivo Correlation Approach for Designing Extended-Release Oral Dosage Formulation.

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    Kim, Tae Hwan; Shin, Soyoung; Bulitta, Jürgen B; Youn, Yu Seok; Yoo, Sun Dong; Shin, Beom Soo

    2017-01-03

    Establishing a level A in vitro-in vivo correlation (IVIVC) for a drug with complex absorption kinetics is challenging. The objective of the present study was to develop an IVIVC approach based on population pharmacokinetic (POP-PK) modeling that incorporated physiologically relevant absorption kinetics. To prepare three extended release (ER) tablets of loxoprofen, three types of hydroxypropyl methylcellulose (HPMC 100, 4000, and 15000 cps) were used as drug release modifiers, while lactose and magnesium stearate were used as the diluent and lubricant, respectively. An in vitro dissolution test in various pH conditions showed that loxoprofen dissolution was faster at higher pH. The in vivo pharmacokinetics of loxoprofen was assessed following oral administration of the different loxoprofen formulations to Beagle dogs (n = 22 in total). Secondary peaks or shoulders were observed in many of the individual plasma concentration vs time profiles after ER tablet administration, which may result from secondary absorption in the intestine due to a dissolution rate increase under intestinal pH compared to that observed at stomach pH. In addition, in vivo oral bioavailability was found to decrease with prolonged drug dissolution, indicating site-specific absorption. Based on the in vitro dissolution and in vivo absorption data, a POP-PK IVIVC model was developed using S-ADAPT software. pH-dependent biphasic dissolution kinetics, described using modified Michaelis-Menten kinetics with varying Vmax, and site-specific absorption, modeled using a changeable absorbed fraction parameter, were applied to the POP-PK IVIVC model. To experimentally determine the biphasic dissolution profiles of the ER tablets, another in vitro dissolution test was conducted by switching dissolution medium pH based on an in vivo estimate of gastric emptying time. The model estimated, using linear regression, that in vivo initial maximum dissolution rate (Vmax(0)in vivo) was highly correlated (r2 > 0

  7. Anti-inflammatory homoeopathic drug dilutions restrain lipopolysaccharide-induced release of pro-inflammatory cytokines: In vitro and in vivo evidence

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    Umesh B Mahajan

    2017-01-01

    Full Text Available Context: The lipopolysaccharide (LPS-induced cytokine release and oxidative stress are validated experimental parameters used to test anti-inflammatory activity. We investigated the effects of homoeopathic mother tinctures, 6 CH, 30 CH and 200 CH dilutions of Arnica montana, Thuja occidentalis and Bryonia alba against LPS (1 μg/ml-induced cytokine release from RAW-264.7 cells and human whole-blood culture. Materials and Methods: For in vivo evaluations, mice were orally treated with 0.1 ml drug dilutions twice a day for 5 days followed by an intraperitoneal injection of 0.5 mg/kg LPS. After 24 h, the mice were sacrificed and serum levels of pro-inflammatory cytokines and nitric oxide were determined. The extent of oxidative stress was determined in the liver homogenates as contents of reduced glutathione, malondialdehyde, superoxide dismutase and catalase. Results: The tested drug dilutions significantly reduced in vitro LPS-induced release of tumour necrosis factor-α, interleukin-1 (IL-1 and IL-6 from the RAW-264.7 cells and human whole blood culture. Similar suppression of cytokines was evident in mice serum samples. These drugs also protected mice from the LPS-induced oxidative stress in liver tissue. Conclusions: Our findings substantiate the protective effects of Arnica, Thuja and Bryonia homoeopathic dilutions against LPS-induced cytokine elevations and oxidative stress. This study authenticates the claims of anti-inflammatory efficacy of these homoeopathic drugs.

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

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    Wen-Hao Wei

    2015-03-01

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

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

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    Schubert Jochen

    2008-11-01

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

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

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    Räthel Thomas R.

    2003-01-01

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

  11. A BIOMECHANICAL STUDY OF LATERAL RELEASE AND ELMSLIE-TRILLAT PROCEDURES TO RESTABILISETHE MALTRACKTNG PATELLA

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    MM. Tahmasbi

    1999-09-01

    Full Text Available  The resistant* of pateSa against lateral displacement (Le. the stability, was studied tinder a range of conditions in vitro, at a range of knee flexion angles. Muscle forces were applied in physiological directions along the separate quadriceps muscles. Normal muscle actions with constant tension showed constant patellar stability up to sixty degrees knee flexion, and then a significant increase at ninety degrees. A pathological knee was simulated by relaxing vastus medians, and ■ lateral stability then dropped by 47%. Isolated rttlnaeular release in the pathological knee did not improve stability significantly towards normal, while 6mm tibial tubercle medlaEsatum restored stabtBty by 52% towards normal, except neat JuM extension. Combined release phis tubercle medtafisathm. restored stability 59% towards normal In knee flexion, and 23% up to ten degrees flexion.

  12. Pulse release of doxazosin from hydroxyethylcellulose compression coated tablet: mechanistic and in vivo study.

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    Biswas, Nikhil; Guha, Arijit; Sahoo, Ranjan Kumar; Kuotsu, Ketousetuo

    2015-01-01

    Chronotherapeutically programmed hydroxyethylcellulose (HEC) based compression coated doxazosin tablets were prepared and the influence of disintegrants croscarmellose sodium, L-hydroxypropylcellulose (L-HPC), gellan gum on drug release and in vivo performance were investigated. Infrared spectroscopy and differential scanning calorimetric studies did not indicate any excipient incompatibility in the tablets. The disintegrants induced a continuous water influx resulting in a rapid expansion of the membrane. The subsequent formation of fractures into the coats leads to a fast drug release after an initial lag time. Release rates indicated that croscarmellose sodium and L-HPC were directly proportional to their concentration in the formulations. In vitro optimized croscarmellose sodium-HEC matrix showed significantly faster (p 0.99). The mechanism involved in release was anomalous transport and super case II transport with matrix swelling. The pulsatile tablets showed no changes either in physicochemical appearance, drug content or in dissolution pattern during its accelerated stability studies. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Macromolecular confinement of therapeutic protein in polymeric particles for controlled release: insulin as a case study

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    Luiz Henrique Guerreiro

    2017-06-01

    Full Text Available ABSTRACT Sustained release systems for therapeutic proteins have been widely studied targeting to improve the action of these drugs. Molecular entrapping of proteins is particularly challenging due to their conformational instability. We have developed a micro-structured poly-epsilon-caprolactone (PCL particle system loaded with human insulin using a simple double-emulsion w/o/w method followed by solvent evaporation method. This formulation is comprised by spheric-shaped microparticles with average size of 10 micrometers. In vitro release showed a biphasic behavior such as a rapid release with about 50% of drug delivered within 2 hours and a sustained phase for up to 48 h. The subcutaneous administration of microencapsulated insulin showed a biphasic effect on glycemia in streptozotocin-induced diabetic mice, compatible with short and intermediate-acting behaviors, with first transition peak at about 2 h and the second phase exerting effect for up to 48h after s.c. administration. This study reveals that a simplified double-emulsion system results in biocompatible human-insulin-loaded PCL microparticles that might be used for further development of optimized sustained release formulations of insulin to be used in the restoration of hormonal levels.

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

    Science.gov (United States)

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

    2012-01-01

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

  15. Estudio in vitro de la citotoxicidad y genotoxicidad de los productos liberados del acero inoxidable 316L con recubrimientos cerámicos bioactivos Cytotoxic and genotoxic study of in Vitro released products of stainless Steel 316l with bioactive ceramic Coatings

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    María Elena Márquez Fernández

    2007-03-01

    species (ERO and damages of the ADN, increasing the possibility of local tumors and mechanical failure of the implant. A strategy used to minimize the generation of ions is the superficial modification of the implants by means of inorganic coatings, ceramic or vitreous, applied by the sol-gel process; this method has a series of comparative advantages, compared to other deposition methods, as good adherence, easy application, minimum drying problems, low densification temperatures and the possibility of adding particles and/or organic groups that improve the adhesion of the cell to the implant, increasing the biocompatibility. In the present work, the citotoxic effects were valuated by means of the MTT technique, and the genotoxic ones by electrophoresis of individual cell gels (Cometa test, on CHO cells, of the released products in a MEM media, after a period of 30 days, of the stainless steel 316L with no coat, coated with a coat of silica glass (MC, or with two coats of the same glass, containing bioactive particles of hydroxyapatite (HA, glass (V or glassceramic powder (VC. The results show that there is not citotoxic effects in a test with an aging of 30 days in MEM media; a genotoxic effect was found in the A and MC samples, but without real risk for cell systems.

  16. Beta amyloid differently modulate nicotinic and muscarinic receptor subtypes which regulate in vitro and in vivo the release of glycine in the rat hippocampus

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    Stefania eZappettini

    2012-07-01

    Full Text Available Using both in vitro (hippocampal synaptosomes in superfusion and in vivo (microdialysis approaches we investigated whether and to what extent β amyloid peptide 1-40 (Aβ 1-40 interferes with the cholinergic modulation of the release of glycine (GLY in the rat hippocampus. The nicotine-evoked overflow of endogenous GLY in hippocampal synaptosomes in superfusion was significantly inhibited by Aβ 1-40 (10 nM while increasing the concentration to 100 nM the inhibitory effect did not further increase. Both the Choline (Ch (α7 agonist; 1 mM and the 5-Iodo-A-85380 dihydrochloride (5IA85380, α4β2 agonist; 10 nM-evoked GLY overflow were inhibited by Aβ1-40 at 100 nM but not at 10nM concentrations. The KCl evoked [3H]GLY and [3H]Acetylcholine (ACh overflow were strongly inhibited in presence of oxotremorine; however this inhibitory muscarinic effect was not affected by Aβ1-40. The effects of Aβ1-40 on the administration of nicotine, veratridine, 5IA85380 and PHA 543613 hydrochloride (PHA543613 (a selective agonist of α7 subtypes on hippocampal endogenous GLY release in vivo were also studied. Aβ 1-40 significantly reduced (at 10 μM but not at 1 μM the nicotine evoked in vivo release of GLY. Aβ 1-40 (at 10 μM but not at 1 μM significantly inhibited the PHA543613 (1 mM-elicited GLY overflow while was ineffective on the GLY overflow evoked by 5IA85380 (1 mM. Aβ 40-1 (10 μM did not produce any inhibitory effect on nicotine evoked GLY overflow both in the in vitro and in vivo experiments. Our results indicate that a the cholinergic modulation of the release of GLY occurs by the activation of both α7 and α4β2 nicotinic ACh receptors (nAChRs as well as by the activation of inhibitory muscarinic ACh receptors (mAChRs and b Aβ 1-40 can modulate cholinergic evoked GLY release exclusively through the interaction with α7 and the α4β2 nAChR nicotinic receptors but not through mAChR subtypes.

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

    Science.gov (United States)

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

    2011-01-01

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

  18. Bioaccessibility of polyphenols associated with dietary fiber and in vitro kinetics release of polyphenols in Mexican 'Ataulfo' mango (Mangifera indica L.) by-products.

    Science.gov (United States)

    Blancas-Benitez, Francisco J; Mercado-Mercado, Gilberto; Quirós-Sauceda, Ana E; Montalvo-González, Efigenia; González-Aguilar, Gustavo A; Sáyago-Ayerdi, Sonia G

    2015-03-01

    The biological properties of polyphenol (PP) depend on its bioaccessibility and bioavailability. Therefore, part of PP released from the food matrix in the gastrointestinal tract through enzymatic hydrolysis is at least partially absorbed. The aim of this study is to determine the bioaccessibility of PP associated with dietary fiber (DF) and the kinetics release of PP in mango (Mangifera indica L.) 'Ataulfo' by-products by an in vitro model. Soluble and insoluble DF values were 7.99 and 18.56% in the mango paste and 6.98 and 22.78% in the mango peel, respectively. PP associated with soluble and insoluble DF was 6.0 and 3.73 g GAE per 100 g in the paste and 4.72 and 4.50 g GAE per 100 g in the peel. The bioaccessibility of PP was 38.67% in the pulp paste and 40.53% in the peel. A kinetics study shows a release rate of 2.66 and 3.27 g PP min(-1) in the paste and peel, respectively. The antioxidant capacity of the paste increased as digestion reached a value of 2.87 mmol TE min(-1) at 180 min. The antioxidant capacity of the peel had its maximum (28.94 mmol TE min(-1)) between 90 and 120 min of digestion; it started with a value of 2.58 mmol TE min(-1), and thereafter increased to 4.20 mmol TE min(-1) at 180 min. The major PPs released during the digestion of paste were gallic and hydroxybenzoic acids, while in the peel, they were hydroxycinnamic and vanillic acids. It was concluded that these phenolic compounds are readily available for absorption in the small intestine and exert different potential health benefits.

  19. In vitro collagen fibril assembly: thermodynamic studies.

    Science.gov (United States)

    Na, G C; Phillips, L J; Freire, E I

    1989-09-05

    The in vitro fibril assembly of calf skin collagen was examined as a function of ionic strength and temperature. In a 0.03 M NaPi, pH 7.0, buffer, fibril assembly required a minimum critical concentration of collagen. At nearly physiological ionic strengths and temperatures, the critical concentration was less than 1 microgram/mL and required a very sensitive method for measurement. Raising the ionic strength of the buffer resulted first in higher and then lower critical concentrations. Raising the temperature led to lower critical concentrations. A van't Hoff plot of the fibril growth constant calculated from the critical concentration gave positive enthalpy changes and positive heat capacity changes which indicate that the fibril growth is driven by both hydrophobic and ionic inter-collagen interactions. Sedimentation equilibrium studies showed the collagen to be monomeric at subcritical concentrations. Differential scanning microcalorimetric studies showed only one very sharp heat absorption peak for the fibril assembly which coincided with the appearance of solution turbidity. Within experimental error, the enthalpy changes of the fibril assembly measured with the microcalorimeter were of the same magnitude as the van't Hoff enthalpy changes. These results are discussed in light of a cooperative nucleation-growth mechanism of collagen fibril assembly proposed earlier.

  20. Study of mesoporous silica/magnetite systems in drug controlled release.

    Science.gov (United States)

    Souza, K C; Ardisson, J D; Sousa, E M B

    2009-02-01

    Ordered mesoporous materials like SBA-15 have a network of channels and pores with well-defined size in the nanoscale range. This particular silica matrix pore architecture makes them suitable for hosting a broad variety of compounds in very promising materials in a range of applications, including drug release magnetic carriers. In this work, magnetic nanoparticles embedded into mesoporous silica were prepared in two steps: first, magnetite was synthesized by oxidation-precipitation method, and next, the magnetic nanoparticles were coated with mesoporous silica by using nonionic block copolymer surfactants as structure-directing agents. The materials were characterized by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), N(2) adsorption, and scanning electron microscopy (SEM). The influence of magnetic nanoparticles on drug release kinetics was studied with cisplatin, carboplatin, and atenolol under in vitro conditions in the absence and in the presence of an external magnetic field (0.25 T) by using NdFeB permanent magnet. The constant external magnetic field did not affect drug release significantly. The low-frequency alternating magnetic field had a large influence on the cisplatin release profile.

  1. [A study on release of propolis extract components from emulsion-type dispersions].

    Science.gov (United States)

    Ramanauskienė, Kristina; Zilius, Modestas; Briedis, Vitalis

    2011-01-01

    Carrier development is one of the essential stages in the formulation of semisolid pharmaceutical dosage form for topical application. The stability of semisolid preparation during storage can be predicted from rheological testing. An adequate composition of semisolid preparation determines its stability and proper release of drug substance, and allows bypassing long-term heating and melting of the cream base components while incorporating complex extracts. Soft propolis extract, well known for its antimicrobial, antiviral, anti-inflammatory, and antioxidant effects, was chosen as a complex biologically active ingredient for the development of emulsion dispersion system. The aim of this study was to evaluate the impact of physical-chemical characteristics of the carrier on the release rate of biologically active ingredients from the modeled dosage form in vitro, thus justifying the relevance of the carrier composition and applied technologies. Soft propolis extract (1%-3%) was incorporated into water-in-oil type emulsion. The quality of the model systems was evaluated referring to their viscosity, quantity of polyphenols and their rate of release from the preparation by applying an in vitro model. Quantitative determination of polyphenols was performed by spectrophotometry using a standard calibration curve of ferulic acid. The results showed that a stable homogeneous semisolid emulsion system containing soft propolis extract could be produced when the concentration of emulsifier was in the range of 3%-12%. The quantity of emulsifier had an impact on the viscosity of semisolid systems, but practically had no effect on the release rate of polyphenols from the cream matrix. The results also demonstrated that the added amount of soft propolis extract had a less significant effect than temperature of the system. It was confirmed that changes in the viscosity of emulsion dispersion systems had no effect on the stability of model dispersion systems when temperature was

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

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    Anjuman Arora

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

  3. Bonding brackets to porcelain: in vitro study

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    Sant'Anna Eduardo Franzotti

    2002-01-01

    Full Text Available The aim of this research was to verify, in vitro, the effect of various porcelain surface treatments on the shear strength of orthodontic brackets bonded to porcelain and the mode of fracture after debonding. Eighty-eight samples of metallic supported feldspathic porcelain were randomly divided into four groups according to their surface preparation as follows: the porcelain was maintained intact (GI, roughened with a diamond bur (GII, etched with 10% hydrofluoric acid (GIII, or sandblasted with aluminum oxide (GIV. The specimens were treated with silane (Scothprime and brackets were bonded with Concise. Each sample was subjected to a shear load at a crosshead speed of 1 mm/min and a recording was made at the point of failure. Bond strengths, adequate to withstand the application of orthodontic forces, were achieved in all groups. The Kruskal-Wallis statistical test showed no significant differences in bond strength between the groups (p>0.05. However, many more porcelain fractures occurred on deglazed porcelain. This study indicates that with the appropriate material selection, the silane/composite procedure alone may be adequate for bonding.

  4. Modelling Simple Experimental Platform for In Vitro Study of Drug Elution from Drug Eluting Stents (DES)

    Science.gov (United States)

    Kalachev, L. V.

    2016-06-01

    We present a simple model of experimental setup for in vitro study of drug release from drug eluting stents and drug propagation in artificial tissue samples representing blood vessels. The model is further reduced using the assumption on vastly different characteristic diffusion times in the stent coating and in the artificial tissue. The model is used to derive a relationship between the times at which the measurements have to be taken for two experimental platforms, with corresponding artificial tissue samples made of different materials with different drug diffusion coefficients, to properly compare the drug release characteristics of drug eluting stents.

  5. Investigation into drug release from colon-specific azoreductase-activated steroid prodrugs using in-vitro models.

    Science.gov (United States)

    Ruiz, Juan F Marquez; Kedziora, Kinga; Windle, Henry; Kelleher, Dermot P; Gilmer, John F

    2011-06-01

    The aim of this study was to investigate drug release from a double steroid prodrug, OPN501, which incorporates a phenylpropionate linker, and its phenylacetate analogue. The prodrugs, which were designed to deliver prednisolone to the colon for the treatment of inflammatory bowel disease, are based on a novel design that requires sequential azoreductase activity and cyclization of an amino ester to trigger drug release. We sought to explain the divergent effects of the two compounds in anti-inflammatory models and to justify the selection of OPN-501 for clinical development. The compounds were incubated in mouse colonic contents (10%) fermented in brain heart infusion under anaerobic conditions. The disappearance of the prodrugs and release of prednisolone was monitored by HPLC. We then developed a method for assessment of prodrug activation using suspensions of Clostridium perfringens, an anaerobe from the human colon. The cyclization of the compounds was studied in various media, assessing the influence of pH and bulk solvent polarity on cyclization rate using HPLC and NMR. The prodrugs were activated via multiple pathways releasing prednisolone in mouse colonic ferment. The compounds released prednisolone by reduction-cyclization in C perfringens suspension. The active OPN-501 generated a stoichiometric amount of prednisolone following azoreductase activation, whereas its analogue did not. The pH rate profile for the cyclization of the amino intermediates of the two compounds revealed significant differences in rate at pH values relevant to the inflamed colon, which explain in part the different amounts of drug produced. The steroid prodrug OPN-501 has optimal drug release characteristics for colon targeting because of a kinetic advantage of a six-membered ring formation in the aminolysis reactions of anilides. The results are relevant to the development of OPN-501 but also to cyclization strategies in prodrug design especially for colon targeting. © 2011 The

  6. 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.

  7. Adenosine triphosphate levels during anaphylactic histamine release in rat mast cells in vitro. Effects of glycolytic and respiratory inhibitors

    DEFF Research Database (Denmark)

    Johansen, Torben

    1979-01-01

    The adenosine triphosphate (ATP) content of rat mast cells was studied during and after anaphylactic histamine release. The almost identical time course of ATP decrease from mast cells treated with either glycolytic or respiratory inhibitors supports the view that the ATP depletion was largely re...

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

    Science.gov (United States)

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

    2017-01-01

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

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

    DEFF Research Database (Denmark)

    Zeeshan, Farrukh; Tabbassum, Misbah; Jorgensen, Lene

    2018-01-01

    Protein biologics are prone to conformational changes during formulation development. Limited methods are available for conformational analysis of proteins in solid state and in the presences of formulation excipients. The aim of this study was to investigate the secondary structures of proteins...... encased in solid lipid matrices as a novel indicator of their stability upon in vitro release. Model proteins namely catalase and lysozyme were incorporated into lipid namely Precirol® AT05 (glycerol palmitostearate, melting point 58°C) at 30% w/w loading using melting and mixing and wet granulation...... methods. Attenuated total reflectance (ATR-FTIR) spectroscopy, size-exclusion chromatography (SEC) and biological activity analyses were performed. The information about secondary structure was acquired using second derivative analysis of amide-I band (1600-1700 cm(-1)). ATR analysis demonstrated...

  10. 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.

  11. Formulation, in vitro drug release and in vivo human X-ray investigation of polysaccharide based drug delivery systems for targeting 5-fluorouracil to the colon

    Directory of Open Access Journals (Sweden)

    Sidramappa Mallikarjun Chickpetty

    2013-06-01

    Full Text Available The purpose of this research study was to develop 5-fluorouracil compression coated tablets by using biodegradable polysaccharide polymer locust bean gum (LBG and hydroxyl propyl methyl cellulose (HPMC as coating materials. The fast disintegrating core tablets containing 50 mg of 5-fluorouracil were compression coated with LBG and HPMC in different ratios (8:1, 7:2 and 6:3 with a coat weight of 300, 400 and 500 mg. In vitro dissolution data indicated that the formulation (CLH63 with a coat weight of 500 mg containing LBG and HPMC in the ratio 6:3 gave the best release profile (0% in first 5 hour and 96.18% in 24 hours. DSC and FTIR results indicated no possibility of interaction between drug and polymers or other excipients. In vivo human X-ray studies revealed that formulation CLH63 was able to resist breakdown in the stomach and small intestine. The disintegration of the tablet occurred in the colon between 8 to 16 hours of post dose. By the present study, it can be concluded that the LBG and HPMC based compression coated tablets of 5-fluorouracil will be useful strategy for colonic delivery of 5-fluorouracil without being released in upper gastrointestinal region for the safe and effective management of colon cancer.

  12. Formulation and In-vitro Characterization of Sustained Release Matrix Type Ocular Timolol Maleate Mini-Tablet

    OpenAIRE

    Mortazavi, Seyed Alireza; Jafariazar, Zahra; Ghadjahani, Yasaman; Mahmoodi, Hoda; Mehtarpour, Farzaneh

    2014-01-01

    The purpose of this study was preparation and evaluation of sustained release matrix type ocular mini-tablets of timolol maleate, as a potential formulation for the treatment of glaucoma. Following the initial studies on timolol maleate powder, it was formulated into ocular mini-tablets. The polymers investigated in this study included cellulose derivatives (HEC, CMC, EC) and Carbopol 971P. Mannitol was used as the solubilizing agent and magnesium stearate as the lubricant. Mini-tablets were ...

  13. In vitro study of interaction between quinine and Garcinia kola

    African Journals Online (AJOL)

    Purpose: To investigate the interaction between quinine and Garcinia kola using an in vitro adsorption study. Methods: In vitro interaction between quinine and G. kola was conducted at 37 ± 0.1 °C. Adsorption of quinine (2.5 - 40 µg/ml) to 2.5 % w/v G. kola suspension was studied. Thereafter, quinine desorption process ...

  14. Atorvastatin calcium loaded chitosan nanoparticles: in vitro evaluation and in vivo pharmacokinetic studies in rabbits

    Directory of Open Access Journals (Sweden)

    Abdul Baquee Ahmed

    2015-06-01

    Full Text Available In this study, we prepared atorvastatin calcium (AVST loaded chitosan nanoparticles to improve the oral bioavailability of the drug. Nanoparticles were prepared by solvent evaporation technique and evaluated for its particle size, entrapment efficiency, zeta potential, in vitro release and surface morphology by scanning electron microscopy (SEM. In addition, the pharmacokinetics of AVST from the optimized formulation (FT5 was compared with marketed immediate release formulation (Atorva(r in rabbits. Particle size of prepared nanoparticles was ranged between 179.3 ± 7.12 to 256.8 ± 8.24 nm with a low polydispersity index (PI value. Zeta potential study showed that the particles are stable with positive values between 13.03 ± 0.32 to 46.90 ± 0.49 mV. FT-IR studies confirmed the absence of incompatibility of AVST with excipient used in the formulations. In vitro release study showed that the drug release was sustained for 48 h. Results of pharmacokinetics study showed significant changes in the pharmacokinetic parameter (2.2 fold increase in AUC of the optimized formulation as compared to marketed formulation (Atorva(r. Thus, the developed nanoparticles evidenced the improvement of oral bioavailability of AVST in rabbit model.

  15. 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.

  16. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Ramey, J.W.

    1986-01-01

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

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

    Science.gov (United States)

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

    2012-03-15

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

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

    Science.gov (United States)

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

    2013-03-25

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

  20. Antimicrobial and release study of drug loaded PVA/PEO/CMC wound dressings.

    Science.gov (United States)

    Gupta, Bhuvanesh; Agarwal, Roopali; Sarwar Alam, M

    2014-06-01

    The aim of the present study was to develop PVA/PEO/CMC/aloe vera (PPCAV) and PVA/PEO/CMC/curcumin (PPCCu) dressings with nonwoven polyester fabric as the support layer via freeze-drying (FD) approach. Tetracycline hydrochloride drug (TC) was loaded along with curcumin and aloe vera on these dressings. The morphology of the dressings was characterized by scanning electron microscopy. The swelling behavior, water vapor transmission rate (WVTR), in vitro drug release and antimicrobial nature were analyzed to assess the applicability of these freeze-dried membranes as wound dressing materials. The results show that these dressings made from PPCAVTC and PPCCuTC were highly porous with three-dimensional interconnected porous morphology. The cumulative release of drug from the dressings increases with increasing immersion time and continued up to 24 h, after that it gets leveled off. These dressings evidenced wonderful antimicrobial nature in vitro. These dressings were found to have more than 900 % PBS uptake, WVTR was found to be in the range 2,000-2,500 gm(-2) day(-1). These dressings possess many characteristics desirable in an ideal wound dressing material.

  1. 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.

  2. 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...

  3. Wrist immobilization after carpal tunnel release: a prospective study.

    Science.gov (United States)

    Martins, Roberto S; Siqueira, Mario G; Simplício, Hougelli

    2006-09-01

    This prospective study evaluates the possible advantages of wrist immobilization after open carpal tunnel release comparing the results of two weeks immobilization and no immobilization. Fifty two patients with idiopathic carpal tunnel syndrome were randomly selected in two groups after open carpal tunnel release. In one group (A, n=26) the patients wore a neutral-position wrist splint continuously for two weeks. In the other group (B, n=26) no wrist immobilization was used. Clinical assessment was done pre-operatively and at 2 weeks follow-up and included the two-point discrimination test at the second finger and two questionnaires as an outcome measurement of symptoms severity and intensity. All the patients presented improvement in the postoperative evaluations in the three analyzed parameters. There was no significant difference between the two groups for any of the outcome measurements at the final follow-up. We conclude that wrist immobilization in the immediate post-operative period have no advantages when compared with no immobilization in the end result of carpal tunnel release.

  4. Formulation and in vitro evaluation of theophylline-Eudragit® sustained-release tablets Desenvolvimento e avaliação in vitro de comprimidos de liberação prolongada de teofilina preparados com Eudragit®

    Directory of Open Access Journals (Sweden)

    Evelyn Ojoe

    2005-09-01

    Full Text Available Tablets containing theophylline (66.67% based on a Eudragit® RS 30D and NE 30D matrices containing 10% to 30% of either of the polymer were produced by compression method. The influence of the different proportions of methacrylic esters, the use of lactose and tribasic calcium phosphate as diluents and also the effects of the addition of magnesium stearate as a hydrophobic agent lubricant on the theophylline release, were studied. Physicochemical analyses and drug content was evaluated. In vitro drug release studies were carried out in simulated gastric fluid without pepsin (pH1.2 and simulated intestinal fluid without pancreatin (pH7.5. A relatively prolonged release of theophylline from the polymer matrices for a 7 hr-release period was detected. Magnesium stearate at 0.5% and Eudragit® NE 30D at 10% was considered a better sustained-release matrix compressed theophylline tablets comparing with Eudragit® RS 30D in the same conditions (USP. Results from physicochemical analyses were in accordance with specifications. The release patterns were analyzed from the viewpoint of square-root of time and as a first-order, zero-order kinetics, and Higuchi. Additionally, half-life of release (Td50% and dissolution rates (kd were calculated. Higuchi was the model that better fitted theophylline kinetic, and diffusion controlled was involved.Comprimidos contendo teofilina (66.67% e polímeros de Eudragit® NE 30D e RS 30D entre 10 e 30% foram produzidos por compressão. A influência das diferentes proporções de ésteres do ácido metacrílico, uso da lactose e fosfato de cálcio tribásico como diluente, bem como os efeitos da adição de estearato de magnésio como agente lubrificante hidrofóbico na liberação da teofilina foram estudados. Análises físico-químicas e teor de fármaco foram avaliados. Estudos da liberação do fármaco in vitro foram conduzidos em fluido gástrico simulado (pH 1,2 e fluido intestinal simulado sem pancreatina (p

  5. Rosiglitazone Suppresses In Vitro Seizures in Hippocampal Slice by Inhibiting Presynaptic Glutamate Release in a Model of Temporal Lobe Epilepsy.

    Directory of Open Access Journals (Sweden)

    Shi-Bing Wong

    Full Text Available Peroxisomal proliferator-activated receptor gamma (PPARγ is a nuclear hormone receptor whose agonist, rosiglitazone has a neuroprotective effect to hippocampal neurons in pilocarpine-induced seizures. Hippocampal slice preparations treated in Mg2+ free medium can induce ictal and interictal-like epileptiform discharges, which is regarded as an in vitro model of N-methyl-D-aspartate (NMDA receptor-mediated temporal lobe epilepsy (TLE. We applied rosiglitazone in hippocampal slices treated in Mg2+ free medium. The effects of rosiglitazone on hippocampal CA1-Schaffer collateral synaptic transmission were tested. We also examined the neuroprotective effect of rosiglitazone toward NMDA excitotoxicity on cultured hippocampal slices. Application of 10 μM rosiglitazone significantly suppressed amplitude and frequency of epileptiform discharges in CA1 neurons. Pretreatment with the PPARγ antagonist GW9662 did not block the effect of rosiglitazone on suppressing discharge frequency, but reverse the effect on suppressing discharge amplitude. Application of rosiglitazone suppressed synaptic transmission in the CA1-Schaffer collateral pathway. By miniature excitatory-potential synaptic current (mEPSC analysis, rosiglitazone significantly suppressed presynaptic neurotransmitter release. This phenomenon can be reversed by pretreating PPARγ antagonist GW9662. Also, rosiglitazone protected cultured hippocampal slices from NMDA-induced excitotoxicity. The protective effect of 10 μM rosiglitazone was partially antagonized by concomitant high dose GW9662 treatment, indicating that this effect is partially mediated by PPARγ receptors. In conclusion, rosiglitazone suppressed NMDA receptor-mediated epileptiform discharges by inhibition of presynaptic neurotransmitter release. Rosiglitazone protected hippocampal slice from NMDA excitotoxicity partially by PPARγ activation. We suggest that rosiglitazone could be a potential agent to treat patients with TLE.

  6. Real-time in vitro dissolution of 5-aminosalicylic acid from single ethyl cellulose coated extrudates studied by UV imaging

    DEFF Research Database (Denmark)

    Gaunø, Mette Høg; Vilhelmsen, Thomas; Larsen, Crilles Casper

    2013-01-01

    dissolution testing. The release from defect extrudates was visualized by the absorbance maps and the release was highest from the compromised part of the extrudates. UV imaging has proven to be a useful technique to visualize the release of 5-aminosalicylic acid from single film coated extrudates and it has......The purpose of this study was to investigate the in vitro release of 5-aminosalicylic acid from single extrudates by UV imaging and to explore the technique as a visualization tool for detecting film coating defects on extrudates coated with a thin ethyl cellulose layer. 5-Aminosalicylic acid...... from four different coating levels were placed in agarose gels and UV imaging was performed for a total of 240min. Absorbance maps were obtained thus visualizing the release of 5-aminosalicylic acid over time and it was possible to detect a decrease in release as a function of increased ethyl cellulose...

  7. 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.

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

    African Journals Online (AJOL)

    HP

    A fair correlation between the dissolution profile and bioavailability for the optimized formulation ... Diltiazem HCl is a water soluble calcium-channel .... bioavailability and bioequivalence studies (CDSCO, DGHS, India). [16]. The subjects enrolled in the study were presented with full details of the investigation, both verbally ...

  9. Validation of an in vitro digestive system for studying macronutrient decomposition in humans.

    Science.gov (United States)

    Kopf-Bolanz, Katrin A; Schwander, Flurina; Gijs, Martin; Vergères, Guy; Portmann, Reto; Egger, Lotti

    2012-02-01

    The digestive process transforms nutrients and bioactive compounds contained in food to physiologically active compounds. In vitro digestion systems have proven to be powerful tools for understanding and monitoring the complex transformation processes that take place during digestion. Moreover, the investigation of the physiological effects of certain nutrients demands an in vitro digestive process that is close to human physiology. In this study, human digestion was simulated with a 3-step in vitro process that was validated in depth by choosing pasteurized milk as an example of a complex food matrix. The evolution and decomposition of the macronutrients was followed over the entire digestive process to the level of intestinal enterocyte action, using protein and peptide analysis by SDS-PAGE, reversed-phase HPLC, size exclusion HPLC, and liquid chromatography-MS. The mean peptide size after in vitro digestion of pasteurized milk was 5-6 amino acids (AA). Interestingly, mostly essential AA (93.6%) were released during in vitro milk digestion, a significantly different relative distribution compared to the total essential AA concentration of bovine milk (44.5%). All TG were degraded to FFA and monoacylglycerols. Herein, we present a human in vitro digestion model validated for its ability to degrade the macronutrients of dairy products comparable to physiological ranges. It is suited to be used in combination with a human intestinal cell culture system, allowing ex vivo bioavailability measurements and assessment of the bioactive properties of food components.

  10. Focal release of neurotrophic factors by biodegradable microspheres enhance motor and sensory axonal regeneration in vitro and in vivo

    OpenAIRE

    Santos, Daniel

    2016-01-01

    Neurotrophic factors (NTFs) promote nerve regeneration and neuronal survival after peripheral nerve injury. However, drawbacks related with administration and bioactivity during long periods limit their therapeutic application. In this study, PLGA microspheres (MPs) were used to locally release different NTFs and evaluate whether they accelerate axonal regeneration in comparison with free NTFs or controls. ELISA, SEM, UV/visible light microscopy, organotypic cultures of DRG explants and spina...

  11. Increased in vitro release of soluble interleukin 2 receptor by colonic lamina propria mononuclear cells in inflammatory bowel disease.

    OpenAIRE

    Schreiber, S; Raedler, A; Conn, A R; Rombeau, J. L.; MacDermott, R P

    1992-01-01

    Increased concentrations of the soluble form of the interleukin 2 receptor have been observed in the sera of Crohn's disease and ulcerative colitis patients. In this study we have observed the spontaneous release of soluble interleukin 2 receptor by unstimulated, isolated normal and inflammatory bowel disease colonic lamina propria mononuclear cells. Lamina propria mononuclear cells from Crohn's disease patients (median = 204 U/ml (interquartile range 126-396, n 17) secreted significantly (p ...

  12. Schwann cells are activated by ATP released from neurons in an in vitro cellular model of Miller Fisher syndrome.

    Science.gov (United States)

    Rodella, Umberto; Negro, Samuele; Scorzeto, Michele; Bergamin, Elisanna; Jalink, Kees; Montecucco, Cesare; Yuki, Nobuhiro; Rigoni, Michela

    2017-05-01

    The neuromuscular junction is exposed to different types of insult, including mechanical trauma, toxins and autoimmune antibodies and, accordingly, has retained through evolution a remarkable ability to regenerate. Regeneration is driven by multiple signals that are exchanged among the cellular components of the junction. These signals are largely unknown. Miller Fisher syndrome is a variant of Guillain-Barré syndrome caused by autoimmune antibodies specific for epitopes of peripheral axon terminals. Using an animal model of Miller Fisher syndrome, we recently reported that a monoclonal anti-polysialoganglioside GQ1b antibody plus complement damages nerve terminals with production of mitochondrial hydrogen peroxide, which activates Schwann cells. Several additional signaling molecules are likely to be involved in the activation of the regeneration program in these cells. Using an in vitro cellular model consisting of co-cultured primary neurons and Schwann cells, we found that ATP is released by neurons injured by the anti-GQ1b antibody plus complement. Neuron-derived ATP acts as an alarm messenger for Schwann cells, where it induces the activation of intracellular pathways, including calcium signaling, cAMP and CREB, which, in turn, produce signals that promote nerve regeneration. These results contribute to defining the cross-talk taking place at the neuromuscular junction when it is attacked by anti-gangliosides autoantibodies plus complement, which is crucial for nerve regeneration and is also likely to be important in other peripheral neuropathies. © 2017. Published by The Company of Biologists Ltd.

  13. Schwann cells are activated by ATP released from neurons in an in vitro cellular model of Miller Fisher syndrome

    Directory of Open Access Journals (Sweden)

    Umberto Rodella

    2017-05-01

    Full Text Available The neuromuscular junction is exposed to different types of insult, including mechanical trauma, toxins and autoimmune antibodies and, accordingly, has retained through evolution a remarkable ability to regenerate. Regeneration is driven by multiple signals that are exchanged among the cellular components of the junction. These signals are largely unknown. Miller Fisher syndrome is a variant of Guillain–Barré syndrome caused by autoimmune antibodies specific for epitopes of peripheral axon terminals. Using an animal model of Miller Fisher syndrome, we recently reported that a monoclonal anti-polysialoganglioside GQ1b antibody plus complement damages nerve terminals with production of mitochondrial hydrogen peroxide, which activates Schwann cells. Several additional signaling molecules are likely to be involved in the activation of the regeneration program in these cells. Using an in vitro cellular model consisting of co-cultured primary neurons and Schwann cells, we found that ATP is released by neurons injured by the anti-GQ1b antibody plus complement. Neuron-derived ATP acts as an alarm messenger for Schwann cells, where it induces the activation of intracellular pathways, including calcium signaling, cAMP and CREB, which, in turn, produce signals that promote nerve regeneration. These results contribute to defining the cross-talk taking place at the neuromuscular junction when it is attacked by anti-gangliosides autoantibodies plus complement, which is crucial for nerve regeneration and is also likely to be important in other peripheral neuropathies.

  14. Injectable Chitosan/β-Glycerophosphate System for Sustained Release: Gelation Study, Structural Investigation, and Erosion Tests.

    Science.gov (United States)

    Dalmoro, Annalisa; Abrami, Michela; Galzerano, Barbara; Bochicchio, Sabrina; Barba, Anna Angela; Grassi, Mario; Larobina, Domenico

    2017-01-01

    Hydrogels can constitute reliable delivery systems of drugs, including those based on nucleic acids (NABDs) such as small interfering ribonucleic acid (siRNA). Their nature, structure, and response to physiological or external stimuli strongly influence the delivery mechanisms of entrapped active molecules, and, in turn, their possible uses in pharmacological and biomedical applications. In this study, a thermo-gelling chitosan/β-glycero-phosphate system has been optimized in order to assess its use as injectable system able to: i) gelling at physiological pH and temperature, and ii) modulate the release of included active ingredients. To this aim, we first analyzed the effect of acetic acid concentration on the gelation temperature. We then found the "optimized composition", namely, the one in which the Tgel is equal to the physiological temperature. The resulting gel was tested, by low field nuclear magnetic resonance (LF-NMR), to evaluate its average mesh-size, which can affect release kinetics of loaded drug. Finally, films of gelled chitosan, loaded with a model drug, have been tested in vitro to monitor their characteristic times, i.e. diffusion and erosion time, when they are exposed to a medium mimicking a physiological environment (buffer solution at pH 7.4). Results display that the optimized system is deemed to be an ideal candidate as injectable gelling material for a sustained release. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. The Regulation of Endogenous Glutamate and GABA Release from In Vitro Preparations of Rat Striatum

    Science.gov (United States)

    1997-09-19

    Butcher SP~ JW Lazarewicz and A Hamberger, In vivo microdialysis studies on the effects of decortication and excitotoxic lesions on kainic acid-induced...striatum and cerebral cortex of guinea pig and rat. Neurosci. 31 (1989). 313-25. Lapper SR and JP Bolam. Input from the frontal cortex and the papafascicuIar

  16. A Smart pH-responsive Nano-Carrier as a Drug Delivery System: A hybrid system comprised of mesoporous nanosilica MCM-41 (as a nano-container) & a pH-sensitive polymer (as smart reversible gatekeepers): Preparation, characterization and in vitro release studies of an anti-cancer drug.

    Science.gov (United States)

    Abbaszad Rafi, Abdolrahim; Mahkam, Mehrdad; Davaran, Soodabeh; Hamishehkar, Hamed

    2016-10-10

    A smart pH-responsive drug nano-carrier for controlled release of anti-cancer therapeutics was developed through a facile route. The nano-carrier consisted of two main parts: first, the nano-container part (that mesoporous silica nanoparticles (MCM-41) were selected for this aim); and second, pH-sensitive gatekeepers (that a pH-sensitive polymer, Poly4-vinylpyridine, played this role). In the first step, MCM-41 was synthesized via template assisted sol-gel process. In the second step, polymerizable functional groups were attached onto pore entrances rather than inside walls. In the third step, polymeric gatekeepers were introduced onto pore entrances via precipitation polymerization of functionalized MCM-41 with monomers. Different methods and analysis, such as Fourier Transform Infrared Spectroscopy (FT-IR), X-ray Powder Diffraction (XRD), Thermo-Gravimetric Analysis (TGA), Energy-Dispersive X-ray Spectroscopy (EDX), Zeta Potentials, Dynamic Light Scattering (DLS), Field Emission Scanning Electron Microscope (FE-SEM) and Transmission Electron Microscopy (TEM) were employed to approve the successful attachment of gatekeepers. Furthermore, the release studies of methotroxate (MTX), an anti-cancer drug, were performed in different media (pH4, 5.8 and 7.4) at 37±1°C. The release profiles and curves show that the release rates are completely pH-dependent and it proceeds with a decrease in pH. It is concluded that in the higher pH the gatekeepers are in their close state, but they switch to the open state as a consequence of repulsive forces between positively charged polymer chains appear in acidic media. The results suggest that this smart nano-carrier can be considered as an appropriate candidate to deliver therapeutics to cancerous tissues. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. 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.

  18. Canine neutrophil extracellular traps release induced by the apicomplexan parasite Neospora Caninum in vitro

    Directory of Open Access Journals (Sweden)

    Zhengkai Wei

    2016-10-01

    Full Text Available Neosporosis is considered as one of the main causes of abortion and severe economic losses in dairy industry. The Canis genus serving as one of the confirmed definitive hosts of the apicomplexan parasite Neospora caninum (N. caninum plays a critical role in its life cycle. However, the effects of N. caninum on its definitive hosts of neutrophils extracellular traps (NETs formation remain unclear. In the present study, N. caninum tachyzoite-induced canine NETs formation was observed by scanning electron microscopy (SEM. Visualization of DNA decorated with H3, NE and MPO within N. caninum tachyzoite-induced NETs were examined using fluorescence confocal microscopy analyses. Furthermore, the formation of canine NETs was quantified using Sytox Green staining, and the LDH levels in supernatants were examined by an LDH Cytotoxicity Assay® kit. The results clearly showed that NETs-like structures were induced by N. caninum tachyzoites, and the major components within these structures induced by N. caninum tachyzoite were further confirmed by fluorescence confocal microscopy visualization. These results suggest that N. caninum tachyzoites strongly induced NETs formation in canine PMN. In functional inhibition assays, the blockings of NADPH oxidase, NE, MPO, SOCE, ERK 1/2 and p38 MAPK signaling pathways significantly inhibited N. caninum tachyzoite-induced NETs formation, which suggests that N. caninum tachyzoite-induced NETs formation is a NADPH oxidase-, NE-, MPO-, SOCE-, ERK 1/2- and p38 MAPK-dependent cell death process. To our knowledge, this study is the first to report the formation of NETs in canine PMN against N. caninum infection.

  19. Characterization and Compatibility Studies of Different Rate Retardant Polymer Loaded Microspheres by Solvent Evaporation Technique: In Vitro-In Vivo Study of Vildagliptin as a Model Drug

    Directory of Open Access Journals (Sweden)

    Irin Dewan

    2015-01-01

    Full Text Available The present study has been performed to microencapsulate the antidiabetic drug of Vildagliptin to get sustained release of drug. The attempt of this study was to formulate and evaluate the Vildagliptin loaded microspheres by emulsion solvent evaporation technique using different polymers like Eudragit RL100, Eudragit RS100, Ethyl cellulose, and Methocel K100M. In vitro dissolution studies were carried out in 0.1 N HCl for 8 hours according to USP paddle method. The maximum and minimum drug release were observed as 92.5% and 68.5% from microspheres, respectively, after 8 hours. Release kinetics were studied in different mathematical release models to find out the linear relationship and release rate of drug. The SEM, DSC, and FTIR studies have been done to confirm good spheres and smooth surface as well as interaction along with drug and polymer. In this experiment, it is difficult to explain the exact mechanism of drug release. But the drug might be released by both diffusion and erosion as the correlation coefficient (R2 best fitted with Korsmeyer model and release exponent (n was 0.45–0.89. At last it can be concluded that all in vitro and in vivo experiments exhibited promising result to treat type II diabetes mellitus with Vildagliptin microspheres.

  20. Characterization and Compatibility Studies of Different Rate Retardant Polymer Loaded Microspheres by Solvent Evaporation Technique: In Vitro-In Vivo Study of Vildagliptin as a Model Drug

    Science.gov (United States)

    Dewan, Irin; Islam, Swarnali; Rana, Md. Sohel

    2015-01-01

    The present study has been performed to microencapsulate the antidiabetic drug of Vildagliptin to get sustained release of drug. The attempt of this study was to formulate and evaluate the Vildagliptin loaded microspheres by emulsion solvent evaporation technique using different polymers like Eudragit RL100, Eudragit RS100, Ethyl cellulose, and Methocel K100M. In vitro dissolution studies were carried out in 0.1 N HCl for 8 hours according to USP paddle method. The maximum and minimum drug release were observed as 92.5% and 68.5% from microspheres, respectively, after 8 hours. Release kinetics were studied in different mathematical release models to find out the linear relationship and release rate of drug. The SEM, DSC, and FTIR studies have been done to confirm good spheres and smooth surface as well as interaction along with drug and polymer. In this experiment, it is difficult to explain the exact mechanism of drug release. But the drug might be released by both diffusion and erosion as the correlation coefficient (R 2) best fitted with Korsmeyer model and release exponent (n) was 0.45–0.89. At last it can be concluded that all in vitro and in vivo experiments exhibited promising result to treat type II diabetes mellitus with Vildagliptin microspheres. PMID:26640713

  1. Drug release into hydrogel-based subcutaneous surrogates studied by UV imaging

    DEFF Research Database (Denmark)

    Ye, Fengbin; Larsen, Susan Weng; Yaghmur, Anan

    2012-01-01

    of the performance of drug delivery systems based on in vitro experiments. The objective of this study was to evaluate a UV imaging-based method for real-time characterization of the release and transport of piroxicam in hydrogel-based subcutaneous tissue mimics/surrogates. Piroxicam partitioning from medium chain...... triglyceride (MCT) into 0.5% (w/v) agarose or 25% (w/v) F127-based hydrogels was investigated by monitoring the concentration profiles of the drug in the gels. The effect of pH on piroxicam distribution and diffusion coefficients was studied. For both hydrogel systems, the diffusion of piroxicam in the gels...... upon the injection of aqueous or MCT solutions into an agarose-based hydrogel were investigated by UV imaging. The spatial distribution of piroxicam around the injection site in the gel matrix was monitored in real-time. The disappearance profiles of piroxicam from the injected aqueous solution were...

  2. In Vitro Evaluation of Nasogastric Tube Delivery Performance of Esomeprazole Magnesium Delayed-Release Capsules.

    Science.gov (United States)

    Hoover, Alicia; Sun, Dajun; Wen, Hong; Jiang, Wenlei; Cui, Minglei; Jiang, Xiaojian; Keire, David; Guo, Changning

    2017-07-01

    Enteral feeding tubes are used to deliver food or drugs to patients who cannot swallow. To deliver delayed-release drugs that are formulated as enteric coated granules to these patients via feeding tubes requires that they be suspended in water before administration. Importantly, the suspension of enteric granules in water of varying pH can cause damage to the enteric coating and affect the bioavailability of the drug. Here, analytical methods for testing acid resistance stability and particle size distribution (PSD) of esomeprazole granules were used to monitor the integrity of the granule enteric coating after water pretreatment and delivery through an oral syringe and nasogastric (NG) tube. Granules from esomeprazole magnesium delayed-release capsules were transferred to an oral syringe, suspended in water, and delivered on the bench through an NG tube. Subsequently, acid resistance stability (i.e., the amount of drug released after 2-h acid dissolution) was determined via high-performance liquid chromatography, and the PSD were measured with a laser diffraction system. All the granules demonstrated acid resistance stability when the granules were delivered immediately (0 min incubation) through the oral syringe and NG tube. In contrast, some granules demonstrated significant drug release during acid exposure after a 15-min incubation period which mimics a possible delay in delivery of the drug from the syringe by the caregiver. A bimodal PSD was observed with these granules, which was attributed to debris from damaged enteric coating and particle agglomeration. The methods developed in this study could be used to distinguish batches with suboptimal product quality for delivery using NG tubes and to confirm the substitutability of generic drug products for this alternative route of administration. Published by Elsevier Inc.

  3. Formulation optimization study for an immediate-release tablet.

    Science.gov (United States)

    Kyriacos, Soula; Dimassi, Hani

    2009-01-01

    A simple method based on statistical analysis was used to optimize an immediate-release tablet formulation that includes a water soluble drug. The objective of this study was to optimize different factors to develop a tablet formulation that has good tablet characteristics (hardness of 85 to 90 Newtons), disintegration time between 3 to 6 minutes, and friability of less than 1%. The critical formulation/process factors were the type and concentration of microcrystalline cellulose, the ratio of lactose to microcrystalline cellulose, the concentration of croscarmellose, and the the compression force. A two-step approach was implemented. First an optimization study was performed to determine the type of microcrystalline cellulose and its ratio to lactose. Subsequently, a final optimization formulation study was performed based on the results obtained in the preliminary study. Data were analyzed using the SPSS 15 (Statistical Software for Social Sciences). The differences in means between the formulation and the targeted product were tested using the independent t-test. The optimization study gave the following results: croscarmellose 1%, anhydrous lactose: Avicel PH-302 at a ratio of 3 to 1, magnesium stearate 0.25% compressed into tablets at a pressure of 2.5 tons. A high P value reflected no statistical difference with the reference product. A final formulation was scaled up to 52 tablets and product quality was confirmed. The new formulation was successfully developed using a simple two-step approach. The results of the study in terms of disintegration, hardness, and friability showed no statistically significant defference between the new and the targeted formulation. Statistical analysis provides a systemic approach and allows a rapid and effective way to compound an immediate-release tablet for a water-soluble drug.

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

    Directory of Open Access Journals (Sweden)

    Ting Zuo

    2016-12-01

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

  5. 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.

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

    Science.gov (United States)

    Wang, Xiang; Wang, Gen; Zhang, Ying

    2017-10-01

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

  7. Bovine oviductal monolayers cultured under three-dimension conditions secrete factors able to release spermatozoa adhering to the tubal reservoir in vitro.

    Science.gov (United States)

    Gualtieri, R; Mollo, V; Braun, S; Barbato, V; Fiorentino, I; Talevi, R

    2013-02-01

    Different in vitro models have been developed to understand the interaction of gametes and embryos with the maternal reproductive tract. We recently showed that bovine oviductal monolayers three-dimensionally cultured in Gray's medium on collagen-coated microporous polycarbonate inserts under liquid-air interface conditions are well polarized, develop cilia, remain viable for at least 3 weeks postconfluence, and mantain the viability of bound spermatozoa significantly better than bidimensionally cultured monolayers. Herein, we used these culture conditions to understand whether: (1) spermatozoa adhering to three-dimensionally cultured oviductal monolayers can be released by heparin or penicillamine as previously shown with bidimensionally cultured oviductal monolayers and explants; and (2) media conditioned by three-dimensionally cultured oviductal monolayers were able to release spermatozoa adhering to oviductal explants. Findings demonstrated that (1) spermatozoa adhering to three-dimensionally cultured oviductal monolayers are readily released by heparin and penicillamine, (2) media conditioned by three-dimensionally cultured oviductal monolayers are able to release spermatozoa bound to oviductal explants, (3) do not depress sperm motility and viability, (4) they improve sperm kinetics, and (5) promote binding to the zona pellucida. In conclusion, in vitro data suggest that the release of spermatozoa adhering to the oviductal reservoir in vivo can be triggered by factors secreted by the oviduct itself that induce sperm capacitation. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. The development of a link model consisting of in vitro drug release and tablets gastric emptying time: application to diclofenac enteric coated tablets

    OpenAIRE

    Mrhar, Aleš; Grabnar, Iztok; Bogataj, Marija; Locatelli, Igor

    2015-01-01

    Objectives: The bioavailability of well permeable drugs administered as single-unit modified release tablet is markedly dependent on the gastric emptying time of such tablet, especially when taken in fasted stomach state. The influence of pH on drug release can be evaluated in vitro. On the other hand, the vector of tablets gastric emptying times is a random variable and can be generated from Weibull distribution function [1,2]. The purpose was to develop a link model consisting of the kineti...

  9. Release of arachidonic and linoleic acid metabolites in skin organ cultures as characteristics of in vitro skin irritancy

    NARCIS (Netherlands)

    Sandt, J.J.M. van de; Maas, W.J.M.; Doornink, P.C.; Rutten, A.A.J.J.L.

    1995-01-01

    In vitro techniques make a major contribution to the development of alternatives to the in vivo 'Draize' skin irritation test, and the development of sensitive and generally applicable in vitro endpoints of cutaneous toxicity is an area of intensive research. To investigate in vitro characteristics

  10. Direct effect of hypothalamic neuropeptides on the release of catecholamines by adrenal medulla in sheep - study ex vivo.

    Science.gov (United States)

    Wrońska, D; Kania, B F; Błachuta, M

    2017-03-01

    Stress causes the activation of both the hypothalamic-pituitary-adrenocortical axis and sympatho-adrenal system, thus leading to the release from the adrenal medulla of catecholamines: adrenaline and, to a lesser degree, noradrenaline. It has been established that in addition to catecholamines, the adrenomedullary cells produce a variety of neuropeptides, including corticoliberine (CRH), vasopressin (AVP), oxytocin (OXY) and proopiomelanocortine (POMC) - a precursor of the adrenocorticotropic hormone (ACTH). The aim of this study was to investigate adrenal medulla activity in vitro depending, on a dose of CRH, AVP and OXY on adrenaline and noradrenaline release. Pieces of sheep adrenal medulla tissue (about 50 mg) were put on 24-well plates and were incubated in 1 mL of Eagle medium without hormone (control) or supplemented only once with CRH, AVP and OXY in three doses (10-7, 10-8 and 10-9 M) in a volume of 10 μL. The results showed that CRH stimulates adrenaline and noradrenaline release from the adrenal medulla tissue. The stimulating influence of AVP on adrenaline release was visible after the application of the two lower doses of this neuropeptide; however, AVP reduced noradrenaline release from the adrenal medulla tissue. A strong, inhibitory OXY effect on catecholamine release was observed, regardless of the dose of this hormone. Our results indicate the important role of OXY in the inhibition of adrenal gland activity and thus a better adaptation to stress on the adrenal gland level.

  11. Zeolite-based hemostat QuikClot releases calcium into blood and promotes blood coagulation in vitro.

    Science.gov (United States)

    Li, Jing; Cao, Wei; Lv, Xiao-xing; Jiang, Li; Li, Yue-jun; Li, Wang-zhou; Chen, Shao-zong; Li, Xue-yong

    2013-03-01

    To examine the changes in electrolyte concentrations after addition of zeolite-based hemostat QuikClot in blood and the effects of zeolite on blood coagulation in vitro. Fresh blood was taken from healthy adult volunteers and sheep, and the electrolyte concentrations in blood were measured using a blood electrolyte analyzer. Zeolite Saline Solution (ZSS) was prepared by addition of 2 g zeolite to 0.9% NaCl solution (4, 8, or 16 mL). The electrolytes in ZSS were measured using inductively coupled plasma atomic emission spectroscopy. The prothrombin time (PT) and activated partial thromboplastin time (APTT) of blood were measured using the test tube method. The activated clotting time (ACT) and clotting rate (CR) of blood were measured with Sonoclot Coagulation and Platelet Function Analyzer. Addition of zeolite (50 and 100 mg) in 2 mL human blood significantly increased Ca(2+) concentration, while Na(+) and K(+) concentrations were significantly decreased. Addition of zeolite (50 and 100 mg) in 0.9% NaCl solution (2 mL) caused similar changes in Ca(2+) and Na(+) concentrations. Si(4+) (0.2434 g/L) and Al(3+) (0.2575 g/L) were detected in ZSS (2 g/8 mL). Addition of ZSS in sheep blood shortened APTT in a concentration dependent manner, without changing PT. ZSS or aqueous solution of CaCl2 that contained Ca(2+) concentration identical to that of ZSS significantly shortened ACT in human blood without significantly changing CR, and the effect of ZSS on ACT was not significantly different from that of CaCl2. Zeolite releases Ca(2+) into blood, thus accelerating the intrinsic pathway of blood coagulation and shortening the clot formation time.

  12. Iron Bioavailability Studies of the First Generation of Iron-Biofortified Beans Released in Rwanda

    Science.gov (United States)

    Glahn, Raymond; Tako, Elad; Hart, Jonathan; Haas, Jere; Beebe, Steve

    2017-01-01

    This paper represents a series of in vitro iron (Fe) bioavailability experiments, Fe content analysis and polyphenolic profile of the first generation of Fe biofortified beans (Phaseolus vulgaris) selected for human trials in Rwanda and released to farmers of that region. The objective of the present study was to demonstrate how the Caco-2 cell bioassay for Fe bioavailability can be utilized to assess the nutritional quality of Fe in such varieties and how they may interact with diets and meal plans of experimental studies. Furthermore, experiments were also conducted to directly compare this in vitro approach with specific human absorption studies of these Fe biofortified beans. The results show that other foods consumed with beans, such as rice, can negatively affect Fe bioavailability whereas potato may enhance the Fe absorption when consumed with beans. The results also suggest that the extrinsic labelling approach to measuring human Fe absorption can be flawed and thus provide misleading information. Overall, the results provide evidence that the Caco-2 cell bioassay represents an effective approach to evaluate the nutritional quality of Fe-biofortified beans, both separate from and within a targeted diet or meal plan. PMID:28754026

  13. Iron Bioavailability Studies of the First Generation of Iron-Biofortified Beans Released in Rwanda.

    Science.gov (United States)

    Glahn, Raymond; Tako, Elad; Hart, Jonathan; Haas, Jere; Lung'aho, Mercy; Beebe, Steve

    2017-07-21

    This paper represents a series of in vitro iron (Fe) bioavailability experiments, Fe content analysis and polyphenolic profile of the first generation of Fe biofortified beans (Phaseolus vulgaris) selected for human trials in Rwanda and released to farmers of that region. The objective of the present study was to demonstrate how the Caco-2 cell bioassay for Fe bioavailability can be utilized to assess the nutritional quality of Fe in such varieties and how they may interact with diets and meal plans of experimental studies. Furthermore, experiments were also conducted to directly compare this in vitro approach with specific human absorption studies of these Fe biofortified beans. The results show that other foods consumed with beans, such as rice, can negatively affect Fe bioavailability whereas potato may enhance the Fe absorption when consumed with beans. The results also suggest that the extrinsic labelling approach to measuring human Fe absorption can be flawed and thus provide misleading information. Overall, the results provide evidence that the Caco-2 cell bioassay represents an effective approach to evaluate the nutritional quality of Fe-biofortified beans, both separate from and within a targeted diet or meal plan.

  14. Polyurethane/hydroxypropyl cellulose electrospun nanofiber mats as potential transdermal drug delivery system: characterization studies and in vitro assays.

    Science.gov (United States)

    Gencturk, A; Kahraman, E; Güngör, S; Özhan, G; Özsoy, Y; Sarac, A S

    2017-05-01

    Donepezil hydrochloride containing polyurethane/hydroxypropyl cellulose (PU/HPC) nanofibers were prepared by the electrospinning for transdermal drug delivery. PU/HPC nanofibers were characterized with SEM, DSC, and Pascal mercury porosimetry. Drug-excipient interaction was studied by ATR-FTIR. In vitro release of PU/HPC nanofiber mat (10:2:1) exhibited Korsmeyer-Peppas release kinetics controlled by the diffusion of drug. In vitro permeation studies across skin resembling synthetic membrane demonstrated the flux of model drug. The in vitro cytotoxicity data obtained via MTT assay indicated that PU/HPC nanofiber mat could be well tolerated by the skin and the components was not irritant for the skin.

  15. In vitro IFN-α release from IFN-α- and pegylated IFN-α-loaded poly(lactic-co-glycolic acid) and pegylated poly(lactic-co-glycolic acid) nanoparticles.

    Science.gov (United States)

    Feczkó, Tivadar; Fodor-Kardos, Andrea; Sivakumaran, Muttuswamy; Haque Shubhra, Quazi Tanminul

    2016-08-01

    Interferon alpha (IFN-α) controlled release of nanoparticles was investigated under in vitro conditions. IFN-α and pegylated IFN-α (PEG-IFN-α) were encapsulated by poly(lactic-co-glycolic acid) (PLGA) and pegylated PLGA (PEG-PLGA) copolymers using double emulsion solvent evaporation method. The size of resulting four nanoparticles (IFN-α in poly(lactic-co-glycolic acids), IFN-α in poly(lactic-co-glycolic acid)-polyethylene glycol, PEG-IFN-α in poly(lactic-co-glycolic acids) and PEG-IFN-α in poly(lactic-co-glycolic acid)-polyethylene glycol) was below 130 nm diameter. IFN-α encapsulation efficiency of the nanoparticles was between 78 and 91%. The in vitro drug release studies conducted in phosphate-buffered saline and human plasma highlighted the role of incubation medium on the IFN release from the nanoparticles. The PEG-IFN-α in poly(lactic-co-glycolic acid)-polyethylene glycol was the most promising nanoparticle among the four formulations because of its remarkably constant release in both phosphate-buffered saline and plasma.

  16. The slow-releasing hydrogen sulfide donor, GYY4137, exhibits novel anti-cancer effects in vitro and in vivo.

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    Zheng Wei Lee

    Full Text Available The slow-releasing hydrogen sulfide (H₂S donor, GYY4137, caused concentration-dependent killing of seven different human cancer cell lines (HeLa, HCT-116, Hep G2, HL-60, MCF-7, MV4-11 and U2OS but did not affect survival of normal human lung fibroblasts (IMR90, WI-38 as determined by trypan blue exclusion. Sodium hydrosulfide (NaHS was less potent and not active in all cell lines. A structural analogue of GYY4137 (ZYJ1122 lacking sulfur and thence not able to release H₂S was inactive. Similar results were obtained using a clonogenic assay. Incubation of GYY4137 (400 µM in culture medium led to the generation of low (<20 µM concentrations of H₂S sustained over 7 days. In contrast, incubation of NaHS (400 µM in the same way led to much higher (up to 400 µM concentrations of H₂S which persisted for only 1 hour. Mechanistic studies revealed that GYY4137 (400 µM incubated for 5 days with MCF-7 but not IMR90 cells caused the generation of cleaved PARP and cleaved caspase 9, indicative of a pro-apoptotic effect. GYY4137 (but not ZYJ1122 also caused partial G₂/M arrest of these cells. Mice xenograft studies using HL-60 and MV4-11 cells showed that GYY4137 (100-300 mg/kg/day for 14 days significantly reduced tumor growth. We conclude that GYY4137 exhibits anti-cancer activity by releasing H₂S over a period of days. We also propose that a combination of apoptosis and cell cycle arrest contributes to this effect and that H₂S donors should be investigated further as potential anti-cancer agents.

  17. Bactericidal Activity of Copper Oxide Nanocomposite/Bioglass for in Vitro Clindamycin Release in Implant Infections Due to Staphylococcus aureus

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    Alijanian

    2016-08-01

    Full Text Available Background In recent years, bioactive bioceramics such as bioglass and hydroxyapatite (HA have been introduced as a remarkable development in the field of medicine due to their bio-adaptability, non-toxicity, and persistence, in vivo. They have many potential applications in the repair of bone defects and hence they have attracted significant interest from scholars. Objectives The aim of this study was to synthesize inorganic matrix CuO-based bioglasses and evaluate their antibacterial activity against aerobic bacterial infections in bone implants. Methods Nano-composite samples of silica-based bioactive glass, 60S BG with nano-powder CuO, were synthesized using the sol-gel method and then assessed with regard to their antibacterial properties against Staphylococcus aureus using well diffusion agar. The samples included BG58S (58%SiO2, 36%CaO, 6%P2O5, BG/10CuO (58%SiO2, 26%CaO, 6%P2O5, 10%CuO, and BG/20CuO (48%SiO2, 26%CaO, 6%P2O5, 20%CuO. To evaluate their bioactivity, the prepared samples of BG/20CuO, BG/10CuO, and BG58S were immersed in simulated body fluids (SBF. The surface morphology and structure of the samples before and after immersion in the SBF were characterized using scanning electron microscopy (SEM and Fourier transform infrared (FTIR, respectively. Then, the BG/20CuO and BG/10CuO samples were loaded in clindamycin, an antibiotic widely used in the treatment of osteomyelitis, and their release profiles were studied in phosphate buffer solution. Results It was observed that the growth inhibition zone increased through clindamycin release due to the increasing CuO percentage in the nanocomposite of bioactive glass. The bioactivity of the nanocomposite/bioglass with CuO was superior to that of bioglass alone. In this study, the BG/20CuO sample showed a sustained release of clindamycin, which is sufficient for a drug delivery system. Conclusions Increasing the Cu nanoparticles in bioactive glass samples leads to the release of Cu2

  18. An Accelerated Release Study to Evaluate Long-Acting Contraceptive Levonorgestrel-Containing in Situ Forming Depot Systems

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    Dileep R. Janagam

    2016-09-01

    Full Text Available Biodegradable polymer-based injectable in situ forming depot (ISD systems that solidify in the body to form a solid or semisolid reservoir are becoming increasingly attractive as an injectable dosage form for sustained (months to years parenteral drug delivery. Evaluation of long-term drug release from the ISD systems during the formulation development is laborious and costly. An accelerated release method that can effectively correlate the months to years of long-term release in a short time such as days or weeks is economically needed. However, no such accelerated ISD system release method has been reported in the literature to date. The objective of the current study was to develop a short-term accelerated in vitro release method for contraceptive levonorgestrel (LNG-containing ISD systems to screen formulations for more than 3-month contraception after a single subcutaneous injection. The LNG-containing ISD formulations were prepared by using biodegradable poly(lactide-co-glycolide and polylactic acid polymer and solvent mixtures containing N-methyl-2-pyrrolidone and benzyl benzoate or triethyl citrate. Drug release studies were performed under real-time (long-term conditions (PBS, pH 7.4, 37 °C and four accelerated (short-term conditions: (A PBS, pH 7.4, 50 °C; (B 25% ethanol in PBS, pH 7.4, 50 °C; (C 25% ethanol in PBS, 2% Tween 20, pH 7.4, 50 °C; and (D 25% ethanol in PBS, 2% Tween 20, pH 9, 50 °C. The LNG release profile, including the release mechanism under the accelerated condition D within two weeks, correlated (r2 ≥ 0.98 well with that under real-time conditions at four months.

  19. Formulation, release characteristics, and bioavailability study of gastroretentive floating matrix tablet and floating raft system of Mebeverine HCl.

    Science.gov (United States)

    El Nabarawi, Mohamed A; Teaima, Mahmoud H; Abd El-Monem, Rehab A; El Nabarawy, Nagla A; Gaber, Dalia A

    2017-01-01

    To prolong the residence time of dosage forms within the gastrointestinal tract until all drug is released at the desired rate is one of the real challenges for oral controlled-release drug delivery systems. This study was designed to develop a controlled-release floating matrix tablet and floating raft system of Mebeverine HCl (MbH) and evaluate different excipients for their floating behavior and in vitro controlled-release profiles. Oral pharmacokinetics of the optimum matrix tablet, raft system formula, and marketed Duspatalin® 200 mg retard as reference were studied in beagle dogs. The optimized tablet formula (FT-10) and raft system formula (FRS-11) were found to float within 34±5 sec and 15±7 sec, respectively, and both remain buoyant over a period of 12 h in simulated gastric fluid. FT-10 (Compritol/HPMC K100M 1:1) showed the slowest drug release among all prepared tablet formulations, releasing about 80.2% of MbH over 8 h. In contrast, FRS-11 (Sodium alginate 3%/HPMC K100M 1%/Precirol 2%) had the greatest retardation, providing sustained release of 82.1% within 8 h. Compared with the marketed MbH product, the Cmax of FT-10 was almost the same, while FRS-11 maximum concentration was higher. The tmax was 3.33, 2.167, and 3.0 h for marketed MbH product, FT-10, and FRS-11, respectively. In addition, the oral bioavailability experiment showed that the relative bioavailability of the MbH was 104.76 and 116.01% after oral administration of FT-10 and FRS-11, respectively, compared to marketed product. These results demonstrated that both controlled-released floating matrix tablet and raft system would be promising gastroretentive delivery systems for prolonging drug action.

  20. Spectral studies of Donepezil release from streched PVA polymer films

    Science.gov (United States)

    Nechifor, Cristina-Delia; Zelinschi, Carmen-Beatrice; Stoica, Iuliana; Closca, Valentina; Dorohoi, Dana-Ortansa

    2013-07-01

    The focus of this research is to obtain poly vinyl alcohol (PVA) polymer foils containing Donepezil in different concentration, in order to be used in controlled drug release as a palliative treatment of mild to moderate Alzheimer's disease. The influence of polymeric foil stretching degree on drug release was analyzed using spectral measurements.

  1. Mesoporous nano-bioglass designed for the release of imatinib and in vitro inhibitory effects on cancer cells.

    Science.gov (United States)

    Shoaib, Muhammad; Saeed, Aamer; Rahman, Muhammad Saif Ur; Naseer, Muhammad Moazzam

    2017-08-01

    For treating bone cancer, controlled drug delivery is an important strategy. Bioactive scaffolds are widely used biomaterials due to their usefulness in localized drug delivery. The aim of this study was to develop mesoporous bioglass (MBG) with improved bioactivity and controllable drug delivery rate. By using pluronic 123 (P123) as a template, a facile sol-gel route was employed for the synthesis of MBG nanoparticles (NPs). The composition of the prepared sample was estimated by using energy dispersive X-ray spectroscopy (EDX). These nanoparticles demonstrated the specific surface area of 310m 2 /g and pore size of 13nm as measured by brunauer-emmett-teller (BET) and barrett-joyner-halenda (BJH) method, respectively. The spherical shape of NPs was confirmed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Imatinib (IMT); an anti-cancer drug was loaded with the efficiency of 77.59%. The drug release kinetics were precisely controlled by changing the pH (4.4 to 10.4) as well as drug loading concentration (0.2-1.0mg/mL). The maximum cumulative drug release of 81% was observed over a time period of 250h at pH of 4.4. Importantly, significant inhibitory effects on the viability of the MG-63 osteocarcinoma cancer cells at 12.19μg/mL of IMT-MBG were observed. Furthermore, MBG demonstrated ionic dissolution with the release of Ca, K, Si, Na, and P ions upon immersion in simulated body fluid (SBF), which support the formation of hydroxycarbonate apatite (HCA), as confirmed by wide-angle X-ray diffraction (WAXD) pattern and fourier transform infrared (FTIR) spectroscopy. These features proved that IMT-MBG system is effective for bone tissue regeneration and bone cancer treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Synthesis and Characterization of Sodium Alginate Conjugate and Study of Effect of Conjugation on Drug Release from Matrix Tablet.

    Science.gov (United States)

    Satheeshababu, B K; Mohamed, I

    2015-01-01

    The aim of the present research work to study the effect of conjugation of the polymer on drug release from the matrix tablets. Sodium alginate L-cysteine conjugate was achieved by covalent attachment of thiol group of L-cysteine with the primary amino group of sodium alginate through the amide bonds formed by primary amino groups of the sodium alginate and the carboxylic acid group of L-cysteine. The synthesised sodium alginate L-cysteine conjugate was characterised by determining of charring point, Fourier transmission-infrared and differential scanning calorimetric analysis. To study the effect of conjugation on drug release pattern, the matrix tablets were prepared using various proportions of sodium alginate and sodium alginate L-cysteine conjugate along with atorvastatin calcium as model drug. The wet granulation technique was adopted and prepared matrix tablets were evaluated for various physical parameters. The in vitro drug release study results suggested that tablet formulated in combination of sodium alginate and sodium alginate L-cysteine conjugate S4 showed 100% after 8 h drug release whereas formulated with only sodium alginate S0 released 40% in 8 h.

  3. Elution of ciprofloxacin from acrylic bone cement and fibrin clot: an in vitro study.

    Science.gov (United States)

    Tsourvakas, Stefanos; Alexandropoulos, Christos; Karatzios, Christos; Egnatiadis, Nikolaos; Kampagiannis, Nikolaos

    2009-08-01

    The purpose of this study was to investigate the release of ciprofloxacin from acrylic bone cement and fibrin clot. Under sterile conditions, bone cement and fibrin clot were individually mixed with ciprofloxacin. Ten specimens of each complex were placed in 1 ml of nutrient broth and incubated at 37 degrees C. The nutrient broth was changed daily, and the removed samples were stored at -70 degrees C until the antibiotic concentration in each sample was determined by a microbiological method. The maximum level in bone cement specimens was obtained at the second day (80.80 microg/ml) and its diffusion was rapid at first, decreasing gradually over a period of 365 days. Fibrin clot biodegradable specimens released high concentrations of ciprofloxacin (1.52-49.91 microg/ml) in vitro for the period of time needed to treat bone infections (i.e. 65 days). We conclude that the high release of ciprofloxacin in vitro from acrylic bone cement and fibrin clot is very promising since the obtained levels are much higher than the required minimal inhibitory concentration (MIC) against the implicated pathogens in soft tissue and bone infections. The in vivo relevance of the obtained results requires carefully performed studies in animal models.

  4. 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.

  5. Effect of Sulindac Binary System on In Vitro and In Vivo Release Profiles: An Assessment of Polymer Type and Its Ratio

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    Gamal A. Shazly

    2016-01-01

    Full Text Available The bioavailability of sulindac (SDC, a nonsteroidal anti-inflammatory drug, is low due to poor aqueous solubility and poor dissolution rate. For this reason it is necessary to enhance the solubility and enhance dissolution of the drug by dispersing SDC in polyethylene glycols 6000 (PEG 6000 and polyvinyl pyrrolidone 40000 (PVP 40000 matrices using the coevaporation technique. Studying the influence of SDC to polymer ratio on drug content, percent yield, particle size, and in vitro release was performed. Differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy were used to characterize any change in crystal habit of SDC in the prepared formulae. The anti-inflammatory effect of SDC was studied using the hind paw edema model. It was found that incorporation of SDC in PEG 6000 and PVP 40000 matrices resulted in improving the dissolution rate, which was found to depend on the polymer and its weight ratio of the drug. It is clearly obvious that the dissolution rate was remarkably improved in drug PVP 40000 molecular dispersions when compared to drug PEG 6000 systems. Solid dispersion of SDC in PEG and PVP improved the anti-inflammatory effect of SDC and it was found that formula SDV5 exhibited a more pronounced inhibition of swelling than other formulae.

  6. Effect of Sulindac Binary System on In Vitro and In Vivo Release Profiles: An Assessment of Polymer Type and Its Ratio.

    Science.gov (United States)

    Shazly, Gamal A

    2016-01-01

    The bioavailability of sulindac (SDC), a nonsteroidal anti-inflammatory drug, is low due to poor aqueous solubility and poor dissolution rate. For this reason it is necessary to enhance the solubility and enhance dissolution of the drug by dispersing SDC in polyethylene glycols 6000 (PEG 6000) and polyvinyl pyrrolidone 40000 (PVP 40000) matrices using the coevaporation technique. Studying the influence of SDC to polymer ratio on drug content, percent yield, particle size, and in vitro release was performed. Differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy were used to characterize any change in crystal habit of SDC in the prepared formulae. The anti-inflammatory effect of SDC was studied using the hind paw edema model. It was found that incorporation of SDC in PEG 6000 and PVP 40000 matrices resulted in improving the dissolution rate, which was found to depend on the polymer and its weight ratio of the drug. It is clearly obvious that the dissolution rate was remarkably improved in drug PVP 40000 molecular dispersions when compared to drug PEG 6000 systems. Solid dispersion of SDC in PEG and PVP improved the anti-inflammatory effect of SDC and it was found that formula SDV5 exhibited a more pronounced inhibition of swelling than other formulae.

  7. Microfluidic synthesis of dye-loaded polycaprolactone-block-poly(ethylene oxide) nanoparticles: Insights into flow-directed loading and in vitro release for drug delivery.

    Science.gov (United States)

    Bains, Aman; Wulff, Jeremy E; Moffitt, Matthew G

    2016-08-01

    Using the fluorescent probe dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) as a surrogate for hydrophobic drugs, we investigate the effects of water content and on-chip flow rate on the multiscale structure, loading and release properties of DiI-loaded poly(ε-caprolactone)-block-poly(ethylene oxide) (PCL-b-PEO) nanoparticles produced in a gas-liquid segmented microfluidic device. We find a linear increase in PCL crystallinity within the nanoparticle cores with increasing flow rate, while mean nanoparticle sizes first decrease and then increase with flow rate coincident with the disappearance and reappearance of long filament nanoparticles. Loading efficiencies at the lower water content (cwc+10wt%) are generally higher (up to 94%) compared to loading efficiencies (up to 53%) at the higher water content (cwc+75wt%). In vitro release times range between ∼2 and 4days for nanoparticles produced at cwc+10wt% and >15days for nanoparticles produced at cwc+75wt%. At the lower water content, slower release of DiI is found for nanoparticles produced at higher flow rate, while at high water content, release times first decrease and then increase with flow rate. Finally, we investigate the effects of the chemical and physical characteristics of the release medium on the kinetics of in vitro DiI release and nanoparticle degradation. This work demonstrates the general utility of dye-loaded nanoparticles as model systems for screening chemical and flow conditions for producing drug delivery formulations within microfluidic devices. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Epigallocatechin Gallate/Layered Double Hydroxide Nanohybrids: Preparation, Characterization, and In Vitro Anti-Tumor Study.

    Directory of Open Access Journals (Sweden)

    Seyedeh Sara Shafiei

    Full Text Available In recent years, nanotechnology in merging with biotechnology has been employed in the area of cancer management to overcome the challenges of chemopreventive strategies in order to gain promising results. Since most biological processes occur in nano scale, nanoparticles can act as carriers of certain drugs or agents to deliver it to specific cells or targets. In this study, we intercalated Epigallocatechin-3-Gallate (EGCG, the most abundant polyphenol in green tea, into Ca/Al-NO3 Layered double hydroxide (LDH nanoparticles, and evaluated its efficacy compared to EGCG alone on PC3 cell line. The EGCG loaded LDH nanohybrids were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy (TEM and nanosizer analyses. The anticancer activity of the EGCG-loaded LDH was investigated in prostate cancer cell line (PC3 while the release behavior of EGCG from LDH was observed at pH 7.45 and 4.25. Besides enhancing of apoptotic activity of EGCG, the results showed that intercalation of EGCG into LDH can improve the anti- tumor activity of EGCG over 5-fold dose advantages in in-vitro system. Subsequently, the in-vitro release data showed that EGCG-loaded LDH had longer release duration compared to physical mixture, and the mechanism of diffusion through the particle was rate-limiting step. Acidic attack was responsible for faster release of EGCG molecules from LDH at pH of 4.25 compared to pH of 7.4. The results showed that Ca/Al-LDH nanoparticles could be considered as an effective inorganic host matrix for the delivery of EGCG to PC3 cells with controlled release properties.

  9. Epigallocatechin Gallate/Layered Double Hydroxide Nanohybrids: Preparation, Characterization, and In Vitro Anti-Tumor Study

    Science.gov (United States)

    Shafiei, Seyedeh Sara; Solati-Hashjin, Mehran; Samadikuchaksaraei, Ali; Kalantarinejad, Reza; Asadi-Eydivand, Mitra; Abu Osman, Noor Azuan

    2015-01-01

    In recent years, nanotechnology in merging with biotechnology has been employed in the area of cancer management to overcome the challenges of chemopreventive strategies in order to gain promising results. Since most biological processes occur in nano scale, nanoparticles can act as carriers of certain drugs or agents to deliver it to specific cells or targets. In this study, we intercalated Epigallocatechin-3-Gallate (EGCG), the most abundant polyphenol in green tea, into Ca/Al-NO3 Layered double hydroxide (LDH) nanoparticles, and evaluated its efficacy compared to EGCG alone on PC3 cell line. The EGCG loaded LDH nanohybrids were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy (TEM) and nanosizer analyses. The anticancer activity of the EGCG-loaded LDH was investigated in prostate cancer cell line (PC3) while the release behavior of EGCG from LDH was observed at pH 7.45 and 4.25. Besides enhancing of apoptotic activity of EGCG, the results showed that intercalation of EGCG into LDH can improve the anti- tumor activity of EGCG over 5-fold dose advantages in in-vitro system. Subsequently, the in-vitro release data showed that EGCG-loaded LDH had longer release duration compared to physical mixture, and the mechanism of diffusion through the particle was rate-limiting step. Acidic attack was responsible for faster release of EGCG molecules from LDH at pH of 4.25 compared to pH of 7.4. The results showed that Ca/Al-LDH nanoparticles could be considered as an effective inorganic host matrix for the delivery of EGCG to PC3 cells with controlled release properties. PMID:26317853

  10. 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.

  11. Percutaneous planter fasciitis release under local anesthesia: A prospective study

    Directory of Open Access Journals (Sweden)

    Ramji Lal Sahu

    2017-04-01

    Conclusion: Percutaneous planter fasciitis release under local anesthesia is a minimally invasive procedure that can be performed in the outpatient setting. It is easy, quick, effective and moreover with few complications.

  12. Release of Pro-Inflammatory Cytokines from Muscle and Bone Causes Tenocyte Death in a Novel Rotator Cuff In Vitro Explant Culture Model.

    Science.gov (United States)

    Connizzo, Brianne K; Grodzinsky, Alan J

    2018-02-15

    Tendinopathy is a significant clinical problem thought to be associated with altered mechanical loading. Explant culture models allow researchers to alter mechanical loading in a controlled in vitro environment while maintaining tenocytes in their native matrix. However, current models do not accurately represent commonly injured tendons