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

Science.gov (United States)

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

2017-04-01

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

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

Science.gov (United States)

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

2017-05-01

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

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.

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

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Lee JM

2014-09-01

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

Sintering of wax for controlling release from pellets

OpenAIRE

Singh, Reena; Poddar, S. S.; Chivate, Amit

2007-01-01

The purpose of the present study was to investigate incorporation of hydrophobic (ie, waxy) material into pellets using a thermal sintering technique and to evaluate the pellets in vitro for controlled release. Pellets prepared by extrusion-spheronization technology were formulated with a water-soluble drug, microcrystalline cellulose, and carnauba wax. Powdered carnauba wax (4%–20%) prepared by grinding or by emulsification was studied with an attempt to retard the drug release. The inclusio...

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

Science.gov (United States)

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

2014-12-01

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

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

Science.gov (United States)

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

2015-01-01

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

Sintering of wax for controlling release from pellets.

Science.gov (United States)

Singh, Reena; Poddar, S S; Chivate, Amit

2007-09-14

The purpose of the present study was to investigate incorporation of hydrophobic (ie, waxy) material into pellets using a thermal sintering technique and to evaluate the pellets in vitro for controlled release. Pellets prepared by extrusion-spheronization technology were formulated with a water-soluble drug, microcrystalline cellulose, and carnauba wax. Powdered carnauba wax (4%-20%) prepared by grinding or by emulsification was studied with an attempt to retard the drug release. The inclusion of ground or emulsified carnauba wax did not sustain the release of theophylline for more than 3 hours. Matrix pellets of theophylline prepared with various concentrations of carnauba wax were sintered thermally at various times and temperatures. In vitro drug release profiles indicated an increase in drug release retardation with increasing carnauba wax concentration. Pellets prepared with ground wax showed a higher standard deviation than did those prepared with emulsified wax. There was incomplete release at the end of 12 hours for pellets prepared with 20% ground or emulsified wax. The sintering temperature and duration were optimized to allow for a sustained release lasting at least 12 hours. The optimized temperature and duration were found to be 100 degrees C and 140 seconds, respectively. The sintered pellets had a higher hydrophobicity than did the unsintered pellets. Scanning electron micrographs indicated that the carnauba wax moved internally, thereby increasing the surface area of wax within the pellets.

Photoresponsive lipid-polymer hybrid nanoparticles for controlled doxorubicin release

Science.gov (United States)

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

2017-06-01

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

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

Directory of Open Access Journals (Sweden)

Xin Hua

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

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

Science.gov (United States)

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

2014-01-01

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

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

African Journals Online (AJOL)

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

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

Energy Technology Data Exchange (ETDEWEB)

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

1976-01-01

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

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

Science.gov (United States)

DONG, Xinrui; SHU, Xueye; WANG, Yingnan; NIU, Zhaohuan; XU, Shixia; ZHANG, Yue; ZHAO, Shuchun

2017-01-01

Valnemulin, successfully developed by Sandoz in 1984, is a new generation derivative of pleuromutilin related to tiamulin. Valnemulin has low water-solubility, a short half-life period, low bioavailability, and instability. The application of valnemulin was restricted. Therefore, finding a more moderate delivery system is necessary to improve the shortcomings of valnemulin. The purpose of the study was to improve the strong stability and the irritation caused by of valnemulin hydrochloride power through pegylated-valnemulin prodrug mode. The prepared pegylated-valnemulin prodrug was characterized and evaluated by in vitro release performance under buffer solutions with pH levels of 7.4 and 3.6. The loading rate of valnemulin in PEG-succinic-valnemulin prodrug was determined by ultraviolet spectrophotometer and high performance liquid chromatography (HPLC). HPLC with evaporative light scattering detector was applied to determine the amount of PEG-succinic acid. The loading rate of valnemulin in PEG-succinic-valnemulin prodrug was 6.46%. PEG-succinic-valnemulin prodrug demonstrated a satisfactory solubility of valnemulin with 523 mg·ml−1 and excellent stability verified by the stability experiment. The result of the in vitro release test showed that the prepared PEG-valnemulin prodrug has controlled release ability and the release rate of valnemulin from PEG-valnemulin prodrug with a pH of 7.4 was 64.98%, which was higher than that of pH3.6 with release rate of 31.90%. Therefore, the prepared PEG-succinic-valnemulin prodrug has great application potential. PMID:29187697

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.

Stimulatory effects of neuronally released norepinephrine on renin release in vitro

Energy Technology Data Exchange (ETDEWEB)

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

1988-10-01

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

Role of various natural, synthetic and semi-synthetic polymers on drug release kinetics of losartan potassium oral controlled release tablets.

Science.gov (United States)

Jayasree, J; Sivaneswari, S; Hemalatha, G; Preethi, N; Mounika, B; Murthy, S Vasudeva

2014-10-01

The objective of the present work was to formulate and to characterize controlled release matrix tablets of losartan potassium in order to improve bioavailability and to minimize the frequency of administration and increase the patient compliance. Losartan potassium controlled release matrix tablets were prepared by direct compression technique by the use of different natural, synthetic and semisynthetic polymers such as gum copal, gum acacia, hydroxypropyl methyl cellulose K100 (HPMC K100), eudragit RL 100 and carboxy methyl ethyl cellulose (CMEC) individually and also in combination. Studies were carried out to study the influence of type of polymer on drug release rate. All the formulations were subjected to physiochemical characterization such as weight variation, hardness, thickness, friability, drug content, and swelling index. In vitro dissolution studies were carried out simulated gastric fluid (pH 1.2) for first 2 h and followed by simulated intestinal fluid (pH 6.8) up to 24 h, and obtained dissolution data were fitted to in vitro release kinetic equations in order to know the order of kinetics and mechanism of drug release. Results of physiochemical characterization of losartan potassium matrix tablets were within acceptable limits. Formulation containing HPMC K100 and CMEC achieved the desired drug release profile up to 24 h followed zero order kinetics, release pattern dominated by Korsmeyer - Peppas model and mechanism of drug release by nonfickian diffusion. The good correlation obtained from Hixson-Crowell model indicates that changes in surface area of the tablet also influences the drug release. Based on the results, losartan potassium controlled release matrix tablets prepared by employing HPMC K100 and CMEC can attain the desired drug release up to 24 h, which results in maintaining steady state concentration and improving bioavailability.

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

Science.gov (United States)

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

2015-12-30

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

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

Science.gov (United States)

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

2017-11-01

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

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

Directory of Open Access Journals (Sweden)

Luo YL

2016-07-01

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

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

Science.gov (United States)

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

2006-02-17

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

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

International Nuclear Information System (INIS)

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

2013-01-01

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

A modified SILCS contraceptive diaphragm for long-term controlled release of the HIV microbicide dapivirine.

Science.gov (United States)

Major, Ian; Boyd, Peter; Kilbourne-Brook, Maggie; Saxon, Gene; Cohen, Jessica; Malcolm, R Karl

2013-07-01

There is considerable interest in developing new multipurpose prevention technologies to address women's reproductive health needs. This study describes an innovative barrier contraceptive device--based on the SILCS diaphragm--that also provides long-term controlled release of the lead candidate anti-HIV microbicide dapivirine. Diaphragm devices comprising various dapivirine-loaded polymer spring cores overmolded with a nonmedicated silicone elastomer sheath were fabricated by injection molding processes. In vitro release testing, thermal analysis and mechanical characterization were performed on the devices. A diaphragm device containing a polyoxymethylene spring core loaded with 10% w/w dapivirine provided continuous and controlled release of dapivirine over a 6-month period, with a mean in vitro daily release rate of 174 mcg/day. The mechanical properties of the new diaphragm were closely matched to the SILCS diaphragm. The study demonstrates proof of concept for a dapivirine-releasing diaphragm with daily release quantities potentially capable of preventing HIV transmission. In discontinuous clinical use, release of dapivirine may be readily extended over 1 or more years. Copyright © 2013 Elsevier Inc. All rights reserved.

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.

In vitro labelled neurotransmitters release for the study of neuro toxins

International Nuclear Information System (INIS)

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

1995-01-01

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

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

Science.gov (United States)

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

2016-11-21

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

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

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Rezaul H. Ansary

2017-10-01

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

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

International Nuclear Information System (INIS)

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

1990-01-01

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

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

Science.gov (United States)

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

2016-01-01

Natural silk protein nanoparticles are a promising biomaterial for drug delivery due to their pleiotropic properties, including biocompatibility, high bioavailability, and biodegradability. Chinese oak tasar Antheraea pernyi silk fibroin (ApF) nanoparticles are easily obtained using cations as reagents under mild conditions. The mild conditions are potentially advantageous for the encapsulation of sensitive drugs and therapeutic molecules. In the present study, silk fibroin protein nanoparticles are loaded with differently-charged small-molecule drugs, such as doxorubicin hydrochloride, ibuprofen, and ibuprofen-Na, by simple absorption based on electrostatic interactions. The structure, morphology and biocompatibility of the silk nanoparticles in vitro are investigated. In vitro release of the drugs from the nanoparticles depends on charge-charge interactions between the drugs and the nanoparticles. The release behavior of the compounds from the nanoparticles demonstrates that positively-charged molecules are released in a more prolonged or sustained manner. Cell viability studies with L929 demonstrated that the ApF nanoparticles significantly promoted cell growth. The results suggest that Chinese oak tasar Antheraea pernyi silk fibroin nanoparticles can be used as an alternative matrix for drug carrying and controlled release in diverse biomedical applications. PMID:27916946

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 ...

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

Science.gov (United States)

Atkins, E; Bodel, P; Francis, L

1967-08-01

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

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

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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.

Controlling Release of Integral Lipid Nanoparticles Based on Osmotic Pump Technology.

Science.gov (United States)

Tian, Zhiqiang; Yu, Qin; Xie, Yunchang; Li, Fengqian; Lu, Yi; Dong, Xiaochun; Zhao, Weili; Qi, Jianping; Wu, Wei

2016-08-01

To achieve controlled release of integral nanoparticles by the osmotic pump strategy using nanostructured lipid carriers (NLCs) as model nanoparticles. NLCs was prepared by a hot-homogenization method, transformed into powder by lyophilization, and formulated into osmotic pump tablets (OPTs). Release of integral NLCs was visualized by live imaging after labeling with a water-quenching fluorescent probe. Effects of formulation variables on in vitro release characteristics were evaluated by measuring the model drug fenofibrate. Pharmacokinetics were studied in beagle dogs using the core tablet and a micronized fenofibrate formulation as references. NLCs are released through the release orifices of the OPTs as integral nanoparticles. Near zero-order kinetics can be achieved by optimizing the influencing variables. After oral administration, decreased C max and steady drug levels for as long as over 24 h are observed. NLC-OPTs show an oral bioavailability of the model drug fenofibrate similar to that of the core tablets, which is about 1.75 folds that of a fast-release formulation. Controlled release of integral NLCs is achieved by the osmotic pump strategy.

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

Science.gov (United States)

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

2015-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

Hammad, Mohaned; Nica, Valentin; Hempelmann, Rolf, E-mail: r.hempelmann@mx.uni-saarland.de [Saarland University, Department of Physical Chemistry (Germany)

2016-08-15

A switch-controlled drug release system is designed by coating of core/shell bimagnetic nanoparticles with a pH- and thermo-responsive polymer shell, which can be used as hyperthermic agent, drug carrier, and for controlled release. Doxorubicin is loaded onto the surface of the last coating layer, and a high loading efficiency of 90.5 % is obtained. The nanocarriers are characterized by FTIR, dynamic light scattering, Zeta potential, TEM, In vitro hyperthermia, and vibrating sample magnetometry. The core/shell magnetic nanoparticles (Zn{sub 0.4}Co{sub 0.6}Fe{sub 2}O{sub 4}@Zn{sub 0.4}Mn{sub 0.6}Fe{sub 2}O{sub 4}) exhibit a superparamagnetic behavior with a saturation magnetization around 45.6 emu/g and a high specific absorption rate of up to 360 W/g. The in vitro drug release experiments confirm that only a small amount of doxorubicin is released at body temperature and physiological pH, whereas a high drug release is obtained at acidic tumor pH under hyperthermia conditions (43 °C). The functionalized core/shell bimagnetic nanocarriers facilitate controllable release of doxorubicin as an effect of induced thermo- and pH-responsiveness of the polymer when are subjected to a high-frequency alternating magnetic field at acidic pH; thereby the drug release rate is controlled using on–off cycles of the applied field.Graphical Abstract.

Design of a controlled release liquid formulation of lamotrigine

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V Kumar

2011-05-01

Full Text Available "n  "n  Background and the purpose of the study: Lamotrigine is a broad spectrum anticonvulsant drug widely used as mono- or adjunct- therapy in adults and children. The aim of this study was to develop controlled release liquid formulation of lamotrigine to improve bioavailability and compliance of pediatric and geriatric epileptic patients. "n  Methods: Multiple (w/o/w emulsion was prepared using one step emulsification technique. It was evaluated for entrapment efficiency (EE, morphology, zeta potential (ZP, polydispersity index (PI, rheology, thermal property, in vitro drug release behavior and stability. In vivo studies in albino mice were carried out using maximal electroshock seizure (MES test and strychnine induced seizure (SIS pattern test and results were compared with marketed formulation. "n  Results: The EE of the formulations varied from 84.37% to 98.11%. The ZP and PI values of the prepared batches were in the range of +23.46 to +28.07 and 0.256 and 0.365, respectively. Microscopic observation clearly indicated the stability of the emulsions during the storage period. All batches exhibited controlled in vitro drug release up to 12 hrs. Batch C11 exhibited significantly longer duration of protection of seizure in mice against MES and exhibited comparable efficacy in SIS as compared to the marketed formulation. "n  Major Conclusion: Multiple emulsion of lamotrigine compared to the marketed tablet showed plasma drug concentration within therapeutic range for longer time and comparable efficacy.

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

Science.gov (United States)

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

2005-01-01

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

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.

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

International Nuclear Information System (INIS)

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

2011-01-01

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

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

Science.gov (United States)

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

2013-01-01

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

Comparison of metal release from various metallic biomaterials in vitro.

Science.gov (United States)

Okazaki, Yoshimitsu; Gotoh, Emiko

2005-01-01

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

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.

Formulation and Pharmacokinetic Evaluation of Controlled-Release ...

African Journals Online (AJOL)

A coating layer was then applied with a mixture of HPMC, ethylcellulose, shellac, and HPMC phthalate. The effect of several formulation variables on in vitro drug release was studied; furthermore, the drug release kinetics of the optimized formulation was evaluated. The in vivo pharmacokinetics of the optimized formulation ...

Controlled release of simvastatin from biomimetic β-TCP drug delivery system.

Directory of Open Access Journals (Sweden)

Joshua Chou

Full Text Available Simvastatin have been shown to induce bone formation and there is currently a urgent need to develop an appropriate delivery system to sustain the release of the drug to increase therapeutic efficacy whilst reducing side effects. In this study, a novel drug delivery system for simvastatin by means of hydrothermally converting marine exoskeletons to biocompatible beta-tricalcium phosphate was investigated. Furthermore, the release of simvastatin was controlled by the addition of an outer apatite coating layer. The samples were characterized by x-ray diffraction analysis, fourier transform infrared spectroscopy, scanning electron microscopy and mass spectroscopy confirming the conversion process. The in-vitro dissolution of key chemical compositional elements and the release of simvastatin were measured in simulated body fluid solution showing controlled release with reduction of approximately 25% compared with un-coated samples. This study shows the potential applications of marine structures as a drug delivery system for simvastatin.

Production and Investigation of Controlled Drug Release Properties of Tamoxifen Loaded Alginate-Gum Arabic Microbeads

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Rukiye Yavaşer

2016-08-01

Full Text Available The entrapment of tamoxifen onto alginate-gum arabic beads and the production of controlled drug release was investigated in this study. The polymeric system that would provide the controlled release of tamoxifen was formed using alginate and gum arabic. In the first phase of the study, the optimization of the alginate-gum arabic beads production was conducted; then the study continued with drug entrapment experiments. Tamoxifen entrapment yield was found to be approximately 90% of initial tamoxifen concentration. In vitro drug release experiments were performed in simulated gastric juice and intestinal fluid where the tamoxifen release was 20% and 53% of the initial drug present, respectively. As a result of this study, it is expected that a valuable contribution to the field of controlled drug release system production is realized.

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

Science.gov (United States)

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

2016-10-03

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

Externally controlled on-demand release of anti-HIV drug using magneto-electric nanoparticles as carriers.

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Nair, Madhavan; Guduru, Rakesh; Liang, Ping; Hong, Jeongmin; Sagar, Vidya; Khizroev, Sakhrat

2013-01-01

Although highly active anti-retroviral therapy has resulted in remarkable decline in the morbidity and mortality in AIDS patients, inadequately low delivery of anti-retroviral drugs across the blood-brain barrier results in virus persistence. The capability of high-efficacy-targeted drug delivery and on-demand release remains a formidable task. Here we report an in vitro study to demonstrate the on-demand release of azidothymidine 5'-triphosphate, an anti-human immunodeficiency virus drug, from 30 nm CoFe2O4@BaTiO3 magneto-electric nanoparticles by applying a low alternating current magnetic field. Magneto-electric nanoparticles as field-controlled drug carriers offer a unique capability of field-triggered release after crossing the blood-brain barrier. Owing to the intrinsic magnetoelectricity, these nanoparticles can couple external magnetic fields with the electric forces in drug-carrier bonds to enable remotely controlled delivery without exploiting heat. Functional and structural integrity of the drug after the release was confirmed in in vitro experiments with human immunodeficiency virus-infected cells and through atomic force microscopy, spectrophotometry, Fourier transform infrared and mass spectrometry studies.

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

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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.

IONP-doped nanoparticles for highly effective NIR-controlled drug release and combination tumor therapy

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Fu X

2017-05-01

Full Text Available Xudong Fu,1 Xinjun Wang,1 Shaolong Zhou,1 Yanyan Zhang2 1The Fifth Affiliated Hospital of Zhengzhou University, 2School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China Abstract: Despite advances in controlled drug delivery, drug delivery systems (DDSs with controlled activated drug release and high spatial and temporal resolution are still required. Theranostic nanomedicine is capable of diagnosis, therapy, and monitoring the delivery and distribution of drug molecules and has received growing interest. In this study, a near-infrared light-controlled “off–on” DDS with magnetic resonance imaging and magnetic targeting properties was developed using a hybrid nanoplatform (carbon nanotubes [CNTs]-iron oxide nanoparticle. Doxorubicin (DOX and distearoyl-sn-glycero-3-phosphoethanolamine-PEG were adsorbed onto CNTs-iron oxide nanoparticle, and then to avoid the unexpected drug release during circulation, 1-myristyl alcohol was used to encapsulate the CNTs–drug complex. Herein, multifunctional DOX-loaded nanoparticles (NPs with “off–on” state were developed. DOX-NPs showed an obvious “off–on” effect (temperature increase, drug release controlled by near-infrared light in vitro and in vivo. In the in vivo and in vitro studies, DOX-NPs exhibited excellent magnetic resonance imaging ability, magnetic targeting property, high biosafety, and high antitumor combined therapeutic efficacy (hyperthermia combined with chemotherapy. These results highlight the great potential of DOX-NPs in the treatment of cancer. Keywords: controlled drug release, magnetic targeting, MRI, combination therapy

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

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

2010-01-01

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

Sol-gel encapsulation for controlled drug release and biosensing

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Fang, Jonathan

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

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

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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

Core/shell PLGA microspheres with controllable in vivo release profile via rational core phase design.

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Yu, Meiling; Yao, Qing; Zhang, Yan; Chen, Huilin; He, Haibing; Zhang, Yu; Yin, Tian; Tang, Xing; Xu, Hui

2018-02-27

Highly soluble drugs tend to release from preparations at high speeds, which make them need to be taken at frequent intervals. Additionally, some drugs need to be controlled to release in vivo at certain periods, so as to achieve therapeutic effects. Thus, the objective of this study is to design injectable microparticulate systems with controllable in vivo release profile. Biodegradable PLGA was used as the matrix material to fabricate microspheres using the traditional double emulsification-solvent evaporation method as well as improved techniques, with gel (5% gelatine or 25% F127) or LP powders as the inner phases. Their physicochemical properties were systemically investigated. Microspheres prepared by modified methods had an increase in drug loading (15.50, 16.72, 15.66%, respectively) and encapsulation efficiencies (73.46, 79.42, 74.40%, respectively) when compared with traditional methods (12.01 and 57.06%). The morphology of the particles was characterized by optical microscope (OM) and scanning electron microscopy (SEM), and the amorphous nature of the encapsulated drug was confirmed by differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis. To evaluate their release behaviour, the in vitro degradation, in vitro release and in vivo pharmacodynamics were subsequently studied. Traditional microspheres prepared in this study with water as the inner phase had a relatively short release period within 16 d when compared with modified microspheres with 5% gelatine as the inner phase, which resulted in a smooth release profile and appropriate plasma LP concentrations over 21 d. Thus this type of modified microspheres can be better used in drugs requiring sustained release. The other two formulations containing 25% F127 and LP micropowders presented two-stage release profiles, resulting in fluctuant plasma LP concentrations which may be suitable for drugs requiring controlled release. All the results suggested that drug release rates from

Development of controlled release spheroids using Buchananiacochinchinesis gum

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Narayan Babulal Gaikwad

2013-03-01

Full Text Available Chirauli nut gum was isolated from the bark of Buchanania cochinchinesis (fam. Anacadiacea and was used as a release modifier for the preparation of Diclofenac sodium spheroids using the extrusion spheronization technique. The process was studied for the effects on variables when making spheroids with satisfactory particle shape, size and size distribution. The prepared spheroids were characterized for surface morphology, qualitative surface porosity, friability, bulk density and flow properties. In vitro studies demonstrated that the release exhibited Fickian diffusion kinetics which was confirmed by the Higuchi and the Korsmeyer-Peppas models. The physico-chemical parameters of the gum could be correlated to the in vitro dissolution profile of the spheroids. The spheroids were not able to sustain the drug releases over 12 hours. A greater concentration of Chirauli nut gum and a process that can accommodate such greater concentrations may produce a formulation capable of significant sustained release.

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

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

2002-10-01

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

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

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

2014-09-16

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

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

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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.

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

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

2017-09-28

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

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

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

2017-01-01

Sinomenine hydrochloride (SH) is an ideal drug for the treatment of rheumatoid arthritis and osteoarthritis. However, high plasma concentration of systemically administered SH can release histamine, which can cause rash and gastrointestinal side effects. Topical delivery can increase SH concentration in the synovial fluid without high plasma level, thus minimizing systemic side effects. However, passive diffusion of SH was found to be inefficient because of the presence of the stratum corneum layer. Therefore, an effective method is required to compensate for the low efficiency of SH passive diffusion. In this study, transdermal experiments in vitro and clinical tests were utilized to explore the optimized parameters for electroporation of topical delivery for SH. Fluorescence experiment and hematoxylin and eosin staining analysis were performed to reveal the mechanism by which electroporation promoted permeation. In vitro, optimized electroporation parameters were 3 KHz, exponential waveform, and intensity 10. Using these parameters, transdermal permeation of SH was increased by 1.9–10.1 fold in mice skin and by 1.6–47.1 fold in miniature pig skin compared with passive diffusion. After the electroporation stimulation, the intercellular intervals and epidermal cracks in the skin increased. In clinical tests, SH concentration in synovial fluid was 20.84 ng/mL after treatment with electroporation. Therefore, electroporation with optimized parameters could significantly enhance transdermal permeation of SH. The mechanism by which electroporation promoted permeation was that the electronic pulses made the skin structure looser. To summarize, electroporation may be an effective complementary method for transdermal permeation of SH. The controlled release of electroporation may be a promising clinical method for transdermal drug administration. PMID:28670109

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

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Shen, Jie; Burgess, Diane J

2012-01-17

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

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

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ATKINS, E; HEIJN, C

1965-08-01

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

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

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Dolinina, Ekaterina S; Parfenyuk, Elena V

2017-01-01

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

Controlled release of glaucocalyxin - a self-nanoemulsifying system from osmotic pump tablets with enhanced bioavailability.

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Yanfei, Miao; Guoguang, Chen; Lili, Ren; Pingkai, Ouyang

2017-03-01

The purpose of this study was to develop a new formulation to enhance the bioavailability simultaneously with controlled release of glaucocalyxin A (GLA). In this study, controlled release of GLA was achieved by the osmotic release strategy taking advantage of the bioavailability enhancing capacity of self-nanoemulsifying drug delivery systems (SNEDDS). The formulation of GLA-SNEDDS was selected by the solubility and pseudoternary-phase diagrams studies. The prepared GLA-SNEDDS formulations were characterized for self-emulsification time, effect of pH and robustness to dilution, droplet size analysis and zeta potential. The optimized GLA-SNEDDS were used to prepare GLA-SNEDDS osmotic pump tablet via direct powder compression method. The effect of formulation variables on the release characteristic was investigated. GLA-SNEDDS osmotic pump tablets were administered to beagle dogs and their pharmacokinetics were compared to GLA and GLA-SNEDDS as a control. In vitro drug release studies indicated that the GLA-SNEDDS osmotic pump tablet showed sustained release profiles with 90% released within 12 h. Pharmacokinetic study showed steady blood GLA with prolonged T max and mean residence time (MRT), and enhanced bioavailability for GLA-SNEDDS osmotic pump tablet. It was concluded that simultaneous controlling on GLA release and enhanced bioavailability had been achieved by a combination of osmotic pump tablet and SNEDDS.

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

International Nuclear Information System (INIS)

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

2013-01-01

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

3D printed, controlled release, tritherapeutic tablet matrix for advanced anti-HIV-1 drug delivery.

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Siyawamwaya, Margaret; du Toit, Lisa C; Kumar, Pradeep; Choonara, Yahya E; Kondiah, Pierre P P D; Pillay, Viness

2018-04-12

A 3D-Bioplotter® was employed to 3D print (3DP) a humic acid-polyquaternium 10 (HA-PQ10) controlled release fixed dose combination (FDC) tablet comprising of the anti-HIV-1 drugs, efavirenz (EFV), tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC). Chemical interactions, surface morphology and mechanical strength of the FDC were ascertained. In vitro drug release studies were conducted in biorelevant media followed by in vivo study in the large white pigs, in comparison with a market formulation, Atripla®. In vitro-in vivo correlation of results was undertaken. EFV, TDF and FTC were successfully entrapped in the 24-layered rectangular prism-shaped 3DP FDC with a loading of ∼12.5 mg/6.3 mg/4 mg of EFV/TDF/FTC respectively per printed layer. Hydrogen bonding between the EFV/TDF/FTC and HA-PQ10 was detected which was indicative of possible drug solubility enhancement. The overall surface of the tablet exhibited a fibrilla structure and the 90° inner pattern was determined to be optimal for 3DP of the FDC. In vitro and in vivo drug release profiles from the 3DP FDC demonstrated that intestinal-targeted and controlled drug release was achieved. A 3DP FDC was successfully manufactured with the aid of a 3D-Bioplotter in a single step process. The versatile HA-PQ10 entrapped all drugs and achieved an enhanced relative bioavailability of EFV, TDF, and FTC compared to the market formulation for potentially enhanced HIV treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

In vitro release of doxycycline from bioabsorbable materials and acrylic strips

DEFF Research Database (Denmark)

Larsen, T

1990-01-01

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

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

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Tariq Ali

2014-12-01

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

Montmorillonite/Poly (L-Lactide microcomposite spheres as reservoirs of antidepressant drugs and their controlled release property

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Shalini Rajkumar

2015-10-01

Full Text Available This work evaluates intercalation of Nortriptyline (NT and Venlafaxine (VFX in an interlayer gallery of Na+-MMT (Montmorillonite, which was further compounded with Poly (L-Lactide (PLLA to form microcomposite spheres (MPs for oral controlled drug delivery. The XRD patterns, thermal and spectroscopic analyses indicated intercalation of drugs into the MMT interlayer that was stabilized by electrostatic interaction. No significant changes in structural and functional properties of drugs were found in the MMT layers. In vitro drug release studies showed controlled release pattern.

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

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Gurpreet Arora

2011-01-01

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

STUDIES ON NATURAL AND SYNTHETIC POLYMERS FOR CONTROLLED RELEASE MATRIX TABLET OF ACECLOFENAC

OpenAIRE

Abhishek S. Joshi *, Deepak A. Joshi , Avinash V. Dhobale , Sandhya S. Bundel , Vijay R. Chakote, Gunesh N. Dhembre

2018-01-01

The present study was aimed to design new oral controlled release matrix tablets of new NSAID Aceclofenac for once a day by using 10, 15, 20 and 25% of GG:HPMC and XG:HPMC mixture in the ratio 1:1 by wet granulation method. The prepared tablets subjected to in vitro drug release studies in pH 7.4 buffer solution. All the formulation meets the pre-compression and compression characteristics. All the tablets prepared with 10, 15, 20 and 25% of HPMC: XG mixture in the ratio 1:1 fails to meet the...

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

Science.gov (United States)

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

2017-08-01

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

A novel automated alternating current biosusceptometry method to characterization of controlled-release magnetic floating tablets of metronidazole.

Science.gov (United States)

Ferrari, Priscileila Colerato; dos Santos Grossklauss, Dany Bruno Borella; Alvarez, Matheus; Paixão, Fabiano Carlos; Andreis, Uilian; Crispim, Alexandre Giordano; de Castro, Ana Dóris; Evangelista, Raul Cesar; de Arruda Miranda, José Ricardo

2014-08-01

Alternating Current Biosusceptometry is a magnetically method used to characterize drug delivery systems. This work presents a system composed by an automated ACB sensor to acquire magnetic images of floating tablets. The purpose of this study was to use an automated Alternating Current Biosusceptometry (ACB) to characterize magnetic floating tablets for controlled drug delivery. Floating tablets were prepared with hydroxypropyl methylcellulose (HPMC) as hydrophilic gel material, sodium bicarbonate as gas-generating agent and ferrite as magnetic marker. ACB was used to characterize the floating lag time and the tablet hydration rate, by quantification of the magnetic images to magnetic area. Besides the buoyancy, the floating tablets were evaluated for weight uniformity, hardness, swelling and in vitro drug release. The optimized tablets were prepared with equal amounts of HPMC and ferrite, and began to float within 4 min, maintaining the flotation during more than 24 h. The data of all physical parameters lied within the pharmacopeial limits. Drug release at 24 h was about 40%. The ACB results showed that this study provided a new approach for in vitro investigation of controlled-release dosage forms. Moreover, using automated ACB will also be possible to test these parameters in humans allowing to establish an in vitro.in vivo correlation (IVIVC).

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

International Nuclear Information System (INIS)

Eriksson, E.; Christensson, E.

1990-01-01

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

Controlled release gelatin hydrogels and lyophilisates with potential application as ocular inserts

Energy Technology Data Exchange (ETDEWEB)

Natu, Madalina V [Department of Chemical Engineering, University of Coimbra, Polo II, Pinhal de Marrocos, 3030-290 Coimbra (Portugal); Sardinha, Jose P [Department of Chemical Engineering, University of Coimbra, Polo II, Pinhal de Marrocos, 3030-290 Coimbra (Portugal); Correia, IlIdio J [Centro de Investigacao em Ciencias da Saude, Faculdade de Ciencias da Saude, Universidade da Beira Interior, Covilha (Portugal); Gil, M H [Department of Chemical Engineering, University of Coimbra, Polo II, Pinhal de Marrocos, 3030-290 Coimbra (Portugal)

2007-12-15

Hydrogels and lyophilisates were obtained by chemical crosslinking of gelatin using N-hydroxysuccinimide and N, N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride. The systems were characterized with respect to the degree of crosslinking, morphology, water uptake, in vitro drug release and biocompatibility studies. Pilocarpine hydrochloride, a drug for the treatment of glaucoma, was loaded by soaking in an aqueous solution containing the drug. In vitro, the released drug percentage varied between 29.2% and 99.2% in 8 h of study. The release data were fitted to the Korsmeyer-Peppas equation to calculate the release exponent, which indicated anomalous transport for the release of pilocarpine. The corneal endothelial cell culture tests indicated that the prepared biomaterials are not cytotoxic.

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

Science.gov (United States)

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

2015-12-01

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

Phenobarbital loaded microemulsion: development, kinetic release and quality control

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Kayo Alves Figueiredo

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

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

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Kifayat Ullah Shah

2012-01-01

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

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

DEFF Research Database (Denmark)

Guo, Wenjia; Quan, Peng; Fang, Liang

2015-01-01

-solvent evaporation method. The optimized formulation which avoided the crushing of microspheres during the preparation process was characterized in terms of particle size, morphology, drug loading and EE, physical state of DP in the matrix and in vitro and in vivo release behavior. DP microspheres were prepared...... release mechanism. After single-dose administration of DP microspheres via subcutaneous injection in rats, the plasma concentration of DP reached peak concentration at 0.50 d, and then declined gradually, but was still detectable at 15 d. A good correlation between in vitro and in vivo data was obtained...

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

Energy Technology Data Exchange (ETDEWEB)

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

2011-03-15

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

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

Science.gov (United States)

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

2002-09-01

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

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

Science.gov (United States)

Wada, Yasuaki; Lönnerdal, Bo

2015-04-01

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

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

Science.gov (United States)

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

2015-04-10

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

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

Science.gov (United States)

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

2010-08-16

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

In vitro release kinetics of Tolmetin from tabletted Eudragit microparticles.

Science.gov (United States)

Pignatello, R; Consoli, P; Puglisi, G

2000-01-01

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

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

Science.gov (United States)

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

2015-01-01

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

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

Workload Control with Continuous Release

NARCIS (Netherlands)

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

2009-01-01

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

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

Science.gov (United States)

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

2015-10-15

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

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

NARCIS (Netherlands)

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

1984-01-01

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

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

Science.gov (United States)

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

2014-07-19

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

Controlled Release from Recombinant Polymers

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Price, Robert; Poursaid, Azadeh; Ghandehari, Hamidreza

2014-01-01

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

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

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

2013-11-26

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

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

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

2014-01-23

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

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

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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.

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

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Tsai, S M; Phillips, D A

1991-05-01

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

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

International Nuclear Information System (INIS)

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

1985-01-01

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

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

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Elliott Donaghue, Irja; Shoichet, Molly S

2015-10-01

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

Controlled drug release for tissue engineering.

Science.gov (United States)

Rambhia, Kunal J; Ma, Peter X

2015-12-10

Tissue engineering is often referred to as a three-pronged discipline, with each prong corresponding to 1) a 3D material matrix (scaffold), 2) drugs that act on molecular signaling, and 3) regenerative living cells. Herein we focus on reviewing advances in controlled release of drugs from tissue engineering platforms. This review addresses advances in hydrogels and porous scaffolds that are synthesized from natural materials and synthetic polymers for the purposes of controlled release in tissue engineering. We pay special attention to efforts to reduce the burst release effect and to provide sustained and long-term release. Finally, novel approaches to controlled release are described, including devices that allow for pulsatile and sequential delivery. In addition to recent advances, limitations of current approaches and areas of further research are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

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

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

2013-10-01

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

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.

Ethyl cellulose microcapsules for protecting and controlled release of folic acid.

Science.gov (United States)

Prasertmanakit, Satit; Praphairaksit, Nalena; Chiangthong, Worawadee; Muangsin, Nongnuj

2009-01-01

Ethyl cellulose microcapsules were developed for use as a drug-delivery device for protecting folic acid from release and degradation in the undesirable environmental conditions of the stomach, whilst allowing its release in the intestinal tract to make it available for absorption. The controlled release folic acid-loaded ethyl cellulose microcapsules were prepared by oil-in-oil emulsion solvent evaporation using a mixed solvent system, consisting of a 9:1 (v/v) ratio of acetone:methanol and light liquid paraffin as the dispersed and continuous phase. Span 80 was used as the surfactant to stabilize the emulsion. Scanning electron microscopy revealed that the microcapsules had a spherical shape. However, the particulate properties and in vitro release profile depended on the concentrations of the ethyl cellulose, Span 80 emulsifier, sucrose (pore inducer), and folic acid. The average diameter of the microcapsules increased from 300 to 448 microm, whilst the folic acid release rate decreased from 52% to 40%, as the ethyl cellulose concentration was increased from 2.5% to 7.5% (w/v). Increasing the Span 80 concentration from 1% to 4% (v/v) decreased the average diameter of microcapsules from 300 to 141 microm and increased the folic acid release rate from 52% to 79%. The addition of 2.5-7.5% (w/v) of sucrose improved the folic acid release from the microcapsules. The entrapment efficiency was improved from 64% to 88% when the initial folic acid concentration was increased from 1 to 3 mg/ml.

Local control of striatal dopamine release

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Roger eCachope

2014-05-01

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

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

Science.gov (United States)

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

2015-06-01

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

Development of In Vitro-In Vivo Correlation for Amorphous Solid Dispersion Immediate-Release Suvorexant Tablets and Application to Clinically Relevant Dissolution Specifications and In-Process Controls.

Science.gov (United States)

Kesisoglou, Filippos; Hermans, Andre; Neu, Colleen; Yee, Ka Lai; Palcza, John; Miller, Jessica

2015-09-01

Although in vitro-in vivo correlations (IVIVCs) are commonly pursued for modified-release products, there are limited reports of successful IVIVCs for immediate-release (IR) formulations. This manuscript details the development of a Multiple Level C IVIVC for the amorphous solid dispersion formulation of suvorexant, a BCS class II compound, and its application to establishing dissolution specifications and in-process controls. Four different 40 mg batches were manufactured at different tablet hardnesses to produce distinct dissolution profiles. These batches were evaluated in a relative bioavailability clinical study in healthy volunteers. Although no differences were observed for the total exposure (AUC) of the different batches, a clear relationship between dissolution and Cmax was observed. A validated Multiple Level C IVIVC against Cmax was developed for the 10, 15, 20, 30, and 45 min dissolution time points and the tablet disintegration time. The relationship established between tablet tensile strength and dissolution was subsequently used to inform suitable tablet hardness ranges within acceptable Cmax limits. This is the first published report for a validated Multiple Level C IVIVC for an IR solid dispersion formulation demonstrating how this approach can facilitate Quality by Design in formulation development and help toward clinically relevant specifications and in-process controls. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

A Novel Delivery System for the Controlled Release of Antimicrobial Peptides: Citropin 1.1 and Temporin A

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Urszula Piotrowska

2018-05-01

Full Text Available Antimicrobial peptides (AMPs are prospective therapeutic options for treating multiple-strain infections. However, clinical and commercial development of AMPs has some limitations due to their limited stability, low bioavailability, and potential hemotoxicity. The purpose of this study was to develop new polymeric carriers as highly controlled release devices for amphibian peptides citropin 1.1 (CIT and temporin A (TEMP. The release rate of the active pharmaceutical ingredients (APIs was strongly dependent on the API characteristics and the matrix microstructure. In the current work, we investigated the effect of the polymer microstructure on in vitro release kinetics of AMPs. Non-contact laser profilometry, scanning electron microscopy (SEM, and differential scanning calorimetry (DSC were used to determine the structural changes during matrix degradation. Moreover, geno- and cytotoxicity of the synthesized new carriers were evaluated. The in vitro release study of AMPs from the obtained non-toxic matrices shows that peptides were released with near-zero-order kinetics. The peptide “burst release” effect was not observed. New devices have reached the therapeutic concentration of AMPs within 24 h and maintained it for 28 days. Hence, our results suggest that these polymeric devices could be potentially used as therapeutic options for the treatment of local infections.

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

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Li J

2015-12-01

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

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

International Nuclear Information System (INIS)

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

2007-01-01

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

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

International Nuclear Information System (INIS)

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

1981-01-01

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

Characterization of hybrid microparticles/Montmorillonite composite with raspberry-like morphology for Atorvastatin controlled release.

Science.gov (United States)

García-Guzmán, Perla; Medina-Torres, Luis; Calderas, Fausto; Bernad-Bernad, María Josefa; Gracia-Mora, Jesús; Mena, Baltasar; Manero, Octavio

2018-07-01

In this work, we prepared a novel composite based on hybrid gelatin carriers and montmorillonite clay (MMT) to analyze its viability as controlled drug delivery system. The objective of this research involves the characterization of composites formed by structured lipid-gelatin micro-particles (MP) and MMT clay. This analysis included the evaluation of the composite according to its rheological properties, morphology (SEM), particle size, XRD, FT-IR, and in vitro drug release. The effect of pH in the properties of the composite is evaluated. A novel raspberry-like or armor MP/MMT clay composite is reported, in which the pH has an important effect on the final structure of the composite for ad-hoc drug delivery systems. For pH values below the isoelectric point, we obtained defined morphologies with entrapment efficiencies up to 67%. The pH level controls the MP/MMT composite release mechanism, restringing drug release in the stomach-like environment. Intended for oral administration, these results evidence that the MP/MMT composite represents an attractive alternative for intestinal-colonic controlled drug delivery systems. Copyright © 2018 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

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

2013-06-01

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

Stimuli responsive nanomaterials for controlled release applications

KAUST Repository

Li, Song

2012-01-01

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

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

International Nuclear Information System (INIS)

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

2011-01-01

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

Sustained Release of a Water-Soluble Drug from Directly ...

African Journals Online (AJOL)

Okra gum was evaluated as a controlled-release agent in modified release matrices in comparison with sodium carboxymethylcellulose (NaCMC) using aspirin as the model drug. Tablets were produced by direct compression and the in vitro drug release was assessed under conditions similar to those in the gastrointestinal ...

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

Science.gov (United States)

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

2014-12-01

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

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

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Shahid Bashir

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

Physically Targeted Intravenous Polyurethane Nanoparticles for Controlled Release of Atorvastatin Calcium

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Eftekhari, Behnaz Sadat; Karkhaneh, Akbar; Alizadeh, Ali

2017-01-01

Background: Intravenous drug delivery is an advantageous choice for rapid administration, immediate drug effect, and avoidance of first-pass metabolism in oral drug delivery. In this study, the synthesis, formulation, and characterization of atorvastatin-loaded polyurethane (PU) nanoparticles were investigated for intravenous route of administration. Method: First, PU was synthesized and characterized. Second, nanoparticles were prepared in four different ratios of drug to polymer through two different techniques, including emulsion-diffusion and single-emulsion. Finally, particle size and polydispersity index, shape and surface morphology, drug entrapment efficiency (EE), drug loading, and in vitro release were evaluated by dynamics light scattering, scanning electron microscopy, and UV visible spectroscopy, respectively. Results: Within two methods, the prepared nanoparticles had a spherical shape and a smooth surface with a diversity of size ranged from 174.04 nm to 277.24 nm in emulsion-diffusion and from 306.5 nm to 393.12 in the single-emulsion method. The highest EE was 84.76%, for (1:4) sample in the emulsion-diffusion method. It has also been shown that in vitro release of nanoparticles, using the emulsion-diffusion method, was sustained up to eight days by two mechanisms: drug diffusion and polymer relaxation. Conclusion: PU nanoparticles, that were prepared by the emulsion-diffusion method, could be used as effective carriers for the controlled drug delivery of poorly water soluble drugs such as atorvastatin calcium. PMID:28532144

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

International Nuclear Information System (INIS)

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

2012-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2012-08-15

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

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

Science.gov (United States)

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

2012-08-01

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

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

Science.gov (United States)

Burka, J F; Eyre, P

1975-01-01

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

Double targeting and aptamer-assisted controlled release delivery of epirubicin to cancer cells by aptamers-based dendrimer in vitro and in vivo.

Science.gov (United States)

Taghdisi, Seyed Mohammad; Danesh, Noor Mohammad; Ramezani, Mohammad; Lavaee, Parirokh; Jalalian, Seyed Hamid; Robati, Rezvan Yazdian; Abnous, Khalil

2016-05-01

Clinical use of epirubicin (Epi) in the treatment of cancer has been limited, due to its cardiotoxicity. Targeted delivery of chemotherapeutic agents could increase their efficacy and reduce their off-target effects. High drug loading and excellent stability of DNA dendrimers make these DNA nanostructures unique candidates for biological applications. In this study a modified and promoted dendrimer using three kinds of aptamers (MUC1, AS1411 and ATP aptamers) was designed for targeted delivery of Epi and its efficacy was evaluated in target cells including MCF-7 cells (breast cancer cell) and C26 cells (murine colon carcinoma cell). Aptamers (Apts)-Dendrimer-Epi complex formation was analyzed by fluorometric analysis and gel retardation assay. Release profiles of Epi from the designed complex were assessed at pHs 5.4 and 7.4. For MTT assay (cytotoxic study) MCF-7 and C26 cells (target cells) and CHO cells (Chinese hamster ovary cell, nontarget) were treated with Epi, Apts-Dendrimer-Epi complex and Apts-Dendrimer conjugate. Internalization was evaluated using flow cytometry analysis. Finally, the developed complex was used for inhibition of tumor growth in vivo. 25μM Epi was efficiently intercalated to 1μM dendrimer. Epi was released from the Apts-Dendrimer-Epi complex in a pH-sensitive manner (more release at pH 5.5). The results of flow cytometry analysis indicated that the designed complex was efficiently internalized into target cells, but not into control cells. The internalization data were confirmed by the results of MTT assay. Apts-Dendrimer-Epi complex had less cytotoxicity in CHO cells compared to Epi alone. The complex had more cytotoxicity in C26 and MCF-7 cells compared to Epi alone. Moreover, the Apts-Dendrimer-Epi complex could efficiently prohibit tumor growth in vivo. In conclusion, the designed targeted drug delivery system inherited characteristics of pH-dependent drug release, high drug loading and tumor targeting in vitro and in vivo

Development and evaluation of diltiazem hydrochloride controlled-release pellets by fluid bed coating process

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Mikkilineni Bhanu Prasad

2013-01-01

Full Text Available The aim of the present study was to develop controlled-release pellets of diltiazem HCl with ethyl cellulose and hydroxylpropyl methylcellulose phthalate as the release rate retarding polymers by fluid bed coating technique. The prepared pellets were evaluated for drug content, particle size, subjected to Scanning Electron Microscopy (SEM and Differential Scanning Calori metry (DSC, and evaluated for in vitro release. Stability studies were carried out on the optimized formulations for a period of 3 months. The drug content was in the range of 97%-101%. The mean particle size of the drug-loaded pellets was in the range 700-785 μm. The drug release rate decreased as the concentration of ethyl cellulose increased in the pellet formulations. Among the prepared formulations, FDL10 and FDL11 showed 80% drug release in 16 h, matching with USP dissolution test 6 for diltiazem HCl extended-release capsules. SEM photographs confirmed that the prepared formulations were spherical in nature with a smooth surface. The compatibility between drug and polymers in the drug-loaded pellets was confirmed by DSC studies. Stability studies indicated that the pellets were stable.

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

International Nuclear Information System (INIS)

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

1986-01-01

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

Controlled release of ketorolac through nanocomposite films of hydrogel and LDH nanoparticles

International Nuclear Information System (INIS)

Xu Zhiping; Gu Zi; Cheng Xiaoxi; Rasoul, Firas; Whittaker, Andrew K.; Lu Gaoqing Max

2011-01-01

A novel nanocomposite film for sustained release of anionic ophthalmic drugs through a double-control process has been examined in this study. The film, made as a drug-loaded contact lens, consists principally of a polymer hydrogel of 2-hydroxyethyl methacrylate (HEMA), in whose matrix MgAl-layered double hydroxide (MgAl-LDH) nanoparticles intercalated with the anionic drug are well dispersed. Such nanocomposite films (hydrogel-LDH-drug) contained 0.6–0.8 mg of MgAl-LDH and 0.08–0.09 mg of the ophthalmic drug (ketorolac) in 1.0 g of hydrogel. MgAl-drug-LDH nanoparticles were prepared with the hydrodynamic particle size of 40–200 nm. TEM images show that these nanoparticles are evenly dispersed in the hydrogel matrix. In vitro release tests of hydrogel-LDH-drug in pH 7.4 PBS solution at 32 °C indicate a sustained release profile of the loaded drug for 1 week. The drug release undergoes a rapid initial burst and then a monotonically decreasing rate up to 168 h. The initial burst release is determined by the film thickness and the polymerization conditions, but the following release rate is very similar, with the effective diffusion coefficient being nearly constant (3.0 × 10 −12 m 2 /s). The drug release from the films is mechanistically attributed to anionic exchange and the subsequent diffusion in the hydrogel matrix.

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

International Nuclear Information System (INIS)

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

1989-01-01

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

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

Science.gov (United States)

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

2002-01-01

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

Encapsulation of naproxen in lipid-based matrix microspheres: characterization and release kinetics.

Science.gov (United States)

Bhoyar, P K; Morani, D O; Biyani, D M; Umekar, M J; Mahure, J G; Amgaonkar, Y M

2011-04-01

The objective of this study was to microencapsulate the anti-inflammatory drug (naproxen) to provide controlled release and minimizing or eliminating local side effect by avoiding the drug release in the upper gastrointestinal track. Naproxen was microencapsulated with lipid-like carnauba wax, hydrogenated castor oil using modified melt dispersion (modified congealable disperse phase encapsulation) technique. Effect of various formulation and process variables such as drug-lipid ratio, concentration of modifier, concentration of dispersant, stirring speed, stirring time, temperature of external phase, on evaluatory parameters such as size, entrapment efficiency, and in vitro release of naproxen were studied. The microspheres were characterized for particle size, scanning electron microscopy (SEM), FT-IR spectroscopy, drug entrapment efficiency, in vitro release studies, for in vitro release kinetics. The shape of microspheres was found to be spherical by SEM. The drug entrapment efficiency of various batches of microspheres was found to be ranging from 60 to 90 %w/w. In vitro drug release studies were carried out up to 24 h in pH 7.4 phosphate buffer showing 50-65% drug release. In vitro drug release from all the batches showed better fitting with the Korsmeyer-Peppas model, indicating the possible mechanism of drug release to be by diffusion and erosion of the lipid matrix.

Dual-controlled release system of drugs for bone regeneration.

Science.gov (United States)

Kim, Yang-Hee; Tabata, Yasuhiko

2015-11-01

Controlled release systems have been noted to allow drugs to enhance their ability for bone regeneration. To this end, various biomaterials have been used as the release carriers of drugs, such as low-molecular-weight drugs, growth factors, and others. The drugs are released from the release carriers in a controlled fashion to maintain their actions for a long time period. Most research has been focused on the controlled release of single drugs to demonstrate the therapeutic feasibility. Controlled release of two combined drugs, so-called dual release systems, are promising and important for tissue regeneration. This is because the tissue regeneration process of bone formation is generally achieved by multiple bioactive molecules, which are produced from cells by other molecules. If two types of bioactive molecules, (i.e., drugs), are supplied in an appropriate fashion, the regeneration process of living bodies will be efficiently promoted. This review focuses on the bone regeneration induced by dual-controlled release of drugs. In this paper, various dual-controlled release systems of drugs aiming at bone regeneration are overviewed explaining the type of drugs and their release materials. Copyright © 2015 Elsevier B.V. All rights reserved.

Novel Brassinosteroid-Modified Polyethylene Glycol Micelles for Controlled Release of Agrochemicals.

Science.gov (United States)

Pérez Quiñones, Javier; Brüggemann, Oliver; Kjems, Jørgen; Shahavi, Mohammad Hassan; Peniche Covas, Carlos

2018-02-21

Two synthetic analogues of brassinosteroids (DI31 and S7) exhibit good plant growth enhancer activity. However, their hydrophobicity and quick metabolism in plants have limited their application and benefits in agriculture. Our objective was to prepare novel brassinosteroid-modified polyethylene glycol (PEG) micelles to achieve controlled release with extended stability while retaining agrochemical activity. Spectroscopic studies confirmed quantitative disubstitution of studied PEGs with the brassinosteroids, while elemental analysis assessed purity of the synthesized conjugates. Conjugates were also characterized by X-ray diffraction and thermal analysis. Dynamic and static light scattering showed stable and homogeneous approximately spherical micelles with average hydrodynamic diameters of 22-120 nm and almost neutral ζ potential. Spherical 30-140 nm micelles were observed by electron microscopy. Sustained in vitro releases at pH 5.5 were extended up to 96 h. Prepared PEG micelles showed good agrochemical activity in the radish seed bioassay and no cytotoxicity to the human microvascular endothelial cell line in the MTS test.

How controlled release technology can aid gene delivery.

Science.gov (United States)

Jo, Jun-Ichiro; Tabata, Yasuhiko

2015-01-01

Many types of gene delivery systems have been developed to enhance the level of gene expression. Controlled release technology is a feasible gene delivery system which enables genes to extend the expression duration by maintaining and releasing them at the injection site in a controlled manner. This technology can reduce the adverse effects by the bolus dose administration and avoid the repeated administration. Biodegradable biomaterials are useful as materials for the controlled release-based gene delivery technology and various biodegradable biomaterials have been developed. Controlled release-based gene delivery plays a critical role in a conventional gene therapy and genetic engineering. In the gene therapy, the therapeutic gene is released from biodegradable biomaterial matrices around the tissue to be treated. On the other hand, the intracellular controlled release of gene from the sub-micro-sized matrices is required for genetic engineering. Genetic engineering is feasible for cell transplantation as well as research of stem cells biology and medicine. DNA hydrogel containing a sequence of therapeutic gene and the exosome including the individual specific nucleic acids may become candidates for controlled release carriers. Technologies to deliver genes to cell aggregates will play an important role in the promotion of regenerative research and therapy.

In vitro immunomodulation of a whole blood IFN-γ release assay enhances T cell responses in subjects with latent tuberculosis infection.

Directory of Open Access Journals (Sweden)

Rajiv L Gaur

Full Text Available Activation of innate immunity via pathogen recognition receptors (PRR modulates adaptive immune responses. PRR ligands are being exploited as vaccine adjuvants and as therapeutics, but their utility in diagnostics has not been explored. Interferon-gamma (IFN-γ release assays (IGRAs are functional T cell assays used to diagnose latent tuberculosis infection (LTBI; however, novel approaches are needed to improve their sensitivity.In vitro immunomodulation of a whole blood IGRA (QuantiFERON®-TB GOLD In-Tube with Toll-like receptor agonists poly(I:C, LPS, and imiquimod was performed on blood from subjects with LTBI and negative controls.In vitro immunomodulation significantly enhanced the response of T cells stimulated with M. tuberculosis antigens from subjects with LTBI but not from uninfected controls. Immunomodulation of IGRA revealed T cell responses in subjects with LTBI whose T cells otherwise do not respond to in vitro stimulation with antigens alone. Similar to their in vivo functions, addition of poly(I:C and LPS to whole blood induced secretion of inflammatory cytokines and IFN-α and enhanced the surface expression of antigen presenting and costimulatory molecules on antigen presenting cells.In vitro immunomodulation of whole blood IGRA may be an effective strategy for enhancing the sensitivity of T cells for diagnosis of LTBI.

WE-AB-BRA-03: Non-Invasive Controlled Release from Implantable Hydrogel Scaffolds Using Ultrasound

Energy Technology Data Exchange (ETDEWEB)

Moncion, A; Kripfgans, O.D; Putnam, A.J; Frances chi, R.T; Fabiilli, M.L [University of Michigan, Ann Arbor, MI (United States)

2016-06-15

Purpose: To control release of a model payload in acoustically responsive scaffolds (ARSs) using focused ultrasound (FUS). Methods: Fluorescently-labeled dextran (10 kDa) was encapsulated in sonosensitive perfluorocarbon (C{sub 6}F{sub 14} or C{sub 5}F{sub 12}) double emulsions (mean diameter: 2.9±0.1 µm). For in vitro release studies, 0.5 mL ARSs (10 mg/mL fibrin, 1% (v/v) emulsion) were polymerized in 24 well plates and covered with 0.5 mL medium. Starting one day after polymerization, ARSs were exposed to FUS (2.5 MHz, Pr = 8 MPa, 13 cycles, 100 Hz PRF) for 2 min daily. The amount of dextran released into the media was quantified. For in vivo studies, 0.25 mL ARSs were prepared as described previously and injected subcutaneously in the lower back of BALB/c mice. After polymerization, a subset of the implanted ARSs were exposed to FUS (as previously described). Animals were imaged longitudinally using a fluorescence imaging system to quantify the amount of dextran released from the ARSs. Results: In vitro: Over 6 days, +FUS displayed an 8.2-fold increase in dextran release compared to −FUS (−FUS: 2.7±0.6%; +FUS: 22.2±3.0%) for C{sub 6}F{sub 14} ARSs, and a 6.7-fold increase (−FUS: 5.0±0.8%; +FUS: 38.5±1.6%) for C{sub 5}F{sub 12}:C{sub 6}F{sub 14} ARSs. In vivo: +FUS displayed statistically greater dextran release compared to −FUS one day after implantation for C{sub 5}F{sub 12}:C{sub 6}F{sub 14} ARSs (−FUS: 55.1±1.5%; +FUS: 74.1±2.2%) and three days after implantation for C{sub 6}F{sub 14} ARSs (−FUS: 1.4±6.5%; +FUS: 30.4±5.4%). Conclusion: FUS enables non-invasive control of payload release from an ARS, which could benefit growth factor delivery for tissue regeneration. ARS are versatile due to their tunability (i.e. stiffness, emulsion composition, FUS pressure, FUS frequency, etc.) and can be modified to for optimal payload release. Future work will optimize ARS formulations for in vivo use to minimize payload release in the absence of

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

Science.gov (United States)

ATKINS, E; CRONIN, M; ISACSON, P

1964-12-11

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

Bone induction through controlled release of novel BMP-2-related peptide from PTMC11-F127-PTMC11 hydrogels

International Nuclear Information System (INIS)

Tang Shuo; Li Jingfeng; Teng Yu; Guo Xiaodong; Zhao Jingjing; Xu Shuyun; Quan Daping

2012-01-01

Bone morphogenetic protein 2 (BMP-2) is the most powerful osteogenic factor; its effectiveness in enhancing osteoblastic activation has been confirmed both in vitro and in vivo. We developed a novel peptide (designated P24) derived from the ‘knuckle’ epitope of BMP-2 and found it also had osteogenic bioactivity to some extent. The main objective of this study was to develop a controlled release system based on poly(trimethylene carbonate)–F127–poly(trimethylene carbonate) (PTMC 11 -F127-PTMC 11 ) hydrogels for the P24 peptide, to promote bone formation. By varying the copolymer concentrations, we demonstrated that P24/PTMC 11 -F127-PTMC 11 hydrogels were an efficient system for the sustained release of P24 over 21–35 days. The P24-loaded hydrogels elevated alkaline phosphatase activity and promoted the expression of osteocalcin mRNA in bone marrow stromal cells (BMSCs) in vitro. Radiographic and histological examination showed that P24-loaded hydrogels could induce more effective ectopic bone formation in vivo than P24-free hydrogels. These results indicate that the PTMC 11 -F127-PTMC 11 hydrogel is a suitable carrier for the controlled release of P24, and is a promising injectable biomaterial for the induction of bone regeneration. (paper)

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

Science.gov (United States)

Bodel, P

1974-01-01

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

Serotonin binding in vitro by releasable proteins from human blood platelets

International Nuclear Information System (INIS)

Heemstra, V.L.

1983-11-01

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

28 CFR 541.50 - Release from a control unit.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Release from a control unit. 541.50... INMATE DISCIPLINE AND SPECIAL HOUSING UNITS Control Unit Programs § 541.50 Release from a control unit. (a) Only the Executive Panel may release an inmate from a control unit. The following factors are...

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

Science.gov (United States)

Verma, Sanjay; Rudraraju, Varma S

2015-02-01

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

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.

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

Directory of Open Access Journals (Sweden)

Zhang Hu

2012-01-01

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

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

Science.gov (United States)

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

2017-07-28

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

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

Science.gov (United States)

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

2012-04-01

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

EPICS application source/release control

International Nuclear Information System (INIS)

Zieman, B.; Anderson, J.; Kraimer, M.

1995-01-01

This manual describes a set of Application Source/Release Control tools (appSR) that can be used to develop software for EPICS based control systems. The Application Source/Release Control System (appSR) has been unbundled from base EPICS and is now available as an EPICS extension. Due to this unbundling, two new directories must be added to a user's path (see section ''Environment'' on page 3 for more information) and a new command getapp must be issued after the getrel command to get a specific version of appSR (see section ''Creating The Initial Application System Area'' on page 7 for more information). It is now required that GNU make version 3.71 or later be used for makes instead of SUN make. Users should now type gmake instead of make

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

Science.gov (United States)

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

1990-01-01

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

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

Organic-Inorganic Hybrid Hollow Mesoporous Organosilica Nanoparticles for Efficient Ultrasound-Based Imaging and Controlled Drug Release

Directory of Open Access Journals (Sweden)

Xiaoqin Qian

2014-01-01

Full Text Available A novel anticancer drug delivery system with contrast-enhanced ultrasound-imaging performance was synthesized by a typical hard-templating method using monodispersed silica nanoparticles as the templates, which was based on unique molecularly organic/inorganic hybrid hollow periodic mesoporous organosilicas (HPMOs. The highly dispersed HPMOs show the uniform spherical morphology, large hollow interior, and well-defined mesoporous structures, which are very beneficial for ultrasound-based theranostics. The obtained HPMOs exhibit excellent performances in contrast-enhanced ultrasonography both in vitro and in vivo and can be used for the real-time determination of the progress of lesion tissues during the chemotherapeutic process. Importantly, hydrophobic paclitaxel- (PTX- loaded HPMOs combined with ultrasound irradiation show fast ultrasound responsiveness for controlled drug release and higher in vitro and in vivo tumor inhibition rates compared with free PTX and PTX-loaded HPMOs, which is due to the enhanced ultrasound-triggered drug release and ultrasound-induced cavitation effect. Therefore, the achieved novel HPMOs-based nanoparticle systems will find broad application potentials in clinically ultrasound-based imaging and auxiliary tumor chemotherapy.

MRI observation of the light-induced release of a contrast agent from photo-controllable polymer micelles

International Nuclear Information System (INIS)

Lepage, Martin; Jiang Jinqiang; Babin, Jerome; Qi, Bo; Tremblay, Luc; Zhao Yue

2007-01-01

The encapsulation of molecules into nanocarriers is studied for its potential in delivering a high dose of anticancer drugs to a tumor, while minimizing side effects. Most systems either release their content in a non-specific manner or under specific environmental conditions such as temperature or pH. We have synthesized a novel class of photo-controllable polymer micelles that can stably encapsulate a hydrophilic compound and subsequently release it upon absorption of UV light. Here, we describe an in vitro magnetic resonance imaging assay that can evaluate the state of incorporation of a small Gd-based contrast agent. Our results indicate that the contrast agent alone can diffuse through a filter, but that the same agent incorporated into micelles cannot. After exposure to UV light, the micelles released the contrast agent, which could then diffuse through the filter. (note)

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.

Design and characterization of controlled-release edible packaging films prepared with synergistic whey-protein polysaccharide complexes.

Science.gov (United States)

Liu, Fei; Jiang, Yanfeng; Du, Bingjian; Chai, Zhi; Jiao, Tong; Zhang, Chunyue; Ren, Fazheng; Leng, Xiaojing

2013-06-19

This paper describes an investigation into the properties of a doubly emulsified film incorporated with protein-polysaccharide microcapsules, which serves as a multifunctional food packaging film prepared using common edible materials in place of petroleum--based plastics. The relationships between the microstructural properties and controlled release features of a series of water-in-oil-in-water (W/O/W) microcapsulated edible films prepared in thermodynamically incompatible conditions were analyzed. The hydrophilic riboflavin (V(B2)) nano-droplets (13-50 nm) dispersed in α-tocopherol (V(E)) oil phase were embedded in whey protein-polysaccharide (WPs) microcapsules with a shell thickness of 20-56 nm. These microcapsules were then integrated in 103 μm thick WPs films. Different polysaccharides, including gum arabic (GA), low-methoxyl pectin (LMP), and κ-carrageenan (KCG), exhibited different in vitro synergistic effects on the ability of both films to effect enteric controlled release of both vitamins. GA, which showed a strong emulsifying ability, also showed better control of V(E) than other polysaccharides, and the highly charged KCG showed better control of V(B2) than GA did.

Stimuli-Responsive Materials for Controlled Release Applications

KAUST Repository

Li, Song

2015-04-01

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

Controlled release profiles of dipyridamole from biodegradable microspheres on the base of poly(3-hydroxybutyrate.

Directory of Open Access Journals (Sweden)

2007-12-01

Full Text Available Novel biodegradable microspheres on the base of poly(3-hydroxybutyrate (PHB designed for controlled release of antithrombotic drug, namely dipyridamole (DPD, have been kinetically studied. The profiles of release from the microspheres with different diameters 4, 9, 63, and 92 µm present the progression of nonlinear and linear stages. Diffusionkinetic equation describing both linear (PHB hydrolysis and nonlinear (diffusion stages of the DPD release profiles from the spherical subjects has been written down as the sum of two terms: desorption from the homogeneous sphere in accordance with diffusion mechanism and the zero-order release. In contrast to the diffusivity dependence on microsphere size, the constant characteristics (k of linearity are scarcely affected by the diameter of PHB microparticles. The view of the kinetic profiles as well as the low rate of DPD release are in satisfactory agreement with kinetics of weight loss measured in vitro for the PHB films. Taking into account kinetic results, we suppose that the degradation of both films and PHB microspheres is responsible for the linear stage of DPD release profiles. In the nearest future, combination of biodegradable PHB and DPD as a representative of proliferation cell inhibitors will give possibility to elaborate the novel injectable therapeutic system for a local, long-term, antiproliferative action.

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

Science.gov (United States)

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

2013-01-01

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

UV-screening chitosan nanocontainers: increasing the photostability of encapsulated materials and controlled release

International Nuclear Information System (INIS)

Anumansirikul, Nattaporm; Wittayasuporn, Mayura; Klinubol, Patcharawalai; Tachaprutinun, A; Wanichwecharungruang, Supason P

2008-01-01

Methyl ether terminated poly(ethylene glycol)-4-methoxycinnamoylphthaloylchitosan (PCPLC), a UV absorptive polymer, and methyl ether terminated poly(ethylene glycol)-phthaloylchitosan (PPLC) were synthesized, characterized and self-assembled into stable water-dispersible spherical nanoparticles. The encapsulation of a model compound, 2-ethylhexyl-4-methoxycinnamate (EHMC), was carried out to give particles with 67% (w/w) EHMC loading. The E to Z photoisomerization of EHMC encapsulated inside both particles was monitored and compared to non-encapsulated EHMC. Minimal E to Z photoisomerization was observed when EHMC was encapsulated in PCPLC particles prepared from a polymer with a maximum degree of 4-methoxycinnamoyl substitution. The results indicated that the grafted UVB absorptive chromophore, 4-methoxycinnamoyl moieties, situated at the shell of PCPLC nanoparticles acted as a UV-filtering barrier, protecting the encapsulated EHMC from the UVB radiation, thus minimizing its photoisomerization. In vitro experiments revealed the pH-dependent controlled release of EHMC from PCPLC and PPLC particles. Ex vivo experiments, using a Franz diffusion cell with baby mouse skin, indicated that neither PPLC nor PCPLC particles could penetrate the skin into the receptor medium after a 24 h topical application. When applied on the baby mouse skin, both EHMC-encapsulated PPLC and EHMC-encapsulated PCPLC showed comparable controlled releases of the EHMC. The released EHMC could transdermally penetrate the baby mouse skin

UV-screening chitosan nanocontainers: increasing the photostability of encapsulated materials and controlled release

Science.gov (United States)

Anumansirikul, Nattaporm; Wittayasuporn, Mayura; Klinubol, Patcharawalai; Tachaprutinun, A.; Wanichwecharungruang, Supason P.

2008-05-01

Methyl ether terminated poly(ethylene glycol)-4-methoxycinnamoylphthaloylchitosan (PCPLC), a UV absorptive polymer, and methyl ether terminated poly(ethylene glycol)-phthaloylchitosan (PPLC) were synthesized, characterized and self-assembled into stable water-dispersible spherical nanoparticles. The encapsulation of a model compound, 2-ethylhexyl-4-methoxycinnamate (EHMC), was carried out to give particles with 67% (w/w) EHMC loading. The E to Z photoisomerization of EHMC encapsulated inside both particles was monitored and compared to non-encapsulated EHMC. Minimal E to Z photoisomerization was observed when EHMC was encapsulated in PCPLC particles prepared from a polymer with a maximum degree of 4-methoxycinnamoyl substitution. The results indicated that the grafted UVB absorptive chromophore, 4-methoxycinnamoyl moieties, situated at the shell of PCPLC nanoparticles acted as a UV-filtering barrier, protecting the encapsulated EHMC from the UVB radiation, thus minimizing its photoisomerization. In vitro experiments revealed the pH-dependent controlled release of EHMC from PCPLC and PPLC particles. Ex vivo experiments, using a Franz diffusion cell with baby mouse skin, indicated that neither PPLC nor PCPLC particles could penetrate the skin into the receptor medium after a 24 h topical application. When applied on the baby mouse skin, both EHMC-encapsulated PPLC and EHMC-encapsulated PCPLC showed comparable controlled releases of the EHMC. The released EHMC could transdermally penetrate the baby mouse skin.

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

DEFF Research Database (Denmark)

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

1994-01-01

Fast-scan cyclic voltammetry with carbon fibre microelectrodes was used to detect endogenous dopamine (DA) and 5-hydroxytryptamine (5-HT) release from three distinct regions of guinea-pig mid-brain in vitro: rostral and caudal substantia nigra (SN) and the ventral tegmental area (VTA). Previous...... these regions with in situ electrodes and demonstrates the utility of fast-scan cyclic voltammetry to investigate the mechanisms and possible non-classical functions of somato-dendritic DA release....

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

Energy Technology Data Exchange (ETDEWEB)

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

1976-02-01

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

Controlled release studies of calcium alginate hydrogels

International Nuclear Information System (INIS)

Rendevski, S.; Andonovski, A.; Mahmudi, N.

2012-01-01

Controlled release of substances in many cases may be achieved from calcium alginate hydrogels. In this research, the time dependence of the mass of released model substance bovine serum albumin (BSA) from calcium alginate spherical hydrogels of three different types (G/M ratio) have been investigated. The hydrogels were prepared with the drop-wise method of sodium alginate aqueous solutions with concentration of 0.02 g/cm 3 with 0.01 g/cm 3 BSA and a gelling water bath of chitosan in 0.2 M CH 3 COOH/0.4 M CH 3 COONa with added 0.2 M CaCl 2 .The hydrogel structures were characterized by dynamic light scattering and scanning electron microscopy. The controlled release studies were conducted by UV-Vis spectrophotometry of the released medium with p H=7 at 37 °C. The results showed that the model of osmotic pumping is the dominant mechanism of the release. Also, large dependences of the release profile on the homogeneity of the hydrogels were found. (Author)

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

International Nuclear Information System (INIS)

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

2017-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2017-01-01

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

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

Science.gov (United States)

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

2017-05-01

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

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.

'Breath figure' PLGA films as implant coatings for controlled drug release

Science.gov (United States)

Ponnusamy, Thiruselvam

The breath figure method is a versatile and facile approach of generating ordered micro and nanoporous structures in polymeric materials. When a polymer solution (dissolved in a high vapor pressure organic solvent) is evaporated out in the presence of a moist air stream, the evaporative cooling effect causes the condensation and nucleation of water droplets onto the polymer solution surface. This leads to the formation of an imprinted porous structure upon removal of the residual solvent and water. The facile removal of the water droplet template leaving its structural imprint is a specifically appealing aspect of the breath figure film technology. The first part of the dissertation work involves the fabrication of drug loaded breath figure thin films and its utilization as a controlled drug release carrier and biomaterial scaffold. In a single fabrication step, single layer/multilayer porous thin films were designed and developed by combining the breath figure process and a modified spin or dip coating technique. Using biodegradable polymers such as poly (lactic-co-glycolic acid) (PLGA) and poly (ethylene glycol) (PEG), drug loaded films were fabricated onto FDA approved medical devices (the Glaucoma drainage device and the Surgical hernia mesh). The porosity of the films is in the range of 2-4 microm as characterized by scanning electron microscope. The drug coated medical implants were characterized for their surface and bulk morphology, the degradation rate of the film, drug release rate and cell cytotoxicity. The results suggest that the use of breath figure morphologies in biodegradable polymer films adds an additional level of control to drug release. In comparison to non-porous films, the breath figure films showed an increased degradation and enhanced drug release. Furthermore, the porous nature of the film was investigated as a biomaterial scaffold to construct three dimensional in vitro tissue model systems. The breath figure film with interconnected

Birth control - slow release methods

Science.gov (United States)

Contraception - slow-release hormonal methods; Progestin implants; Progestin injections; Skin patch; Vaginal ring ... might want to consider a different birth control method. SKIN PATCH The skin patch is placed on ...

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

Science.gov (United States)

Mohammed, Irfan A.

To optimize the clinical efficacy of Ketoconazole from an externally applied product, this project was undertaken to evaluate the drug release/permeation profile from various dermatological vehicles using regular powder, nanoparticles and solid dispersion forms with reduced level of drug. Nanoparticles of drug were prepared by wet media milling method using Polyvinylpyrrolidone (PVP-10K) as a stabilizer. The nanoparticles were in the size range of 250-300nm. Solid dispersion was prepared by solvent evaporation method using drug to PVP-10K at a weight ratio of (1:2). Formulations containing 1% w/w drug were developed using HPMC gel, Carbomer gel and a cationic cream as the vehicles. Penetration enhancers including propylene glycol (PG), dimethylsulfoxide (DMSO) and polyethylene glycol 400 (PEG-400) at various levels were evaluated. A commercial 2% w/w ketoconazole product was included as a control for comparison. Studies were carried out with Franz Diffusion Cells using cellulose membrane and human cadaver skin for two and six hour studies. Among the formulations evaluated, the general rank order of the drug release through the cellulose membrane was observed to be: HPMC gel base > Anionic gel base > Cationic gel base > Commercial product. The addition of penetration enhancers showed variable effects in all samples evaluated. However, the HPMC gel-based vehicle showed significant effect in enhancing the drug release in the presence of DMSO. The formulation containing 1% w/w ketoconazole and 20% w/w DMSO gave a maximum drug release of 20.21% when compared to only 1.60% from the commercial product. This represents a twelve fold increase in the release of ketoconazole from the formulation. Furthermore, when the optimum gel-based formulation containing 1% w/w ketoconazole was studied over an extended period of 6 hours, it gave 36.01% drug release from the sample formulation compared to only 2.00% from the commercial product. Finally, this formulation was selected to

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.

Electrically controlled drug release from nanostructured polypyrrole coated on titanium

International Nuclear Information System (INIS)

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

2011-01-01

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

Electrically controlled drug release from nanostructured polypyrrole coated on titanium

Science.gov (United States)

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

2011-02-01

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

Electrically controlled drug release from nanostructured polypyrrole coated on titanium

Energy Technology Data Exchange (ETDEWEB)

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

2011-02-25

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

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

Science.gov (United States)

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

2016-01-01

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

Controlled release of tocopherols from polymer blend films

Science.gov (United States)

Obinata, Noe

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

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

Science.gov (United States)

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

2016-04-01

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

Model-based computer-aided design for controlled release of pesticides

DEFF Research Database (Denmark)

Muro Sunè, Nuria; Gani, Rafiqul; Bell, G.

2005-01-01

In the field of controlled release technology for pesticides or active ingredients (AI), models that can predict its delivery during application are important for purposes of design and marketing of the pesticide product. Appropriate models for the controlled release of pesticides, if available, ...... extended models have been developed and implemented into a computer-aided system. The total model consisting of the property models embedded into the release models are then employed to study the release of different combinations of AIs and polymer-based microcapsules.......In the field of controlled release technology for pesticides or active ingredients (AI), models that can predict its delivery during application are important for purposes of design and marketing of the pesticide product. Appropriate models for the controlled release of pesticides, if available...

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

International Nuclear Information System (INIS)

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

2014-01-01

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

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

Science.gov (United States)

Klein, S

2013-07-01

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

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

Science.gov (United States)

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

2015-06-01

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

Distinct presynaptic control of dopamine release in striosomal and matrix areas of the cat caudate nucleus

International Nuclear Information System (INIS)

Kemel, M.L.; Desban, M.; Glowinski, J.; Gauchy, C.

1989-01-01

By use of a sensitive in vitro microsuperfusion method, the cholinergic presynaptic control of dopamine release was investigated in a prominent striosome (areas poor in acetylcholinesterase activity) located within the core of cat caudate nucleus and also in adjacent matrix area. The spontaneous release of [ 3 H]dopamine continuously synthesized from [ 3 H]tyrosine in the matrix area was found to be twice that in the striosomal area; the spontaneous and potassium-evoked releases of [ 3 H]dopamine were calcium-dependent in both compartments. With 10 -6 M tetrodotoxin, 5 x 10 -5 M acetylcholine stimulated [ 3 H]dopamine release in both striosomal and matrix areas, effects completely antagonized by atropine, thus showing the involvement of muscarinic receptors located on dopaminergic nerve terminals. Experiments without tetrodotoxin revealed a more complex regulation of dopamine release in the matrix: (i) in contrast to results seen in the striosome, acetylcholine induced only a transient stimulatory effect on matrix dopamine release. (ii) Although 10 -6 M atropine completely abolished the cholinergic stimulatory effect on [ 3 H]dopamine release in striosomal area, delayed and prolonged stimulation of [ 3 H] dopamine release was seen with atropine in the matrix. The latter effect was completely abolished by the nicotinic antagonist pempidine. Therefore, in the matrix, in addition to its direct (tetrodotoxin-insensitive) facilitatory action on [ 3 H]dopamine release, acetylcholine exerts two indirect (tetrodotoxin-sensitive) opposing effects: an inhibition and a stimulation of [ 3 H]dopamine release mediated by muscarinic and nicotinic receptors, respectively

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.

In vitro evaluation of (99m)Tc-EDDA/tricine-HYNIC-Q-Litorin in gastrin-releasing peptide receptor positive tumor cell lines.

Science.gov (United States)

Yurt Lambrecht, Fatma; Durkan, Kübra; Ozgür, Aykut; Gündüz, Cumhur; Avcı, Cığır Biray; Susluer, Sunde Yılmaz

2013-05-01

Bombesin and its derivatives exhibit a high affinity for gastrin-releasing peptide receptor (GRPr), which is over-expressed in a variety of human cancers (prostate, pancreatic, lung, etc.). The aim of this study was to investigate the in vitro potential of the hydrazinonicotinamide (HYNIC)-Q-Litorin. (99m)Tc labeling was performed by using different co-ligands: tricine and ethylenediamine diacetic acid (EDDA). The radiochemical stability of radiolabeled peptide conjugates was checked at room temperature and in cysteine solution up to 24 h. The in vitro cell uptake of (99m)Tc-EDDA-HYNIC-Q-Litorin and (99m)Tc-tricine-HYNIC-Q-Litorin were evaluated on pancreatic tumor and control cell lines. Optimum specific activity and incubation time were determined for all the cell lines. The results showed that the cell uptake of the radiolabeled peptide conjugates in tumor cell lines were higher than in the control cell line. The findings of this study indicated the need for further development of in vivo study as a radiopharmaceutical for pancreatic tumor imaging.

Grafting of GMA and some comonomers onto chitosan for controlled release of diclofenac sodium.

Science.gov (United States)

Sharma, Rajeev Kr; Lalita; Singh, Anirudh P; Chauhan, Ghanshyam S

2014-03-01

In order to develop pH sensitive hydrogels for controlled drug release we have graft copolymerized glycidyl methacrylate (GMA) with comonomers acrylic acid, acrylamide and acrylonitrile, onto chitosan (Ch) by using potassium persulphate (KPS) as free radical initiator in aqueous solution. The optimum percent grafting for GMA was recorded for 1g chitosan at [KPS]=25.00 × 10(-3)mol/L, [GMA]=0.756 × 10(-3)mol/L, reaction temperature=60 °C and reaction time=1h in 20 mL H2O. Binary monomers were grafted for five different concentrations at optimum grafting conditions evaluated for GMA alone onto chitosan. The graft copolymers were characterized by FTIR, XRD, TGA and SEM. The swelling properties of chitosan and graft copolymers were investigated at different pH to define their end uses in sustained release of an anti-inflammatory drug, diclofenac sodium. Percent drug release w.r.t. drug loaded in polymeric sample was studied as function of time in buffer solutions of pH 2.0 and 7.4. In vitro release data was analyzed using Fick's Law. Chitosan grafted with binary monomers, GMA-co-AAm and GMA-co-AN showed very good results for sustained release of drug at 7.4 pH. Copyright © 2014 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

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

2017-03-01

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

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.

Composite poly(vinyl alcohol/poly(vinyl acetate electrospun nanofibrous mats as a novel wound dressing matrix for controlled release of drugs

Directory of Open Access Journals (Sweden)

Jannesari M

2011-05-01

Full Text Available Marziyeh Jannesari1, Jaleh Varshosaz2, Mohammad Morshed1, Maedeh Zamani11Department of Textile Engineering, Isfahan University of Technology, Isfahan, Iran; 2Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, IranAbstract: The aim of this study was to develop novel biomedicated nanofiber electrospun mats for controlled drug release, especially drug release directly to an injury site to accelerate wound healing. Nanofibers of poly(vinyl alcohol (PVA, poly(vinyl acetate (PVAc, and a 50:50 composite blend, loaded with ciprofloxacin HCl (CipHCl, were successfully prepared by an electrospinning technique for the first time. The morphology and average diameter of the electrospun nanofibers were investigated by scanning electron microscopy. X-ray diffraction studies indicated an amorphous distribution of the drug inside the nanofiber blend. Introducing the drug into polymeric solutions significantly decreased solution viscosities as well as nanofiber diameter. In vitro drug release evaluations showed that both the kind of polymer and the amount of drug loaded greatly affected the degree of swelling, weight loss, and initial burst and rate of drug release. Blending PVA and PVAc exhibited a useful and convenient method for electrospinning in order to control the rate and period of drug release in wound healing applications. Also, the thickness of the blend nanofiber mats strongly influenced the initial release and rate of drug release.Keywords: biodegradable polymers, drug delivery, controlled release, electrospun nanofibers, wound dressing

Mechanical properties, biological activity and protein controlled release by poly(vinyl alcohol)–bioglass/chitosan–collagen composite scaffolds: A bone tissue engineering applications

Energy Technology Data Exchange (ETDEWEB)

Pon-On, Weeraphat, E-mail: fsciwpp@ku.ac.th [Department of Physics, Faculty of Science, Kasetsart University, Bangkok 10900 (Thailand); Charoenphandhu, Narattaphol; Teerapornpuntakit, Jarinthorn; Thongbunchoo, Jirawan; Krishnamra, Nateetip [Center of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol University (Thailand); Department of Physiology, Faculty of Science, Mahidol University (Thailand); Tang, I-Ming [ThEP Center, Commission of Higher Education, 328 Si Ayutthaya Rd. (Thailand); Department of Materials Science, Faculty of Science, Kasetsart University, Bangkok 10900 (Thailand)

2014-05-01

In the present study, composite scaffolds made with different weight ratios (0.5:1, 1:1 and 2:1) of bioactive glass (15Ca:80Si:5P) (BG)/polyvinyl alcohol (PVA) (PVABG) and chitosan (Chi)/collagen (Col) (ChiCol) were prepared by three mechanical freeze–thaw followed by freeze-drying to obtain the porous scaffolds. The mechanical properties and the in vitro biocompatibility of the composite scaffolds to simulated body fluid (SBF) and to rat osteoblast-like UMR-106 cells were investigated. The results from the studies indicated that the porosity and compressive strength were controlled by the weight ratio of PVABG:ChiCol. The highest compressive modulus of the composites made was 214.64 MPa which was for the 1:1 weight ratio PVABG:ChiCol. Mineralization study in SBF showed the formation of apatite crystals on the PVABG:ChiCol surface after 7 days of incubation. In vitro cell availability and proliferation tests confirmed the osteoblast attachment and growth on the PVABG:ChiCol surface. MTT and ALP tests on the 1:1 weight ratio PVABG:ChiCol composite indicated that the UMR-106 cells were viable. Alkaline phosphatase activity was found to increase with increasing culturing time. In addition, we showed the potential of PVABG:ChiCol drug delivery through PBS solution studies. 81.14% of BSA loading had been achieved and controlled release for over four weeks was observed. Our results indicated that the PVABG:ChiCol composites, especially the 1:1 weight ratio composite exhibited significantly improved mechanical, mineral deposition, biological properties and controlled release. This made them potential candidates for bone tissue engineering applications. - Graphical abstract: Mechanical properties, biological activity and protein controlled release by poly(vinyl alcohol)–bioglass/chitosan–collagen composite scaffolds: A bone tissue engineering applications. - Highlights: • Preparation of PVABG:ChiCol hybrid composites and their bioactivities • Mechanical

Mechanical properties, biological activity and protein controlled release by poly(vinyl alcohol)–bioglass/chitosan–collagen composite scaffolds: A bone tissue engineering applications

International Nuclear Information System (INIS)

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

2014-01-01

In the present study, composite scaffolds made with different weight ratios (0.5:1, 1:1 and 2:1) of bioactive glass (15Ca:80Si:5P) (BG)/polyvinyl alcohol (PVA) (PVABG) and chitosan (Chi)/collagen (Col) (ChiCol) were prepared by three mechanical freeze–thaw followed by freeze-drying to obtain the porous scaffolds. The mechanical properties and the in vitro biocompatibility of the composite scaffolds to simulated body fluid (SBF) and to rat osteoblast-like UMR-106 cells were investigated. The results from the studies indicated that the porosity and compressive strength were controlled by the weight ratio of PVABG:ChiCol. The highest compressive modulus of the composites made was 214.64 MPa which was for the 1:1 weight ratio PVABG:ChiCol. Mineralization study in SBF showed the formation of apatite crystals on the PVABG:ChiCol surface after 7 days of incubation. In vitro cell availability and proliferation tests confirmed the osteoblast attachment and growth on the PVABG:ChiCol surface. MTT and ALP tests on the 1:1 weight ratio PVABG:ChiCol composite indicated that the UMR-106 cells were viable. Alkaline phosphatase activity was found to increase with increasing culturing time. In addition, we showed the potential of PVABG:ChiCol drug delivery through PBS solution studies. 81.14% of BSA loading had been achieved and controlled release for over four weeks was observed. Our results indicated that the PVABG:ChiCol composites, especially the 1:1 weight ratio composite exhibited significantly improved mechanical, mineral deposition, biological properties and controlled release. This made them potential candidates for bone tissue engineering applications. - Graphical abstract: Mechanical properties, biological activity and protein controlled release by poly(vinyl alcohol)–bioglass/chitosan–collagen composite scaffolds: A bone tissue engineering applications. - Highlights: • Preparation of PVABG:ChiCol hybrid composites and their bioactivities • Mechanical

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

Science.gov (United States)

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

1998-04-01

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

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

Science.gov (United States)

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

2016-01-01

The aim of the present study was to improve the bioavailability of itopride (ITO) and sustain its action by formulating as a floating dosage form. Sustained-release floating tablets of ITO hydrochloride (HCl) were prepared by direct compression using different hydrocolloid polymers such as hydroxypropyl methylcellulose and ethylcellulose and/or methacrylic acid polymers Eudragit RSPM and Carbopol 934P. The floating property was achieved using an effervescent mixture of sodium bicarbonate and anhydrous citric acid (1:1 mol/mol). Hardness, friability, content uniformity, and dissolution rate of the prepared floating tablets were evaluated. The formulation F 10 composed of 28.5% Eudragit RSPM, 3% NaHCO 3 , and 7% citric acid provided sustained drug release. In vitro results showed sustained release of F 10 where the drug release percentage was 96.51%±1.75% after 24 hours ( P =0.031). The pharmacokinetic results indicated that the area under the curve (AUC 0-∞ ) of the prepared sustained-release floating tablets at infinity achieved 93.69 µg·h/mL compared to 49.89 µg·h/mL for the reference formulation (Ganaton ® ) and the relative bioavailability of the sustained-release formulation F 10 increased to 187.80% ( P =0.022). The prepared floating tablets of ITO HCl (F 10 ) could be a promising drug delivery system with sustained-release action and enhanced drug bioavailability.

Duloxetine inhibits effects of MDMA ("ecstasy" in vitro and in humans in a randomized placebo-controlled laboratory study.

Directory of Open Access Journals (Sweden)

Cédric M Hysek

Full Text Available This study assessed the effects of the serotonin (5-HT and norepinephrine (NE transporter inhibitor duloxetine on the effects of 3,4-methylenedioxy-methamphetamine (MDMA, ecstasy in vitro and in 16 healthy subjects. The clinical study used a double-blind, randomized, placebo-controlled, four-session, crossover design. In vitro, duloxetine blocked the release of both 5-HT and NE by MDMA or by its metabolite 3,4-methylenedioxyamphetamine from transmitter-loaded human cells expressing the 5-HT or NE transporter. In humans, duloxetine inhibited the effects of MDMA including elevations in circulating NE, increases in blood pressure and heart rate, and the subjective drug effects. Duloxetine inhibited the pharmacodynamic response to MDMA despite an increase in duloxetine-associated elevations in plasma MDMA levels. The findings confirm the important role of MDMA-induced 5-HT and NE release in the psychotropic effects of MDMA. Duloxetine may be useful in the treatment of psychostimulant dependence.Clinicaltrials.gov NCT00990067.

Bioactive Glass Nanoparticles as a New Delivery System for Sustained 5-Fluorouracil Release: Characterization and Evaluation of Drug Release Mechanism

Directory of Open Access Journals (Sweden)

Abeer M. El-Kady

2015-01-01

Full Text Available Bioactive glass nanoparticles were synthesized and tested for the first time as a new delivery system for sustained 5-fluorouracil (5-FU release. They were characterized by TEM, DTA, TGA, and FT-IR. The porosity % and specific surface area of glass nanoparticles were 85.59% and 378.36 m2/g, respectively. The in vitro bioactivity evaluation confirmed that bioactive glass disks prepared from these nanoparticles could induce hydroxyapatite layer over their surfaces in simulated body fluid. The in vitro drug release experiment indicated that glass nanoparticles could serve as long-term local delivery vehicles for sustained 5-FU release. The release profile of 5-FU showed an initial fast release stage followed by a second stage of slower release. The initial burst release of 5-FU in the first day was about 23% (28.92 mg·L−1 of the total amount of loaded 5-FU, while the final cumulative percentage of the 5-FU released after 32 days was about 45.6% (57.31 mg·L−1 of the total amount of loaded 5-FU. The application of different mathematical models indicated that 5-FU was released by diffusion controlled mechanism and suggested that its release rate was dependent on glass particles dissolution, changes of surface area as well as diameter of glass particles, and concentration of loaded drug.

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

Operational control of material release and discharges from nuclear power plant

International Nuclear Information System (INIS)

Szabo, I. C.; Ranga, T.; Daroczi, L.; Deme, S.; Kerekes, A.

2003-01-01

The operational control of radioactive materials during atmospheric release and aquatic discharge from nuclear power plant is a licensing criterion for NPPs. Originally at the Paks NPP the release control was based on activity limits for four groups of elements. These groups were noble gases, long living radio-aerosols, radioiodine and radiostrontium for atmospheric release and specified activity limit for beta emitters, strontium and tritium for aquatic discharge into Danube. These groups were controlled with proper sampling and/or measuring instrumentation. The limit for atmospheric release was given as a 30-day moving average, for liquid discharges the annual limit was stipulated. The new release and discharge limitation system is based on the environmental dose limitation. The dose constraint for Paks NPP is 90 Sv/year of the critical group for all release pathways and the investigation dose limit is equal to 27 Sv/year. The regulation did not subdivide the dose limit for atmospheric and liquid components but for operational control subdivision of dose limits for atmospheric release and aquatic discharge and shorter time period (one day-one month) seems to be useful. The subdivision can be based on past release data and/or previous activity limits. To satisfy dose below the investigation dose limit there should be a proper operation control level for each separately measured component and pathway belonging to reasonable time interval significantly shorter than one year. The main task of the NPP staff is elaboration of reasonable control levels and reference time intervals for different radionuclide and element groups to be used in operational control. Operational control levels are based on measured daily or monthly release rates. In case of noble gases, aerosols and iodine the daily release rates have several sharp peaks per year. Operational control levels give opportunity to detect these peaks for internal investigation purposes. Investigation release limits

A comparative histological study of alginate beads as a promising controlled release delivery for mefenamic acid.

Science.gov (United States)

Sevgi, Ferhan; Kaynarsoy, Buket; Ozyazici, Mine; Pekcetin, Cetin; Ozyurt, Dogan

2008-01-01

The new mefenamic acid-alginate bead formulation prepared by ionotropic gelation method using 3 x 2(2) factorial design has shown adequate controlled release properties in vitro. In the present study, the irritation effects of mefenamic acid (MA), a prominent non-steroidal anti-inflammatory (NSAI) drug, were evaluated on rat gastric and duodenal mucosa when suspended in 0.5% (w/v) sodiumcarboxymethylcellulose (NaCMC) solution and loaded in alginate beads. Wistar albino rats weighing 200 +/- 50 g were used during in vivo animal studies. In this work, biodegradable controlled release MA beads and free MA were evaluated according to the degree of gastric or duodenal damage following oral administration in rats. The gastric and duodenal mucosa was examined for any haemorrhagic changes. Formulation code A10 showing both Case II transport and zero order drug release and t(50) % value of 5.22 h was chosen for in vivo animal studies. For in vivo trials, free MA (100 mgkg(-1)), blank and MA (100 mgkg(-1)) loaded alginate beads (formulation code A10) were suspended in 0.5% (w/v) NaCMC solution and each group was given to six rats orally by gavage. NaCMC solution was used as a control in experimental studies. In vivo data showed that the administration of MA in alginate beads prevented the gastric lesions.

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

Energy Technology Data Exchange (ETDEWEB)

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

2013-07-01

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

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

International Nuclear Information System (INIS)

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

2013-01-01

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

A poly({epsilon}-caprolactone) device for sustained release of an anti-glaucoma drug

Energy Technology Data Exchange (ETDEWEB)

Natu, Madalina V; De Sousa, HermInio C; Gil, M H [Department of Chemical Engineering, University of Coimbra, Polo II, Pinhal de Marrocos, 3030-290, Coimbra (Portugal); Gaspar, Manuel N; Fontes Ribeiro, Carlos A [Institute of Pharmacology and Experimental Therapeutics, University of Coimbra, Azinhaga de Santa Comba, Celas, 3000-354, Coimbra (Portugal); Correia, IlIdio J; Silva, Daniela, E-mail: hgil@eq.uc.pt [Centro de Investigacao em Ciencias da Saude, Faculdade de Ciencias da Saude, Universidade da Beira Interior, Covilha (Portugal)

2011-04-15

Implantable dorzolamide-loaded discs were prepared by blending poly({epsilon}-caprolactone), PCL, with poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide), Lu. By blending, crystallinity, water uptake and mass loss were modified relative to the pure polymers. Burst was diminished by coating the discs with a PCL shell. All samples presented burst release except PCL-coated samples that showed controlled release during 18 days. For PCL-coated samples, barrier control of diffusion coupled with partition control from the core slowed down the release, while for 50/50 Lu/PCL-coated samples, the enhancement in the porosity of the core diminished partition control of drug release. Nonlinear regression analysis suggested that a degradation model fully describes the release curve considering a triphasic release mechanism: the instantaneous diffusion (burst), diffusion and polymer degradation stages. The MTT test indicated that the materials are not cytotoxic for corneal endothelial cells. A good in vitro-in vivo correlation was obtained, with similar amounts of drug released in vitro and in vivo. The discs decreased intraocular pressure (IOP) in normotensive rabbit eyes by 13.0% during 10 days for PCL-coated and by 13.0% during 4 days for 50/50 Lu/PCL-coated samples. The percentages of IOP decrease are similar to those obtained by dorzolamide eyedrop instillation (11.0%).

Massive radiological releases profoundly differ from controlled releases

International Nuclear Information System (INIS)

Pascucci-Cahen, Ludivine; Patrick, Momal

2012-11-01

Preparing for a nuclear accident implies understanding potential consequences. While many specialized experts have been working on different particular aspects, surprisingly little effort has been dedicated to establishing the big picture and providing a global and balanced image of all major consequences. IRSN has been working on the cost of nuclear accidents, an exercise which must strive to be as comprehensive as possible since any omission obviously underestimates the cost. It therefore provides (ideally) an estimate of all cost components, thus revealing the structure of accident costs, and hence sketching a global picture. On a French PWR, it appears that controlled releases would cause an 'economical' accident with limited radiological consequences when compared to other costs; in contrast, massive releases would trigger a major crisis with strong radiological consequences. The two types of crises would confront managers with different types of challenges. (authors)

Improved wound healing in pressure-induced decubitus ulcer with controlled release of basic fibroblast growth factor

International Nuclear Information System (INIS)

Jiang Wei; Wang Hailun; Jin Faguang; Yu Chunyan; Chu Dongling; Wang Lin; Lu Xian

2008-01-01

The purpose was to evaluate the efficacy of the wound dressing containing basic fibroblast growth factor (bFGF)-loaded microspheres on promoting healing in pressure-induced decubitus ulcer. In this study, the pressure-induced ulcer in swine was used as a model to demonstrate the hypothesis that controlled release of bFGF has the potential to provide optimal healing milieu for chronic wounds in the repair process. Average size of the microspheres was 14.36 ± 3.56 μm and the network gelatin sponges were characterized with an average pore size of 80-160 μm. Both the in vitro release efficiency and the protein bioactivity revealed that bFGF was released from the microspheres in a controlled manner and it was biologically active as assessed by its ability to induce the proliferation of fibroblasts. Pressure-induced ulcer was created at 500 g/cm 2 pressure loaded on swine dorsal skin 12 h daily for 2 consecutive days. After removal of the pressure load, the gelatin sponge containing bFGF gelatin microspheres or bFGF in solution was implanted into the wound. Swine were sacrificed at 7, 14, and 21 days after implantation, and a full-thickness biopsy was taken and stained for histological analysis. It was observed that controlled release of bFGF provided an accelerated recovery in the wound areas. Histological investigations showed that the dressings were biocompatible and had capability of proliferating fibroblasts and inducing neovascularisation. The present study implied the clinical potential of gelatin sponge with bFGF microspheres to promote the healing in pressure-induced decubitus ulcer

Improved wound healing in pressure-induced decubitus ulcer with controlled release of basic fibroblast growth factor

Energy Technology Data Exchange (ETDEWEB)

Jiang Wei [Department of Respiratory Diseases, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China); Wang Hailun [Department of Dermatology, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China); Jin Faguang [Department of Respiratory Diseases, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China)], E-mail: nidewenzhang@163.com; Yu Chunyan [Department of Dermatology, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China); Chu Dongling [Department of Respiratory Diseases, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China); Wang Lin [Department of Internal Medicine, 316 Hospital of PLA, Beijing 100093 (China); Lu Xian [93942 Unit Hospital of PLA, Xianyang 710012 (China)

2008-07-14

The purpose was to evaluate the efficacy of the wound dressing containing basic fibroblast growth factor (bFGF)-loaded microspheres on promoting healing in pressure-induced decubitus ulcer. In this study, the pressure-induced ulcer in swine was used as a model to demonstrate the hypothesis that controlled release of bFGF has the potential to provide optimal healing milieu for chronic wounds in the repair process. Average size of the microspheres was 14.36 {+-} 3.56 {mu}m and the network gelatin sponges were characterized with an average pore size of 80-160 {mu}m. Both the in vitro release efficiency and the protein bioactivity revealed that bFGF was released from the microspheres in a controlled manner and it was biologically active as assessed by its ability to induce the proliferation of fibroblasts. Pressure-induced ulcer was created at 500 g/cm{sup 2} pressure loaded on swine dorsal skin 12 h daily for 2 consecutive days. After removal of the pressure load, the gelatin sponge containing bFGF gelatin microspheres or bFGF in solution was implanted into the wound. Swine were sacrificed at 7, 14, and 21 days after implantation, and a full-thickness biopsy was taken and stained for histological analysis. It was observed that controlled release of bFGF provided an accelerated recovery in the wound areas. Histological investigations showed that the dressings were biocompatible and had capability of proliferating fibroblasts and inducing neovascularisation. The present study implied the clinical potential of gelatin sponge with bFGF microspheres to promote the healing in pressure-induced decubitus ulcer.

Regulation of somatostatin release in the nervous system of the rat

International Nuclear Information System (INIS)

Sheppard, M.

1979-08-01

This thesis represents the work done to study the release of somatostatin from the rat central nervous system in vitro, providing some evidence for a physiological role for somatostatin. Somatostatin was measured by a sensitive and specific radioimmunoassay devoloped in the laboratory. Chapter 2 reviews the literature on hypothalamic peptides and control of an anterior pituitary function, somatostatin, other central nervous system peptides and neurosecretion. Chapter 3 describes the central nervous system tissue dissection technique, the radioimmunoassay for somatostatin and the tissue levels of somatostatin immunoreactivity in different areas of the central nervous system. Chapter 4 deals with the release of immunoreactive somatostatin from incubated rat hypothalamus in vitro and the influence of other hormones and neuropeptides on this release. Chapter 5 describes the preparation of isolated nerve endings (synaptosomes) from four different areas of rat brain, the localisation of somatostatin to the synaptosome fraction of brain homogenates and the release of somatostatin from these synaptosomes. Chapter 6 deals with the release of somatostatin from incubated rat spinal cord in vitro. Chapter 7 presents the results of the characterisation of released immunoreactive material, the technique utilised being serial dilution of immunoreactive material and comparison to the standard curve, Sephadex gel chromatography, affinity chromatography, and the effect of released immunoreactive somatostatin on growth hormone release from perifused hemipituitaries in vitro, i.e. biological activity. Chapter 8 provides a summary of the main conclusions reached in this study and is followed by the Appendix describing chemical and biochemical methods, histological techniques, and statistical methods

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

Science.gov (United States)

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

2014-01-01

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

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

Science.gov (United States)

King, William J.; Krebsbach, Paul H.

2013-01-01

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

The effect of solvents and hydrophilic additive on stable coating and controllable sirolimus release system for drug-eluting stent.

Science.gov (United States)

Kim, Seong Min; Park, Sung-Bin; Bedair, Tarek M; Kim, Man-Ho; Park, Bang Ju; Joung, Yoon Ki; Han, Dong Keun

2017-09-01

Various drug-eluting stents (DESs) have been developed to prevent restenosis after stent implantation. However, DES still needs to improve the drug-in-polymer coating stability and control of drug release for effective clinical treatment. In this study, the cobalt-chromium (CoCr) alloy surface was coated with biodegradable poly(D,L-lactide) (PDLLA) and sirolimus (SRL) mixed with hydrophilic Pluronic F127 additive by using ultrasonic spray coating system in order to achieve a stable coating surface and control SRL release. The degradation of PDLLA/SRL coating was studied under physiological solution. It was found that adding F127 reduced the degradation of PDLLA and improved the coating stability during 60days. The effects of organic solvent such as chloroform and tetrahydrofuran (THF) on the coating uniformity were also examined. It was revealed that THF produced a very smooth and uniform coating compared to chloroform. The patterns of in vitro drug release according to the type of organic solvent and hydrophilic additive proposed the possibility of controllable drug release design in DES. It was found that using F127 the drug release was sustained regardless of the organic solvent used. In addition, THF was able to get faster and controlled release profile when compared to chloroform. The structure of SRL molecules in different organic solvents was investigated using ultra-small angle neutron scattering. Furthermore, the structure of SRL is concentration-dependent in chloroform with tight nature under high concentration, but concentration-independent in THF. These results strongly demonstrated that coating stability and drug release patterns can be changed by physicochemical properties of various parameters such as organic solvents, additive, and coating strategy. Copyright © 2017 Elsevier B.V. All rights reserved.

Controlled Release Formulations of Auxinic Herbicides

Science.gov (United States)

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

2013-04-01

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

Electrosprayed nanoparticle delivery system for controlled release

Energy Technology Data Exchange (ETDEWEB)

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

2016-09-01

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

Development of a Controlled Release of Salicylic Acid Loaded Stearic Acid-Oleic Acid Nanoparticles in Cream for Topical Delivery

Directory of Open Access Journals (Sweden)

J. O. Woo

2014-01-01

Full Text Available Lipid nanoparticles are colloidal carrier systems that have extensively been investigated for controlled drug delivery, cosmetic and pharmaceutical applications. In this work, a cost effective stearic acid-oleic acid nanoparticles (SONs with high loading of salicylic acid, was prepared by melt emulsification method combined with ultrasonication technique. The physicochemical properties, thermal analysis and encapsulation efficiency of SONs were studied. TEM micrographs revealed that incorporation of oleic acid induces the formation of elongated spherical particles. This observation is in agreement with particle size analysis which also showed that the mean particle size of SONs varied with the amount of OA in the mixture but with no effect on their zeta potential values. Differential scanning calorimetry analysis showed that the SONs prepared in this method have lower crystallinity as compared to pure stearic acid. Different amount of oleic acid incorporated gave different degree of perturbation to the crystalline matrix of SONs and hence resulted in lower degrees of crystallinity, thereby improving their encapsulation efficiencies. The optimized SON was further incorporated in cream and its in vitro release study showed a gradual release for 24 hours, denoting the incorporation of salicylic acid in solid matrix of SON and prolonging the in vitro release.

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

Science.gov (United States)

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

2009-02-01

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

Meltable magnetic biocomposites for controlled release

Energy Technology Data Exchange (ETDEWEB)

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

2017-06-01

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

Natural gum as mucoadhesive controlled release carriers: evaluation of cefpodoxime proxetil by D-optimal design technique.

Science.gov (United States)

Patil, Satish H; Talele, Gokul S

2014-03-01

The present study deals with the development of mucoadhesive controlled release tablets of Cefpodoxime Proxetil to increase the gastric residence time and thus prolong drug release, reduce dosing frequency and improve oral bioavailability. Tablets were prepared using sodium alginate and karaya gum, a natural polymer, with a synthetic polymer hydroxypropylmethylcellulose (K100LV) and Karaya gum with HPMC K100LV in various ratios to optimize the drug release profile using D-Optimal technique. Pre- and post-compression parameters of tablets prepared with various formulations (S1-S9, C1-C9) were evaluated. The FTIR and DSC studies revealed that no physiochemical interaction between excipients and drug. The formulation S7 showed prolonged drug release, and the mechanism of drug release from the optimized formulation was confirmed using the Korsmeyer-Peppas model to be non-Fickian release transport and n value was found 0.605 indicating both diffusion and erosion mechanism from these natural gums. The optimized formulation showed mucoadhesive strength >35 g. An in vivo study was performed on rabbits using an X-ray imaging technique. The radiological evidence suggests that the tablets adheres (more than 10 hours) to a rabbit's stomach. No significant changes were found in the physical appearance, drug content, mucoadhesive study and in vitro dissolution pattern after storage at 40 °C/75% relative humidity for 3 months.

Development of controlled release silicone adhesive-based mupirocin patch demonstrates antibacterial activity on live rat skin against Staphylococcus aureus.

Science.gov (United States)

David, Sheba R; Malek, Nurafiqah; Mahadi, Abdul Hanif; Chakravarthi, Srikumar; Rajabalaya, Rajan

2018-01-01

Peritonitis is the most serious complication of peritoneal dialysis. Staphylococcus aureus infections could lead to peritonitis which causes reversal of peritoneal dialysis treatment back to hemodialysis. The aim of this study was to develop a controlled release silicone adhesive-based mupirocin patch for prophylactic effect and analyze its antibacterial effectiveness against S. aureus . The matrix patches were prepared by using different polymers, with and without silicone adhesive, dibutyl sebacate and mupirocin. The patches were characterized for mechanical properties, drug content, moisture content, water absorption capacity and Fourier transform infrared spectrum. In vitro release studies were performed by using Franz diffusion cell. In vitro disk diffusion assay was performed on the Mueller-Hinton Agar plate to measure the zone of inhibition of the patches. The in vivo study was performed on four groups of rats with bacterial counts at three different time intervals, along with skin irritancy and histopathologic studies. The patches showed appropriate average thickness (0.63-1.12 mm), tensile strength (5.08-10.08 MPa) and modulus of elasticity (21.53-42.19 MPa). The drug content ranged from 94.5% to 97.4%, while the moisture content and water absorption capacities at two relative humidities (75% and 93%) were in the range of 1.082-3.139 and 1.287-4.148 wt%, respectively. Fourier transform infrared spectra showed that there were no significant interactions between the polymer and the drug. The highest percentage of drug release at 8 hours was 47.94%. The highest zone of inhibition obtained was 28.3 mm against S. aureus . The in vivo studies showed that the bacterial colonies were fewer at 1 cm (7×10 1 CFU/mL) than at 2 cm (1.3×10 2 CFU/mL) over a 24-hour period. The patches were nonirritant to the skin, and histopathologic results also showed no toxic or damaging effects to the skin. The in vitro and in vivo studies indicated that controlled release patches

Matrix and reservoir-type multipurpose vaginal rings for controlled release of dapivirine and levonorgestrel.

Science.gov (United States)

Boyd, Peter; Fetherston, Susan M; McCoy, Clare F; Major, Ian; Murphy, Diarmaid J; Kumar, Sandeep; Holt, Jonathon; Brimer, Andrew; Blanda, Wendy; Devlin, Brid; Malcolm, R Karl

2016-09-10

A matrix-type silicone elastomer vaginal ring providing 28-day continuous release of dapivirine (DPV) - a lead candidate human immunodeficiency virus type 1 (HIV-1) microbicide compound - has recently demonstrated moderate levels of protection in two Phase III clinical studies. Here, next-generation matrix and reservoir-type silicone elastomer vaginal rings are reported for the first time offering simultaneous and continuous in vitro release of DPV and the contraceptive progestin levonorgestrel (LNG) over a period of between 60 and 180days. For matrix-type vaginal rings comprising initial drug loadings of 100, 150 or 200mg DPV and 0, 16 or 32mg LNG, Day 1 daily DPV release values were between 4132 and 6113μg while Day 60 values ranged from 284 to 454μg. Daily LNG release ranged from 129 to 684μg on Day 1 and 2-91μg on Day 60. Core-type rings comprising one or two drug-loaded cores provided extended duration of in vitro release out to 180days, and maintained daily drug release rates within much narrower windows (either 75-131μg/day or 37-66μg/day for DPV, and either 96-150μg/day or 37-57μg/day for LNG, depending on core ring configuration and ignoring initial lag release effect for LNG) compared with matrix-type rings. The data support the continued development of these devices as multi-purpose prevention technologies (MPTs) for HIV prevention and long-acting contraception. Copyright © 2016 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

Hanno, Ibrahim; Anselmi, Cecilia; Bouchemal, Kawthar

2012-02-01

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

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

Directory of Open Access Journals (Sweden)

Silla Aimee J

2010-11-01

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

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

Directory of Open Access Journals (Sweden)

Suman Jangra

2016-09-01

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

Duloxetine Inhibits Effects of MDMA (“Ecstasy") In Vitro and in Humans in a Randomized Placebo-Controlled Laboratory Study

Science.gov (United States)

Nicola, Valentina G.; Vischer, Nerina; Donzelli, Massimiliano; Krähenbühl, Stephan; Grouzmann, Eric; Huwyler, Jörg; Hoener, Marius C.; Liechti, Matthias E.

2012-01-01

This study assessed the effects of the serotonin (5-HT) and norepinephrine (NE) transporter inhibitor duloxetine on the effects of 3,4–methylenedioxy­methamphetamine (MDMA, ecstasy) in vitro and in 16 healthy subjects. The clinical study used a double-blind, randomized, placebo-controlled, four-session, crossover design. In vitro, duloxetine blocked the release of both 5-HT and NE by MDMA or by its metabolite 3,4-methylenedioxyamphetamine from transmitter-loaded human cells expressing the 5-HT or NE transporter. In humans, duloxetine inhibited the effects of MDMA including elevations in circulating NE, increases in blood pressure and heart rate, and the subjective drug effects. Duloxetine inhibited the pharmacodynamic response to MDMA despite an increase in duloxetine-associated elevations in plasma MDMA levels. The findings confirm the important role of MDMA-induced 5-HT and NE release in the psychotropic effects of MDMA. Duloxetine may be useful in the treatment of psychostimulant dependence. Trial Registration Clinicaltrials.gov NCT00990067 PMID:22574166

Controlled Release Formulation of Indomethacin Prepared With Bee ...

African Journals Online (AJOL)

Erah

2010-12-27

Dec 27, 2010 ... Results: The results show that, although the release rate of formulations F1 - F7 did not show any ... Keywords: Propolis (bee glue), Indomethacin, Controlled release, Zero order kinetics, Waxy materials ... focus of interest.

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

International Nuclear Information System (INIS)

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

2006-01-01

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

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.

Molecular weight-dependent degradation and drug release of surface-eroding poly(ethylene carbonate).

Science.gov (United States)

Bohr, Adam; Wang, Yingya; Harmankaya, Necati; Water, Jorrit J; Baldursdottír, Stefania; Almdal, Kristoffer; Beck-Broichsitter, Moritz

2017-06-01

Poly(ethylene carbonate) (PEC) is a unique biomaterial showing significant potential for controlled drug delivery applications. The current study investigated the impact of the molecular weight on the biological performance of drug-loaded PEC films. Following the preparation and thorough physicochemical characterization of diverse PEC (molecular weights: 85, 110, 133, 174 and 196kDa), the degradation and drug release behavior of rifampicin- and bovine serum albumin-loaded PEC films was investigated in vitro (in the presence and absence of cholesterol esterase), in cell culture (RAW264.7 macrophages) and in vivo (subcutaneous implantation in rats). All investigated samples degraded by means of surface erosion (mass loss, but constant molecular weight), which was accompanied by a predictable, erosion-controlled drug release pattern. Accordingly, the obtained in vitro degradation half-lives correlated well with the observed in vitro half-times of drug delivery (R 2 =0.96). Here, the PEC of the highest molecular weight resulted in the fastest degradation/drug release. When incubated with macrophages or implanted in animals, the degradation rate of PEC films superimposed the results of in vitro incubations with cholesterol esterase. Interestingly, SEM analysis indicated a distinct surface erosion process for enzyme-, macrophage- and in vivo-treated polymer films in a molecular weight-dependent manner. Overall, the molecular weight of surface-eroding PEC was identified as an essential parameter to control the spatial and temporal on-demand degradation and drug release from the employed delivery system. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

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

2015-07-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2015-02-15

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

Effects of metamorphosis and captivity on the in vitro sensitivity of thyroid glands from the tiger salamander, Ambystoma tigrinum, to bovine thyrotropin

International Nuclear Information System (INIS)

Norman, M.F.; Norris, D.O.

1987-01-01

The sensitivity of thyroid glands from the tiger salamander, Ambystoma tigrinum, to bovine thyrotropin (bTSH) was tested in vitro. Thyroids were taken from subjects representing metamorphic stages I (premetamorphic larvae), II (onset of climax), and VII (completion of gill resorption), as well as from captivity control larvae. Exogenous TSH reduced the cumulative uptake of 125 I in vitro by thyroids from stage I larvae after 24 and 48 hr. The capacity of thyroids to release thyroxine (T4) in vitro was used subsequently as a measure of their responsiveness to TSH. Baseline levels of T4 release in vitro were variable but did not differ significantly among developmental stages. A low dose of bTSH (5 X 10(-6) IU/ml) did not increase in vitro T4 release compared with that of controls. A larger dose (5 X 10(-4) IU/ml) caused greater increases in T4 release from thyroids of stage II and VII subjects than from those of controls. This dose produced only a small response by thyroids from captivity-control subjects. The results suggest that the thyroids of Ambystoma increase in their capacity to respond to TSH during the process of metamorphosis

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

NARCIS (Netherlands)

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

2006-01-01

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

Controlled release of diuron from an alginate-bentonite formulation: water release kinetics and soil mobility study.

Science.gov (United States)

Fernández-Pérez, M; Villafranca-Sánchez, M; González-Pradas, E; Flores-Céspedes, F

1999-02-01

The herbicide diuron was incorporated in alginate-based granules to obtain controlled release (CR) properties. The standard formulation (alginate-herbicide-water) was modified by the addition of different sorbents. The effect on diuron release rate caused by incorporation of natural and acid-treated bentonites in alginate formulation was studied by immersion of the granules in water under static conditions. The release of diuron was diffusion-controlled. The time taken for 50% release of active ingredient to be released into water, T(50), was calculated for the comparison of formulations. The addition of bentonite to the alginate-based formulation produced the higher T(50) values, indicating slower release of the diuron. The mobility of technical and formulated diuron was compared by using soil columns. The use of alginate-based CR formulations containing bentonite produced a less vertical distribution of the active ingredient as compared to the technical product and commercial formulation. Sorption capacities of the various soil constituents for diuron were also determined using batch experiments.

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

Science.gov (United States)

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

2018-01-01

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

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

Science.gov (United States)

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

2014-09-01

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

Building Adjustable Pre-storm Reservoir Flood-control Release Rules

Science.gov (United States)

Yang, Shun-Nien; Chang, Li-Chiu; Chang, Fi-John; Hsieh, Cheng-Daw

2017-04-01

Typhoons hit Taiwan several times every year, which could cause serious flood disasters. Because mountainous terrains and steep landforms can rapidly accelerate the speed of flood flow during typhoon events, rivers cannot be a stable source of water supply. Reservoirs become the most effective floodwater storage facilities for alleviating flood damages in Taiwan. The pre-storm flood-control release can significantly increase reservoir storage capacity available to store floodwaters for reducing downstream flood damage, while the uncertainties of total forecasted rainfalls are very high in different stages of an oncoming typhoon, which may cause the risk of water shortage in the future. This study proposes adjustable pre-storm reservoir flood-control release rules in three designed operating stages with various hydrological conditions in the Feitsui Reservoir, a pivot reservoir for water supply to Taipei metropolitan in Taiwan, not only to reduce the risk of reservoir flood control and downstream flooding but also to consider water supply. The three operating stages before an oncoming typhoon are defined upon the timings when: (1) typhoon news is issued (3-7days before typhoon hit); (2) the sea warning is issued (2-4 days before typhoon hit); and (3) the land warning is issued (1-2 days before typhoon hit). We simulate 95 historical typhoon events with 3000 initial water levels and build some pre-storm flood-control release rules to adjust the amount of pre-release based on the total forecasted rainfalls at different operating stages. A great number of simulations (68.4 millions) are conducted to extract their major consequences and then build the adjustable pre-storm reservoir flood-control release rules. Accordingly, given a total forecasted rainfall and a water level, reservoir decision makers can easily identify the corresponding rule to tell the amount of pre-release in any stage. The results show that the proposed adjustable pre-release rules can effectively

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

International Nuclear Information System (INIS)

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

2007-01-01

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

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

Profile of Fluoride Release from a Nanohybrid Composite Resin

Directory of Open Access Journals (Sweden)

Raquel Assed Bezerra Silva

2015-02-01

Full Text Available The aim of this study was to evaluate in vitro the amount and profile of fluoride release from a fluoride-containing nanohybrid composite resin (Tetric® N-Ceram by direct potentiometry. Thirty specimens (5 mm diameter x 3 mm high; n=10/material were made of Tetric® N-Ceram, Vitremer® resin-modified glass ionomer cement (RMGIC (positive control or Filtek® Z350 nanofill composite resin (negative control. The specimens were stored individually in plastic tubes containing 1 mL of artificial saliva at 37°C, which was daily renewed during 15 days. At each renewal of saliva, the amount of fluoride ions released in the solution was measured using a fluoride ion-selective electrode with ion analyzer, and the values obtained in mV were converted to ppm (µg/mL. Data were analyzed statistically by ANOVA and Tukey’s post-hoc test at a significance level of 5%. The results showed that the resins Tetric® N-Ceram and Filtek® Z350 did not release significant amounts of fluoride during the whole period of evaluation (p>0.05. Only Vitremer® released significant amounts of fluoride ions during the 15 days of the experiment, with greater release in first 2 days (p0.05. In conclusion, the nanohybrid composite resin Tetric® N-Ceram did not present in vitro fluoride-releasing capacity throughout the 15 days of study.

Biocompatible magnetic and molecular dual-targeting polyelectrolyte hybrid hollow microspheres for controlled drug release.

Science.gov (United States)

Du, Pengcheng; Zeng, Jin; Mu, Bin; Liu, Peng

2013-05-06

Well-defined biocompatible magnetic and molecular dual-targeting polyelectrolyte hybrid hollow microspheres have been accomplished via the layer-by-layer (LbL) self-assembly technique. The hybrid shell was fabricated by the electrostatic interaction between the polyelectrolyte cation, chitosan (CS), and the hybrid anion, citrate modified ferroferric oxide nanoparticles (Fe3O4-CA), onto the uniform polystyrene sulfonate microsphere templates. Then the magnetic hybrid core/shell composite particles were modified with a linear, functional poly(ethylene glycol) (PEG) monoterminated with a biotargeting molecule (folic acid (FA)). Afterward the dual targeting hybrid hollow microspheres were obtained after etching the templates by dialysis. The dual targeting hybrid hollow microspheres exhibit exciting pH response and stability in high salt-concentration media. Their pH-dependent controlled release of the drug molecule (anticancer drug, doxorubicin (DOX)) was also investigated in different human body fluids. As expected, the cell viability of the HepG2 cells which decreased more rapidly was treated by the FA modified hybrid hollow microspheres rather than the unmodified one in the in vitro study. The dual-targeting hybrid hollow microspheres demonstrate selective killing of the tumor cells. The precise magnetic and molecular targeting properties and pH-dependent controlled release offers promise for cancer treatment.

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

OpenAIRE

S Tiwari; B Nandlal

2013-01-01

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

5-Fluorouracil Encapsulated Chitosan Nanoparticles for pH-Stimulated Drug Delivery: Evaluation of Controlled Release Kinetics

Directory of Open Access Journals (Sweden)

R. Seda Tığlı Aydın

2012-01-01

Full Text Available Nanoparticles consisting of human therapeutic drugs are suggested as a promising strategy for targeted and localized drug delivery to tumor cells. In this study, 5-fluorouracil (5-FU encapsulated chitosan nanoparticles were prepared in order to investigate potentials of localized drug delivery for tumor environment due to pH sensitivity of chitosan nanoparticles. Optimization of chitosan and 5-FU encapsulated nanoparticles production revealed 148.8±1.1 nm and 243.1±17.9 nm particle size diameters with narrow size distributions, which are confirmed by scanning electron microscope (SEM images. The challenge was to investigate drug delivery of 5-FU encapsulated chitosan nanoparticles due to varied pH changes. To achieve this objective, pH sensitivity of prepared chitosan nanoparticle was evaluated and results showed a significant swelling response for pH 5 with particle diameter of ∼450 nm. In vitro release studies indicated a controlled and sustained release of 5-FU from chitosan nanoparticles with the release amounts of 29.1–60.8% due to varied pH environments after 408 h of the incubation period. pH sensitivity is confirmed by mathematical modeling of release kinetics since chitosan nanoparticles showed stimuli-induced release. Results suggested that 5-FU encapsulated chitosan nanoparticles can be launched as pH-responsive smart drug delivery agents for possible applications of cancer treatments.

The synergistic action of imidacloprid and flumethrin and their release kinetics from collars applied for ectoparasite control in dogs and cats

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Stanneck Dorothee

2012-04-01

Full Text Available Abstract Background The control of tick and flea burdens in dogs and cats has become essential to the control of important and emerging vector borne diseases, some of which are zoonoses. Flea worry and flea bite hypersensitivity are additionally a significant disease entity in dogs and cats. Owner compliance in maintaining the pressure of control measures has been shown to be poor. For these reasons efforts are continuously being made to develop ectoparasiticides and application methods that are safe, effective and easy to apply for pet owners. A new polymer matrix collar has recently been developed which is registered for 8 months use in cats and dogs. The basic properties of this collar have been investigated in several in vitro and in vivo studies. Methods The effects of imidacloprid, flumethrin and the combination were evaluated in vitro by means of whole cell voltage clamp measurement experiments conducted on isolated neuron cells from Spodoptera frugiperda. The in vitro efficacy of the two compounds and the combination against three species of ticks and their life stages and fleas were evaluated in a dry surface glass vial assay. The kinetics of the compounds over time in the collar were evaluated by the change in mass of the collar and measurement of the surface concentrations and concentrations of the actives in the collar matrix by HPLC. Hair clipped from collar treated dogs and cats, collected at various time points, was used to assess the acaricidal efficacy of the actives ex vivo. Results An in vitro isolated insect nerve model demonstrated the synergistic neurotoxic effects of the pyrethroid flumethrin and the neonicotinoid imidacloprid. An in vitro glass vial efficacy and mortality study against various life stages of the ticks Ixodes ricinus, Rhipicephalus sanguineus and Dermacentor reticulatus and against the flea (Ctenocephalides felis demonstrated that the combination of these products was highly effective against these

The synergistic action of imidacloprid and flumethrin and their release kinetics from collars applied for ectoparasite control in dogs and cats

Science.gov (United States)

2012-01-01

Background The control of tick and flea burdens in dogs and cats has become essential to the control of important and emerging vector borne diseases, some of which are zoonoses. Flea worry and flea bite hypersensitivity are additionally a significant disease entity in dogs and cats. Owner compliance in maintaining the pressure of control measures has been shown to be poor. For these reasons efforts are continuously being made to develop ectoparasiticides and application methods that are safe, effective and easy to apply for pet owners. A new polymer matrix collar has recently been developed which is registered for 8 months use in cats and dogs. The basic properties of this collar have been investigated in several in vitro and in vivo studies. Methods The effects of imidacloprid, flumethrin and the combination were evaluated in vitro by means of whole cell voltage clamp measurement experiments conducted on isolated neuron cells from Spodoptera frugiperda. The in vitro efficacy of the two compounds and the combination against three species of ticks and their life stages and fleas were evaluated in a dry surface glass vial assay. The kinetics of the compounds over time in the collar were evaluated by the change in mass of the collar and measurement of the surface concentrations and concentrations of the actives in the collar matrix by HPLC. Hair clipped from collar treated dogs and cats, collected at various time points, was used to assess the acaricidal efficacy of the actives ex vivo. Results An in vitro isolated insect nerve model demonstrated the synergistic neurotoxic effects of the pyrethroid flumethrin and the neonicotinoid imidacloprid. An in vitro glass vial efficacy and mortality study against various life stages of the ticks Ixodes ricinus, Rhipicephalus sanguineus and Dermacentor reticulatus and against the flea (Ctenocephalides felis) demonstrated that the combination of these products was highly effective against these parasites. The release kinetics of

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

Directory of Open Access Journals (Sweden)

Qin LL

2013-05-01

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

Critical review of controlled release packaging to improve food safety and quality.

Science.gov (United States)

Chen, Xi; Chen, Mo; Xu, Chenyi; Yam, Kit L

2018-03-19

Controlled release packaging (CRP) is an innovative technology that uses the package to release active compounds in a controlled manner to improve safety and quality for a wide range of food products during storage. This paper provides a critical review of the uniqueness, design considerations, and research gaps of CRP, with a focus on the kinetics and mechanism of active compounds releasing from the package. Literature data and practical examples are presented to illustrate how CRP controls what active compounds to release, when and how to release, how much and how fast to release, in order to improve food safety and quality.

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

Science.gov (United States)

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

2011-03-01

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

Characteristics of eugenol loaded chitosan-tripolyphosphate particles as affected by initial content of eugenol and their in-vitro release characteristic

Science.gov (United States)

Cahyono, B.; A’yun, Qurrotu; Suzery, M.; Hadiyanto

2018-04-01

The aim of this research was to determine encapsulation efficiency, loading capacity and controlled release of eugenol loaded chitosan-tpp products which prepared by coaservation method. The characteristic of eugenol-loaded chitosan showed that %EE and % LC increased by increasing the initial eugenol content. The optimum of %EE (72.63%) and %LC (43.96%) were obtained at the ratio of chitosan to eugenol of 1:1.5. The FTIR spectrum showed the characteristic peaks of eugenol appearing on spectrum of eugenol encapsulated and blue-shift in the hydroxyl band from 3425.58 cm-1 in chitosan-tpp to 3417.86 cm-1 and 3394.72 cm-1 in eugenol loaded chitosan-tpp indicating that eugenol was successfully encapsulated. The surface morphologies of freeze-dried particles with the optimum %EE showed that more surface roughness and porosity than plain particles. Furthermore, the in vitro release of particles with minimum and optimum %EE were also investigated in acid (Simulated Gastric Fluid) and base (Simulated Intestinal Fluid) medium at ambient temperature.

Strategies for neurotrophin-3 and chondroitinase ABC release from freeze-cast chitosan-alginate nerve-guidance scaffolds.

Science.gov (United States)

Francis, Nicola L; Hunger, Philipp M; Donius, Amalie E; Wegst, Ulrike G K; Wheatley, Margaret A

2017-01-01

Freeze casting, or controlled unidirectional solidification, can be used to fabricate chitosan-alginate (C-A) scaffolds with highly aligned porosity that are suitable for use as nerve-guidance channels. To augment the guidance of growth across a spinal cord injury lesion, these scaffolds are now evaluated in vitro to assess their ability to release neurotrophin-3 (NT-3) and chondroitinase ABC (chABC) in a controlled manner. Protein-loaded microcapsules were incorporated into C-A scaffolds prior to freeze casting without affecting the original scaffold architecture. In vitro protein release was not significantly different when comparing protein loaded directly into the scaffolds with release from scaffolds containing incorporated microcapsules. NT-3 was released from the C-A scaffolds for 8 weeks in vitro, while chABC was released for up to 7 weeks. Low total percentages of protein released from the scaffolds over this time period were attributed to limitation of diffusion by the interpenetrating polymer network matrix of the scaffold walls. NT-3 and chABC released from the scaffolds retained bioactivity, as determined by a neurite outgrowth assay, and the promotion of neurite growth across an inhibitory barrier of chondroitin sulphate proteoglycans. This demonstrates the potential of these multifunctional scaffolds for enhancing axonal regeneration through growth-inhibiting glial scars via the sustained release of chABC and NT-3. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

A novel gel based on an ionic complex from a dendronized polymer and ciprofloxacin: Evaluation of its use for controlled topical drug release

International Nuclear Information System (INIS)

García, Mónica C.; Cuggino, Julio C.; Rosset, Clarisa I.; Páez, Paulina L.; Strumia, Miriam C.

2016-01-01

The development and characterization of a novel, gel-type material based on a dendronized polymer (DP) loaded with ciprofloxacin (CIP), and the evaluation of its possible use for controlled drug release, are presented in this work. DP showed biocompatible and non-toxic behaviors in cultured cells, both of which are considered optimal properties for the design of a final material for biomedical applications. These results were encouraging for the use of the polymer loaded with CIP (as a drug model), under gel form, in the development of a new controlled-release system to be evaluated for topical administration. First, DP-CIP ionic complexes were obtained by an acid-base reaction using the high density of carboxylic acid groups of the DP and the amine groups of the CIP. The complexes obtained in the solid state were broadly characterized using FTIR spectroscopy, XRP diffraction, DSC-TG analysis and optical microscopy techniques. Gels based on the DP-CIP complexes were easily prepared and presented excellent mechanical behaviors. In addition, optimal properties for application on mucosal membranes and skin were achieved due to their high biocompatibility and acute skin non-irritation. Slow and sustained release of CIP toward simulated physiological fluids was observed in the assays (in vitro), attributed to ion exchange phenomenon and to the drug reservoir effect. An in vitro bacterial growth inhibition assay showed significant CIP activity, corresponding to 38 and 58% of that exhibited by a CIP hydrochloride solution at similar CIP concentrations, against Staphylococcus aureus and Pseudomonas aeruginosa, respectively. However, CIP delivery was appropriate, both in terms of magnitude and velocity to allow for a bactericidal effect. In conclusion, the final product showed promising behavior, which could be exploited for the treatment of topical and mucosal opportunistic infections in human or veterinary applications. - Highlights: • A novel hydrogel based on

A novel gel based on an ionic complex from a dendronized polymer and ciprofloxacin: Evaluation of its use for controlled topical drug release

Energy Technology Data Exchange (ETDEWEB)

García, Mónica C. [Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA Córdoba (Argentina); Cuggino, Julio C. [Instituto de Desarrollo Tecnológico para la Industria Química (INTEC), CONICET, Colectora Ruta Nac. N° 168, km. 0, Pje. El Pozo, 3000 Santa Fe (Argentina); Rosset, Clarisa I.; Páez, Paulina L. [Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA Córdoba (Argentina); Strumia, Miriam C. [Instituto Multidisciplinario de Biología Vegetal (IMBIV), CONICET and Laboratorio de Materiales Poliméricos (LAMAP), Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA Córdoba (Argentina); and others

2016-12-01

The development and characterization of a novel, gel-type material based on a dendronized polymer (DP) loaded with ciprofloxacin (CIP), and the evaluation of its possible use for controlled drug release, are presented in this work. DP showed biocompatible and non-toxic behaviors in cultured cells, both of which are considered optimal properties for the design of a final material for biomedical applications. These results were encouraging for the use of the polymer loaded with CIP (as a drug model), under gel form, in the development of a new controlled-release system to be evaluated for topical administration. First, DP-CIP ionic complexes were obtained by an acid-base reaction using the high density of carboxylic acid groups of the DP and the amine groups of the CIP. The complexes obtained in the solid state were broadly characterized using FTIR spectroscopy, XRP diffraction, DSC-TG analysis and optical microscopy techniques. Gels based on the DP-CIP complexes were easily prepared and presented excellent mechanical behaviors. In addition, optimal properties for application on mucosal membranes and skin were achieved due to their high biocompatibility and acute skin non-irritation. Slow and sustained release of CIP toward simulated physiological fluids was observed in the assays (in vitro), attributed to ion exchange phenomenon and to the drug reservoir effect. An in vitro bacterial growth inhibition assay showed significant CIP activity, corresponding to 38 and 58% of that exhibited by a CIP hydrochloride solution at similar CIP concentrations, against Staphylococcus aureus and Pseudomonas aeruginosa, respectively. However, CIP delivery was appropriate, both in terms of magnitude and velocity to allow for a bactericidal effect. In conclusion, the final product showed promising behavior, which could be exploited for the treatment of topical and mucosal opportunistic infections in human or veterinary applications. - Highlights: • A novel hydrogel based on

Calcium modified edible Canna (Canna edulis L) starch for controlled released matrix

Science.gov (United States)

Putri, A. P.; Ridwan, M.; Darmawan, T. A.; Darusman, F.; Gadri, A.

2017-07-01

Canna edulis L starch was modified with calcium chloride in order to form controlled released matrix. Present study aim to analyze modified starch characteristic. Four different formulation of ondansetron granules was used to provide dissolution profile of controlled released, two formula consisted of 15% and 30% modified starch, one formula utilized matrix reference standards and the last granules was negative control. Methocel-hydroxypropyl methyl cellulose was used as controlled released matrix reference standards in the third formula. Calcium starch was synthesized in the presence of sodium hydroxide to form gelatinized mass and calcium chloride as the cross linking agent. Physicochemical and dissolution properties of modified starch for controlled released application were investigated. Modified starch has higher swelling index, water solubility and compressibility index. Three of four different formulation of granules provide dissolution profile of controlled released. The profiles indicate granules which employed calcium Canna edulis L starch as matrix are able to resemble controlled drug released profile of matrix reference, however their bigger detain ability lead to lower bioavailability.

Molecularly Imprinted Polymers for 5-Fluorouracil Release in Biological Fluids

Directory of Open Access Journals (Sweden)

Franco Alhaique

2007-04-01

Full Text Available The aim of this work was to investigate the possibility of employing Molecularly Imprinted Polymers (MIPs as a controlled release device for 5-fluorouracil (5-FU in biological fluids, especially gastrointestinal ones, compared to Non Imprinted Polymers (NIPs. MIPs were synthesized using methacrylic acid (MAA as functional monomer and ethylene glycol dimethacrylate (EGDMA as crosslinking agent. The capacity of the polymer to recognize and to bind the template selectively in both organic and aqueous media was evaluated. An in vitro release study was performed both in gastrointestinal and in plasma simulating fluids. The imprinted polymers bound much more 5-Fu than the corresponding non-imprinted ones and showed a controlled/sustained drug release, with MIPs release rate being indeed much more sustained than that obtained from NIPs. These polymers represent a potential valid system for drug delivery and this study indicates that the selective binding characteristic of molecularly imprinted polymers is promising for the preparation of novel controlled release drug dosage form.

Massive radiological releases profoundly differ from controlled releases

International Nuclear Information System (INIS)

Pascucci-Cahen, Ludivine; Patrick, Momal

2013-01-01

In this article, the authors report identification and assessment of different types of costs associated with nuclear accidents. They first outline that these cost assessments must be as exhaustive or comprehensive as possible. While referring to past accidents, they define the different categories of costs: on-site costs (decontamination and dismantling, electricity not produced on the site), off-site costs (health costs, psychological costs, farming losses), image-related costs (impact on food and farm product exports, decrease of other exports), costs related to energy production, costs related to contaminated areas (refugees, lands). They give an assessment of a severe nuclear accident (i.e. an accident with important but controlled radiological releases) in France and outline that it would be a national catastrophe which could be however managed. They discuss the possible variations of the estimated costs. Then, they show that a major accident (i.e. an accident with massive radiological releases) in France would be an unmanageable European catastrophe because of the radiological consequences, of high economic costs, and of huge losses

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

International Nuclear Information System (INIS)

Snyder, R.E.

1988-01-01

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

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.

SOL-Gel microspheres and nanospheres for controlled release applications

International Nuclear Information System (INIS)

Barbe, C.; Beyer, R.; Kong, L.; Blackford, M.; Trautman, R.; Bartlett, J.

2002-01-01

We present a novel approach to the synthesis of inorganic sol-gel microspheres for encapsulating organic and bioactive molecules, and controlling their subsequent release kinetics. The bioactive species are incorporated, at ambient temperature, into the inorganic particles using an emulsion gelation process. Independent control of the release rate (by adapting the nanostructure of the internal pore network to the physico-chemical properties of the bioactive molecules) and particle size (by tailoring the emulsion chemistry) is demonstrated. Sol-gel chemistry has been shown to be a flexible technique for producing inorganic silica matrices with tailored microstructures, which can be used for the encapsulation and controlled release of organic and bioactive molecules. The present paper extends this concept by combining sol-gel chemistry with an emulsion approach for producing inorganic particles with controlled dimensions, and demonstrates how the particle size and microstructure can be independently controlled. Sol-Gel Chemistry and Encapsulation of Model Compounds. A stock solution of 4-(2-hydroxy-l-naphthylazo) benzene sulfonic acid (Orange II) was produced by dissolving Orange II in water (0.1 wt%), and adjusting the pH to the required value. Sol-gel solutions were subsequently prepared by mixing the aqueous solution with tetramethylorthosilicate (TMOS) and methanol (MeOH), to achieve H 2 O:TMOS (W] and MeOH:TMOS mole ratios (D) of four. The resulting solution was stirred and left to age at ambient temperature for one day. A transparent emulsion was prepared by mixing selected surfactants and organic solvents. The surfactants used included sorbitan monooleate, sorbitan monolaurate and bis-2-ethylhexylsulfo-succinate (AOT), while the organic phase was typically chosen from the group consisting of kerosene, hexane, heptane, octane, decane, dodecane and cyclohexane. The sol-gel solution was added to the emulsion, and the resulting mixture was stirred at 500 rpm for

Design and characterization of controlled release tablet of metoprolol

Directory of Open Access Journals (Sweden)

Gautam Singhvi

2012-01-01

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

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

DEFF Research Database (Denmark)

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

2005-01-01

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

alpha-difluoromethylornithine modifies gonadotropin-releasing hormone release and follicle-stimulating hormone secretion in the immature female rat.

Science.gov (United States)

Thyssen, S M; Becú-Villalobos, D; Lacau-Mengido, I M; Libertun, C

1997-06-01

Polyamines play an essential role in tissue growth and differentiation, in body weight increment, in brain organization, and in the molecular mechanisms of hormonal action, intracellular signaling, and cell-to-cell communication. In a previous study, inhibition of their synthesis by alpha-difluoromethylornithine (DFMO), a specific and irreversible inhibitor of ornithine decarboxylase, during development in female rats, was followed by prolonged high follicle-stimulating hormone (FSH) serum level and a delayed puberty onset. Those changes were relatively independent of body mass and did not impair posterior fertility. The present work studies the mechanisms and site of action of polyamine participation in FSH secretion during development. DFMO was injected in female rats between Days 1 and 9 on alternate days. At 10 days of age, hypothalami from control and DFMO rats were perifused in vitro, and basal and potassium-induced gonadotropin-releasing hormone (GnRH) release were measured. The response to membrane depolarization was altered in DFMO hypothalami. Increased GnRH release in response to a low K+ concentration was evidenced. Adenohypophyses of the same treated prepubertal rats were perifused in vitro and the response to GnRH pulses was checked. In DFMO-treated rats, higher FSH release was observed, with no changes in LH or PRL secretion. Finally, pituitary GnRH receptor number in adenohypophyseal membranes from treated and control groups was quantified. A significant reduction in specific binding was evident in hypophyses from DFMO-treated rats when compared with binding in the control group. In summary, DFMO treatment in a critical developmental period in the female rat impacts the immature GnRH neuronal network and immature gonadotropes. A delay in maturation is evidenced by a higher sensitivity to secretagogs in both pituitary glands and hypothalamic explants. These events could explain the prolonged high FSH serum levels and delayed puberty onset seen in

Evaluation of olibanum and its resin as rate controlling matrix for controlled release of diclofenac

OpenAIRE

Chowdary KPR; Mohapatra P; Murali Krishna M

2006-01-01

Olibanum and its resin and carbohydrate fractions were evaluated as rate controlling matrix materials in tablets for controlled release of diclofenac. Diclofenac matrix tablets were formulated employing olibanum and its resin and carbohydrate fractions in different concentrations and the tablets were evaluated for various tablet characters including drug release kinetics and mechanism. Olibanum and its resin component exhibited excellent retarding effect on drug release from the matrix tablet...

Ordered mesoporous polymer-silica hybrid nanoparticles as vehicles for the intracellular controlled release of macromolecules.

Science.gov (United States)

Kim, Tae-Wan; Slowing, Igor I; Chung, Po-Wen; Lin, Victor Shang-Yi

2011-01-25

A two-dimensional hexagonal ordered mesoporous polymer-silica hybrid nanoparticle (PSN) material was synthesized by polymerization of acrylate monomers on the surface of SBA-15 mesoporous silica nanoparticles. The structure of the PSN material was analyzed using a series of different techniques, including transmission electron microscopy, powder X-ray diffraction, and N(2) sorption analysis. These structurally ordered mesoporous polymer-silica hybrid nanoparticles were used for the controlled release of membrane-impermeable macromolecules inside eukaryotic cells. The cellular uptake efficiency and biocompatibility of PSN with human cervical cancer cells (HeLa) were investigated. Our results show that the inhibitory concentration (IC(50)) of PSN is very high (>100 μg/mL per million cells), while the median effective concentration for the uptake (EC(50)) of PSN is low (EC(50) = 4.4 μg/mL), indicating that PSNs are fairly biocompatible and easily up-taken in vitro. A membrane-impermeable macromolecule, 40 kDa FITC-Dextran, was loaded into the mesopores of PSNs at low pH. We demonstrated that the PSN material could indeed serve as a transmembrane carrier for the controlled release of FITC-Dextran at the pH level inside live HeLa cells. We believe that further developments of this PSN material will lead to a new generation of nanodevices for intracellular controlled delivery applications.

pH responsive controlled release of anti-cancer hydrophobic drugs from sodium alginate and hydroxyapatite bi-coated iron oxide nanoparticles.

Science.gov (United States)

Manatunga, Danushika C; de Silva, Rohini M; de Silva, K M Nalin; de Silva, Nuwan; Bhandari, Shiva; Yap, Yoke Khin; Costha, N Pabakara

2017-08-01

Developing a drug carrier system which could perform targeted and controlled release over a period of time is utmost concern in the pharmaceutical industry. This is more relevant when designing drug carriers for poorly water soluble drug molecules such as curcumin and 6-gingerol. Development of a drug carrier system which could overcome these limitations and perform controlled and targeted drug delivery is beneficial. This study describes a promising approach for the design of novel pH sensitive sodium alginate, hydroxyapatite bilayer coated iron oxide nanoparticle composite (IONP/HAp-NaAlg) via the co-precipitation approach. This system consists of a magnetic core for targeting and a NaAlg/HAp coating on the surface to accommodate the drug molecules. The nanocomposite was characterized using FT-IR spectroscopy, X-ray diffraction, scanning electron microscopy, transmission electron microscopy and thermogravimetric analysis. The loading efficiency and loading capacity of curcumin and 6-gingerol were examined. In vitro drug releasing behavior of curcumin and 6-gingerol was studied at pH 7.4 and pH 5.3 over a period of seven days at 37°C. The mechanism of drug release from the nanocomposite of each situation was studied using kinetic models and the results implied that, the release is typically via diffusion and a higher release was observed at pH 5.3. This bilayer coated system can be recognized as a potential drug delivery system for the purpose of curcumin and 6-gingerol release in targeted and controlled manner to treat diseases such as cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Preparation and characterization of controlled-release fertilizers coated with marine polysaccharide derivatives

Science.gov (United States)

Wang, Jing; Liu, Song; Qin, Yukun; Chen, Xiaolin; Xing, Rong'e.; Yu, Huahua; Li, Kecheng; Li, Pengcheng

2017-09-01

Encapsulation of water-soluble nitrogen fertilizers by membranes can be used to control the release of nutrients to maximize the fertilization effect and reduce environmental pollution. In this research, we formulated a new double-coated controlled-release fertilizer (CRF) by using food-grade microcrystalline wax (MW) and marine polysaccharide derivatives (calcium alginate and chitosan-glutaraldehyde copolymer). The pellets of water-soluble nitrogen fertilizer were coated with the marine polysaccharide derivatives and MW. A convenient and eco-friendly method was used to prepare the CRF. Scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) were used to characterize the morphology and composition of the products. The nitrogen-release properties were determined in water using UV-Vis spectrophotometry. The controlled-release properties of the fertilizer were improved dramatically after coating with MW and the marine polysaccharide derivatives. The results show that the double-coated CRFs can release nitrogen in a controlled manner, have excellent controlled-release features, and meet the European Standard for CRFs.

Controlled release of insect sex pheromones from paraffin wax and emulsions.

Science.gov (United States)

Atterholt, C A; Delwiche, M J; Rice, R E; Krochta, J M

1999-02-22

Paraffin wax and aqueous paraffin emulsions can be used as controlled release carriers for insect sex pheromones for mating disruption of orchard pests. Paraffin can be applied at ambient temperature as an aqueous emulsion, adheres to tree bark or foliage, releases pheromone for an extended period of time, and will slowly erode from bark and biodegrade in soil. Pheromone emulsions can be applied with simple spray equipment. Pheromone release-rates from paraffin were measured in laboratory flow-cell experiments. Pheromone was trapped from an air stream with an adsorbent, eluted periodically, and quantified by gas chromatography. Pheromone release from paraffin was partition-controlled, providing a constant (zero-order) release rate. A typical paraffin emulsion consisted of 30% paraffin, 4% pheromone, 4% soy oil, 1% vitamin E, 2% emulsifier, and the balance water. Soy oil and vitamin E acted as volatility suppressants. A constant release of oriental fruit moth pheromone from paraffin emulsions was observed in the laboratory for more than 100 days at 27 degreesC, with release-rates ranging from 0.4 to 2 mg/day, depending on the concentration and surface area of the dried emulsion. The use of paraffin emulsions is a viable method for direct application of insect pheromones for mating disruption. Sprayable formulations can be designed to release insect pheromones to the environment at a rate necessary for insect control by mating disruption. At temperatures below 38 degreesC, zero-order release was observed. At 38 degreesC and higher, pheromone oxidation occurred. A partition-controlled release mechanism was supported by a zero-order pheromone release-rate, low air/wax partition coefficients, and pheromone solubility in paraffin.

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.

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

Science.gov (United States)

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

2018-10-15

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

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.

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

Science.gov (United States)

Dyja, R; Jankowski, A

2017-08-01

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

Stepwise encapsulation and controlled two-stage release system for cis-Diamminediiodoplatinum

Directory of Open Access Journals (Sweden)

Chen Y

2014-06-01

Full Text Available Yun Chen,1,* Qian Li,1,2,* Qingsheng Wu1 1Department of Chemistry, Key Laboratory of Yangtze River Water Environment, Ministry of Education, Tongji University, Shanghai; 2Shanghai Institute of Quality Inspection and Technical Research, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: cis-Diamminediiodoplatinum (cis-DIDP is a cisplatin-like anticancer drug with higher anticancer activity, but lower stability and price than cisplatin. In this study, a cis-DIDP carrier system based on micro-sized stearic acid was prepared by an emulsion solvent evaporation method. The maximum drug loading capacity of cis-DIDP-loaded solid lipid nanoparticles was 22.03%, and their encapsulation efficiency was 97.24%. In vitro drug release in phosphate-buffered saline (pH =7.4 at 37.5°C exhibited a unique two-stage process, which could prove beneficial for patients with tumors and malignancies. MTT (3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide assay results showed that cis-DIDP released from cis-DIDP-loaded solid lipid nanoparticles had better inhibition activity than cis-DIDP that had not been loaded. Keywords: stearic acid, emulsion solvent evaporation method, drug delivery, cis-DIDP, in vitro

Simulated food effects on drug release from ethylcellulose: PVA-PEG graft copolymer-coated pellets.

Science.gov (United States)

Muschert, Susanne; Siepmann, Florence; Leclercq, Bruno; Carlin, Brian; Siepmann, Juergen

2010-02-01

Food effects might substantially alter drug release from oral controlled release dosage forms in vivo. The robustness of a novel type of controlled release film coating was investigated using various types of release media and two types of release apparatii. Importantly, none of the investigated conditions had a noteworthy impact on the release of freely water-soluble diltiazem HCl or slightly water-soluble theophylline from pellets coated with ethylcellulose containing small amounts of PVA-PEG graft copolymer. In particular, the presence of significant amounts of fats, carbohydrates, surfactants, bile salts, and calcium ions in the release medium did not alter drug release. Furthermore, changes in the pH and differences in the mechanical stress the dosage forms were exposed to did not affect drug release from the pellets. The investigated film coatings allowing for oral controlled drug delivery are highly robust in vitro and likely to be poorly sensitive to classical food effects in vivo.

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

DEFF Research Database (Denmark)

Zeeshan, Farrukh; Tabbassum, Misbah; Jorgensen, Lene

2018-01-01

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

Controlled release of curcumin from poly(HEMA-MAPA) membrane.

Science.gov (United States)

Caka, Müşerref; Türkcan, Ceren; Aktaş Uygun, Deniz; Uygun, Murat; Akgöl, Sinan; Denizli, Adil

2017-05-01

In this work, poly(HEMA-MAPA) membranes were prepared by UV-polymerization technique. These membranes were characterized by SEM, FTIR, and swelling studies. Synthesized membranes had high porous structure. These membranes were used for controlled release of curcumin which is already used as folk remedy and used as drug for some certain diseases and cancers. Curcumin release was investigated for various pHs and temperatures. Optimum drug release yield was found to be as 70% at pH 7.4 and 37 °C within 2 h period. Time-depended release of curcumin was also investigated and its slow release from the membrane demonstrated within 48 h.

Effects of adenosine on renin release from isolated rat glomeruli and kidney slices

DEFF Research Database (Denmark)

Skøtt, O; Baumbach, L

1985-01-01

was used. The specificity of the renin release process was validated by measuring adenylate kinase as a marker for cytoplasmatic leak. Adenosine (10 micrograms/ml) halved basal renin release from incubated KS as compared to controls (P less than 0.001, n = 8, 8). Renin release from LAG stimulated...... by calcium depletion was also inhibited (P less than 0.05, n = 8, 9) whereas basal release was not affected (n = 6, 12). No effect was detected neither on basal nor on calcium stimulated renin release from SAG. We conclude that adenosine inhibits renin release in vitro by a mechanism independent...

The biopharmaceutics of successful controlled release drug product: Segmental-dependent permeability of glipizide vs. metoprolol throughout the intestinal tract.

Science.gov (United States)

Zur, Moran; Cohen, Noa; Agbaria, Riad; Dahan, Arik

2015-07-15

The purpose of this work was to study the challenges and prospects of regional-dependent absorption in a controlled-release scenario, through the oral biopharmaceutics of the sulfonylurea antidiabetic drug glipizide. The BCS solubility class of glipizide was determined, and its physicochemical properties and intestinal permeability were thoroughly investigated, both in-vitro (PAMPA and Caco-2) and in-vivo in rats. Metoprolol was used as the low/high permeability class boundary marker. Glipizide was found to be a low-solubility compound. All intestinal permeability experimental methods revealed similar trend; a mirror image small intestinal permeability with opposite regional/pH-dependency was obtained, a downward trend for glipizide, and an upward trend for metoprolol. Yet the lowest permeability of glipizide (terminal Ileum) was comparable to the lowest permeability of metoprolol (proximal jejunum). At the colon, similar permeability was evident for glipizide and metoprolol, that was higher than metoprolol's jejunal permeability. We present an analysis that identifies metoprolol's jejunal permeability as the low/high permeability class benchmark anywhere throughout the intestinal tract; we show that the permeability of both glipizide and metoprolol matches/exceeds this threshold throughout the entire intestinal tract, accounting for their success as controlled-release dosage form. This represents a key biopharmaceutical characteristic for a successful controlled-release dosage form. Copyright © 2015 Elsevier B.V. All rights reserved.

Formulation and evaluation of novel controlled release of topical pluronic lecithin organogel of mefenamic acid.

Science.gov (United States)

Jhawat, Vikas; Gupta, Sumeet; Saini, Vipin

2016-11-01

In the present study, pluronic lecithin based organogels (PLO gels) were formulated as topical carrier for controlled delivery of mefenamic acid. Ten organogel formulations were prepared by a method employing lecithin as lipophilic phase and pluronic F-127 as hydrophilic phase in varying concentrations to study various parameters using in vitro diffusion study and in vivo studies. All formulations were found to be off-white, homogenous, and reluctant to be washed easily and have pH value within the range of 5.56-5.80 which is nonirritant. Polymer concentration increased in formulations of F1 to F5 (lecithin) and F6 to F10 (pluronic) resulted in decrease of the gelation temperature, increase of viscosity and reduction of spreadability of gels having polymer tendency to form rigid 3D network. Organogels with higher viscosity were found to be more stable and retard the drug release from the gel. The formulations of F2 and F3 were selected for kinetic studies and stability studies, as they found to have all physical parameters within acceptable limits, highest percent drug content and exhibited highest drug release in eight hours. The order of drug release from various formulations was found to be F2 > F3 > F10 > F4 > F1 > F9 > F8 > F5 > F7 > F6. The optimized formulation F2 was found to follow zero order rate kinetics showing controlled release of the drug from the formulations. In vivo anti-inflammatory activity of optimized mefenamic acid organogel (F2) against a standard marketed preparation (Volini gel) was found satisfactory and significant.

Controlled Pesticide Release from Porous Composite Hydrogels Based on Lignin and Polyacrylic Acid

Directory of Open Access Journals (Sweden)

Yajie Sun

2016-01-01

Full Text Available For the controlled release of pesticides, a novel composite porous hydrogel (LBPAA was prepared based on lignin and polyacrylic acid for use as the support frame of a pore structure for water delivery. The LBPAA was analyzed to determine its water-swelling and slow release properties. The controlled release properties of LBPAA were evaluated through experiments in relation to the cumulative release of pesticides, with particular emphasis on environmental effects and release models. The porous LBPAA hydrogel showed improved properties compared to polyacrylic acid, and could therefore be considered an efficient material for application in controlled release systems in agriculture.

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

Science.gov (United States)

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

2017-01-02

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

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

International Nuclear Information System (INIS)

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

1999-01-01

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

Release kinetics of tocopherol and quercetin from binary antioxidant controlled-release packaging films.

Science.gov (United States)

Chen, Xi; Lee, Dong Sun; Zhu, Xuntao; Yam, Kit L

2012-04-04

This paper investigated the feasibility of manipulating packaging polymers with various degrees of hydrophobicity to release two antioxidants, tocopherol and quercetin, at rates suitable for long-term inhibition of lipid oxidation in food. For example, one antioxidant can be released at a fast rate to provide short-term/intermediate protection, whereas the other antioxidant can be released at a slower rate to provide intermediate/long-term protection of lipid oxidation. Controlled-release packaging films containing tocopherol and quercetin were produced using ethylene vinyl alcohol (EVOH), ethylene vinyl acetate (EVA), low-density polyethylene (LDPE), and polypropylene (PP) polymers; the release of these antioxidants to 95% ethanol (a fatty food simulant) was measured using UV-vis spectrophotometry, and Fickian diffusion models with appropriate initial and boundary conditions were used to fit the data. For films containing only quercetin, the results show that the release of quercetin was much faster but lasted for a much shorter time for hydrophilic polymers (EVOH and EVA) than for hydrophobic polymers (LDPE and PP). For binary antioxidant films containing tocopherol and quercetin, the results show that tocopherol released more rapidly but for a shorter period of time than quercetin in LDPE and EVOH films, and the difference is more pronounced for LDPE films than EVOH films. The results also show the presence of tocopherol can accelerate the release of quercetin. Although none of the films produced is acceptable for long-term lipid oxidation inhibition, the study provides encouraging results suggesting that acceptable films may be produced in the future using polymer blend films.

Conductive polymers for controlled release and treatment of central nervous system injury

Science.gov (United States)

Saigal, Rajiv

[(D,L-lactide-co-glycolide)-co-polyethylene glycol] (PLGA-PEG) nanoparticles and then demonstrated scalable incorporation and controlled release. In a functional application, electronically-controlled release of minocycline nanoparticles was used to rescue primary spinal cord neurons from an excitotoxic environment in vitro. This approach offers a wide range of therapeutic possibilities, especially for treating traumatic lesions of the central nervous system. Finally, we explored use of conductive polymers for directed differentiation of progenitor cells. Retinal progenitors were seeded on custom polypyrrole cell culture devices and subjected to a biomimetic pattern of electrical stimulation. Stimulated cells showed phenotypic changes, increased neurite outgrowth, increased immunocytochemical expression of cone rod homeobox (CRX) and protein kinase C (PK-C), and decreased expression of glial fibrillary acidic protein (GFAP). Biomimetic stimulation thus led cells towards early photoreceptor and bipolar cell fates, and away from an astrocytic cell fate. Electrical stimulation via a conductive polymer offers a novel approach for directing differentiation of progenitor cells.

Preparation of a novel breviscapine-loaded halloysite nanotubes complex for controlled release of breviscapine

Science.gov (United States)

Gao, Min; Lu, Liqian; Wang, Xiaoyue; Lin, Houke; Zhou, Qingsong

2017-11-01

For sustain the release rate and prolong half-life of breviscapine in vivo, the breviscapine-loaded halloysite nanotubes complex was prepared. The breviscapine was encapsulated into halloysite nanotubes (HNTs) using a vacuum process. The complex were investigated by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), transmission electron microscope (TEM), X-ray diffraction (XRD) and fourier transform infrared spectroscopy(FT-IR). The formation of breviscapine-loaded HNTs complex was proved by the test results of SEM, DSC, TEM and IR analysise. The results confirmed that breviscapine was successfully loaded in the halloysite nanotubes. Additionally, the in vitro drug release of breviscapine from breviscapine-loaded HNTs complex was investigated, the result indicated this complex has apparent sustained-release effect.

Poly(dimethylsiloxane) coatings for controlled drug release--polymer modifications.

Science.gov (United States)

Schulze Nahrup, J; Gao, Z M; Mark, J E; Sakr, A

2004-02-11

Modifications of endhydroxylated poly(dimethylsiloxane) (PDMS) formulations were studied for their ability to be applied onto tablet cores in a spray-coating process and to control drug release in zero-order fashion. Modifications of the crosslinker from the most commonly used tetraethylorthosilicate (TEOS) to the trifunctional 3-(2,3-epoxypropoxy)propyltrimethoxysilane (SIG) and a 1:1 mixture of the two were undertaken. Addition of methylpolysiloxane-copolymers were studied. Lactose, microcrystalline cellulose (MCC) and polyethylene glycol 8000 (PEG) were the channeling agents applied. The effects on dispersion properties were characterized by particle size distribution and viscosity. Mechanical properties of resulting free films were studied to determine applicability in a pan-coating process. Release of hydrochlorothiazide (marker drug) was studied from tablets coated in a lab-size conventional coating pan. All dispersions were found suitable for a spray-coating process. Preparation of free films showed that copolymer addition was not possible due to great decline in mechanical properties. Tablets coated with formulations containing PEG were most suitable to control drug release, at only 5% coating weight. Constant release rates could be achieved for formulations with up to 25% PEG; higher amounts resulted in a non-linear release pattern. Upon adding 50% PEG, a drug release of 63% over 24 h could be achieved.

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

NARCIS (Netherlands)

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

2011-01-01

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

Immobilization and controlled release of drug using plasma polymerized thin film

Energy Technology Data Exchange (ETDEWEB)

Myung, Sung-Woon [Department of Dental Materials, School of Dentistry, MRC Center, Chosun University, 309 Pilmun-daero, Dong-gu, Gwangju (Korea, Republic of); Jung, Sang-Chul [Department of Environmental Engineering, Sunchon National University, Sunchon 540-742 (Korea, Republic of); Kim, Byung-Hoon, E-mail: kim5055@chosun.ac.kr [Department of Dental Materials, School of Dentistry, MRC Center, Chosun University, 309 Pilmun-daero, Dong-gu, Gwangju (Korea, Republic of)

2015-06-01

In this study, plasma polymerization of acrylic acid was employed to immobilize drug and control its release. Doxorubicin (DOX) was immobilized covalently on the glass surface deposited with plasma polymerized acrylic acid (PPAAc) thin film containing the carboxylic group. At first, the PPAAc thin film was coated on a glass surface at a pressure of 1.33 Pa and radio frequency (RF) discharge power of 20 W for 10 min. DOX was immobilized on the PPAAc deposition in a two environment of phosphate buffer saline (PBS) and dimethyl sulfoxide (DMSO) solutions. The DOX immobilized surface was characterized by scanning electron microscope, atomic force microscope and attenuated total reflection Fourier transform infrared spectroscopy. The DOX molecules were more immobilized in PBS than DMSO solution. The different immobilization and release profiles of DOX result from the solubility of hydrophobic DOX in aqueous and organic solutions. Second, in order to control the release of the drug, PPAAc thin film was covered over DOX dispersed layer. Different thicknesses and cross-linked PPAAc thin films by adjusting deposition time and RF discharge power were covered on the DOX layer dispersed. PPAAc thin film coated DOX layer reduced the release rate of DOX. The thickness control of plasma deposition allows controlling the release rate of drug. - Highlights: • Doxorubicin was immobilized on the surface of plasma polymerized acrylic acid thin film. • Release profile of doxorubicin was affected by aqueous and organic solutions. • Plasma polymerized acrylic acid thin film can be used to achieve controlled release.

Immobilization and controlled release of drug using plasma polymerized thin film

International Nuclear Information System (INIS)

Myung, Sung-Woon; Jung, Sang-Chul; Kim, Byung-Hoon

2015-01-01

In this study, plasma polymerization of acrylic acid was employed to immobilize drug and control its release. Doxorubicin (DOX) was immobilized covalently on the glass surface deposited with plasma polymerized acrylic acid (PPAAc) thin film containing the carboxylic group. At first, the PPAAc thin film was coated on a glass surface at a pressure of 1.33 Pa and radio frequency (RF) discharge power of 20 W for 10 min. DOX was immobilized on the PPAAc deposition in a two environment of phosphate buffer saline (PBS) and dimethyl sulfoxide (DMSO) solutions. The DOX immobilized surface was characterized by scanning electron microscope, atomic force microscope and attenuated total reflection Fourier transform infrared spectroscopy. The DOX molecules were more immobilized in PBS than DMSO solution. The different immobilization and release profiles of DOX result from the solubility of hydrophobic DOX in aqueous and organic solutions. Second, in order to control the release of the drug, PPAAc thin film was covered over DOX dispersed layer. Different thicknesses and cross-linked PPAAc thin films by adjusting deposition time and RF discharge power were covered on the DOX layer dispersed. PPAAc thin film coated DOX layer reduced the release rate of DOX. The thickness control of plasma deposition allows controlling the release rate of drug. - Highlights: • Doxorubicin was immobilized on the surface of plasma polymerized acrylic acid thin film. • Release profile of doxorubicin was affected by aqueous and organic solutions. • Plasma polymerized acrylic acid thin film can be used to achieve controlled release

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

Science.gov (United States)

Mikulewicz, Marcin; Chojnacka, Katarzyna; Wołowiec, Paulina

2014-01-01

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

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

Directory of Open Access Journals (Sweden)

Wen-Hao Wei

2015-03-01

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

Improved design and characterization of PLGA/PLA-coated Chitosan based micro-implants for controlled release of hydrophilic drugs.

Science.gov (United States)

Manna, Soumyarwit; Donnell, Anna M; Kaval, Necati; Al-Rjoub, Marwan F; Augsburger, James J; Banerjee, Rupak K

2018-05-29

Repetitive intravitreal injections of Methotrexate (MTX), a hydrophilic chemotherapeutic drug, are currently used to treat selected vitreoretinal (VR) diseases, such as intraocular lymphoma. To avoid complications associated with the rapid release of MTX from the injections, a Polylactic acid (PLA) and Chitosan (CS)-based MTX micro-implant prototype was fabricated in an earlier study, which showed a sustained therapeutic release rate of 0.2-2.0 µg/day of MTX for a period ∼1 month in vitro and in vivo. In the current study, different combinations of Poly(lactic-co-glycolic) acid (PLGA)/PLA coatings were used for lipophilic surface modification of the CS-MTX micro-implant, such as PLGA 5050, PLGA 6535 and PLGA 7525 (PLA: PGA - 50:50, 65:35, 75:25, respectively; M.W: 54,400 - 103,000) and different PLA, such as PLA 100 and PLA 250 (MW: 102,000 and 257,000, respectively). This improved the duration of total MTX release from the coated CS-MTX micro-implants to ∼3-5 months. With an increase in PLA content in PLGA and molecular weight of PLA, a) the initial burst of MTX and the mean release rate of MTX can be reduced; and b) the swelling and biodegradation of the micro-implants can be delayed. The controlled drug release mechanism is caused by a combination of diffusion process and hydrolysis of the polymer coating, which can be modulated by a) PLA content in PLGA and b) molecular weight of PLA, as inferred from Korsmeyer Peppas model, Zero order, First order and Higuchi model fits. This improved micro-implant formulation has the potential to serve as a platform for controlled release of hydrophilic drugs to treat selected VR diseases. Copyright © 2018. Published by Elsevier B.V.

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

Directory of Open Access Journals (Sweden)

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

2010-12-01

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

Drug release from non-aqueous suspensions. II. The release of methylxanthines from paraffin suspensions

NARCIS (Netherlands)

Blaey, C.J. de; Fokkens, J.G.

1984-01-01

The release of 3 methylxanthines, i.e. caffeine, theobromine and theophylline, from suspensions in liquid paraffin to an aqueous phase was determined in an in vitro apparatus. The release rates were determined as a function of the pH of the aqueous phase. It was proved that the release process was

Controlled release of biofunctional substances by radiation-induced polymerization

International Nuclear Information System (INIS)

Yoshida, M.; Kumakura, M.; Kaetsu, I.

1978-01-01

The controlled release of potassium chloride from flat circular matrices made by radiation-induced polymerization of a glass-forming monomer at low temperatures has been studied. The water-particle phase content formed in a poly(diethylene glycol dimethacrylate) matrix was controlled by the addition of polyethylene glycol 600. The dispersed water-particle phase content in the matrix was estimated directly and by scanning electron microscopic observations. The release of potassium chloride from the matrix increased linearly with the square root of time. The water content of the matrix had an important effect on the release rate which increases roughly in proportion to water content. This effect can be attributed to the apparent increase of the rate of drug diffusion. (author)

Polyoxometalate coordination induced controllable release of quinolone in hybrid film

Science.gov (United States)

Yang, Fan; Li, Yang; Lv, Yu-Guang; Zhou, Shu-Jing; Li, Si; Gao, Guang-Gang; Liu, Hong

2018-05-01

Due to some side effects of quinolones in vivo, it is an urgent issue to extend their new applications in vitro. In this paper, structure-determined vanadium-quinolone functionalized polymolybdates of (NH4)2 [(γ-Mo8O26){VO(CF)2}2] (1) and (NH4)2 [(γ-Mo8O26){VO(NF)2}2] (2) (CF = ciprofloxacin; NF = norfloxacin) have been designed and synthesized. Complex 1 or 2 features a γ-type [Mo8O26]4- polyanion functionalized by two monocapped vanadium-quinolone complexes. Different H-bonds and π···π interactions allow 1 or 2 to form a 2D layered structure at solid state. When complex 1 or 2 is transferred into polyvinyl alcohol (PVA) film, its release rate in solution is lower than that of CF- or NF-PVA film and thus forming a novel quinolone delivery system. This is the first time that slow release effect of quinolone is achieved by polyoxometalate coordination effect. The slow release of 1 or 2 in PVA film is mainly ascribed to the coordination of quinolone with polyoxometalate anions.

Design and evaluation of nicorandil extended-release tablet

Directory of Open Access Journals (Sweden)

Ju-Young Kim

2015-04-01

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

Stimuli-Responsive Materials for Controlled Release Applications

KAUST Repository

Li, Song

2015-01-01

The controlled release of therapeutics has been one of the major challenges for scientists and engineers during the past three decades. To address this outstanding problem, the design and fabrication of stimuli-responsive materials are pursued

Controlled release from drug microparticles via solventless dry-polymer coating.

Science.gov (United States)

Capece, Maxx; Barrows, Jason; Davé, Rajesh N

2015-04-01

A novel solvent-less dry-polymer coating process employing high-intensity vibrations avoiding the use of liquid plasticizers, solvents, binders, and heat treatments is utilized for the purpose of controlled release. The main hypothesis is that such process having highly controllable processing intensity and time may be effective for coating particularly fine particles, 100 μm and smaller via exploiting particle interactions between polymers and substrates in the dry state, while avoiding breakage yet achieving conformal coating. The method utilizes vibratory mixing to first layer micronized polymer onto active pharmaceutical ingredient (API) particles by virtue of van der Waals forces and to subsequently mechanically deform the polymer into a continuous film. As a practical example, ascorbic acid and ibuprofen microparticles, 50-500 μm, are coated with the polymers polyethylene wax or carnauba wax, a generally recognized as safe material, resulting in controlled release on the order of seconds to hours. As a novelty, models are utilized to describe the coating layer thickness and the controlled-release behavior of the API, which occurs because of a diffusion-based mechanism. Such modeling would allow the design and control of the coating process with application for the controlled release of microparticles, particularly those less than 100 μm, which are difficult to coat by conventional solvent coating methods. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Use of fibrin sealants for the localized, controlled release of cefazolin

Science.gov (United States)

Tredwell, Stephen; Jackson, John K.; Hamilton, Donald; Lee, Vivian; Burt, Helen M.

2006-01-01

Background Fibrin sealants are used increasingly in surgery to reduce bleeding and improve wound healing. They have great potential as biocompatible, biodegradable drug delivery systems, because the sealant may adhere to the target tissue and allow controlled release of the drug over an extended period. We investigated the encapsulation, stability and controlled release of erythromycin and cefazolin from Beriplast fibrin sealants (Aventis Behring Canada). Methods Drug-loaded clots were cast in glass vials and allowed to set. We observed the clots for drug precipitation and aggregation, and we assessed the effect of drug encapsulation on clot strength. Drug stability and release from the clots in phosphate buffered saline (PBS) was quantified by ultraviolet and visible violet absorbance spectroscopy and high-performance liquid chromatography. Results Erythromycin was found to release slowly from the fibrin clots over the first 2 hours but then degrade rapidly. Cefazolin was found to be very stable in clots in PBS (97% stable at 2 d and 93% stable at 5 d). The drug released in a controlled manner over 2 days, with most being released during the first day. The dose of drug released could be varied by changing the amount placed in the thrombin solution. Clot thickness had no effect on the rate of cefazolin release. Conclusion Overall, the 2-day release profile and the excellent stability of the drug suggest that cefazolin-loaded fibrin sealants may offer an effective route of postoperative antibiotic delivery. PMID:17152573

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

Science.gov (United States)

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

2013-01-01

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

Stepwise encapsulation and controlled two-stage release system for cis-Diamminediiodoplatinum.

Science.gov (United States)

Chen, Yun; Li, Qian; Wu, Qingsheng

2014-01-01

cis-Diamminediiodoplatinum (cis-DIDP) is a cisplatin-like anticancer drug with higher anticancer activity, but lower stability and price than cisplatin. In this study, a cis-DIDP carrier system based on micro-sized stearic acid was prepared by an emulsion solvent evaporation method. The maximum drug loading capacity of cis-DIDP-loaded solid lipid nanoparticles was 22.03%, and their encapsulation efficiency was 97.24%. In vitro drug release in phosphate-buffered saline (pH =7.4) at 37.5°C exhibited a unique two-stage process, which could prove beneficial for patients with tumors and malignancies. MTT (3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) assay results showed that cis-DIDP released from cis-DIDP-loaded solid lipid nanoparticles had better inhibition activity than cis-DIDP that had not been loaded.

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

Institute of Scientific and Technical Information of China (English)

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

2012-01-01

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

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

Institute of Scientific and Technical Information of China (English)

BEI Jianzhong; WANG Zhifeng; WANG Shenguo

1995-01-01

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

Ingenious pH-sensitive dextran/mesoporous silica nanoparticles based drug delivery systems for controlled intracellular drug release.

Science.gov (United States)

Zhang, Min; Liu, Jia; Kuang, Ying; Li, Qilin; Zheng, Di-Wei; Song, Qiongfang; Chen, Hui; Chen, Xueqin; Xu, Yanglin; Li, Cao; Jiang, Bingbing

2017-05-01

In this work, dextran, a polysaccharide with excellent biocompatibility, is applied as the "gatekeeper" to fabricate the pH-sensitive dextran/mesoporous silica nanoparticles (MSNs) based drug delivery systems for controlled intracellular drug release. Dextran encapsulating on the surface of MSNs is oxidized by NaIO 4 to obtain three kinds of dextran dialdehydes (PADs), which are then coupled with MSNs via pH-sensitive hydrazone bond to fabricate three kinds of drug carriers. At pH 7.4, PADs block the pores to prevent premature release of anti-cancer drug doxorubicin hydrochloride (DOX). However, in the weakly acidic intracellular environment (pH∼5.5) the hydrazone can be ruptured; and the drug can be released from the carriers. The drug loading capacity, entrapment efficiency and release rates of the drug carriers can be adjusted by the amount of NaIO 4 applied in the oxidation reaction. And from which DOX@MSN-NH-N=C-PAD 10 is chosen as the most satisfactory one for the further in vitro cytotoxicity studies and cellular uptake studies. The results demonstrate that DOX@MSN-NH-N=C-PAD 10 with an excellent pH-sensitivity can enter HeLa cells to release DOX intracellular due to the weakly acidic pH intracellular and kill the cells. In our opinion, the ingenious pH-sensitive drug delivery systems have application potentials for cancer therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Improvement of waste release control in French NPP

International Nuclear Information System (INIS)

Samson, T.; Lucquin, E.; Dupin, M.; Florence, D.; Grisot, M.

2002-01-01

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

Improvement of waste release control in French NPP

Energy Technology Data Exchange (ETDEWEB)

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

2002-07-01

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

Synthesis, characterization, and in vitro evaluation of novel polymer-coated magnetic nanoparticles for controlled delivery of doxorubicin

Directory of Open Access Journals (Sweden)

Akbarzadeh A

2012-02-01

Full Text Available Abolfazl Akbarzadeh1, Nosratollah Zarghami2, Haleh Mikaeili3, Davoud Asgari4, Amir Mohammad Goganian5, Hanie Khaksar Khiabani5, Mohammad Samiei6, Soodabeh Davaran31Department of Medicinal Chemistry, Tabriz University of Medical Sciences, 2Department of Clinical Biochemistry and Laboratory Medicine, Division of Medical Biotechnology, Faculty of Medicine, Tabriz University of Medical Sciences, 3Tuberculosis and Lung Disease Research Center, Tabriz University of Medical Sciences, 4Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, 5Department of Organic Chemistry, Faculty of Chemistry, University of Tabriz, 6Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, IranAbstract: Poly (N-isopropylacrylamide-methyl methacrylic acid, PNIPAAm-MAA-grafted magnetic nanoparticles were synthesized using silane-coated magnetic nanoparticles as a template for radical polymerization of N-isopropylacrylamide and methacrylic acid. Properties of these nanoparticles, such as size, drug-loading efficiency, and drug release kinetics, were evaluated in vitro for targeted and controlled drug delivery. The resulting nanoparticles had a diameter of 100 nm and a doxorubicin-loading efficiency of 75%, significantly higher doxorubicin release at 40°C compared with 37°C, and pH 5.8 compared with pH 7.4, demonstrating their temperature and pH sensitivity, respectively. In addition, the particles were characterized by X-ray powder diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, and vibrating sample magnetometry. In vitro cytotoxicity testing showed that the PNIPAAm-MAA-coated magnetic nanoparticles had no cytotoxicity and were biocompatible, indicating their potential for biomedical application.Keywords: magnetic nanoparticles, drug loading, doxorubicin release, biocompatibility

Polyvinyl alcohol composite nanofibres containing conjugated levofloxacin-chitosan for controlled drug release

International Nuclear Information System (INIS)

Jalvandi, Javid; White, Max; Gao, Yuan; Truong, Yen Bach; Padhye, Rajiv; Kyratzis, Ilias Louis

2017-01-01

A range of biodegradable drug-nanofibres composite mats have been reported as drug delivery systems. However, their main disadvantage is the rapid release of the drug immediately after application. This paper reports an improved system based on the incorporation of drug conjugated-chitosan into polyvinyl alcohol (PVA) nanofibers. The results showed that controlled release of levofloxacin (LVF) could be achieved by covalently binding LVF to low molecular weight chitosan (CS) via a cleavable amide bond and then blending the conjugated CS with polyvinyl alcohol (PVA) nanofibres prior to electrospinning. PVA/LVF and PVA-CS/LVF nanofibres were fabricated as controls. The conjugated CS-LVF was characterized by FTIR, DSC, TGA and 1 H NMR. Scanning electron microscopy (SEM) showed that the blended CS-PVA nanofibres had a reduced fibre diameter compared to the controls. Drug release profiles showed that burst release was decreased from 90% in the control PVA/LVF electrospun mats to 27% in the PVA/conjugated CS-LVF mats after 8 h in phosphate buffer at 37 °C. This slower release is due to the cleavable bond between LVF and CS that slowly hydrolysed over time at neutral pH. The results indicate that conjugation of the drug to the polymer backbone is an effective way of minimizing burst release behaviour and achieving sustained release of the drug, LVF. - Highlights: • A novel drug delivery system for controlled release of drug was designed. • Composite PVA/conjugated CS-LVF nanofibres was fabricated by electrospinning. • Conjugated chitosan and composite nanofibres were characterized by various techniques. • Release profiles of drug were significantly improved in composite nanofibres containing drug conjugated chitosan.

Polyvinyl alcohol composite nanofibres containing conjugated levofloxacin-chitosan for controlled drug release

Energy Technology Data Exchange (ETDEWEB)

Jalvandi, Javid, E-mail: Javid.jlv@gmail.com [CSIRO, Manufacturing Flagship, Bayview Ave, Clayton, Victoria 3168 (Australia); School of Fashion and Textiles, College of Design and Social Context, RMIT University, 25 Dawson Street, Brunswick, Victoria 3056 (Australia); White, Max, E-mail: tamrak@bigpond.com [School of Fashion and Textiles, College of Design and Social Context, RMIT University, 25 Dawson Street, Brunswick, Victoria 3056 (Australia); Gao, Yuan, E-mail: Yuan.Gao@csiro.au [CSIRO, Manufacturing Flagship, Bayview Ave, Clayton, Victoria 3168 (Australia); Truong, Yen Bach, E-mail: Yen.truong@csiro.au [CSIRO, Manufacturing Flagship, Bayview Ave, Clayton, Victoria 3168 (Australia); Padhye, Rajiv, E-mail: rajiv.padhye@rmit.edu.au [School of Fashion and Textiles, College of Design and Social Context, RMIT University, 25 Dawson Street, Brunswick, Victoria 3056 (Australia); Kyratzis, Ilias Louis, E-mail: Louis.kyratzis@csiro.au [CSIRO, Manufacturing Flagship, Bayview Ave, Clayton, Victoria 3168 (Australia)

2017-04-01

A range of biodegradable drug-nanofibres composite mats have been reported as drug delivery systems. However, their main disadvantage is the rapid release of the drug immediately after application. This paper reports an improved system based on the incorporation of drug conjugated-chitosan into polyvinyl alcohol (PVA) nanofibers. The results showed that controlled release of levofloxacin (LVF) could be achieved by covalently binding LVF to low molecular weight chitosan (CS) via a cleavable amide bond and then blending the conjugated CS with polyvinyl alcohol (PVA) nanofibres prior to electrospinning. PVA/LVF and PVA-CS/LVF nanofibres were fabricated as controls. The conjugated CS-LVF was characterized by FTIR, DSC, TGA and {sup 1}H NMR. Scanning electron microscopy (SEM) showed that the blended CS-PVA nanofibres had a reduced fibre diameter compared to the controls. Drug release profiles showed that burst release was decreased from 90% in the control PVA/LVF electrospun mats to 27% in the PVA/conjugated CS-LVF mats after 8 h in phosphate buffer at 37 °C. This slower release is due to the cleavable bond between LVF and CS that slowly hydrolysed over time at neutral pH. The results indicate that conjugation of the drug to the polymer backbone is an effective way of minimizing burst release behaviour and achieving sustained release of the drug, LVF. - Highlights: • A novel drug delivery system for controlled release of drug was designed. • Composite PVA/conjugated CS-LVF nanofibres was fabricated by electrospinning. • Conjugated chitosan and composite nanofibres were characterized by various techniques. • Release profiles of drug were significantly improved in composite nanofibres containing drug conjugated chitosan.

Ultrasound enhanced release of therapeutics from drug-releasing implants based on titania nanotube arrays.

Science.gov (United States)

Aw, Moom Sinn; Losic, Dusan

2013-02-25

A non-invasive and external stimulus-driven local drug delivery system (DDS) based on titania nanotube (TNT) arrays loaded with drug encapsulated polymeric micelles as drug carriers and ultrasound generator is described. Ultrasound waves (USW) generated by a pulsating sonication probe (Sonotrode) in phosphate buffered saline (PBS) at pH 7.2 as the medium for transmitting pressure waves, were used to release drug-loaded nano-carriers from the TNT arrays. It was demonstrated that a very rapid release in pulsatile mode can be achieved, controlled by several parameters on the ultrasonic generator. This includes pulse length, time, amplitude and power intensity. By optimization of these parameters, an immediate drug-micelles release of 100% that spans a desirable time of 5-50 min was achieved. It was shown that stimulated release can be generated and reproduced at any time throughout the TNT-Ti implant life, suggesting considerable potential of this approach as a feasible and tunable ultrasound-mediated drug delivery system in situ via drug-releasing implants. It is expected that this concept can be translated from an in vitro to in vivo regime for therapeutic applications using drug-releasing implants in orthopedic and coronary stents. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Controlled drug release from bifunctionalized mesoporous silica

Science.gov (United States)

Xu, Wujun; Gao, Qiang; Xu, Yao; Wu, Dong; Sun, Yuhan; Shen, Wanling; Deng, Feng

2008-10-01

Serial of trimethylsilyl-carboxyl bifunctionalized SBA-15 (TMS/COOH/SBA-15) have been studied as carriers for controlled release of drug famotidine (Famo). To load Famo with large capacity, SBA-15 with high content of carboxyl groups was successfully synthesized by one-pot synthesis under the assistance of KCl. The mesostructure of carboxyl functionalized SBA-15 (COOH/SBA-15) could still be kept even though the content of carboxyl groups was up to 57.2%. Increasing carboxyl content could effectively enhance the loading capacity of Famo. Compared with pure SBA-15, into which Famo could be hardly adsorbed, the largest drug loading capacity of COOH/SBA-15 could achieve 396.9 mg/g. The release of Famo from mesoporous silica was studied in simulated intestine fluid (SIF, pH=7.4). For COOH/SBA-15, the release rate of Famo decreased with narrowing pore size. After grafting TMS groups on the surface of COOH/SBA-15 with hexamethyldisilazane, the release of Famo was greatly delayed with the increasing content of TMS groups.

Controlled antiseptic release by alginate polymer films and beads.

Science.gov (United States)

Liakos, Ioannis; Rizzello, Loris; Bayer, Ilker S; Pompa, Pier Paolo; Cingolani, Roberto; Athanassiou, Athanassia

2013-01-30

Biodegradable polymeric materials based on blending aqueous dispersions of natural polymer sodium alginate (NaAlg) and povidone iodine (PVPI) complex, which allow controlled antiseptic release, are presented. The developed materials are either free standing NaAlg films or Ca(2+)-cross-linked alginate beads, which properly combined with PVPI demonstrate antibacterial and antifungal activity, suitable for therapeutic applications, such as wound dressing. Glycerol was used as the plasticizing agent. Film morphology was studied by optical and atomic force microscopy. It was found that PVPI complex forms well dispersed circular micro-domains within the NaAlg matrix. The beads were fabricated by drop-wise immersion of NaAlg/PVPI/glycerol solutions into aqueous calcium chloride solutions to form calcium alginate beads encapsulating PVPI solution (CaAlg/PVPI). Controlled release of PVPI was possible when the composite films and beads were brought into direct contact with water or with moist media. Bactericidal and fungicidal properties of the materials were tested against Escherichia coli bacteria and Candida albicans fungi. The results indicated very efficient antibacterial and antifungal activity within 48 h. Controlled release of PVPI into open wounds is highly desired in clinical applications to avoid toxic doses of iodine absorption by the wound. A wide variety of applications are envisioned such as external and internal wound dressings with controlled antiseptic release, hygienic and protective packaging films for medical devices, and polymer beads as water disinfectants. Copyright © 2012 Elsevier Ltd. All rights reserved.

HABIT, Toxic and Radioactive Release Hazards in Reactor Control Room

International Nuclear Information System (INIS)

Stage, S.A.

2005-01-01

1 - Description of program or function: HABIT is a package of computer codes designed to be used for the evaluation of control room habitability in the event of an accidental release of toxic chemicals or radioactive materials. 2 - Methods: Given information about the design of a nuclear power plant, a scenario for the release of toxic or radionuclides, and information about the air flows and protection systems of the control room, HABIT can be used to estimate the chemical exposure or radiological dose to control room personnel

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.

Stimuli responsive nanomaterials for controlled release applications

KAUST Repository

Li, Song; Li, Wengang; Khashab, Niveen M.

2012-01-01

applications. Stimuli-responsive nanomaterials guarantee the controlled release of cargo to a given location, at a specific time, and with an accurate amount. In this review, we have combined the major stimuli that are currently used to achieve the ultimate

Controlled release of 18-β-glycyrrhetic acid by nanodelivery systems increases cytotoxicity on oral carcinoma cell line

Science.gov (United States)

Cacciotti, Ilaria; Chronopoulou, Laura; Palocci, Cleofe; Amalfitano, Adriana; Cantiani, Monica; Cordaro, Massimo; Lajolo, Carlo; Callà, Cinzia; Boninsegna, Alma; Lucchetti, Donatella; Gallenzi, Patrizia; Sgambato, Alessandro; Nocca, Giuseppina; Arcovito, Alessandro

2018-07-01

The topical treatment for oral mucosal diseases is often based on products optimized for dermatologic applications; consequently, a lower therapeutic effect may be present. 18-β-glycyrrhetic acid (GA) is extracted from Glycirrhiza glabra. The first aim of this study was to test the cytotoxicity of GA on PE/CA-PJ15 cells. The second aim was to propose and test two different delivery systems, i.e. nanoparticles and fibers, to guarantee a controlled release of GA in vitro. We used chitosan and poly(lactic-co-glycolic) acid based nanoparticles and polylactic acid fibers. We tested both delivery systems in vitro on PE/CA-PJ15 cells and on normal human gingival fibroblasts (HGFs). The morphology of GA-loaded nanoparticles (GA-NPs) and fibers (GA-FBs) was investigated by electron microscopy and dynamic light scattering; GA release kinetics was studied spectrophotometrically. MTT test was used to assess GA cytotoxicity on both cancer and normal cells. Cells were exposed to different concentrations of GA (20–500 μmol l‑1) administered as free GA (GA-f), and to GA-NPs or GA-FBs. ROS production was evaluated using dichlorodihydrofluorescein as a fluorescent probe. Regarding the cytotoxic effect of GA on PE/CA-PJ15 cells, the lowest TC50 value was 200 μmol l‑1 when GA was added as GA-NPs. No cytotoxic effects were observed when GA was administered to HGFs. N-acetyl Cysteine reduced mortality induced by GA-f in PE/CA-PJ15 cells. The specific effect of GA on PE/CA-PJ15 cells is mainly due to the different sensitivity of cancer cells to ROS over-production; GA-NPs and GA-FBs formulations increase, in vitro, this toxic effect on oral cancer cells.

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

Science.gov (United States)

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

2017-10-01

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

Design and in vivo evaluation of oxycodone once-a-day controlled-release tablets

Directory of Open Access Journals (Sweden)

Kim JY

2015-01-01

Full Text Available Ju-Young Kim,1,* Sung-Hoon Lee,2,3,* Chun-Woong Park,4 Yun-Seok Rhee,5 Dong-Wook Kim,6 Junsang Park,3 Moonseok Lee,3 Jeong-Woong Seo,2 Eun-Seok Park2 1College of Pharmacy, Woosuk University, Wanju-gun, Republic of Korea; 2School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea; 3GL Pharmtech, Seongnam, Republic of Korea; 4College of Pharmacy, Chungbuk National University, Cheongju, Republic of Korea; 5College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju, Republic of Korea; 6Department of Pharmaceutical Engineering, Cheongju University, Cheongju, Republic of Korea *These authors contributed equally to this work Abstract: The aim of present study was to design oxycodone once-a-day controlled-release (CR tablets and to perform in vitro/in vivo characterizations. Release profiles to achieve desired plasma concentration versus time curves were established by using simulation software and reported pharmacokinetic parameters of the drug. Hydroxypropyl methylcellulose (HPMC 100,000 mPa·s was used as a release modifier because the polymer was found to be resistant to changes in conditions of the release study, including rotation speed of paddle and ion strength. The burst release of the drug from the CR tablets could be suppressed by applying an additional HPMC layer as a physical barrier. Finally, the oxycodone once-a-day tablet was comprised of two layers, an inert HPMC layer and a CR layer containing drug and HPMC. Commercial products, either 10 mg bis in die (bid [twice a day] or once-a-day CR tablets (20 mg were administered to healthy volunteers, and calculated pharmacokinetic parameters indicated bioequivalence of the two different treatments. The findings of the present study emphasize the potential of oxycodone once-a-day CR tablets for improved patient compliance, safety, and efficacy, which could help researchers to develop new CR dosage forms of oxycodone. Keywords

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

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

Science.gov (United States)

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

2014-09-01

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

One-pot synthesis of redox-responsive polymers-coated mesoporous silica nanoparticles and their controlled drug release.

Science.gov (United States)

Sun, Jiao-Tong; Piao, Ji-Gang; Wang, Long-Hai; Javed, Mohsin; Hong, Chun-Yan; Pan, Cai-Yuan

2013-09-01

A versatile one-pot strategy for the preparation of reversibly cross-linked polymer-coated mesoporous silica nanoparticles (MSNs) via surface reversible addition-fragmentation chain transfer (RAFT) polymerization is presented for the first time in this paper. The less reactive monomer oligo(ethylene glycol) acrylate (OEGA) and the more reactive cross-linker N,N'-cystaminebismethacrylamide (CBMA) are chosen to be copolymerized on the external surfaces of RAFT agent-functionalized MSNs to form the cross-linked polymer shells. Owing to the reversible cleavage and restoration of disulfide bonds via reduction/oxidation reactions, the polymer shells can control the on/off switching of the nanopores and regulate the drug loading and release. The redox-responsive release of doxorubicin (DOX) from this drug carrier is realized. The protein adsorption, in vitro cytotoxicity assays, and endocytosis studies demonstrate that this biocompatible vehicle is a potential candidate for delivering drugs. It is expected that this versatile grafting strategy may help fabricate satisfying MSN-based drug delivery systems for clinical application. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Magnetic molecularly imprinted polymer for aspirin recognition and controlled release

Energy Technology Data Exchange (ETDEWEB)

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

2009-04-22

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

Magnetic molecularly imprinted polymer for aspirin recognition and controlled release

International Nuclear Information System (INIS)

Kan Xianwen; Geng Zhirong; Zhao Yao; Wang Zhilin; Zhu Junjie

2009-01-01

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

Lactobacillus GG has in vitro effects on enhanced interleukin-10 and interferon-gamma release of mononuclear cells but no in vivo effects in supplemented mothers and their neonates.

Science.gov (United States)

Kopp, M V; Goldstein, M; Dietschek, A; Sofke, J; Heinzmann, A; Urbanek, R

2008-04-01

The value of probiotics for primary prevention is controversial. Moreover, only little is known about the underlying immunological mechanisms of action. Therefore, we assessed the proliferative response and cytokine release in cultures of isolated mononuclear cells from pregnant women and their neonates supplemented with Lactobacillus GG (LGG) or placebo. In a double-blind, placebo-controlled prospective trial, pregnant women with at least one first-degree relative or a partner with an atopic disease were randomly assigned to receive either the probiotic LGG (ATCC 53103; 5 x 10(9) colony-forming units LGG twice daily) or placebo 4-6 weeks before expected delivery, followed by a post-natal period of 6 months. Cord blood mononuclear cells (CBMC) and peripheral blood mononuclear cells (PBMC) of the corresponding mother were isolated from cord blood and peripheral blood (n=68). The proliferative response of CBMC and PBMC was expressed as the stimulation index (SI), which was calculated according to the ratio between the mean counts per minute (c.p.m.) values measured in the wells with stimulated cells and the mean c.p.m. values measured in the wells with unstimulated cells. Additionally, the cytokines IFN-gamma, IL-10 and IL-13 in the cell culture supernatants were measured using the ELISA technique. No difference was observed between the LGG-supplemented group and the placebo group in terms of the proliferative capacity of maternal or neonatal cord blood cells in response to IL-2, beta-lactoglobulin or LGG. In vitro stimulation with LGG resulted in significantly enhanced release of IL-10 and IFN-gamma, compared with cytokine release in unstimulated controls. However, this phenomenon was observed in supernatants of maternal and neonatal MC in both groups, independent of prior supplementation with LGG. LGG has in vitro effects on enhanced IL-10 and IFN-gamma release of mononuclear cells. However, supplementation with LGG during pregnancy did not alter the proliferative

Design and evaluation of lornoxicam bilayered tablets for biphasic release

Directory of Open Access Journals (Sweden)

Songa Ambedkar Sunil

2012-12-01

Full Text Available The objective of the present investigation was to develop bilayered tablets of lornoxicam to achieve biphasic release pattern. A bilayered tablet, consisting of an immediate and controlled release layer, was prepared by direct compression technique. The controlled release effect was achieved by using various hydrophilic natural, semi synthetic and synthetic controlled release polymers such as xanthan gum, hydroxypropyl methylcellulose (HPMC and polyethylene oxide (PEO to modulate the release of the drug. The in vitro drug release profiles showed the biphasic release behavior in which the immediate release (IR layer containing the lornoxicam was released within 15 minutes, whereas the controlled release (CR layer controlled the drug release for up to 24 h. All the bilayered tablets formulated have followed the zero order release with non-Fickian diffusion controlled release mechanism after the initial burst release. FTIR studies revealed that there was no interaction between the drug and polymers used in the study. Statistical analysis (ANOVA showed no significant difference in the cumulative amount of drug release after 15 min, but significant difference (p O objetivo do presente trabalho foi desenvolver comprimidos bicamada de lornoxicam para atingir padrão de liberação bifásica. Preparou-se, por compressão direta, comprimido bicamada, consistindo de uma camada de liberação imediata e uma de liberação controlada. A liberação controlada foi obtida pelo uso de vários polímeros naturais hidrofílicos, semi-sintéticos e sintéticos, tais como goma xantana, hidroxipropilmetil celulose (HPMC e óxido de polietileno (PEO para modular a liberação do fármaco. Os perfis de liberação in vitro mostraram comportamento bifásico em que a camada de liberação imediata (IR contendo lornoxicam foi liberada em 15 minutos, enquanto a camada de liberação controlada (CR liberou o fármaco em mais de 24 horas, Todos os comprimidos bicamada

Optimization of matrix tablets controlled drug release using Elman dynamic neural networks and decision trees.

Science.gov (United States)

Petrović, Jelena; Ibrić, Svetlana; Betz, Gabriele; Đurić, Zorica

2012-05-30

The main objective of the study was to develop artificial intelligence methods for optimization of drug release from matrix tablets regardless of the matrix type. Static and dynamic artificial neural networks of the same topology were developed to model dissolution profiles of different matrix tablets types (hydrophilic/lipid) using formulation composition, compression force used for tableting and tablets porosity and tensile strength as input data. Potential application of decision trees in discovering knowledge from experimental data was also investigated. Polyethylene oxide polymer and glyceryl palmitostearate were used as matrix forming materials for hydrophilic and lipid matrix tablets, respectively whereas selected model drugs were diclofenac sodium and caffeine. Matrix tablets were prepared by direct compression method and tested for in vitro dissolution profiles. Optimization of static and dynamic neural networks used for modeling of drug release was performed using Monte Carlo simulations or genetic algorithms optimizer. Decision trees were constructed following discretization of data. Calculated difference (f(1)) and similarity (f(2)) factors for predicted and experimentally obtained dissolution profiles of test matrix tablets formulations indicate that Elman dynamic neural networks as well as decision trees are capable of accurate predictions of both hydrophilic and lipid matrix tablets dissolution profiles. Elman neural networks were compared to most frequently used static network, Multi-layered perceptron, and superiority of Elman networks have been demonstrated. Developed methods allow simple, yet very precise way of drug release predictions for both hydrophilic and lipid matrix tablets having controlled drug release. Copyright © 2012 Elsevier B.V. All rights reserved.

FERLENT - a controlled release fertilizer produced from a polymer material

International Nuclear Information System (INIS)

Gonzalez, Mayra; Arces, Milagros; Cuesta, Ernesto; Corredera, Pilar; Sardina, Carmen; Rieumont, Jacques; Quintana, Patricia; Bartolo, Pascual; Guenther, Bluma

2011-01-01

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

Synthesis, characterization and in vitro cytotoxicity analysis of a novel cellulose based drug carrier for the controlled delivery of 5-fluorouracil, an anticancer drug

Science.gov (United States)

Anirudhan, Thayyath S.; Nima, Jayachandran; Divya, Peethambaran L.

2015-11-01

The present investigation concerns the development and evaluation of a novel drug delivery system, aminated-glycidylmethacrylate grafted cellulose-grafted polymethacrylic acid-succinyl cyclodextrin (Cell-g-(GMA/en)-PMA-SCD) for the controlled release of 5-Fluorouracil, an anticancer drug. The prepared drug carrier was characterized by FT-IR, XRD and SEM techniques. Binding kinetics and isotherm studies of 5-FU onto Cell-g-(GMA/en)-PMA-SCD were found to follow pseudo-second-order and Langmuir model respectively. Maximum binding capacity of drug carrier was found to be 149.09 mg g-1 at 37 °C. Swelling studies, in vitro release kinetics, drug loading efficiency and encapsulation efficiency of Cell-g-(GMA/en)-PMA-SCD were studied. The release kinetics was analyzed using Ritger-Peppas equation at pH 7.4. Cytotoxicity analysis on MCF-7 (human breast carcinoma) cells indicated that the drug carrier shows sustained and controlled release of drug to the target site. Hence, it is evident from this investigation that Cell-g-(GMA/en)-PMA-SCD could be a promising carrier for 5-FU.

Application of tumbling melt granulation (TMG) method to prepare controlled-release fine granules.

Science.gov (United States)

Maejima, T; Kubo, M; Osawa, T; Nakajima, K; Kobayashi, M

1998-03-01

The tumbling melt granulation (TMG) method was applied to prepare controlled-release fine granules of diltiazem hydrochloride (DH). The entire process, from the preparation of the cores by the adherence of DH to the sucrose crystal to the subsequent coating of the controlled-release layer, was performed without using any solvent. A mixture of meltable material, talc, and ethylcellulose was used for the controlled-release layer and controlled-release fine granules approximately 400 microns in diameter were obtained with excellent producibility. The dissolution rate of DH from these fine granules was similar to that of a once-a-day dosage form obtained in the market; further, the dependency of the dissolution profile on pH of the media was less. Thus, it was concluded that this TMG method was very useful for preparing not only controlled-release beads of granule size (usually 500 to 1400 microns) but also fine granules.

Bioadhesive Controlled Release Clotrimazole Vaginal Tablets | Bhat ...

African Journals Online (AJOL)

Conclusion: This study indicates the possible use of suitable mixtures of natural and semi-synthetic cellulosic polymers for the preparation of clotrimazole mucoadhesive tablets for application as a vaginal controlled delivery system. Keywords: Clotrimazole, Swelling, Cellulosic polymers, Guar gum, Bioadhesion, Release ...

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

Science.gov (United States)

Siddique, Sabahuddin; Khanam, Jasmina; Bigoniya, Papiya

2010-09-01

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

Molecular weight-dependent degradation and drug release of surface-eroding poly(ethylene carbonate)

DEFF Research Database (Denmark)

Bohr, Adam; Wang, Yingya; Harmankaya, Necati

2017-01-01

.7 macrophages) and in vivo (subcutaneous implantation in rats). All investigated samples degraded by means of surface erosion (mass loss, but constant molecular weight), which was accompanied by a predictable, erosion-controlled drug release pattern. Accordingly, the obtained in vitro degradation half......Poly(ethylene carbonate) (PEC) is a unique biomaterial showing significant potential for controlled drug delivery applications. The current study investigated the impact of the molecular weight on the biological performance of drug-loaded PEC films. Following the preparation and thorough...... to control the spatial and temporal on-demand degradation and drug release from the employed delivery system....

Control of accidental releases of hydrogen selenide in vented storage cabinets

Science.gov (United States)

Fthenakis, V. M.; Moskowitz, P. D.; Sproull, R. D.

1988-07-01

Highly toxic hydrogen selenide and hydrogen sulfide gases are used in the production of copper-indium-diselenide photovoltaic cells by reactive sputtering. In the event of an accident, these gases may be released to the atmosphere and pose hazards to public and occupational safety and health. This paper outlines an approach for designing systems for the control of these releases given the uncertainty in release conditions and lack of data on the chemical systems involved. Accidental releases of these gases in storage cabinets can be controlled by either a venturi and packed-bed scrubber and carbon adsorption bed, or containment scrubbing equipment followed by carbon adsorption. These systems can effectively reduce toxic gas emissions to levels needed to protect public health. The costs of these controls (˜0.012/Wp) are samll in comparison with current (˜6/Wp) and projected (˜I/Wp) production costs.

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

Organosilane functionalization of halloysite nanotubes for enhanced loading and controlled release

International Nuclear Information System (INIS)

Yuan Peng; Southon, Peter D; Kepert, Cameron J; Liu Zongwen

2012-01-01

The surfaces of naturally occurring halloysite nanotubes were functionalized with γ-aminopropyltriethoxysilane (APTES), which was found to have a substantial effect on the loading and subsequent release of a model dye molecule. APTES was mostly anchored at the internal lumen surface of halloysite through covalent grafting, forming a functionalized surface covered by aminopropyl groups. The dye loading of the functionalized halloysite was 32% greater than that of the unmodified sample, and the release from the functionalized halloysite was dramatically prolonged as compared to that from the unmodified one. Dye release was prolonged at low pH and the release at pH 3.5 was approximately three times slower than that at pH 10.0. These results demonstrate that organosilane functionalization makes pH an external trigger for controlling the loading of guest on halloysite and the subsequent controlled release. (paper)

Organosilane functionalization of halloysite nanotubes for enhanced loading and controlled release.

Science.gov (United States)

Yuan, Peng; Southon, Peter D; Liu, Zongwen; Kepert, Cameron J

2012-09-21

The surfaces of naturally occurring halloysite nanotubes were functionalized with γ-aminopropyltriethoxysilane (APTES), which was found to have a substantial effect on the loading and subsequent release of a model dye molecule. APTES was mostly anchored at the internal lumen surface of halloysite through covalent grafting, forming a functionalized surface covered by aminopropyl groups. The dye loading of the functionalized halloysite was 32% greater than that of the unmodified sample, and the release from the functionalized halloysite was dramatically prolonged as compared to that from the unmodified one. Dye release was prolonged at low pH and the release at pH 3.5 was approximately three times slower than that at pH 10.0. These results demonstrate that organosilane functionalization makes pH an external trigger for controlling the loading of guest on halloysite and the subsequent controlled release.

Preparation of Starch/Gelatin Blend Microparticles by a Water-in-Oil Emulsion Method for Controlled Release Drug Delivery.

Science.gov (United States)

Phromsopha, Theeraphol; Baimark, Yodthong

2014-01-01

Information on the preparation and properties of starch/gelatin blend microparticles with and without crosslinking for drug delivery is presented. The blend microparticles were prepared by the water-in-oil emulsion solvent diffusion method. Glutaraldehyde and methylene blue were used as the crosslinker and the water-soluble drug model, respectively. The blend microparticles were characterized by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, and UV-Vis spectroscopy. The functional groups of the starch and gelatin blend matrices were determined from the FTIR spectra. Blend microparticles with a nearly spherical shape and internal porous structure were observed from SEM images. The average particle size of the gelatin microparticles depended on the crosslinker ratio but not on the starch/gelatin blend ratio. The in vitro drug release content significantly decreased as the crosslinker ratio increased and the starch blend ratio decreased. The results demonstrated that the starch/gelatin blend microparticles should be a useful controlled release delivery carrier for water-soluble drugs.

Effect of Nisin's Controlled Release on Microbial Growth as Modeled for Micrococcus luteus.

Science.gov (United States)

Balasubramanian, Aishwarya; Lee, Dong Sun; Chikindas, Michael L; Yam, Kit L

2011-06-01

The need for safe food products has motivated food scientists and industry to find novel technologies for antimicrobial delivery for improving food safety and quality. Controlled release packaging is a novel technology that uses the package to deliver antimicrobials in a controlled manner and sustain antimicrobial stress on the targeted microorganism over the required shelf life. This work studied the effect of controlled release of nisin to inhibit growth of Micrococcus luteus (a model microorganism) using a computerized syringe pump system to mimic the release of nisin from packaging films which was characterized by an initially fast rate and a slower rate as time progressed. The results show that controlled release of nisin was strikingly more effective than instantly added ("formulated") nisin. While instant addition experiments achieved microbial inhibition only at the beginning, controlled release experiments achieved complete microbial inhibition for a longer time, even when as little as 15% of the amount of nisin was used as compared to instant addition.

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

Science.gov (United States)

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

2014-04-01

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

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

Science.gov (United States)

Tiwari, S; Nandlal, B

2013-01-01

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

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

Science.gov (United States)

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

2016-01-01

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

Comparative evaluation of fluoride release and recharge of pre-reacted glass ionomer composite and nano-ionomeric glass ionomer with daily fluoride exposure: An in vitro study

Directory of Open Access Journals (Sweden)

Jayanthi Mungara

2013-01-01

Full Text Available Aim: This in vitro study was designed to investigate the effects of daily fluoride exposures on fluoride release and recharge by prereacted glass ionomer (PRG composite and nano-ionomeric glass ionomer. Materials and Methods: Seventy-two specimens (36 of each material were prepared and by placing the restorative materials into Teflon mold. Each specimen was subjected to one of three daily treatments (n = 12: (1 No fluoride treatment (control; (2 application of a fluoride dentifrice (1,000 ppm once daily; and (3 the same regimen as (2, plus immersion in a 0.05% sodium fluoride (NaF mouth rinse (225 ppm immediately following the dentifrice application. Specimens were suspended in a storage vial containing 10 ml demineralizing solution for 6 h and transferred to a new test tube containing 10 ml remineralizing solution for 18 h. Fluoride treatments of the specimens were completed every day prior to their immersion in the demineralizing solution. Media solutions were buffered with equal volumes of total ionic strength adjustment buffer (TISAB II; fluoride levels were measured using a digital ion analyzer and fluoride electrode throughout the 21 day duration of the experiment. Results: Nano-ionomeric glass ionomer showed a better amount of fluoride release than PRG composite irrespective of the fluoride treatment supplementation (P < 0.01. Additional fluoride supplementation improved fluoride release and recharge ability for both the materials when compared to their respective control groups. The fluoride recharge for both materials did not show any sustained pattern of release. Conclusion: Nano-ionomeric glass ionomer demonstrated a greater ability to release and recharge compared with that of PRG composite.

Method and apparatus for controlling accidental releases of tritium

International Nuclear Information System (INIS)

Galloway, T.R.

1980-01-01

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

Method and apparatus for controlling accidental releases of tritium

Science.gov (United States)

Galloway, Terry R. [Berkeley, CA

1980-04-01

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

[Anti-tumor effects of DDP-PLLA-CNTs on human cholangiocarcinoma cell line in vitro].

Science.gov (United States)

Li, Maolan; Lu, Wei; Zhang, Fei; Ding, Qichen; Wu, Xiangsong; Tan, Zhujun; Wu, Wenguang; Weng, Hao; Wang, Xuefeng; Shi, Weibin; Dong, Ping; Gu, Jun; Liu, Yingbin

2014-11-04

To explore the antitumor effects of DDP-PLLA-CNTs on human cholangiocarcinoma cell line. DDP-PLLA-CNTs were prepared with the method of ultrasound emulsification. The morphology of DDP-PLLA-CNTs was determined by scanning electron microscope (SEM). And its drug loading and drug release curve in vitro was detected by UV-Vis-NIR spectrophotometer. CCK8 was used to test the cytotoxic effects of DDP-PLLA-CNTs at different concentrations on QBC939 cell proliferation.Flow cytometry was employed to measure the changes of apoptotic rate. With excellent controlled-release characteristic of in vitro drug release, DDP-PLLA-CNTs inhibited the proliferation and significantly increased the apoptotic rate of QBC939 cell line. DDP-PLLA-CNTs have drug sustained-release characteristics and can significantly inhibit the proliferation of QBC939 cell line.

Microfluidic synthesis of microfibers for magnetic-responsive controlled drug release and cell culture.

Directory of Open Access Journals (Sweden)

Yung-Sheng Lin

Full Text Available This study demonstrated the fabrication of alginate microfibers using a modular microfluidic system for magnetic-responsive controlled drug release and cell culture. A novel two-dimensional fluid-focusing technique with multi-inlets and junctions was used to spatiotemporally control the continuous laminar flow of alginate solutions. The diameter of the manufactured microfibers, which ranged from 211 µm to 364 µm, could be well controlled by changing the flow rate of the continuous phase. While the model drug, diclofenac, was encapsulated into microfibers, the drug release profile exhibited the characteristic of a proper and steady release. Furthermore, the diclofenac release kinetics from the magnetic iron oxide-loaded microfibers could be controlled externally, allowing for a rapid drug release by applying a magnetic force. In addition, the successful culture of glioblastoma multiforme cells in the microfibers demonstrated a good structural integrity and environment to grow cells that could be applied in drug screening for targeting cancer cells. The proposed microfluidic system has the advantages of ease of fabrication, simplicity, and a fast and low-cost process that is capable of generating functional microfibers with the potential for biomedical applications, such as drug controlled release and cell culture.

Blood histamine release: A new allergy blood test

International Nuclear Information System (INIS)

Faraj, B.A.; Gottlieb, G.R.; Camp, V.M.; Lollies, P.

1985-01-01

Allergen-mediated histamine release from human leukocytes represents an important model for in vitro studies of allergic reactions. The purpose of this study was to determine whether the measurement of histamine released in allergic patients (pts) by radioenzymatic assay following mixing of their blood with common allergens represents a reliable index for diagnosis of atopic allergy. Three categories of allergies were used: (1) housedust and mite; (2) cat and dog dander; (3) trees and grasses and ragweed mixture. The presence of allergy was established by intradermal skin testing in the study group of 82 pts. Significant atopy was defined as ≥ 3+ (overall range 0-4 +, negative to maximum) on skin testing. The test was carried out in tubes with 0.5 ml heparinized blood, 0.5 ml tris albumin buffer, and one of the allergens (60-100 PNU/ml). In 20 controls without allergy, there always was ≤ 4% histamine release (normal response). A significant allergen-mediated histamine release, ranging from 12 to 30% of the total blood histamine content, was observed in 96% of the pts with skin test sensitivity of ≥ 3+. There was good agreement between skin testing and histamine release in terms of the allergen causing the response. Thus, measurement of histamine release in blood in response to allergen challenge represents a clinically useful in vitro test for the diagnosis of atopic allergy. Because data can be obtained from a single sample and are highly quantitative, this new method should have application to the longitudinal study of allergic pts and to the assessment of interventions

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

Directory of Open Access Journals (Sweden)

Nagalakshmi Kamaraj

2017-07-01

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

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

Directory of Open Access Journals (Sweden)

Wei Zhu

2016-01-01

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

POLYURETHANE COMPOSITES AS DRUG CARRIERS:: RELEASE PATTERNS

Directory of Open Access Journals (Sweden)

M. V. Grigoreva

2013-10-01

Full Text Available Biodegradable polyurethanes attract interest of those developing composite materials for biomedical applications. One of their features is their ability to serve as carriers, or matrixes, for medicines and other bioactive compounds to produce a therapeutic effect in body through targeted and/or prolonged delivery of these compounds in the process of their controlled release from matrix. The review presents polyurethane composites as matrices for a number of drugs. The relation between structure of the composites and their degradability both in vitro and in vivo and the dependence of drug release kinetics on physicochemical properties of polyurethane matrix are highlighted. The release of drugs (cefazolin, naltrexone and piroxicam from the composites based on cross-linked polyurethanes (synthesized from laprols, Mw between 1,500 and 2,000 Da and toluylene diisocyanate demonstrated more or less the same pattern (about 10 days in vitro and three to five days in vivo. In contrast, the composites with dioxydine based on a linear polyurethanes (synthesized from oligotetramethilene glycol, Mw 1,000 Da, diphenylmethane-4,4’-diisocyanate and 1,4-butanediol retained their antimicrobial activity at least 30 days. They also showed a significantly higher breaking strength as compared to that of the composites based on cross-linked polyurethanes.

A review of mathematical modeling and simulation of controlled-release fertilizers.

Science.gov (United States)

Irfan, Sayed Ameenuddin; Razali, Radzuan; KuShaari, KuZilati; Mansor, Nurlidia; Azeem, Babar; Ford Versypt, Ashlee N

2018-02-10

Nutrients released into soils from uncoated fertilizer granules are lost continuously due to volatilization, leaching, denitrification, and surface run-off. These issues have caused economic loss due to low nutrient absorption efficiency and environmental pollution due to hazardous emissions and water eutrophication. Controlled-release fertilizers (CRFs) can change the release kinetics of the fertilizer nutrients through an abatement strategy to offset these issues by providing the fertilizer content in synchrony with the metabolic needs of the plants. Parametric analysis of release characteristics of CRFs is of paramount importance for the design and development of new CRFs. However, the experimental approaches are not only time consuming, but they are also cumbersome and expensive. Scientists have introduced mathematical modeling techniques to predict the release of nutrients from the CRFs to elucidate fundamental understanding of the dynamics of the release processes and to design new CRFs in a shorter time and with relatively lower cost. This paper reviews and critically analyzes the latest developments in the mathematical modeling and simulation techniques that have been reported for the characteristics and mechanisms of nutrient release from CRFs. The scope of this review includes the modeling and simulations techniques used for coated, controlled-release fertilizers. Copyright © 2017 Elsevier B.V. All rights reserved.

Controlled release of agrochemicals intercalated into montmorillonite interlayer space.

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Wanyika, Harrison

2014-01-01

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

Drug Release Profile from Calcium-Induced Alginate-Phosphate Composite Gel Beads

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Yoshifumi Murata

2009-01-01

Full Text Available Calcium-induced alginate-phosphate composite gel beads were prepared, and model drug release profiles were investigated in vitro. The formation of calcium phosphate in the alginate gel matrix was observed and did not affect the rheological properties of the hydrogel beads. X-ray diffraction patterns showed that the calcium phosphate does not exist in crystalline form in the matrix. The initial release amount and release rate of a water-soluble drug, diclofenac, from the alginate gel beads could be controlled by modifying the composition of the matrix with calcium phosphate. In contrast, the release profile was not affected by the modification for hydrocortisone, a drug only slightly soluble in water.

Laser-activated nano-biomaterials for tissue repair and controlled drug release

International Nuclear Information System (INIS)

Matteini, P; Ratto, F; Rossi, F; Pini, R

2014-01-01

We present recent achievements of minimally invasive welding of biological tissue and controlled drug release based on laser-activated nano-biomaterials. In particular, we consider new advancements in the biomedical application of near-IR absorbing gold nano-chromophores as an original solution for the photothermal repair of surgical incisions and as nanotriggers of controlled drug release from hybrid biopolymer scaffolds. (laser biophotonics)

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

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S.M. Taghizadeh

2009-12-01

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

Fabrication and characterization of a rapid prototyped tissue engineering scaffold with embedded multicomponent matrix for controlled drug release

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Chen, Muwan; Le, Dang QS; Hein, San; Li, Pengcheng; Nygaard, Jens V; Kassem, Moustapha; Kjems, Jørgen; Besenbacher, Flemming; Bünger, Cody

2012-01-01

Bone tissue engineering implants with sustained local drug delivery provide an opportunity for better postoperative care for bone tumor patients because these implants offer sustained drug release at the tumor site and reduce systemic side effects. A rapid prototyped macroporous polycaprolactone scaffold was embedded with a porous matrix composed of chitosan, nanoclay, and β-tricalcium phosphate by freeze-drying. This composite scaffold was evaluated on its ability to deliver an anthracycline antibiotic and to promote formation of mineralized matrix in vitro. Scanning electronic microscopy, confocal imaging, and DNA quantification confirmed that immortalized human bone marrow-derived mesenchymal stem cells (hMSC-TERT) cultured in the scaffold showed high cell viability and growth, and good cell infiltration to the pores of the scaffold. Alkaline phosphatase activity and osteocalcin staining showed that the scaffold was osteoinductive. The drug-release kinetics was investigated by loading doxorubicin into the scaffold. The scaffolds comprising nanoclay released up to 45% of the drug for up to 2 months, while the scaffold without nanoclay released 95% of the drug within 4 days. Therefore, this scaffold can fulfill the requirements for both bone tissue engineering and local sustained release of an anticancer drug in vitro. These results suggest that the scaffold can be used clinically in reconstructive surgery after bone tumor resection. Moreover, by changing the composition and amount of individual components, the scaffold can find application in other tissue engineering areas that need local sustained release of drug. PMID:22904634

Alginate-polyvinyl alcohol based interpenetrating polymer network for prolonged drug therapy, Optimization and in-vitro characterization.

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Anwar, Hina; Ahmad, Mahmood; Minhas, Muhammad Usman; Rehmani, Sahrish

2017-06-15

A new natural and synthetic polymeric blend to form interpenetrating polymer network (IPN) hydrogels was synthesized utilizing sodium alginate and PVA as polymers by free radical polymerization employing 2-Acylamido-2-methylpropane-sulfonic acid as monomer (AMPS) and tramadol HCl as model drug through 3 2 level full factorial design to evaluate the impact of selected independent factors i.e. polymer (sodium alginate) and monomer (AMPS) contents on swelling index at 18th hour, percent drug release at 18th hour, time required for 80% drug release and drug entrapment efficiency as dependent variables. FTIR, SEM, sol-gel analysis, equilibrium swelling studies and in-vitro release kinetics were performedfor in-vitro characterization of formulated IPN hydrogels. In-vitro studies carried out at pH 1.2 and pH 7.4 revealed pH independent swelling and drug release from polymeric IPN, providing controlled drug release for an extended period of time with improved entrapment efficiency, thereby concluding that this polymeric blend may be a promising system for the prolonged drug delivery. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mesoporous hydroxyapatite: Preparation, drug adsorption, and release properties

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Gu, Lina; He, Xiaomei; Wu, Zhenyu, E-mail: zhenyuwuhn@sina.com

2014-11-14

Mesoporous hydroxyapatite (HA) was synthesized through gas–liquid chemical precipitation method at ambient temperature without any template. Structure, morphology and pore size distribution of HA were analyzed via X-ray powder diffraction, scanning electron microscopy, transmission electron microscopy, high-resolution electron microscopy and N{sub 2} adsorption/desorption. The chemotherapeutic agent doxorubicin (DOX) was used to investigate the drug adsorption and release behavior of HA. The kinetics of DOX adsorption on HA followed the pseudo-second-order rate expression. Adsorption isotherms at various temperatures were obtained, and the equilibrium data fitted the Langmuir model. The values of thermodynamic parameters (Gibbs free energy, entropy, and enthalpy changes) demonstrated that the adsorption process was spontaneous and endothermic. In vitro pH-responsive (pH = 7.4, 5.8) controlled release was investigated. DOX-loaded HA showed a slow, long-term, and steady release rate. The release rate at pH5.8 was larger than that at pH7.4. Consequently, the as-prepared mesoporous HA has potential applications in controlled drug delivery systems. - Highlights: • Mesoporous HA was synthesized by a simple precipitation method without any template. • The kinetics of adsorption followed the pseudo-second-order rate expression. • Thermodynamics investigation showed that adsorption was spontaneous and endothermic. • DOX-loaded HA showed a long-term, steady, and pH-controlled release rate.

Controlled release and angiotensin-converting enzyme inhibition properties of an antihypertensive drug based on a perindopril erbumine-layered double hydroxide nanocomposite

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Hussein Al Ali SH

2012-04-01

Full Text Available Samer Hasan Hussein Al Ali1, Mothanna Al-Qubaisi2, Mohd Zobir Hussein1,3, Maznah Ismail2,4, Zulkarnain Zainal1, Muhammad Nazrul Hakim51Department of Chemistry, Faculty of Science, 2Laboratory of Molecular Biomedicine, Institute of Bioscience, 3Advanced Materials and Nanotechnology Laboratory, Institute of Advanced Technology, 4Department of Nutrition and Dietetics, Faculty of Medicine and Health Science, 5Department of Biomedical Science, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Serdang, Selangor, MalaysiaBackground: The intercalation of perindopril erbumine into Zn/Al-NO3-layered double hydroxide resulted in the formation of a host-guest type of material. By virtue of the ion-exchange properties of layered double hydroxide, perindopril erbumine was released in a sustained manner. Therefore, this intercalated material can be used as a controlled-release formulation.Results: Perindopril was intercalated into the interlayers and formed a well ordered, layered organic-inorganic nanocomposite. The basal spacing of the products was expanded to 21.7 Å and 19.9 Å by the ion-exchange and coprecipitation methods, respectively, in a bilayer and a monolayer arrangement, respectively. The release of perindopril from the nanocomposite synthesized by the coprecipitation method was slower than that of its counterpart synthesized by the ion-exchange method. The rate of release was governed by pseudo-second order kinetics. An in vitro antihypertensive assay showed that the intercalation process results in effectiveness similar to that of the antihypertensive properties of perindopril.Conclusion: Intercalated perindopril showed better thermal stability than its free counterpart. The resulting material showed sustained-release properties and can therefore be used as a controlled-release formulation.Keywords: perindopril erbumine, layered double hydroxides, ion-exchange, coprecipitation, sustained release, angiotensin-converting enzyme

Controlled release of ethylene via polymeric films for food packaging

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

2015-12-01

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

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

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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.

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

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Kipping, Thomas; Rein, Hubert

2016-01-30

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

Development and characterization of controlled release polar lipid microparticles of candesartan cilexetil by solid dispersion

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Kamalakkannan, V; Puratchikody, A; Ramanathan, L

2013-01-01

Candesartan cilexetil (CC) is a newer class of angiotensin II receptor antagonist used for the treatment of hypertension. The solubility of the CC is very poor and its oral bioavailability is only 15%. The controlledrelease polar lipid microparticles of CC (formulations F1, F2, F3 and F4) were prepared using variable erodible lipophilic excipients like hydrogenated castor oil, stearic acid, cetostearyl alcohol and carnauba wax by fusion method. The particle sizes of polar lipid microparticles were less than 50 microns and they were irregular in shape. Drug content ranged between 98.96 ± 2.1 and 101.9 ± 1.6% were present in all the formulations. The formulation F3 showed better drug release throughout the study period in a controlled release manner. Moreover, the in vitro release showed that all the formulations were best fitted to Higuchi model. Accelerated stability studies indicated that there was no significant changes in the chemical and physical characteristics of the formulated drug product during initial and at the end of the study period. The FTIR and DSC studies showed that there was no interaction between the drug and lipophilic excipients and no polymorphic transitions in all formulations. The X-ray diffraction peak of solid dispersion indicated that the crystalline nature of CC disappeared and no new peaks could be observed, suggesting the absence of interaction between drug and excipients. PMID:24019822

Formulation and characterization of modified release tablets containing isoniazid using swellable polymers.

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Akhtar, M F; Rabbani, M; Sharif, A; Akhtar, B; Saleem, A; Murtaza, G

2011-01-01

The aim of this work was to develop swellable modified release (MR) isoniazid tablets using different combinations of polyvinyl acetate (PVAc) and sodium-carboxymethylcellulose (Na-CMC). Granules were prepared by moist granulation technique and then compressed into tablets. In vitro release studies for 12 hr were carried out in dissolution media of varying pH i.e. pH 1.2, 4.5, 7.0 and 7.5. Tablets of all formulations were found to be of good physical quality with respect to appearance (width and thickness), content uniformity, hardness, weight variation and friability. In vitro release data showed that increasing total polymer content resulted in more retarding effect. Formulation with 35% polymer content exhibited zero order release profile and it released 35% of the drug in first hr, later on, controlled drug release was observed upto the 12(th) hour. Formulations with PVAc to Na-CMC ratio 20:80 exhibited zero order release pattern at levels of studied concentrations, which suggested that this combination can be used to formulate zero order release tablets of water soluble drugs like isoniazid. Korsmeyer-Peppas modeling of drug release showed that non-Fickian transport is the primary mechanism of isoniazid release from PVAc and Na-CMC based tablets. The value of mean dissolution time decreased with the increase in the release rate of drug clearly showing the retarding behavior of the swellable polymers. The application of a mixture of PVAc to Na-CMC in a specific ratio may be feasible to formulate zero order release tablets of water soluble drugs like isoniazid.

Electrochemically controlled release of anticancer drug methotrexate using nanostructured polypyrrole modified with cetylpyridinium: Release kinetics investigation

International Nuclear Information System (INIS)

Alizadeh, Naader; Shamaeli, Ehsan

2014-01-01

A new simple strategy for direct electrochemical incorporation of chemotherapeutic methotrexate (MTX) into conductive polypyrrole (PPy) has been suggested for an electrochemically controlled loading and release system. Electropolymerization of MTX doped polypyrrole yielded poor quality with low efficiency of doping, but a well-doped, nanostructure and increased capacity of drug loading (24.5 mg g −1 ) has been obtained in the presence of cetylpyridinium (CP) as a modifier. When CP was preloaded onto PPy, the hydrophobic surface of the PPy serves as a backbone to which the hydrophobic chain of the CP can be attached. Electrostatic interaction between cationic CP with anionic MTX and aromatic interaction between pyridinium head of CP with pyrimidine and pyrazine rings of MTX increases drug doping. Then release kinetics were investigated at various applied potentials and temperatures. Kinetics analysis based on Avrami's equation showed that the drug release was controlled and accelerated by increasing temperature and negative potential and sustained by increasing positive potential. At open circuit condition, the release parameter (n) represented a diffusive mechanism and at applying electrochemical potentials, a first-order mode. Activation energy parameters (E a , ΔG ≠ , ΔH ≠ and ΔS ≠ ) and half-life time (t 1/2 ) of drug release are also analyzed as a function of applied potential. The nanostructured polymer films (PPy/CP/MTX) were characterized by several techniques: scanning electron microscopy, Furrier transforms Infrared, UV-vis spectroscopy. Overall, our results demonstrate that the PPy/CP/MTX films, combined with electrical stimulation, permit a programmable release of MTX by altering the interaction strength between the PPy/CP and MTX

Modified n-HA/PA66 scaffolds with chitosan coating for bone tissue engineering: cell stimulation and drug release.

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Zou, Qin; Li, Junfeng; Niu, Lulu; Zuo, Yi; Li, Jidong; Li, Yubao

2017-09-01

The dipping-drying procedure and cross-linking method were used to make drug-loaded chitosan (CS) coating on nano-hydroxyapatite/polyamide66 (nHA/PA66) composite porous scaffold, endowing the scaffold controlled drug release functionality. The prefabricated scaffold was immersed into an aqueous drug/CS solution in a vacuum condition and then crosslinked by vanillin. The structure, porosity, composition, compressive strength, swelling ratio, drug release and cytocompatibility of the pristine and coating scaffolds were investigated. After coating, the scaffold porosity and pore interconnection were slightly decreased. Cytocompatibility performance was observed through an in vitro experiment based on cell attachment and the MTT assay by MG63 cells which revealed positive cell viability and increasing proliferation over the 11-day period in vitro. The drug could effectively release from the coated scaffold in a controlled fashion and the release rate was sustained for a long period and highly dependent on coating swelling, suggesting the possibility of a controlled drug release. Our results demonstrate that the scaffold with drug-loaded crosslinked CS coating can be used as a simple technique to render the surfaces of synthetic scaffolds active, thus enabling them to be a promising high performance biomaterial in bone tissue engineering.

Synthesis of pH-sensitive poly(β-amino ester)-coated mesoporous silica nanoparticles for the controlled release of drugs

Science.gov (United States)

Talavera-Pech, William A.; Esparza-Ruiz, Adriana; Quintana-Owen, Patricia; Vilchis-Nestor, Alfredo R.; Barrón-Zambrano, Jesus A.; Ávila-Ortega, Alejandro

2018-03-01

This report describes the synthesis of a controlled drug delivery system that was obtained by coating mesoporous silica nanoparticles (MSNs) with poly(β-amino ester) (PbAE), which is a solid and stable material at physiological pH, but is dissolved at acidic pH values, such as those in tumor tissues (from 5.0 to 6.5). To synthesize the system, PbAE chains were grafted onto amino-functionalized MSNs through a reaction between the surface amino groups of MSNs and the ends of acrylate chains of a PbAE. The system was physicochemically characterized by dynamic light scattering (DLS), Fourier transform infrared spectroscopy, transmission electron microscopy, thermogravimetric analysis, X-ray photoelectron spectrometry, and X-ray diffraction analyses. In addition, the in vitro release of doxorubicin (DOX) and doxycycline (DXY) in acidic and physiological media was evaluated. It was observed that the PbAE modification did not affect the mesoporous structure of MSNs. When the amount of 3-aminopropyltriethoxysilane was increased during functionalization, the amount of PbAE binding to MSNs increased as well. With respect to drug release, the sample with the highest amount of PbAE showed better control in the delivery of DXY and DOX in acidic media, because at pH 5.5, the release of both drugs was 40% higher than that at pH 7.4. These results reveal two aspects about the presence of PbAE in MSNs: PbAE does not affect the mesoporous structure of the nanoparticles, and PbAE is the main factor controlling the delivery of drugs in acidic media.

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

Science.gov (United States)

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

2016-12-01

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

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

Science.gov (United States)

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

2018-03-01

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

Materials for Pharmaceutical Dosage Forms: Molecular Pharmaceutics and Controlled Release Drug Delivery Aspects

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Patrick P. DeLuca

2010-09-01

Full Text Available Controlled release delivery is available for many routes of administration and offers many advantages (as microparticles and nanoparticles over immediate release delivery. These advantages include reduced dosing frequency, better therapeutic control, fewer side effects, and, consequently, these dosage forms are well accepted by patients. Advances in polymer material science, particle engineering design, manufacture, and nanotechnology have led the way to the introduction of several marketed controlled release products and several more are in pre-clinical and clinical development.

Multi-unit dosage formulations of theophylline for controlled release applications.

Science.gov (United States)

Uhumwangho, Michael U; Okor, Roland S

2007-01-01

The study was carried out to investigate the drug release profiles of multi-unit dosage formulations of theophylline consisting of both the fast and slow release components in a unit dose. The fast release component consisted of conventional granules of theophylline formed by mixing the drug powder with starch mucilage (20% w/v) while the slow release component consisted of wax granulations of theophylline formed by triturating the drug powder with a melted Carnauba wax (drug:wax ratio, 4:1). The granules were either filled into capsules or tabletted. In the study design, the drug release characteristics of the individual fast or slow release particles were first determined separately and then mixed in various proportions for the purpose of optimizing the drug release profiles. The evaluating parameters were the prompt release in the first 1 h (mp), the maximum release (m infinity) and the time to attain it (t infinity). Total drug content in each capsule or tablet was 300 mg and two of such were used in dissolution studies. The release kinetics and hence the release mechanism was confirmed by measuring the linear regression coefficient (R2 values) of the release data. The release kinetics was generally most consistent with the Higuchi square root of time relationship (R2 = 0.95). indicating a diffusion-controlled mechanism. The mp (mg) and t infinity (h) values for capsules and tablets of the conventional granules were (420 mg, 3 h) and (348 mg, 5 h), respectively, while for the capsules and tablets of the wax granulations mp and t infinity values were (228 mg, 9 h) and (156 mg, 12 h), respectively, indicating that a combination of wax granulation and tableting markedly retarded drug release. In the multi-unit dose formulations where the conventional and wax granulations were mixed in the ratios 2:1, 1:1 and 1:2 (conventional: matrix), the m infinity and t infinity values for the capsules were (378 mg, 6 h), (326 mg, 6 h) and (272 mg, 7 h), reSpectively. The

Development of controlled release silicone adhesive–based mupirocin patch demonstrates antibacterial activity on live rat skin against Staphylococcus aureus

Directory of Open Access Journals (Sweden)

David SR

2018-03-01

Full Text Available Sheba R David,1 Nurafiqah Malek,1 Abdul Hanif Mahadi,2 Srikumar Chakravarthi,3 Rajan Rajabalaya1 1PAPRSB Institute of Health Sciences, Universiti Brunei Darussalam, Bandar Seri Begawan, Brunei Darussalam; 2Centre for Advanced Material and Energy Sciences (CAMES, Universiti Brunei Darussalam, Bandar Seri Begawan, Brunei Darussalam; 3School of Medicine, Perdana University, Jalan MAEPS Perdana, Serdang, Selangor, Malaysia Background: Peritonitis is the most serious complication of peritoneal dialysis. Staphylococcus aureus infections could lead to peritonitis which causes reversal of peritoneal dialysis treatment back to hemodialysis. The aim of this study was to develop a controlled release silicone adhesive-based mupirocin patch for prophylactic effect and analyze its antibacterial effectiveness against S. aureus.Methods: The matrix patches were prepared by using different polymers, with and without silicone adhesive, dibutyl sebacate and mupirocin. The patches were characterized for mechanical properties, drug content, moisture content, water absorption capacity and Fourier transform infrared spectrum. In vitro release studies were performed by using Franz diffusion cell. In vitro disk diffusion assay was performed on the Mueller–Hinton Agar plate to measure the zone of inhibition of the patches. The in vivo study was performed on four groups of rats with bacterial counts at three different time intervals, along with skin irritancy and histopathologic studies. Results: The patches showed appropriate average thickness (0.63–1.12 mm, tensile strength (5.08–10.08 MPa and modulus of elasticity (21.53–42.19 MPa. The drug content ranged from 94.5% to 97.4%, while the moisture content and water absorption capacities at two relative humidities (75% and 93% were in the range of 1.082–3.139 and 1.287–4.148 wt%, respectively. Fourier transform infrared spectra showed that there were no significant interactions between the polymer and the drug

Meticulous Overview on the Controlled Release Fertilizers

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Siafu Ibahati Sempeho

2014-01-01

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

New trends in combined use of gonadotropin-releasing hormone antagonists with gonadotropins or pulsatile gonadotropin-releasing hormone in ovulation induction and assisted reproductive technologies.

Science.gov (United States)

Gordon, K; Danforth, D R; Williams, R F; Hodgen, G D

1992-10-01

The use of gonadotropin-releasing hormone agonists as adjunctive therapy with gonadotropins for ovulation induction in in vitro fertilization and other assisted reproductive technologies has become common clinical practice. With the recent advent of potent gonadotropin-releasing hormone antagonists free from the marked histamine-release effects that stymied earlier compounds, an attractive alternative method may be available. We have established the feasibility of combining gonadotropin-releasing hormone antagonist-induced inhibition of endogenous gonadotropins with exogenous gonadotropin therapy for ovulation induction in a nonhuman primate model. Here, the principal benefits to be gained from using the gonadotropin-releasing hormone antagonist rather than the gonadotropin-releasing hormone agonist are the immediate inhibition of pituitary gonadotropin secretion without the "flare effect," which brings greater safety and convenience for patients and the medical team and saves time and money. We have also recently demonstrated the feasibility of combining gonadotropin-releasing hormone antagonist with pulsatile gonadotropin-releasing hormone therapy for the controlled restoration of gonadotropin secretion and gonadal steroidogenesis culminating in apparently normal (singleton) ovulatory cycles. This is feasible only with gonadotropin-releasing hormone antagonists because, unlike gonadotropin-releasing hormone agonists, they achieve control of the pituitary-ovarian axis without down regulation of the gonadotropin-releasing hormone receptor system. This capacity to override gonadotropin-releasing hormone antagonist-induced suppression of pituitary-ovarian function may allow new treatment modalities to be employed for women who suffer from chronic hyperandrogenemia with polycystic ovarian disease.