Active bio-based food-packaging: Diffusion and release of active substances through and from cellulose nanofiber coating toward food-packaging design.

PubMed

Lavoine, Nathalie; Guillard, Valérie; Desloges, Isabelle; Gontard, Nathalie; Bras, Julien

2016-09-20

Cellulose nanofibers (CNFs) were recently investigated for the elaboration of new functional food-packaging materials. Their nanoporous network was especially of interest for controlling the release of active species. Qualitative release studies were conducted, but quantification of the diffusion phenomenon observed when the active species are released from and through CNF coating has not yet been studied. Therefore, this work aims to model CNF-coated paper substrates as controlled release system for food-packaging using release data obtained for two model molecules, namely caffeine and chlorhexidine digluconate. The applied mathematical model - derived from Fickian diffusion - was validated for caffeine only. When the active species chemically interacts with the release device, another model is required as a non-predominantly diffusion-controlled release was observed. From caffeine modeling data, a theoretical active food-packaging material was designed. The use of CNFs as barrier coating was proved to be the ideal material configuration that best meets specifications. Copyright © 2016. Published by Elsevier Ltd.

Bioavailability of ambroxol sustained release preparations. Part II: Single and multiple oral dose studies in man.

PubMed

Janssen, T J; Guelen, P J; Vree, T B; Botterblom, M H; Valducci, R

1988-01-01

The bioavailability of a new ambroxol sustained release preparation (75 mg) based on a dialyzing membrane for controlled release was studied in healthy volunteers after single and multiple oral dose in comparison with a standard sustained release formulation in a cross-over study under carefully controlled conditions. Plasma concentrations of ambroxol were measured by means of a HPLC method. Based on AUC data both preparations are found to be bioequivalent, but show different plasma concentration profiles. The test preparation showed a more pronounced sustained release profile than the reference preparation (single dose) resulting in significantly higher steady state plasma levels.

Wax-based sustained release matrix pellets prepared by a novel freeze pelletization technique II. In vitro drug release studies and release mechanisms.

PubMed

Cheboyina, Sreekhar; Wyandt, Christy M

2008-07-09

A novel freeze pelletization technique was evaluated for the preparation of wax-based sustained release matrix pellets. Pellets containing water-soluble drugs were successfully prepared using a variety of waxes. The drug release significantly depended on the wax type used and the aqueous drug solubility. The drug release decreased as the hydrophobicity of wax increased and the drug release increased as the aqueous drug solubility increased. In glyceryl monostearate (GMS) pellets, drug release rate decreased as the loading of theophylline increased. On the contrary, the release rate increased as the drug loading of diltiazem HCl increased in Precirol pellets. Theophylline at low drug loads existed in a dissolved state in GMS pellets and the release followed desorption kinetics. At higher loads, theophylline existed in a crystalline state and the release followed dissolution-controlled constant release for all the waxes studied. However, with the addition of increasing amounts of Brij 76, theophylline release rate increased and the release mechanism shifted to diffusion-controlled square root time kinetics. But the release of diltiazem HCl from Precirol pellets at all drug loads, followed diffusion-controlled square root time kinetics. Therefore, pellets capable of providing a variety of release profiles for different drugs can be prepared using this freeze pelletization technique by suitably modifying the pellet forming matrix compositions.

Drug disposition and modelling before and after gastric bypass: immediate and controlled-release metoprolol formulations.

PubMed

Gesquiere, Ina; Darwich, Adam S; Van der Schueren, Bart; de Hoon, Jan; Lannoo, Matthias; Matthys, Christophe; Rostami, Amin; Foulon, Veerle; Augustijns, Patrick

2015-11-01

The aim of the present study was to evaluate the disposition of metoprolol after oral administration of an immediate and controlled-release formulation before and after Roux-en-Y gastric bypass (RYGB) surgery in the same individuals and to validate a physiologically based pharmacokinetic (PBPK) model for predicting oral bioavailability following RYGB. A single-dose pharmacokinetic study of metoprolol tartrate 200 mg immediate release and controlled release was performed in 14 volunteers before and 6-8 months after RYGB. The observed data were compared with predicted results from the PBPK modelling and simulation of metoprolol tartrate immediate and controlled-release formulation before and after RYGB. After administration of metoprolol immediate and controlled release, no statistically significant difference in the observed area under the curve (AUC(0-24 h)) was shown, although a tendency towards an increased oral exposure could be observed as the AUC(0-24 h) was 32.4% [95% confidence interval (CI) 1.36, 63.5] and 55.9% (95% CI 5.73, 106) higher following RYGB for the immediate and controlled-release formulation, respectively. This could be explained by surgery-related weight loss and a reduced presystemic biotransformation in the proximal gastrointestinal tract. The PBPK values predicted by modelling and simulation were similar to the observed data, confirming its validity. The disposition of metoprolol from an immediate-release and a controlled-release formulation was not significantly altered after RYGB; there was a tendency to an increase, which was also predicted by PBPK modelling and simulation. © 2015 The British Pharmacological Society.

Drug disposition and modelling before and after gastric bypass: immediate and controlled-release metoprolol formulations

PubMed Central

Gesquiere, Ina; Darwich, Adam S; Van der Schueren, Bart; de Hoon, Jan; Lannoo, Matthias; Matthys, Christophe; Rostami, Amin; Foulon, Veerle; Augustijns, Patrick

2015-01-01

Aims The aim of the present study was to evaluate the disposition of metoprolol after oral administration of an immediate and controlled-release formulation before and after Roux-en-Y gastric bypass (RYGB) surgery in the same individuals and to validate a physiologically based pharmacokinetic (PBPK) model for predicting oral bioavailability following RYGB. Methods A single-dose pharmacokinetic study of metoprolol tartrate 200 mg immediate release and controlled release was performed in 14 volunteers before and 6–8 months after RYGB. The observed data were compared with predicted results from the PBPK modelling and simulation of metoprolol tartrate immediate and controlled-release formulation before and after RYGB. Results After administration of metoprolol immediate and controlled release, no statistically significant difference in the observed area under the curve (AUC0–24 h) was shown, although a tendency towards an increased oral exposure could be observed as the AUC0–24 h was 32.4% [95% confidence interval (CI) 1.36, 63.5] and 55.9% (95% CI 5.73, 106) higher following RYGB for the immediate and controlled-release formulation, respectively. This could be explained by surgery-related weight loss and a reduced presystemic biotransformation in the proximal gastrointestinal tract. The PBPK values predicted by modelling and simulation were similar to the observed data, confirming its validity. Conclusions The disposition of metoprolol from an immediate-release and a controlled-release formulation was not significantly altered after RYGB; there was a tendency to an increase, which was also predicted by PBPK modelling and simulation. PMID:25917170

Development of formulations to improve the controlled-release of linalool to be applied as an insecticide.

PubMed

Lopez, M D; Maudhuit, A; Pascual-Villalobos, M J; Poncelet, D

2012-02-08

In recent studies, insecticide activity of a monoterpene, linalool, has been demonstrated, finding, however, limitations in application because of its rapid volatilization. Potential effectiveness of microcapsules and effects of various types of matrices on its stability as controlled-release systems for the slow volatilization of linalool to be applied as insecticide were evaluated. To study controlled-release, linalool was entrapped into microcapsules, inclusion complexes, and beads, obtained by different methods, inverse gelation (IG1, IG2, IG3, IG4, and IG5), oil-emulsion-entrapment (OEE), interfacial coacervation (INCO), and chemical precipitation (Cyc5 and Cyc10). The encapsulation yield turned out to be different for each formulation, reaching the maximum retention for IG1 and OEE. In controlled-release, OEE followed by INCO presented a long time necessary for releasing as a result of the presence of glycerol or chitosan. These results pointed out remarkable differences in the release behavior of linalool depending on matrix composition and the method of encapsulation.

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

PubMed

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 the microspheres prepared by various methods were mainly controlled by either the porosity inside the microspheres or the degradation of materials, which could, therefore, lead to different release behaviours. This results indicated great potential of the PLGA microsphere formulation as an injectable depot for controllable in vivo release profile via rational core phase design. Core/shell microspheres fabricated by modified double emulsification-solvent evaporation methods, with various inner phases, to obtain high loading drugs system, as well as appropriate release behaviours. Accordingly, control in vivo release profile via rational core phase design.

Controlled porosity osmotic pump-based controlled release systems of pseudoephedrine. I. Cellulose acetate as a semipermeable membrane.

PubMed

Makhija, Sapna N; Vavia, Pradeep R

2003-04-14

A controlled porosity osmotic pump-based drug delivery system has been described in this study. Unlike the elementary osmotic pump (EOP) which consists of an osmotic core with the drug surrounded by a semipermeable membrane drilled with a delivery orifice, controlled porosity of the membrane is accomplished by the use of different channeling agents in the coating. The usual dose of pseudoephedrine is 60 mg to be taken three or four times daily. It has a short plasma half life of 5-8 h. Hence, pseudoephedrine was chosen as a model drug with an aim to develop a controlled release system for a period of 12 h. Sodium bicarbonate was used as the osmogent. The effect of different ratios of drug:osmogent on the in-vitro release was studied. Cellulose acetate (CA) was used as the semipermeable membrane. Different channeling agents tried were diethylphthalate (DEP), dibutylphthalate (DBP), dibutylsebacate (DBS) and polyethyleneglycol 400 (PEG 400). The effect of polymer loading on in-vitro drug release was studied. It was found that drug release rate increased with the amount of osmogent due to the increased water uptake, and hence increased driving force for drug release. This could be retarded by the proper choice of channeling agent in order to achieve the desired zero order release profile. Also the lag time seen with tablets coated using diethylphthalate as channeling agent was reduced by using a hydrophilic plasticizer like polyethyleneglycol 400 in combination with diethylphthalate. This system was found to deliver pseudoephedrine at a zero order rate for 12 h. The effect of pH on drug release was also studied. The optimized formulations were subjected to stability studies as per ICH guidelines at different temperature and humidity conditions.

A Drug-Eluting Contact Lens

PubMed Central

Ciolino, Joseph B.; Hoare, Todd R.; Iwata, Naomi G.; Behlau, Irmgard; Dohlman, Claes H.; Langer, Robert; Kohane, Daniel S.

2014-01-01

Purpose To formulate and characterize a drug-eluting contact lens designed to provide extended, controlled release of a drug. Methods Prototype contact lenses were created by coating PLGA (poly[lactic-co-glycolic acid]) films containing test compounds with pHEMA (poly[hydroxyethyl methacrylate]) by ultraviolet light polymerization. The films, containing encapsulated fluorescein or ciprofloxacin, were characterized by scanning electron microscopy. Release studies were conducted in phosphate-buffered saline at 37°C with continuous shaking. Ciprofloxacin eluted from the contact lens was studied in an antimicrobial assay to verify antimicrobial effectiveness. Results After a brief and minimal initial burst, the prototype contact lenses demonstrated controlled release of the molecules studied, with zero-order release kinetics under infinite sink conditions for over 4 weeks. The rate of drug release was controlled by changing either the ratio of drug to PLGA or the molecular mass of the PLGA used. Both the PLGA and the pHEMA affected release kinetics. Ciprofloxacin released from the contact lenses inhibited ciprofloxacin-sensitive Staphylococcus aureus at all time-points tested. Conclusions A prototype contact lens for sustained drug release consisting of a thin drug-PLGA film coated with pHEMA could be used as a platform for ocular drug delivery with widespread therapeutic applications. PMID:19136709

The comparison between limited open carpal tunnel release using direct vision and tunneling technique and standard open carpal tunnel release: a randomized controlled trial study.

PubMed

Suppaphol, Sorasak; Worathanarat, Patarawan; Kawinwongkovit, Viroj; Pittayawutwinit, Preecha

2012-04-01

To compare the operative outcome of carpal tunnel release between limited open carpal tunnel release using direct vision and tunneling technique (group A) with standard open carpal tunnel release (group B). Twenty-eight patients were enrolled in the present study. A single blind randomized control trial study was conducted to compare the postoperative results between group A and B. The study parameters were Levine's symptom severity and functional score, grip and pinch strength, and average two-point discrimination. The postoperative results between two groups were comparable with no statistical significance. Only grip strength at three months follow up was significantly greater in group A than in group B. The limited open carpal tunnel release in the present study is effective comparable to the standard open carpal tunnel release. The others advantage of this technique are better cosmesis and improvement in grip strength at the three months postoperative period.

Development of novel sustained-release system, disintegration-controlled matrix tablet (DCMT) with solid dispersion granules of nilvadipine.

PubMed

Tanaka, Nobuyuki; Imai, Keiji; Okimoto, Kazuto; Ueda, Satoshi; Tokunaga, Yuji; Ohike, Atsuo; Ibuki, Rinta; Higaki, Kazutaka; Kimura, Toshikiro

2005-11-28

The goal of this study is to develop a novel sustained-release (SR) system for poorly water-soluble drugs by applying solid dispersion (SD) technique for improving the solubility. The developed SR system, disintegration-controlled matrix tablet (DCMT), consists of hydrogenated soybean oil (HSO) as wax and SD granules containing low-substituted hydroxypropylcellulose (L-HPC) as a disintegrant. In this study, nilvadipine (NiD) was chosen as a model compound. Sustained-release profiles of NiD from DCMT were identically controlled in several dissolution mediums in spite of varying pH and agitation speed. The release of NiD from DCMT was sustained more effectively by increasing the amount of wax or by decreasing the amount of disintegrant, and supersaturation of NiD was achieved without any re-crystallization in dissolution medium. The release rate of NiD from DCMT was controlled by the disintegration rate of tablet. The release profile of NiD was described by the Hixson-Crowell's model better than zero-order kinetics, first-order kinetics and Higuchi's model, which supports that the release of NiD from DCMT is regulated by the disintegration of the tablet. From this study, it was clarified that DCMT was one of the promising SR systems applying SD for the poorly water-soluble drugs.

Evaluation of the resistance of a geopolymer-based drug delivery system to tampering.

PubMed

Cai, Bing; Engqvist, Håkan; Bredenberg, Susanne

2014-04-25

Tamper-resistance is an important property of controlled-release formulations of opioid drugs. Tamper-resistant formulations aim to increase the degree of effort required to override the controlled release of the drug molecules from extended-release formulations for the purpose of non-medical use. In this study, the resistance of a geopolymer-based formulation to tampering was evaluated by comparing it with a commercial controlled-release tablet using several methods commonly used by drug abusers. Because of its high compressive strength and resistance to heat, much more effort and time was required to extract the drug from the geopolymer-based formulation. Moreover, in the drug-release test, the geopolymer-based formulation maintained its controlled-release characteristics after milling, while the drug was released immediately from the milled commercial tablets, potentially resulting in dose dumping. Although the tampering methods used in this study does not cover all methods that abuser could access, the results obtained by the described methods showed that the geopolymer matrix increased the degree of effort required to override the controlled release of the drug, suggesting that the formulation has improved resistance to some common drug-abuse tampering methods. The geopolymer matrix has the potential to make the opioid product less accessible and attractive to non-medical users. Copyright © 2014 Elsevier B.V. All rights reserved.

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

PubMed

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.

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

PubMed

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.

Effects of formulation variables and post-compression curing on drug release from a new sustained-release matrix material: polyvinylacetate-povidone.

PubMed

Shao, Z J; Farooqi, M I; Diaz, S; Krishna, A K; Muhammad, N A

2001-01-01

A new commercially available sustained-release matrix material, Kollidon SR, composed of polyvinylacetate and povidone, was evaluated with respect to its ability to modulate the in vitro release of a highly water-soluble model compound, diphenhydramine HCl. Kollidon SR was found to provide a sustained-release effect for the model compound, with certain formulation and processing variables playing an important role in controlling its release kinetics. Formulation variables affecting the release include the level of the polymeric material in the matrix, excipient level, as well as the nature of the excipients (water soluble vs. water insoluble). Increasing the ratio of a water-insoluble excipient, Emcompress, to Kollidon SR enhanced drug release. The incorporation of a water-soluble excipient, lactose, accelerated its release rate in a more pronounced manner. Stability studies conducted at 40 degrees C/75% RH revealed a slow-down in dissolution rate for the drug-Kollidon SR formulation, as a result of polyvinylacetate relaxation. Further studies demonstrated that a post-compression curing step effectively stabilized the release pattern of formulations containing > or = 47% Kollidon SR. The release mechanism of Kollidon-drug and drug-Kollidon-Emcompress formulations appears to be diffusion controlled, while that of the drug-Kollidon-lactose formulation appears to be controlled predominantly by diffusion along with erosion.

Recidivism Among Licensed-Released Prisoners Who Participated in the EM Program in Israel.

PubMed

Shoham, Efrat; Yehosha-Stern, Shirley; Efodi, Rotem

2015-08-01

Toward the end of 2006, a pilot program was launched in Israel wherein licensed-released prisoners were put under electronic monitoring (EM). In addition to EM, the pilot program, operated by the Prisoners' Rehabilitation Authority, provides programs of occupational supervision and personal therapy and is designed to allow for early release of those prisoners who, without increased supervision, would have been found unsuitable for early release. The aim of this study was to ascertain whether participation in the EM program among licensed-released prisoners in Israel might bring about lessened recidivism. For that matter, rates of arrests and incarceration were examined during a follow-up period of up to 4 years, among the entirety of licensed-released prisoners participating in the EM program between the years 2007 and 2009 (n = 155). To compare recidivism rates, a control group was assembled from among the entirety of released prisoners who were found unsuitable for early release in judicial conditions, and had therefore served the full term of their incarceration, to be released between the years 2005 and 2006 (a period of time during which an EM program was not yet operated among licensed-released prisoners in Israel). Study findings clearly show that while among the control group, 42% of released prisoners were re-incarcerated, at the end of a 4-year follow-up period, only 15% among the study group had returned to prison. These findings can be explained by combining the Social Control theory and the Self-Control theory which consider the period of time under EM program and the occupational and familial integration tools for reducing criminal connections and enhancing pro-social behavior. © The Author(s) 2014.

Control-release microcapsule of famotidine loaded biomimetic synthesized mesoporous silica nanoparticles: Controlled release effect and enhanced stomach adhesion in vitro.

PubMed

Li, Jing; Wang, Hongyu; Yang, Baixue; Xu, Lu; Zheng, Nan; Chen, Hongtao; Li, Sanming

2016-01-01

In the present work, control-release microcapsule of famotidine (FMT) loaded biomimetic synthesized mesoporous silica nanoparticles (B-MSNs) was developed, and controlled release effect and stomach adhesion of this formulation in vitro were mainly investigated. B-MSN was previously synthesized and it was amorphous mesoporous nanoparticles with helical channels. Cytotoxicity of B-MSN was studied using human breast cancer cells (MCF-7) and the result indicated that cytotoxicity of B-MSN can be neglected. After loading FMT into B-MSN, specific surface area, pore volume and pore diameter of B-MSN were obviously reduced. In vitro dissolution test showed that B-MSN had the ability to slow down FMT release for 15 min. In order to prolong controlled release effect and remained the advantage of B-MSN (improve drug stability due to its rigid silica framework), the combined application of control-release microcapsule (using cellulose and hydroxypropyl methylcellulose K15M as excipients) with B-MSN was designed. It was obvious that newly designed formulation significantly controlled FMT release with Fickian diffusion mechanism and showed enhanced stomach adhesion in vitro, which has significant value in widening the application of B-MSN in formulation design. Copyright © 2015 Elsevier B.V. All rights reserved.

The controlled release of tilmicosin from silica nanoparticles.

PubMed

Song, Meirong; Li, Yanyan; Fai, Cailing; Cui, Shumin; Cui, Baoan

2011-06-01

The aim of this study was to use silica nanoparticles as the carrier for controlled release of tilmicosin. Tilmicosin was selected as a drug model molecule because it has a lengthy elimination half-life and a high concentration in milk after subcutaneous administration. Three samples of tilmicosin-loaded silica nanoparticles were prepared with different drug-loading weight. The drug-loading weight in three samples, as measured by thermal gravimetric analysis, was 29%, 42%, and 64%, respectively. With increased drug-loading weight, the average diameter of the drug-loaded silica nanoparticles was increased from 13.4 to 25.7 nm, and the zeta potential changed from-30.62 to-6.78 mV, indicating that the stability of the drug-loaded particles in the aqueous solution decreases as drug-loading weight increases. In vitro release studies in phosphate-buffered saline showed the sample with 29% drug loading had a slow and sustained drug release, reaching 44% after 72 h. The release rate rose with increased drug-loading weight; therefore, the release of tilmicosin from silica nanoparticles was well-controlled by adjusting the drug loading. Finally, kinetics analysis suggested that drug released from silica nanoparticles was mainly a diffusion-controlled process.

Controlled delivery of basal insulin from phase-sensitive polymeric systems after subcutaneous administration: in vitro release, stability, biocompatibility, in vivo absorption, and bioactivity of insulin.

PubMed

Al-Tahami, Khaled; Oak, Mayura; Singh, Jagdish

2011-06-01

The purpose of this study was to investigate the phase-sensitive delivery systems (D,L-polylactide in triacetin) for controlled delivery of insulin at basal level. The effect of varying concentration of zinc, polymer, and insulin on the in vitro release of insulin was evaluated. Stability of released insulin was investigated by differential scanning calorimetry, circular dichroism, and matrix-assisted laser desorption/ionization time of flight mass spectrometry. In Vivo insulin absorption and bioactivity were studied in diabetic rats. In vitro and In Vivo biocompatibility of delivery systems were evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay and skin histology, respectively. Extended release profiles of insulin for 2, 4, and 8 weeks from delivery systems containing 20%, 30%, and 40% (w/v) polymer concentration was observed. A ratio of 1:5 insulin hexamer to zinc was shown to be optimum. Physical and chemical stability of released insulin was greatly conserved. In Vivo studies demonstrated controlled release of insulin with reduction in blood glucose for approximately 1 month. In vitro and In Vivo studies demonstrated that the delivery system was biocompatible and controlled the delivery of insulin for longer durations after single subcutaneous injection. Copyright © 2010 Wiley-Liss, Inc.

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

PubMed Central

Shah, Kifayat Ullah; Khan, Gul Majid

2012-01-01

The design and fabrication of sustained/controlled release dosage forms, employing new excipients capable of extending/controlling the release of drugs from the dosage forms over prolonged periods, has worked well in achieving optimally enhanced therapeutic levels of the drugs. In this sense, the objective of this study was to investigate the suitability of selected cellulose ether derivatives for use in direct compression (DC) and as efficient drug release controlling agents. Controlled release matrix tablets of ciprofloxacin were prepared at different drug-to-polymer (D : P) ratios by direct compression using a fine particle sized ethylcellulose ether derivative (ETHOCEL Standard Premium 7FP) as rate controlling polymer. The tablets obtained were evaluated for various physico-chemical characteristics and in-vitro drug release studies were conducted in phosphate buffer (pH 7.4) using PharmaTest dissolution apparatus at constant temperature of 37°C ± 0.1. Similarity factor f 2 was employed to the release profiles of test formulations and were compared with marketed ciprofloxacin conventional tablets. Drug release mechanism and the kinetics involved were investigated by fitting the release profile data to various kinetic models. It was found that with increasing the proportion of ethylcellulose ether derivative in the matrix, the drug release was significantly extended up to 24 hours. The tablets exhibited zero order or nearly zero order drug transport mechanism. In vivo drug release performance of the developed controlled release tablets and reference conventional tablets containing ciprofloxacin were determined in rabbit serum according to randomized two-way crossover study design using High Performance Liquid Chromatography. Several bioavailability parameters of both the test tablets and conventional tablets including C max⁡, T max⁡ and AUC0-t were compared which showed an optimized C max⁡ and T max⁡ (P < 0.05). A good correlation was obtained between in vitro drug release and in vivo drug absorption with correlation value (R 2 = 0.934). Relative bioavailability was found to be 93%. Reproducibility of manufacturing process and accelerated stability of the developed tablets were performed in stability chamber at 40 ± 2°C and 75 ± 5% relative humidity for a period of 6 months and were found to be stable throughout the stability period. PMID:22649325

Letrozole dispersed on poly (vinyl alcohol) anchored maleic anhydride grafted low density polyethylene: a controlled drug delivery system for treatment of breast cancer.

PubMed

Siddiqa, Akhtar Jahan; Chaudhury, Koel; Adhikari, Basudam

2014-04-01

The present work focuses on the design of a drug delivery system for systemic, controlled release of the poorly soluble breast cancer drug, letrozole. The drug delivery system was prepared in two steps: a low density polyethylene (LDPE) substrate surface was grafted with maleic anhydride (MA) via solution grafting technique. Next, the grafted substrate was used to anchor a hydrophilic polymeric drug release system consisting of poly (vinyl alcohol) (PVA). The PVA anchored MA grafted LDPE (PVA/MA-g-LDPE) drug release system was used for the controlled release of letrozole. This system was characterized using ATR-FTIR spectrophotometry, surface profilometry, and scanning electron microscopy. Biocompatibility studies were also carried out. In vitro release studies of letrozole from the system were performed in distilled water and phosphate buffer saline (PBS) at 37°C. Release of ∼90% letrozole from hydrophilic PVA matrix was observed within a period of 35 days. A high correlation coefficient (R(2)=0.99) was seen between the release of letrozole in distilled water and PBS. Cytotoxicity studies using MTT colorimetric assay suggested that all samples were biocompatible. It is concluded that the letrozole delivery system appears to overcome the limitations associated with letrozole by providing enhanced drug dissolution rate, controlled release and improved bioavailability of the incorporated drug and, therefore, seems to have extended therapeutic effects. Copyright © 2014 Elsevier B.V. All rights reserved.

[Studies on preparation of sustained-release Shuxiong formulation, a traditional Chinese medicine compound recipe, using time-controlled release techniques].

PubMed

Song, Hong-Tao; Zhang, Qian; Jiang, Peng; Guo, Tao; Chen, Da-Wei; He, Zhong-Gui

2006-09-01

To prepare a sustained-release formulation of traditional Chinese medicine compound recipe by adopting time-controlled release techniques. Shuxiong tablets were chosen as model drug. The prescription and technique of core tablets were formulated with selecting disintegrating time and swelling volume of core tablets in water as index. The time-controlled release tablets were prepared by adopting press-coated techniques, using PEG6000, HCO and EVA as coating materials. The influences of compositions, preparation process and dissolution conditions in vitro on the lag time (T(lag)) of drug release were investigated. The composition of core tablets was as follow: 30% of drug, 50% MCC and 20% CMS-Na. The T(lag) of time-controlled release tablets was altered remarkably by PEG6000 content of the outer layer, the amount of outer layer and hardness of tablet. The viscosity of dissolution media and basket rotation had less influence on the T(lag) but more on rate of drug release. The core tablets pressed with the optimized composition had preferable swelling and disintegrating properties. The shuxiong sustained-release formulations which contained core tablet and two kinds of time-controlled release tablets with 3 h and 6 h of T(lag) could release drug successively at 0 h, 3 h and 6 h in vitro. The technique made it possible that various components with extremely different physicochemical properties in these preparations could release synchronously.

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

PubMed

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.

Formulation, in vitro evaluation and study of variables on tri-layered gastro-retentive delivery system of diltiazem HCl.

PubMed

Raut Desai, Shilpa; Rohera, Bhagwan D

2014-03-01

Tri-layered floating tablets using only one grade of polyethylene oxide (PEO) would enable easy manufacturing, reproducibility and controlled release for highly soluble drugs. To evaluate the potential of PEO as a sole polymer for the controlled release and to study the effect of formulation variables on release and gastric retention of highly soluble Diltiazem hydrochloride (DTZ). Tablets were compressed with middle layer consisting of drug and polymer while outer layers consisted of polymer with sodium bicarbonate. Design of formulation to obtain 12 h, zero-order release and rapid floatation was done by varying the grades, quantity of PEO and sodium bicarbonate. Dissolution data were fitted in drug release models and swelling/erosion studies were undertaken to verify the drug release mechanism. Effect of formulation variables and tablet surface morphology using scanning electron microscopy were studied. The optimized formula passed the criteria of USP dissolution test I and exhibited floating lag-time of 3-4 min. Drug release was faster from low molecular weight (MW) PEO as compared to high MW. With an increase in the amount of sodium bicarbonate, faster buoyancy was achieved due to the increased CO2 gas formation. Drug release followed zero-order and gave a good fit to the Korsmeyer-Peppas model, which suggested that drug release was due to diffusion through polymer swelling. Zero-order, controlled release profile with the desired buoyancy can be achieved by using optimum formula quantities of sodium bicarbonate and polymer. The tri-layered system shows promising delivery of DTZ, and possibly other water-soluble drugs.

Controlled and extended drug release behavior of chitosan-based nanoparticle carrier.

PubMed

Yuan, Q; Shah, J; Hein, S; Misra, R D K

2010-03-01

Controlled drug release is presently gaining significant attention. In this regard, we describe here the synthesis (based on the understanding of chemical structure), structural morphology, swelling behavior and drug release response of chitosan intercalated in an expandable layered aluminosilicate. In contrast to pure chitosan, for which there is a continuous increase in drug release with time, the chitosan-aluminosilicate nanocomposite carrier was characterized by controlled and extended release. Drug release from the nanocomposite particle carrier occurred by degradation of the carrier to its individual components or nanostructures with a different composition. In both the layered aluminosilicate-based mineral and chitosan-aluminosilicate nanocomposite carriers the positively charged chemotherapeutic drug strongly bound to the negatively charged aluminosilicate and release of the drug was slow. Furthermore, the pattern of drug release from the chitosan-aluminosilicate nanocomposite carrier was affected by pH and the chitosan/aluminosilicate ratio. The study points to the potential application of this hybrid nanocomposite carrier in biomedical applications, including tissue engineering and controlled drug delivery. Copyright 2009 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

A biodegradable device for the controlled release of Piper nigrum (Piperaceae) standardized extract to control Aedes aegypti (Diptera, Culicidae) larvae.

PubMed

Custódio, Kauê Muller; Oliveira, Joice Guilherme de; Moterle, Diego; Zepon, Karine Modolon; Prophiro, Josiane Somariva; Kanis, Luiz Alberto

2016-01-01

The significant increase in dengue, Zika, and chikungunya and the resistance of the Aedes aegypti mosquito to major insecticides emphasize the importance of studying alternatives to control this vector. The aim of this study was to develop a controlled-release device containing Piper nigrum extract and to study its larvicidal activity against Aedes aegypti. Piper nigrum extract was produced by maceration, standardized in piperine, and incorporated into cotton threads, which were inserted into hydrogel cylinders manufactured by the extrusion of carrageenan and carob. The piperine content of the extract and thread reservoirs was quantified by chromatography. The release profile from the device was assessed in aqueous medium and the larvicidal and residual activities of the standardized extract as well as of the controlled-release device were examined in Aedes aegypti larvae. The standardized extract contained 580mg/g of piperine and an LC50 value of 5.35ppm (24h) and the 3 cm thread reservoirs contained 13.83 ± 1.81mg of piperine. The device showed zero-order release of piperine for 16 days. The P. nigrum extract (25ppm) showed maximum residual larvicidal activity for 10 days, decreasing progressively thereafter. The device had a residual larvicidal activity for up to 37 days. The device provided controlled release of Piper nigrum extract with residual activity for 37 days. The device is easy to manufacture and may represent an effective alternative for the control of Aedes aegypti larvae in small water containers.

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

PubMed Central

Jannesari, Marziyeh; Varshosaz, Jaleh; Morshed, Mohammad; Zamani, Maedeh

2011-01-01

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. PMID:21720511

Simulation and parametric study of a film-coated controlled-release pharmaceutical.

PubMed

Borgquist, Per; Zackrisson, Gunnar; Nilsson, Bernt; Axelsson, Anders

2002-04-23

Pharmaceutical formulations can be designed as Multiple Unit Systems, such as Roxiam CR, studied in this work. The dose is administrated as a capsule, which contains about 100 individual pellets, which in turn contain the active drug remoxipride. Experimental data for a large number of single pellets can be obtained by studying the release using microtitre plates. This makes it possible to study the release of the individual subunits making up the total dose. A mathematical model for simulating the release of remoxipride from single film-coated pellets is presented including internal and external mass transfer hindrance apart from the most important film resistance. The model can successfully simulate the release of remoxipride from single film-coated pellets if the lag phase of the experimental data is ignored. This was shown to have a minor influence on the release rate. The use of the present model is demonstrated by a parametric study showing that the release process is film-controlled, i.e. is limited by the mass transport through the polymer coating. The model was used to fit the film thickness and the drug loading to the experimental release data. The variation in the fitted values was similar to that obtained in the experiments.

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

PubMed

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

2017-02-01

To develop a nanofiber hydrogel (NF-hydrogel) for sustained and controlled release of the recombinant receptor activator of NF-kB ligand; (RANKL) and to characterize the release kinetics and bioactivity of the released RANKL. Various concentrations of fluorescently-labelled RANKL protein were added to NF-hydrogels, composed of Acetyl-(Arg-Ala-Asp-Ala) 4 -CONH 2 [(RADA) 4 ] of different concentrations, to investigate the resulting in vitro release rates. The nano-structures of NF-hydrogel, with and without RANKL, were determined using atomic force microscopy (AFM). Released RANKL was further analyzed for changes in secondary and tertiary structure using CD spectroscopy and fluorescent emission spectroscopy, respectively. Bioactivity of released RANKL protein was determined using NFATc1 gene expression and tartrate resistant acid phosphatase (TRAP) activity of osteoclast cells as biomarkers. NF-hydrogel concentration dependent sustained release of RANKL protein was measured at concentrations between 0.5 and 2%(w/v). NF-hydrogel at 2%(w/v) concentration exhibited a sustained and slow-release of RANKL protein up to 48h. Secondary and tertiary structure analyses confirmed no changes to the RANKL protein released from NF-hydrogel in comparison to native RANKL. The results of NFATc1 gene mRNA expression and TRAP activities of osteoclast, showed that the release process did not affect the bioactivity of released RANKL. This novel study is the first of its kind to attempt in vitro characterization of NF-hydrogel based delivery of RANKL protein to induce osteoclastogenesis. We have shown the self-assembling NF-hydrogel peptide system is amenable to the sustained and controlled release of RANKL locally; that could in turn increase local concentration of RANKL to induce osteoclastogenesis, for application to the controlled mobilization of tooth movement in orthodontic procedures. Orthodontic tooth movement (OTM) occurs through controlled application of light forces to teeth, facilitating the required changes in the surrounding alveolar bone through the process of bone remodelling. The RANKL system regulates alveolar bone remodelling and controls root resorption during OTM. The use of exogenous RANKL to accelerate OTM has not been attempted to date because large quantities of RANKL for systemic therapy may subsequently cause serious systemic loss of skeletal bone. The controlled and sustained local release of RANKL from a carrier matrix could maximize its therapeutic benefit whilst minimizing systemic side effects. In this study a NF-hydrogel was used for sustained and controlled release of RANKL and the release kinetics and biofunctionality of the released RANKL was characterized. Our results provide fundamental insight for further investigating the role of RANKL NF-hydrogel release systems for inducing osteoclastogenesis in vivo. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Limited mobility of target pests crucially lowers controllability when sterile insect releases are spatiotemporally biased.

PubMed

Ikegawa, Yusuke; Himuro, Chihiro

2017-05-21

The sterile insect technique (SIT) is a genetic pest control method wherein mass-reared sterile insects are periodically released into the wild, thereby impeding the successful reproduction of fertile pests. In Okinawa Prefecture, Japan, the SIT has been implemented to eradicate the West Indian sweet potato weevil Euscepes postfasciatus (Fairmaire), which is a flightless agricultural pest of sweet potatoes. It is known that E. postfasciatus is much less mobile than other insects to which the SIT has been applied. However, previous theoretical studies have rarely examined effects of low mobility of target pests and variation in the spatiotemporal evenness of sterile insect releases. To theoretically examine the effects of spatiotemporal evenness on the regional eradication of less mobile pests, we constructed a simple two-patch population model comprised of a pest and sterile insect moving between two habitats, and numerically simulated different release strategies (varying the number of released sterile insects and release intervals). We found that spatially biased releases allowed the pest to spatially escape from the sterile insect, and thus intensively lowered its controllability. However, we showed that the temporally counterbalancing spatially biased releases by swapping the number of released insects in the two habitats at every release (called temporal balancing) could greatly mitigate this negative effect and promote the controllability. We also showed that the negative effect of spatiotemporally biased releases was a result of the limited mobility of the target insect. Although directed dispersal of the insects in response to habitats of differing quality could lower the controllability in the more productive habitat, the temporal balancing could promote and eventually maximize the controllability as released insects increased. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bioavailability and in vivo release behavior of controlled-release multiple-unit theophylline dosage forms in beagle dogs, cynomolgus monkeys, and göttingen minipigs.

PubMed

Ikegami, Kengo; Tagawa, Kozo; Osawa, Takashi

2006-09-01

To determine the usefulness of monkey as an animal model, bioavailability and in vivo release behaviors of theophylline (TP) after oral administration of controlled-release beads in dogs, monkeys, and minipigs were evaluated. Controlled-release beads were prepared using a centrifugal-fluid type granulator, that is, CF-granulator, and Ethylcellulose (EC) was used as controlled-release coating agent. Aqueous solution and EC-coated beads, which contained TP were orally administered to animals after at least 1-week intervals. In dogs and minipigs, their relative bioavailabilities of EC-coated beads were 33.1% and 47.0%, respectively, and in vivo TP release from EC-coated beads in the gastrointestinal tract of dogs and minipigs were not reflected in vitro data. In monkeys, relative bioavailability of EC-coated beads was 80.0% and the highest among the three species, and release amount of TP from EC-coated beads at 24 h after oral administration was 82.8% and 92.4%, which was almost correlated to in vitro data. Therefore, the discrepancy of the relative bioavailability in three species is considered to be due to the difference of in vivo release behavior of TP. The monkey may be useful animal model for bioavailability studies of controlled-release dosage forms of TP from the viewpoint of in vitro-in vivo release correlation. (c) 2006 Wiley-Liss, Inc. and the American Pharmacists Association.

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

PubMed

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.

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

NASA Astrophysics Data System (ADS)

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

2015-12-01

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

Synchronized and sustained release of multiple components in silymarin from erodible glyceryl monostearate matrix system.

PubMed

Lu, Cheng; Lu, Yi; Chen, Jian; Zhang, Wentong; Wu, Wei

2007-05-01

Development of sustained delivery systems for herbal medicines was very difficult because of their complexity in composition. The concept of synchronized release from sustained release systems, which is characterized by release of multiple components in their original ratio that defines a herbal medicine, served as the basis for keeping the original pharmacological activity. In this study, erodible matrix systems based on glyceryl monostearate and polyethylene glycol 6000 or poloxamer 188 were prepared to perform strict control on synchronized release of the five active components of silymarin, i.e. taxifolin, silychrystin, silydianin, isosilybin and silybin. The matrix system was prepared by a melt fusion method. Synchronized release was achieved with high similarity factor f(2) values between each two of the five components. Erosion profiles of the matrix were in good correlation with release profiles of the five components, showing erosion-controlled release mechanisms. Through tuning some of the formulation variables, the system can be adjusted for synchronized and sustained release of silymarin for oral administration. In vitro hemolysis study indicated that the synchronized release samples showed a much better stabilizing effect on erythrocyte membrane.

Ibuprofen-loaded poly(lactic-co-glycolic acid) films for controlled drug release.

PubMed

Pang, Jianmei; Luan, Yuxia; Li, Feifei; Cai, Xiaoqing; Du, Jimin; Li, Zhonghao

2011-01-01

Ibuprofen- (IBU) loaded biocompatible poly(lactic-co-glycolic acid) (PLGA) films were prepared by spreading polymer/ibuprofen solution on the nonsolvent surface. By controlling the weight ratio of drug and polymer, different drug loading polymer films can be obtained. The synthesized ibuprofen-loaded PLGA films were characterized with scanning electron microscopy, powder X-ray diffraction, and differential scanning calorimetry. The drug release behavior of the as-prepared IBU-loaded PLGA films was studied to reveal their potential application in drug delivery systems. The results show the feasibility of the as-obtained films for controlling drug release. Furthermore, the drug release rate of the film could be controlled by the drug loading content and the release medium. The development of a biodegradable ibuprofen system, based on films, should be of great interest in drug delivery systems.

Use of a Fish Transportation Barge for Increasing Returns of Steelhead Imprinted for Homing, Final Report.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harmon, Jerrel R.

1989-08-01

The objective of this 7-year National Fisheries Service study, which began is 1982, was to determine if transporting juvenile steelhead (Oncorhynchus mykiss) by truck and barge from Dworshak National Fish Hatchery (NFH), on the Clearwater River, to a release site on the Columbia River below Bonneville Dam would result in increased returns of adults to the various fisheries and to the hatchery homing site. During 1982 and 1983, over 500,000 marked juvenile steelhead were serially released as controls from the hatchery or barged as test fish to below Bonneville Dam. Recoveries of marked adults to various recovery sites are complete.more » Fish released in 1983 showed a stronger homing ability and more rapid upstream migration than test fish released in 1982. Most adults from both control and test releases in 1983 and control releases in 1982 migrated a considerable distance upstream and overwintered in the Snake and Clearwater Rivers--behavior similar to Clearwater River fish previously transported from Lower Granite Dam. In contrast, many of the adults from test releases in 1982 failed to migrate upstream during the fall, overwintered in the Columbia River, and migrated upstream the following spring. Survival of control fish released at Dworshak NFH in late April 1982 was substantially higher than survival of those released in mid-May. Survival and homing of control fish released in late April and early May 1983 were over 10 times that for fish released in late May. Return of adults from normal hatchery releases in 1982 was the highest ever observed at Dworshak NFH.« less

Development and Evaluation of Oral Controlled Release Chlorpheniramine-Ion Exchange Resinate Suspension

PubMed Central

Kadam, A. U.; Sakarkar, D. M.; Kawtikwar, P. S.

2008-01-01

An oral controlled release suspension of chlorpheniramine maleate was prepared using ion-exchange resin technology. A strong cation exchange resin Indion 244 was utilized for the sorption of the drug and the drug resinates was evaluated for various physical and chemical parameters. The drug-resinate complex was microencapsulated with a polymer Eudragit RS 100 to further retard the release characteristics. Both the drug-resinate complex and microencapsulated drug resinate were suspended in a palatable aqueous suspension base and were evaluated for controlled release characteristic. Stability study indicated that elevated temperature did not alter the sustained release nature of the dosage form indicating that polymer membrane surrounding the core material remained intact throughout the storage period. PMID:20046790

Enzyme-triggered compound release using functionalized antimicrobial peptide derivatives† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c6sc04435b Click here for additional data file.

PubMed Central

Kashibe, Masayoshi; Matsumoto, Kengo; Hori, Yuichiro

2017-01-01

Controlled release is one of the key technologies for medical innovation, and many stimulus-responsive nanocarriers have been developed to utilize this technology. Enzyme activity is one of the most useful stimuli, because many enzymes are specifically activated in diseased tissues. However, controlled release stimulated by enzyme activity has not been frequently reported. One of the reasons for this is the lack of versatility of carriers. Most of the reported stimulus-responsive systems involve a sophisticated design and a complicated process for the synthesis of stimulus-responsive nanocarrier components. The purpose of this study was to develop versatile controlled release systems triggered by various stimuli, including enzyme activity, without modifying the nanocarrier components. We developed two controlled release systems, both of which comprised a liposome as the nanocarrier and a membrane-damaging peptide, temporin L (TL), and its derivatives as the release-controllers. One system utilized branched peptides for proteases, and the other utilized phosphopeptides for phosphatases. In our systems, the target enzymes converted the non-membrane-damaging TL derivatives into membrane-damaging peptides and released the liposome inclusion. We demonstrated the use of our antimicrobial peptide-based controlled release systems for different enzymes and showed the promise of this technology as a novel theranostic tool. PMID:28451373

Guidance for Evaluating the Safety of Experimental Releases of Mosquitoes, Emphasizing Mark-Release-Recapture Techniques.

PubMed

Benedict, Mark Q; Charlwood, J Derek; Harrington, Laura C; Lounibos, L Philip; Reisen, William K; Tabachnick, Walter J

2018-01-01

Experimental releases of mosquitoes are performed to understand characteristics of populations related to the biology, ability to transmit pathogens, and ultimately their control. In this article, we discuss considerations related to the safety of experimental releases of living mosquitoes, applying principles of good practice in vector biology that protect human health and comfort. We describe specific factors of experimental releases of mosquitoes that we believe are critical to inform institutional biosafety committees and similar review boards to which proposals to conduct mosquito release experiments have been submitted. In this study, "experimental releases" means those that do not significantly increase vector capacity or nuisance biting relative to the unperturbed natural baseline. This document specifically does not address releases of mosquitoes for ongoing control programs or trials of new control methods for which broader assessments of risk are required. It also does not address releases of transgenic or exotic (non-native) mosquito species, both of which require particular regulatory approval. Experimental releases may include females and males and evaluation must consider their effects based on the number released, their genotype and phenotype, the environment into which they are released, and postrelease collection activities. We consider whether increases of disease transmission and nuisance biting might result from proposed experimental releases against the backdrop of natural population size variation. We recommend that experimental releases be conducted in a manner that can be reasonably argued to have insignificant negative effects. Reviewers of proposals for experimental releases should expect applicants to provide such an argument based on evidence from similar studies and their planned activities. This document provides guidance for creating and evaluating such proposals.

The sustaining effect of three polymers on the release of chlorhexidine from a controlled release drug device for root canal disinfection.

PubMed

Lee, Doug-Youn; Spångberg, Larz S W; Bok, Young-Bin; Lee, Chang-Young; Kum, Kee-Yeon

2005-07-01

The aim of this in vitro study was to evaluate the suitability of using chitosan, poly (lactide-co-glycolide) (PLGA), and polymethyl methacrylate (PMMA) to control the release of chlorhexidine digluconate (CHX) from a prototype of controlled release drug device for root canal disinfection. Four different prototypes with different formulations were prepared. Group A (n = 12): the device (absorbent paper point) was loaded with CHX as control. Group B (n = 12): same as group A, but the device was coated with chitosan (Texan MedTech). In Groups C and D, the device was treated in the same way as group A and then coated 3 times with 5% PMMA (Group C, n = 12, Aldrich), or coated 3 times with 3% PLGA (Group D, n = 12, Sigma). The devices were randomly allocated to experimental groups of 12 each. All the prototypes of controlled release drug device were soaked in 3 mL distilled water. The concentrations of CHX were determined using a UV spectrophotometer. The surface characteristics of each prototype were observed using a scanning electron microscope. The result showed that release rate of CHX was the greatest in the noncoated group, followed by the chitosan-coated group, the PLGA-coated group, and the PMMA-coated group (P < 0.05). Pores were observed on the surface of the prototypes that were coated with PLGA and PMMA. When the pore size was smaller, the release rate was lower. These data indicate that polymer coating can control the release rate of CHX from the prototypes of controlled release drug device.

Modulation of the release of ( sup 3 H)norepinephrine from the base and body of the rat urinary bladder by endogenous adrenergic and cholinergic mechanisms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Somogyi, G.T.; de Groat, W.C.

Modulation of (3H)NE release was studied in rat urinary bladder strips prelabeled with (3H)NE. (3H)NE uptake occurred in strips from the bladder base and body, but was very prominent in the base where the noradrenergic innervation is most dense. Electrical field stimulation markedly increased (3H)NE outflow from the superfused tissue. The quantity of (3H)NE release was approximately equal during three consecutive periods of stimulation. Activation of presynaptic muscarinic receptors by 1.0 microM oxotremorine reduced (3H)NE release to 46% of the control. Atropine (1 microM) blocked the effect of oxotremorine and increased the release to 147% of predrug control levels. Activationmore » of presynaptic alpha-2 adrenoceptors by 1 microM clonidine reduced (3H)NE release to 55% of control. Yohimbine blocked the action of clonidine and increased the release to 148% of control. The release of (3H)NE from the bladder base and body was increased by both 1 microM atropine (to 167% and 174% of control, respectively) and 1 microM yohimbine (to 286% and 425% of control, respectively). Atropine and yohimbine administered in combination had similar facilitatory effects as when administered alone. We conclude that the release of (3H)NE from adrenergic nerve endings in electrically stimulated bladder strips is modulated via endogenous transmitters acting on both muscarinic and alpha-2 adrenergic presynaptic receptors and that the latter provide the most prominent control.« less

Rate-programming of nano-particulate delivery systems for smart bioactive scaffolds in tissue engineering.

PubMed

Izadifar, Mohammad; Haddadi, Azita; Chen, Xiongbiao; Kelly, Michael E

2015-01-09

Development of smart bioactive scaffolds is of importance in tissue engineering, where cell proliferation, differentiation and migration within scaffolds can be regulated by the interactions between cells and scaffold through the use of growth factors (GFs) and extra cellular matrix peptides. One challenge in this area is to spatiotemporally control the dose, sequence and profile of release of GFs so as to regulate cellular fates during tissue regeneration. This challenge would be addressed by rate-programming of nano-particulate delivery systems, where the release of GFs via polymeric nanoparticles is controlled by means of the methods of, such as externally-controlled and physicochemically/architecturally-modulated so as to mimic the profile of physiological GFs. Identifying and understanding such factors as the desired release profiles, mechanisms of release, physicochemical characteristics of polymeric nanoparticles, and externally-triggering stimuli are essential for designing and optimizing such delivery systems. This review surveys the recent studies on the desired release profiles of GFs in various tissue engineering applications, elucidates the major release mechanisms and critical factors affecting release profiles, and overviews the role played by the mathematical models for optimizing nano-particulate delivery systems. Potentials of stimuli responsive nanoparticles for spatiotemporal control of GF release are also presented, along with the recent advances in strategies for spatiotemporal control of GF delivery within tissue engineered scaffolds. The recommendation for the future studies to overcome challenges for developing sophisticated particulate delivery systems in tissue engineering is discussed prior to the presentation of conclusions drawn from this paper.

Controlling Release Kinetics of PLG Microspheres Using a Manufacturing Technique

NASA Astrophysics Data System (ADS)

Berchane, Nader

2005-11-01

Controlled drug delivery offers numerous advantages compared with conventional free dosage forms, in particular: improved efficacy and patient compliance. Emulsification is a widely used technique to entrap drugs in biodegradable microspheres for controlled drug delivery. The size of the formed microspheres has a significant influence on drug release kinetics. Despite the advantages of controlled drug delivery, previous attempts to achieve predetermined release rates have seen limited success. This study develops a tool to tailor desired release kinetics by combining microsphere batches of specified mean diameter and size distribution. A fluid mechanics based correlation that predicts the average size of Poly(Lactide-co-Glycolide) [PLG] microspheres from the manufacturing technique, is constructed and validated by comparison with experimental results. The microspheres produced are accurately represented by the Rosin-Rammler mathematical distribution function. A mathematical model is formulated that incorporates the microsphere distribution function to predict the release kinetics from mono-dispersed and poly-dispersed populations. Through this mathematical model, different release kinetics can be achieved by combining different sized populations in different ratios. The resulting design tool should prove useful for the pharmaceutical industry to achieve designer release kinetics.

Evaluation of acetylated moth bean starch as a carrier for controlled drug delivery

PubMed Central

Singh, Akhilesh V.; Nath, Lila K.

2012-01-01

The present investigation concerns with the development of controlled release tablets of lamivudine using acetylated moth bean starch. The acetylated starch was synthesized with acetic anhydride in pyridine medium. The acetylated moth bean starch was tested for acute toxicity and drug–excipient compatibility study. The formulations were evaluated for physical characteristics like hardness, friability, % drug content and weight variations. The in vitro release study showed that the optimized formulation exhibited highest correlation (R) value in case of Higuchi kinetic model and the release mechanism study proved that the formulation showed a combination of diffusion and erosion process. There was a significant difference in the pharmacokinetic parameters (Tmax, Cmax, AUC, Vd, T1/2 and MDT) of the optimized formulation as compared to the marketed conventional tablet Lamivir®, which proved controlled release potential of acetylated moth bean starch. PMID:22210486

Colon-specific delivery of 5-aminosalicylic acid from chitosan-Ca-alginate microparticles.

PubMed

Mladenovska, K; Raicki, R S; Janevik, E I; Ristoski, T; Pavlova, M J; Kavrakovski, Z; Dodov, M G; Goracinova, K

2007-09-05

Chitosan-Ca-alginate microparticles for colon-specific delivery and controlled release of 5-aminosalicylic acid after peroral administration were prepared using spray drying method followed by ionotropic gelation/polyelectrolyte complexation. Physicochemical characterization pointed to the negatively charged particles with spherical morphology having a mean diameter less than 9 microm. Chitosan was localized dominantly in the particle wall, while for alginate, a homogeneous distribution throughout the particles was observed. (1)H NMR, FTIR, X-ray and DSC studies indicated molecularly dispersed drug within the particles with preserved stability during microencapsulation and in simulated in vivo drug release conditions. In vitro drug release studies carried out in simulated in vivo conditions in respect to pH, enzymatic and salt content confirmed the potential of the particles to release the drug in a controlled manner. The diffusional exponents according to the general exponential release equation indicated anomalous (non-Fickian) transport in 5-ASA release controlled by a polymer relaxation, erosion and degradation. Biodistribution studies of [(131)I]-5-ASA loaded chitosan-Ca-alginate microparticles, carried out within 2 days after peroral administration to Wistar male rats in which TNBS colitis was induced, confirmed the dominant localization of 5-ASA in the colon with low systemic bioavailability.

Exploitation of novel gum Prunus cerasoides as mucoadhesive beads for a controlled-release drug delivery.

PubMed

Seelan, T Veenus; Kumari, Henry Linda Jeeva; Kishore, Narra; Selvamani, Palanisamy; Lalhlenmawia, H; Thanzami, K; Pachuau, Lalduhsanga; Ruckmani, Kandasamy

2016-04-01

The present study deals with the formulation of pH-sensitive mucoadhesive beads using natural gum isolated from Prunus cerasoides (PC) in combination with sodium alginate (SA) for the controlled release of diclofenac sodium (DS). PC and SA composite (PC-SA), DS loaded SA (DS-SA) and DS loaded PC-SA (DS-PC-SA) beads were prepared by ionotropic gelation method. The absence of interaction between DS and PC-SA was shown by FTIR, DSC and TGA analyses. The optimized DS-PC-SA formulation exhibited mucoadhesive property and the controlled release of DS was achieved 68% in 12h. The in vitro release kinetics follows zero order with anomalous diffusion mechanism. Therefore, the formulated mucoadhesive beads with the novel gum are preferable for the controlled release of DS by prolonging the residence time of the drug in the gastrointestinal tract, overcoming the problems associated with the immediate release dosage forms of DS. Copyright © 2016 Elsevier B.V. All rights reserved.

Intravenous nitroglycerin for controlled cord traction in the management of retained placenta.

PubMed

Visalyaputra, Shusee; Prechapanich, Japarath; Suwanvichai, Sukanya; Yimyam, Suwimol; Permpolprasert, Ladda; Suksopee, Pattipa

2011-02-01

To determine the effect of 200 μg of intravenous nitroglycerin in the release of retained placenta by controlled cord traction. In this randomized controlled study, 40 women with a placenta retained for 30 minutes received intravenously 200 μg of nitroglycerin or a normal saline solution before umbilical cord traction was initiated. The rates of successful removal of the retained placenta in the study (n=20) and control (n=20) groups were compared, as were blood pressure, pulse rate, blood loss, and adverse effects. The placenta was released in only 15% and 20% of the participants in the study and control group, respectively. The remainder of the participants required general anesthesia and manual removal of the retained placenta regardless of group assignation. Blood pressure fell in significantly more women in the study group, but there were no differences in estimated blood loss or minor adverse effects. Intravenously administered nitroglycerin did not facilitate the release of retained placenta by umbilical cord traction. However, cord traction may be performed longer than 30 minutes to attempt releasing the placenta before operative manual removal is initiated. Copyright © 2010 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Hydrogels containing redispersible spray-dried melatonin-loaded nanocapsules: a formulation for transdermal-controlled delivery

NASA Astrophysics Data System (ADS)

Hoffmeister, Cristiane RD; Durli, Taís L.; Schaffazick, Scheila R.; Raffin, Renata P.; Bender, Eduardo A.; Beck, Ruy CR; Pohlmann, Adriana R.; Guterres, Sílvia S.

2012-05-01

The aim of the present study was to develop a transdermal system for controlled delivery of melatonin combining three strategies: nanoencapsulation of melatonin, drying of melatonin-loaded nanocapsules, and incorporation of nanocapsules in a hydrophilic gel. Nanocapsules were prepared by interfacial deposition of the polymer and were spray-dried using water-soluble excipients. In vitro drug release profiles were evaluated by the dialysis bag method, and skin permeation studies were carried out using Franz cells with porcine skin as the membrane. The use of 10% ( w/ v) water-soluble excipients (lactose or maltodextrin) as spray-drying adjuvants furnished redispersible powders (redispersibility index approximately 1.0) suitable for incorporation into hydrogels. All formulations showed a better controlled in vitro release of melatonin compared with the melatonin solution. The best controlled release results were achieved with hydrogels prepared with dried nanocapsules (hydrogels > redispersed dried nanocapsules > nanocapsule suspension > melatonin solution). The skin permeation studies demonstrated a significant modulation of the transdermal melatonin permeation for hydrogels prepared with redispersible nanocapsules. In this way, the additive effect of the different approaches used in this study (nanoencapsulation, spray-drying, and preparation of semisolid dosage forms) allows not only the control of melatonin release, but also transdermal permeation.

An alternative approach based on artificial neural networks to study controlled drug release.

PubMed

Reis, Marcus A A; Sinisterra, Rubén D; Belchior, Jadson C

2004-02-01

An alternative methodology based on artificial neural networks is proposed to be a complementary tool to other conventional methods to study controlled drug release. Two systems are used to test the approach; namely, hydrocortisone in a biodegradable matrix and rhodium (II) butyrate complexes in a bioceramic matrix. Two well-established mathematical models are used to simulate different release profiles as a function of fundamental properties; namely, diffusion coefficient (D), saturation solubility (C(s)), drug loading (A), and the height of the device (h). The models were tested, and the results show that these fundamental properties can be predicted after learning the experimental or model data for controlled drug release systems. The neural network results obtained after the learning stage can be considered to quantitatively predict ideal experimental conditions. Overall, the proposed methodology was shown to be efficient for ideal experiments, with a relative average error of <1% in both tests. This approach can be useful for the experimental analysis to simulate and design efficient controlled drug-release systems. Copyright 2004 Wiley-Liss, Inc. and the American Pharmacists Association

Development of Novel Warfarin-Silica Composite for Controlled Drug Release.

PubMed

Parfenyuk, Elena V; Dolinina, Ekaterina S

2017-04-01

The work is devoted to synthesis and study of warfarin composites with unmodified, methyl and phenyl modified silica in order to develop controlled release formulation of the anticoagulant. The composites were prepared by two routes, adsorption and sol-gel, and characterized with FTIR spectroscopy, dynamic light scattering and DSC methods. The drug release behavior from the composites in media with pH 1.6, 6.8 and 7.4 was analyzed in vitro. The release kinetics of the warfarin - silica composites prepared by the two routes was compared among each other and with analogous silica composites with water soluble drug molsidomine. The comparative analysis showed that in general the kinetic regularities and mechanisms of release for both drugs are similar and determined by nonuniform distribution of the drugs over the silica matrixes and stability of the matrixes in the studied media for the adsorbed composites and uniformly distributed drug and more brittle structure for the sol-gel composites. The sol-gel composite of warfarin - phenyl modified silica is perspective for further development of novel warfarin formulation with controlled release because it releases warfarin according to zero-order kinetic law with approximately equal rate in the media imitating different segments of gastrointestinal tract.

Guidance for Evaluating the Safety of Experimental Releases of Mosquitoes, Emphasizing Mark-Release-Recapture Techniques

PubMed Central

Charlwood, J. Derek; Harrington, Laura C.; Lounibos, L. Philip; Reisen, William K.; Tabachnick, Walter J.

2018-01-01

Abstract Experimental releases of mosquitoes are performed to understand characteristics of populations related to the biology, ability to transmit pathogens, and ultimately their control. In this article, we discuss considerations related to the safety of experimental releases of living mosquitoes, applying principles of good practice in vector biology that protect human health and comfort. We describe specific factors of experimental releases of mosquitoes that we believe are critical to inform institutional biosafety committees and similar review boards to which proposals to conduct mosquito release experiments have been submitted. In this study, “experimental releases” means those that do not significantly increase vector capacity or nuisance biting relative to the unperturbed natural baseline. This document specifically does not address releases of mosquitoes for ongoing control programs or trials of new control methods for which broader assessments of risk are required. It also does not address releases of transgenic or exotic (non-native) mosquito species, both of which require particular regulatory approval. Experimental releases may include females and males and evaluation must consider their effects based on the number released, their genotype and phenotype, the environment into which they are released, and postrelease collection activities. We consider whether increases of disease transmission and nuisance biting might result from proposed experimental releases against the backdrop of natural population size variation. We recommend that experimental releases be conducted in a manner that can be reasonably argued to have insignificant negative effects. Reviewers of proposals for experimental releases should expect applicants to provide such an argument based on evidence from similar studies and their planned activities. This document provides guidance for creating and evaluating such proposals. PMID:29337660

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

PubMed

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.

Synthesis and characterization of superabsorbent polymer prepared by radiation-induced graft copolymerization of acrylamide onto carboxymethyl cellulose for controlled release of agrochemicals

NASA Astrophysics Data System (ADS)

Hemvichian, Kasinee; Chanthawong, Auraruk; Suwanmala, Phiriyatorn

2014-10-01

Superabsorbent polymer (SAP) was synthesized by radiation-induced grafting of acrylamide (AM) onto carboxymethyl cellulose (CMC) in the presence of a crosslinking agent, N,N‧-methylenebisacrylamide (MBA). The effects of various parameters, such as dose, the amount of CMC, AM, MBA and ionic strength on the swelling ratio were investigated. In order to evaluate its controlled release potential, SAP was loaded with potassium nitrate (KNO3) as an agrochemical model and its potential for controlled release of KNO3 was studied. The amount of released KNO3 was analyzed by an inductively coupled plasma mass spectrometry (ICP-MS). The results from controlled release experiment agreed very well with the results from swelling experiment. The synthesized SAP was characterized by Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA). The obtained SAP exhibited a swelling ratio of 190 g/g of dry gel.

Chitosan nanoparticles/cellulose nanocrystals nanocomposites as a carrier system for the controlled release of repaglinide.

PubMed

Abo-Elseoud, Wafaa S; Hassan, Mohammad L; Sabaa, Magdy W; Basha, Mona; Hassan, Enas A; Fadel, Shaimaa M

2018-05-01

The aim of the present work was to study the use of cellulose nanocrystals (CNC) and chitosan nanoparticles (CHNP) for developing controlled-release drug delivery system of the anti-hyperglycemic drug Repaglinide (RPG). CNC was isolated from palm fruit stalks by sulfuric acid hydrolysis; the dimensions of the isolated nanocrystals were 86-237 nm in length and 5-7 nm in width. Simple and economic method was used for the fabrication of controlled release drug delivery system from CNC and CHNP loaded with RPG drug via ionic gelation of chitosan in the presence of CNC and RPG. The prepared systems showed high drug encapsulation efficiency of about ~98%. Chemical modification of CNC by oxidation to introduce carboxylic groups on their surface (OXCNC) was also carried out for further controlling of RPG release. Particles size analysis showed that the average size of CHNP was about 197 nm while CHNP/CNC/RPG or CHNP/OXCNC/RPG nanoparticles showed average size of 215-310 nm. Compatibility studies by Fourier transform infrared (FTIR) spectroscopy showed no chemical reaction between RPG and the system's components used. By studying the drug release kinetic, all the prepared RPG formulations followed Higuchi model, indicating that the drug released by diffusion through the nanoparticles polymeric matrix. Copyright © 2018 Elsevier B.V. All rights reserved.

Histamine-releasing factor/translationally controlled tumor protein (HRF/TCTP)-induced histamine release is enhanced with SHIP-1 knockdown in cultured human mast cell and basophil models

PubMed Central

Langdon, Jacqueline M.; Schroeder, John T.; Vonakis, Becky M.; Bieneman, Anja P.; Chichester, Kristin; MacDonald, Susan M.

2008-01-01

Previously, we demonstrated a negative correlation between histamine release to histamine-releasing factor/translationally controlled tumor protein (HRF/TCTP) and protein levels of SHIP-1 in human basophils. The present study was conducted to investigate whether suppressing SHIP-1 using small interfering (si)RNA technology would alter the releasability of culture-derived mast cells and basophils, as determined by HRF/TCTP histamine release. Frozen CD34+ cells were obtained from the Fred Hutchinson Cancer Research Center (Seattle, WA, USA). Cells were grown in StemPro-34 medium containing cytokines: mast cells with IL-6 and stem cell factor (100 ng/ml each) for 6–8 weeks and basophils with IL-3 (6.7 ng/ml) for 2–3 weeks. siRNA transfections were performed during Week 6 for mast cells and Week 2 for basophils with siRNA for SHIP-1 or a negative control siRNA. Changes in SHIP-1 expression were determined by Western blot. The functional knockdown was measured by HRF/TCTP-induced histamine release. siRNA knockdown of SHIP-1 in mast cells ranged from 31% to 82%, mean 65 ± 12%, compared with control (n=4). Histamine release to HRF/TCTP was increased only slightly in two experiments. SHIP-1 knockdown in basophils ranged from 34% to 69%, mean 51.8 ± 7% (n=4). Histamine release to HRF/TCTP in these basophils was dependent on the amount of SHIP knockdown. Mast cells and basophils derived from CD34+ precursor cells represent suitable models for transfection studies. Reducing SHIP-1 protein in cultured mast cells and in cultured basophils increases releasability of the cells. PMID:18625911

Formulation and dissolution kinetics study of hydrophilic matrix tablets with tramadol hydrochloride and different co-processed dry binders.

PubMed

Komersová, Alena; Lochař, Václav; Myslíková, Kateřina; Mužíková, Jitka; Bartoš, Martin

2016-12-01

The aim of this study is to present the possibility of using of co-processed dry binders for formulation of matrix tablets with drug controlled release. Hydrophilic matrix tablets with tramadol hydrochloride, hypromellose and different co-processed dry binders were prepared by direct compression method. Hypromelloses Methocel™ K4M Premium CR or Methocel™ K100M Premium CR were used as controlled release agents and Prosolv® SMCC 90 or Disintequik™ MCC 25 were used as co-processed dry binders. Homogeneity of the tablets was evaluated using scanning electron microscopy and energy dispersive X-ray microanalysis. The release of tramadol hydrochloride from prepared formulations was studied by dissolution test method. The dissolution profiles obtained were evaluated by non-linear regression analysis, release rate constants and other kinetic parameters were determined. It was found that matrix tablets based on Prosolv® SMCC 90 and Methocel™ Premium CR cannot control the tramadol release effectively for >12h and tablets containing Disintequik™ MCC 25 and Methocel™ Premium CR >8h. Copyright © 2016 Elsevier B.V. All rights reserved.

A randomized trial of controlled-release oxycodone during inpatient rehabilitation following unilateral total knee arthroplasty.

PubMed

Cheville, A; Chen, A; Oster, G; McGarry, L; Narcessian, E

2001-04-01

Reliance on "as-needed" analgesia following total knee arthroplasty may lead to inadequate control of pain and delayed recovery of function. Preemptive use of controlled-release opioids may improve pain control, accelerate recovery, and reduce the need for inpatient rehabilitative services. This study was designed to determine whether controlled-release opioids enhance post-arthroplasty pain control and facilitate functional recovery during rehabilitation. Fifty-nine patients admitted for inpatient rehabilitation following unilateral total knee arthroplasty were randomized to receive OxyContin (controlled-release oxycodone) (twenty-nine patients) or a placebo (thirty patients) every twelve hours. Both groups could receive on-request, immediate-release oxycodone (5 mg every four hours). The dose of study medication was increased on the basis of the frequency of requests for immediate-release oxycodone. Measures of interest included pain ratings as determined with a visual-analog scale, changes in the range of motion of the knee and quadriceps strength, and improvements in selected Functional Independence Measure scores during the first eight physical therapy sessions. The duration of the hospital stay for rehabilitation also was compared between the two groups. Baseline demographic, clinical, and functional characteristics were similar between the OxyContin and placebo groups. Compared with the placebo group, the patients who received OxyContin reported significantly less pain as well as significantly greater range of motion of the knee (passive motion, p = 0.036; active motion, p< 0.001) and quadriceps strength (p = 0.001) by the eighth physical therapy session. The patients who received OxyContin also were discharged from the rehabilitation hospital at an average of 2.3 days earlier than the patients in the placebo group (p = 0.013). Preemptive use of controlled-release oxycodone during rehabilitation following total knee arthroplasty leads to improved pain control, more rapid functional recovery, and a reduced need for inpatient rehabilitative services.

Biophysical characterization of hydrogel-core, lipid-shell nanoparticles (nanolipogels) for HIV chemoprophylaxis

NASA Astrophysics Data System (ADS)

Mahadevan, Reena

Nanoparticles are emerging as versatile vehicles for drug delivery, providing targeting, protection, and controlled-release capabilities to encapsulated cargo. Polymeric nanoparticles made from poly(lactide-co-glycolide) (PLGA) are biodegradable, exhibit tunable drug release, and have encapsulated a wide variety of biological agents. However, PLGA nanoparticles are relatively inefficient at encapsulating small-molecule hydrophilic drugs. Liposomes encapsulate greater amounts of hydrophilic agents and demonstrate good cellular affinity; however, they lack controlled-release functionality. Hydrogel-core lipid-shell nanoparticles, or nanolipogels, combine the controlled-release capability of polymeric nanocarriers with the hydrophilic and cellular affinity of liposomes into a single drug delivery vehicle. This study establishes a facile, reproducible synthetic protocol for nanolipogels and evaluates hydrogel swelling as a mechanism for release of the small hydrophilic antiretroviral azidothymidine from nanolipogels.

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

PubMed

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.

Micro-/mesoporous carbons for controlled release of antipyrine and indomethacin

DOE PAGES

Saha, Dipendu; Moken, Tara; Chen, Jihua; ...

2015-02-24

Here, we have demonstrated the potential of meso- and microporous carbons in controlled release applications and targeted oral drug delivery. We have employed two mesoporous and two microporous carbons for the sustained release of one water-soluble drug (antipyrine) and one water-insoluble drug (indomethacin), using these as models to examine the controlled release characteristics. The micro-/mesoporous carbons were characterized as having a BET surface area of 372–2251 m 2 g –1 and pore volume 0.63–1.03 cm 3 g –1. The toxicity studies with E. coli bacterial cells did not reveal significant toxicity, which is in accordance with our previous studies onmore » human cells with similar materials. Mucin adsorption tests with type III pork mucin demonstrated 20–30% mucin adsorption by the carbon samples and higher mucin adsorption could be attributed to higher surface area and more oxygen functionalities. Antipyrine and indomethacin loading was 6–78% in these micro-/mesoporous carbons. The signatures in thermogravimetric studies revealed the presence of drug molecules within the porous moieties of the carbon. The partial shifting of the decomposition peak of the drug adsorbed within the carbon pores was caused by the confinement of drug molecules within the narrow pore space of the carbon. The release profiles of both drugs were examined in simulated gastric fluid (pH = 1.2) and in three other release media with respective pH values of 4.5, 6.8 and 7.4, along with varying residence times to simulate the physiological conditions of the stomach, duodenum, small intestine and colon, respectively. All the release profiles manifested diffusion controlled sustained release that corroborates the effective role of micro-/mesoporous carbons as potential drug carriers.« less

Micro-/mesoporous carbons for controlled release of antipyrine and indomethacin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saha, Dipendu; Moken, Tara; Chen, Jihua

Here, we have demonstrated the potential of meso- and microporous carbons in controlled release applications and targeted oral drug delivery. We have employed two mesoporous and two microporous carbons for the sustained release of one water-soluble drug (antipyrine) and one water-insoluble drug (indomethacin), using these as models to examine the controlled release characteristics. The micro-/mesoporous carbons were characterized as having a BET surface area of 372–2251 m 2 g –1 and pore volume 0.63–1.03 cm 3 g –1. The toxicity studies with E. coli bacterial cells did not reveal significant toxicity, which is in accordance with our previous studies onmore » human cells with similar materials. Mucin adsorption tests with type III pork mucin demonstrated 20–30% mucin adsorption by the carbon samples and higher mucin adsorption could be attributed to higher surface area and more oxygen functionalities. Antipyrine and indomethacin loading was 6–78% in these micro-/mesoporous carbons. The signatures in thermogravimetric studies revealed the presence of drug molecules within the porous moieties of the carbon. The partial shifting of the decomposition peak of the drug adsorbed within the carbon pores was caused by the confinement of drug molecules within the narrow pore space of the carbon. The release profiles of both drugs were examined in simulated gastric fluid (pH = 1.2) and in three other release media with respective pH values of 4.5, 6.8 and 7.4, along with varying residence times to simulate the physiological conditions of the stomach, duodenum, small intestine and colon, respectively. All the release profiles manifested diffusion controlled sustained release that corroborates the effective role of micro-/mesoporous carbons as potential drug carriers.« less

Laser-triggered release of encapsulated molecules from polylactic-co-glycolic acid microcapsules

NASA Astrophysics Data System (ADS)

Ariyasu, Kazumasa; Ishii, Atsuhiro; Umemoto, Taiga; Terakawa, Mitsuhiro

2016-08-01

The controlled release of encapsulated molecules from a microcapsule is a promising method of targeted drug delivery. Laser-triggered methods for the release of encapsulated molecules have the advantage of spatial and temporal controllability. In this study, we demonstrated the release of encapsulated molecules from biodegradable polymer-based microcapsules using near-infrared femtosecond laser pulses. The polylactic-co-glycolic acid microcapsules encapsulating fluorescein isothiocyanate-dextran molecules were fabricated using a dual-coaxial nozzle system. Irradiation of femtosecond laser pulses enhanced the release of the molecules from the microcapsules, which was accompanied by a decrease in the residual ratio of the microcapsules. The laser-induced modification of the surface of the shell of the microcapsules indicated the potential for sustained release as well as burst release.

Effects of a Community Toxic Release on the Psychological Status of Children

ERIC Educational Resources Information Center

Greve, Kevin W.; Bianchini, Kevin J.; Stickle, Timothy R.; Love, Jeffrey M.; Doane, Bridget M.; Thompson, Matthew D.

2007-01-01

This study sought to determine the emotional effects of a major community toxic release on children in the exposed community while controlling for the potential effects of response bias. Controlling for the response bias inherent in litigated contexts is an advance over previous studies of toxic exposure in children. A randomly selected…

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

PubMed

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.

Synthesis and characterization of emamectin-benzoate slow-release microspheres with different surfactants.

PubMed

Wang, Yan; Wang, Anqi; Wang, Chunxin; Cui, Bo; Sun, Changjiao; Zhao, Xiang; Zeng, Zhanghua; Shen, Yue; Gao, Fei; Liu, Guoqiang; Cui, Haixin

2017-10-06

Pesticide slow-release formulations provide a way to increase the efficiency of active components by reducing the amount of pesticide that needs to be applied. Slow-release formulations also increase the stability and prolong the control effect of photosensitive pesticides. Surfactants are an indispensable part of pesticide formulations, and the choice of surfactant can strongly affect formulation performance. In this study, emamectin-benzoate (EMB) slow-release microspheres were prepared by the microemulsion polymerization method. We explored the effect of different surfactants on the particle size and dispersity of EMB in slow-release microspheres. The results indicated that the samples had uniform spherical shapes with an average diameter of 320.5 ±5.24 nm and good dispersity in the optimal formulation with the polymeric stabilizer polyvinyl alcohol (PVA) and composite non-ionic surfactant polyoxyethylene castor oil (EL-40). The optimal EMB pesticide slow-release microspheres had excellent anti-photolysis performance, stability, controlled release properties, and good leaf distribution. These results demonstrated that EMB slow-release microspheres are an attractive candidate for improving pesticide efficacy and prolonging the control effect of EMB in the environment.

A Simple Approach for Molecular Controlled Release based on Atomic Layer Deposition Hybridized Organic-Inorganic Layers

PubMed Central

Boehler, Christian; Güder, Firat; Kücükbayrak, Umut M.; Zacharias, Margit; Asplund, Maria

2016-01-01

On-demand release of bioactive substances with high spatial and temporal control offers ground-breaking possibilities in the field of life sciences. However, available strategies for developing such release systems lack the possibility of combining efficient control over release with adequate storage capability in a reasonably compact system. In this study we present a new approach to target this deficiency by the introduction of a hybrid material. This organic-inorganic material was fabricated by atomic layer deposition of ZnO into thin films of polyethylene glycol, forming the carrier matrix for the substance to be released. Sub-surface growth mechanisms during this process converted the liquid polymer into a solid, yet water-soluble, phase. This layer permits extended storage for various substances within a single film of only a few micrometers in thickness, and hence demands minimal space and complexity. Improved control over release of the model substance Fluorescein was achieved by coating the hybrid material with a conducting polymer film. Single dosage and repetitive dispensing from this system was demonstrated. Release was controlled by applying a bias potential of ±0.5 V to the polymer film enabling or respectively suppressing the expulsion of the model drug. In vitro tests showed excellent biocompatibility of the presented system. PMID:26791399

Lack of in vitro-in vivo correlation for a UC781-releasing vaginal ring in macaques.

PubMed

McConville, Christopher; Smith, James M; McCoy, Clare F; Srinivasan, Priya; Mitchell, James; Holder, Angela; Otten, Ron A; Butera, Salvatore; Doncel, Gustavo F; Friend, David R; Malcolm, R Karl

2015-02-01

This study describes the preclinical development of a matrix-type silicone elastomer vaginal ring device designed to provide controlled release of UC781, a non-nucleoside reverse transcriptase inhibitor. Testing of both human- and macaque-sized rings in a sink condition in vitro release model demonstrated continuous UC781 release in quantities considered sufficient to maintain vaginal fluid concentrations at levels 82-860-fold higher than the in vitro IC50 (2.0 to 10.4 nM) and therefore potentially protect against mucosal transmission of HIV. The 100-mg UC781 rings were well tolerated in pig-tailed macaques, did not induce local inflammation as determined by cytokine analysis and maintained median concentrations in vaginal fluids of UC781 in the range of 0.27 to 5.18 mM during the course of the 28-day study. Analysis of residual UC781 content in rings after completion of both the in vitro release and macaque pharmacokinetic studies revealed that 57 and 5 mg of UC781 was released, respectively. The pharmacokinetic analysis of a 100-mg UC781 vaginal ring in pig-tailed macaques showed poor in vivo-in vitro correlation, attributed to the very poor solubility of UC781 in vaginal fluid and resulting in a dissolution-controlled drug release mechanism rather than the expected diffusion-controlled mechanism.

Long-term Controlled Drug Release from bi-component Electrospun Fibers

NASA Astrophysics Data System (ADS)

Xu, Shanshan; Zhang, Zixin; Xia, Qinghua; Han, Charles

Multi-drug delivery systems with timed programmed release are hard to be produced due to the complex drug release kinetics which mainly refers to the diffusion of drug molecules from the fiber and the degradation of the carrier. This study focused on the whole life-time story of the long-term drug releasing fibrous systems. Electrospun membrane utilizing FDA approved polymers and broad-spectrum antibiotics showed specific drug release profiles which could be divided into three stages based on the profile slope. With throughout morphology observation, cumulative release amount and releasing duration, releasing kinetics and critical factors were fully discussed during three stages. Through changing the second component, approximately linear drug release profile and a drug release duration about 13 days was prepared, which is perfect for preventing post-operative infection. The addition of this semi-crystalline polymer in turn influenced the fiber swelling and created drug diffusion channels. In conclusion, through adjusting and optimization of the blending component, initial burst release, delayed release for certain duration, and especially the sustained release profile could all be controlled, as well as specific anti-bacterial behavior could be obtained.

Drug Release and Skin Permeation from Lipid Liquid Crystalline Phases

NASA Astrophysics Data System (ADS)

Costa-Balogh, F. O.; Sparr, E.; Sousa, J. J. S.; Pais, A. A. C. C.

We have studied drug release and skin permeation from several different liquid crystalline lipid formulations that may be used to control the respective release rates. We have studied the release and permeation through human skin of a water-soluble and amphiphilic drug, propranolol hydrochloride, from several formulations prepared with monoolein and phytantriol as permeation enhancers and controlled release excipients. Diolein and cineol were added to selected formulations. We observed that viscosity decreases with drug load, wich is compatible with the occurrence of phase changes. Diolein stabilizes the bicontinuous cubic phases leading to an increase in viscosity and sustained release of the drug. The slowest release was found for the cubic phases with higher viscosity. Studies on skin permeation showed that these latter formulations also presented lower permeability than the less viscous monoolein lamellar phases. Formulations containing cineol originated higher permeability with higher enhancement ratios. Thus, the various formulations are adapted to different circumstances and delivery routes. While a slow release is usually desired for drug sustained delivery, the transdermal route may require a faster release. Lamellar phases, which are less viscous, are more adapted to transdermal applications. Thus, systems involving lamellar phases of monoolein and cineol are good candidates to be used as skin permeation enhancers for propranolol hydrochloride.

Responsiveness of blood and sputum inflammatory cells in Japanese COPD patients, non-COPD smoking controls, and non-COPD nonsmoking controls

PubMed Central

Kawayama, Tomotaka; Kinoshita, Takashi; Matsunaga, Kazuko; Kobayashi, Akihiro; Hayamizu, Tomoyuki; Johnson, Malcolm; Hoshino, Tomoaki

2016-01-01

Purpose To compare pulmonary and systemic inflammatory mediator release, pre- and poststimulation, ex vivo, in cells from Japanese patients with chronic obstructive pulmonary disease (COPD), non-COPD smoking controls, and non-COPD nonsmoking controls (NSC). Patients and methods This was a nontreatment study with ten subjects per group. Inflammatory biomarker release, including interleukin (IL)-6 and -8, matrix metalloproteinase-9, and tumor necrosis factor (TNF)-α, was measured in peripheral blood mononuclear cells (PBMC) and sputum cells with and without lipopolysaccharide or TNF-α stimulation. Results In PBMC, basal TNF-α release (mean ± standard deviation) was significantly different between COPD (81.6±111.4 pg/mL) and nonsmoking controls (9.5±5.2 pg/mL) (P<0.05). No other significant differences were observed. Poststimulation biomarker release tended to increase, with the greatest changes in the COPD group. The greatest mean increases were seen in the lipopolysaccharide-induced release of matrix metalloproteinase-9, TNF-α, and IL-6 from PBMC. Pre- and poststimulation data from sputum samples were more variable and less conclusive than from PBMC. In the COPD group, induced sputum neutrophil levels were higher and macrophage levels were lower than in either control group. Significant correlations were seen between the number of sputum cells (macrophages and neutrophils) and biomarker levels (IL-8, IL-6, and TNF-α). Conclusion This was the first study to compare cellular inflammatory mediator release before and after stimulation among Japanese COPD, smoking controls, and nonsmoking controls populations. Poststimulation levels tended to be higher in patients with COPD. The results suggest that PBMC are already preactivated in the circulation in COPD patients. This provides further evidence that COPD is a multicomponent disease, involving both airway and systemic inflammation. PMID:26929615

Responsiveness of blood and sputum inflammatory cells in Japanese COPD patients, non-COPD smoking controls, and non-COPD nonsmoking controls.

PubMed

Kawayama, Tomotaka; Kinoshita, Takashi; Matsunaga, Kazuko; Kobayashi, Akihiro; Hayamizu, Tomoyuki; Johnson, Malcolm; Hoshino, Tomoaki

2016-01-01

To compare pulmonary and systemic inflammatory mediator release, pre- and poststimulation, ex vivo, in cells from Japanese patients with chronic obstructive pulmonary disease (COPD), non-COPD smoking controls, and non-COPD nonsmoking controls (NSC). This was a nontreatment study with ten subjects per group. Inflammatory biomarker release, including interleukin (IL)-6 and -8, matrix metalloproteinase-9, and tumor necrosis factor (TNF)-α, was measured in peripheral blood mononuclear cells (PBMC) and sputum cells with and without lipopolysaccharide or TNF-α stimulation. In PBMC, basal TNF-α release (mean ± standard deviation) was significantly different between COPD (81.6±111.4 pg/mL) and nonsmoking controls (9.5±5.2 pg/mL) (P<0.05). No other significant differences were observed. Poststimulation biomarker release tended to increase, with the greatest changes in the COPD group. The greatest mean increases were seen in the lipopolysaccharide-induced release of matrix metalloproteinase-9, TNF-α, and IL-6 from PBMC. Pre- and poststimulation data from sputum samples were more variable and less conclusive than from PBMC. In the COPD group, induced sputum neutrophil levels were higher and macrophage levels were lower than in either control group. Significant correlations were seen between the number of sputum cells (macrophages and neutrophils) and biomarker levels (IL-8, IL-6, and TNF-α). This was the first study to compare cellular inflammatory mediator release before and after stimulation among Japanese COPD, smoking controls, and nonsmoking controls populations. Poststimulation levels tended to be higher in patients with COPD. The results suggest that PBMC are already preactivated in the circulation in COPD patients. This provides further evidence that COPD is a multicomponent disease, involving both airway and systemic inflammation.

Evaluation of quality of life and sexual functioning of women using levonorgestrel-releasing intrauterine contraceptive system--Mirena.

PubMed

Skrzypulec, Violetta; Drosdzol, Agnieszka

2008-12-01

The advantages ensuing from the high contraceptive efficacy, positive effect on the parameters of the menstrual cycle as well as other values of the levonorgestrel-releasing intrauterine system may play an important role in women's sexual life. The aim of the study was to evaluate the effect of the levonorgestrel-releasing intrauterine system on the quality of life and sexual functioning of women. The research encompassed 200 women aged between 30 and 45. 52 women using the levonorgestrel-releasing intrauterine system were qualified to the study as the research group (Mirena Group). The control groups consisted of 48 women using a different type of intrauterine device (Control Group I--Other IUD) and 50 women using no contraception (Control Group II). A specific questionnaire with a general part concerning socio-demographic conditions, a part dealing with contraception and Polish version of self-evaluation inventories: Short Form-36 Health Survey, Female Sexual Function Index and Mell-Krat Scale was used as a research tool. Quality of life parameters for women using the Mirena system were higher than for the control groups, especially in the aspect of general health, energy/fatigue and emotional well-being. A significant beneficial effect of the levonorgestrel-releasing intrauterine system on sexual functioning (sexual desire and arousal) was also revealed in the study. Sexual dysfunctions were diagnosed in 20.8% of Other IUD, 34.7% of Control Group II and 9.6% of Mirena Group. Levonorgestrel-releasing intrauterine system increases female quality of life and sexual functioning parameters.

Laboratory-scale column study for remediation of TCE-contaminated aquifers using three-section controlled-release potassium permanganate barriers.

PubMed

Yuan, Baoling; Li, Fei; Chen, Yanmei; Fu, Ming-Lai

2013-05-01

A laboratory-scale study with a sand column was designed to simulate trichloroethylene (TCE) pollution in the aquifer environment with three-section controlled-release potassium permanganate (CRP) barriers. The main objective of this study was to evaluate the feasibility of CRP barriers in remediation of TCE in aquifers in a long-term and controlled manner. CRP particles with a 1:3 molar ratio of KMnO4 to stearic acid showed the best controlled-release properties in pure water, and the theoretical release time was 138.5 days. The results of TCE removal in the test column indicated that complete removal efficiency of TCE in a sand column by three-section CRP barriers could be reached within 15 days. The molar ratio of KMnO4 to TCE in the three-section CRP barriers was 16:1, which was much lower than 82:1 as required when KMnO4 solution is used directly to achieve complete destruction of TCE. This result revealed that the efficiency of CRP for remediation of TCE was highly improved after encapsulation.

Development of gastro intestinal sustained release tablet formulation containing acryl-EZE and pH-dependent swelling HPMC K 15 M.

PubMed

Lamoudi, Lynda; Chaumeil, Jean Claude; Daoud, Kamel

2012-05-01

The aim of this study was to evaluate physical properties and release from matrix tablets containing different ratios of HPMC 15 M and Acryl-EZE. A further aim is to assess their suitability for pH dependent controlled release. Matrix tablets containing HPMC 15 M and Acryl-EZE were manufactured using a fluidized bed. The release from this matrix using Sodium Diclofenac (SD) as model drug is studied in two dissolution media (0.1 N HCl or pH = 6.8 phosphate buffer solution); the release rate, mechanism, and pH dependence were characterized by fitting four kinetic models and by using a similarity factor analysis. The obtained results revealed that the presence of Acryl-EZE in the matrix tablets is effective in protecting the dosage forms from release in acid environments such as gastric fluid. In pH = 6.8 phosphate buffer, the drug release rate and mechanism of release from all matrices is mainly controlled by HPMC 15 M. The model of Korsmeyer-Peppas was found to fit experimental dissolution results.

Effects of release procedures on the primary stress response and post-release survival and growth of hatchery-reared spotted seatrout Cynoscion nebulosus.

PubMed

Guest, T W; Rakocinski, C F; Evans, A N; Blaylock, R B

2017-03-01

To help explain the apparent poor post-release success of hatchery-reared (HR) spotted seatrout Cynoscion nebulosus, this study examined the effects of handling, transport and release procedures on the stress response of two age classes [48 and 80 day post-hatch (dph)] of HR C. nebulosus, as measured by cortisol concentrations and the post-release survival and growth of 48 and 80 dph HR C. nebulosus. As a proxy for stress, tissue cortisol was measured at various times during the handling, tagging (80 dph), transport, acclimation and release process. To consider the implications of the pre-release stressors, growth and survival were monitored in separate field experiments for each age class of acclimated post-transport C. nebulosus using control C. nebulosus that only experienced anaesthesia, transport, acclimation and a net release v. experimental C. nebulosus that underwent the entire routine procedure, including anaesthesia, tagging, transport, acclimation and gravity release through a pipe. For 48 dph C. nebulosus, mean cortisol varied significantly throughout handling and transport, increasing more than six-fold from controls before decreasing in mean concentration just prior to release. For 80 dph C. nebulosus, cortisol varied throughout handling, tagging and transport, first increasing more than three-fold compared with control C. nebulosus, before decreasing and rising slightly just prior to release. For 48 dph C. nebulosus within field enclosures, survival was high and similar for control and experimental groups; experimental C. nebulosus, however, were shorter, lighter and lower in condition than control C. nebulosus. For 80 dph C. nebulosus within field enclosures, fewer experimental C. nebulosus survived and those that did survive were of lower condition than C. nebulosus from the control group. Small untagged C. nebulosus may survive the release procedure better than larger C. nebulosus carrying a coded-wire tag. These findings document some ways in which pre-release practices may translate into detrimental effects on post-release success of HR C. nebulosus. © 2016 The Fisheries Society of the British Isles.

Development of controlled release formulations of azadirachtin-A employing poly(ethylene glycol) based amphiphilic copolymers.

PubMed

Kumar, Jitendra; Shakil, Najam A; Singh, Manish K; Singh, Mukesh K; Pandey, Alka; Pandey, Ravi P

2010-05-01

Controlled release (CR) formulations of azadirachtin-A, a bioactive constituent derived from the seed of Azadirachta indica A. Juss (Meliaceae), have been prepared using commercially available polyvinyl chloride, polyethylene glycol (PEG) and laboratory synthesized poly ethylene glycol-based amphiphilic copolymers. Copolymers of polyethylene glycol and various dimethyl esters, which self assemble into nano micellar aggregates in aqueous media, have been synthesized. The kinetics of azadirachtin-A, release in water from the different formulations was studied. Release from the commercial polyethylene glycol (PEG) formulation was faster than the other CR formulations. The rate of release of encapsulated azadirachtin-A from nano micellar aggregates is reduced by increasing the molecular weight of PEG. The diffusion exponent (n value) of azadirachtin-A, in water ranged from 0.47 to 1.18 in the tested formulations. The release was diffusion controlled with a half release time (t(1/2)) of 3.05 to 42.80 days in water from different matrices. The results suggest that depending upon the polymer matrix used, the application rate of azadirachtin-A can be optimized to achieve insect control at the desired level and period.

Injectable biodegradable temperature-responsive PLGA-PEG-PLGA copolymers: synthesis and effect of copolymer composition on the drug release from the copolymer-based hydrogels.

PubMed

Qiao, Mingxi; Chen, Dawei; Ma, Xichen; Liu, Yanjun

2005-04-27

Injectable biodegradable temperature-responsive poly(DL-lactide-co-glycolide-b-ethylene glycol-b-DL-lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymers with DL-lactide/glycolide molar ratio ranging from 6/1 to 15/l were synthesized from monomers of DL-lactide, glycolide and polyethylene glycol and characterized by 1H NMR. The resulting copolymers are soluble in water to form free flowing fluid at room temperature but become hydrogels at body temperature. The hydrophobicity of the copolymer increased with the increasing of DL-lactide/glycolide molar ratio. In vitro dissolution studies with two different hydrophobic drugs (5-fluorouracil and indomethacin) were performed to study the effect of DL-lactide/glycolide molar ratio on drug release and to elucidate drug release mechanism. The release mechanism for hydrophilic 5-fluorouracil was diffusion-controlled, while hydrophobic indomethacin showed an biphasic profile comprising of an initial diffusion-controlled stage followed by the hydrogel erosion-dominated stage. The effect of DL-lactide/glycolide molar ratio on drug release seemed to be dependent on the drug release mechanism. It has less effect on the drug release during the diffusion-controlled stage, but significantly affected drug release during the hydrogel erosion-controlled stage. Compared with ReGel system, the synthesized copolymers showed a higher gelation temperature and longer period of drug release. The copolymers can solubilize the hydrophobic indomethacin and the solubility (13.7 mg/ml) was increased 3425-fold compared to that in water (4 microg/ml, 25 degrees C). Two methods of physical mixing method and solvent evaporation method were used for drug solubilization and the latter method showed higher solubilization efficiency.

Controlled Release of Imidacloprid from Poly Styrene-Diacetone - Nanoformulation

NASA Astrophysics Data System (ADS)

Qian, Kun; Guo, Yanzhen; He, Lin

2012-01-01

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

Analysis of LNG peakshaving-facility release-prevention systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

1982-05-01

The purpose of this study is to provide an analysis of release prevention systems for a reference LNG peakshaving facility. An overview assessment of the reference peakshaving facility, which preceeded this effort, identified 14 release scenarios which are typical of the potential hazards involved in the operation of LNG peakshaving facilities. These scenarios formed the basis for this more detailed study. Failure modes and effects analysis and fault tree analysis were used to estimate the expected frequency of each release scenario for the reference peakshaving facility. In addition, the effectiveness of release prevention, release detection, and release control systems weremore » evaluated.« less

Dual crosslinked pectin-alginate network as sustained release hydrophilic matrix for repaglinide.

PubMed

Awasthi, Rajendra; Kulkarni, Giriraj T; Ramana, Malipeddi Venkata; de Jesus Andreoli Pinto, Terezinha; Kikuchi, Irene Satiko; Molim Ghisleni, Daniela Dal; de Souza Braga, Marina; De Bank, Paul; Dua, Kamal

2017-04-01

Repaglinide, an oral antidiabetic agent, has a rapid onset of action and short half-life of approximately 1h. Developing a controlled and prolonged release delivery system is required to maintain its therapeutic plasma concentration and to eliminate its adverse effects particularly hypoglycemia. The present study aimed to develop controlled release repaglinide loaded beads using sodium alginate and pectin with dual cross-linking for effective control of drug release. The prepared beads were characterized for size, percentage drug entrapment efficiency, in vitro drug release and the morphological examination using scanning electron microscope. For the comparative study, the release profile of a marketed conventional tablet of repaglinide (Prandin ® tablets 2mg, Novo Nordisk) was determined by the same procedure as followed for beads. The particle size of beads was in the range of 698±2.34-769±1.43μm. The drug entrapment efficiency varied between 55.24±4.61 to 82.29±3.42%. The FTIR results suggest that there was no interaction between repaglinide and excipients. The XRD and DSC results suggest partial molecular dispersion and amorphization of the drug throughout the system. These results suggest that repaglinide did not dissolve completely in the polymer composition and seems not to be involved in the cross-linking reaction. The percent drug release was decreased with higher polymer concentrations. In conclusion, the developed beads could enhance drug entrapment efficiency, prolong the drug release and enhance bioavailability for better control of diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.

Elucidation of release characteristics of highly soluble drug trimetazidine hydrochloride from chitosan-carrageenan matrix tablets.

PubMed

Li, Liang; Wang, Linlin; Shao, Yang; Tian, Ye; Li, Conghao; Li, Ying; Mao, Shirui

2013-08-01

The aim of this study was to better understand the underlying drug release characteristics from matrix tablets based on the combination of chitosan (CS) and different types of carrageenans [kappa (κ)-CG, iota (ι)-CG, and lambda (λ)-CG]. Highly soluble trimetazidine hydrochloride (TH) was used as a model drug. First, characteristics of drug release from different formulations were investigated, and then in situ complexation capacity of CG with TH and CS was studied by differential scanning calorimetry and Fourier transform infrared spectroscopy. Erosion and swelling of matrix were also characterized to better understand the drug-release mechanisms. Effects of pH and ionic strength on drug release were also studied. It was found that not only ι-CG and λ-CG could reduce the burst release of TH by the effect of TH-CG interaction, CS-ι-CG- and CS-λ-CG-based polyelectrolyte film could further modify the controlled-release behavior, but not CS-κ-CG. High pH and high ionic strength resulted in faster drug release from CS-κ-CG- and CS-ι-CG-based matrix, but drug release from CS-λ-CG-based matrix was less sensitive to pH and ionic strength. In conclusion, CS-λ-CG-based matrix tablets are quite promising as controlled-release drug carrier based on multiple mechanisms. Copyright © 2013 Wiley Periodicals, Inc.

Preparation and characterization of cefditoren pivoxil-loaded liposomes for controlled in vitro and in vivo drug release

PubMed Central

Venugopalarao, Gojjala; Lakshmipathy, Rajasekhar; Sarada, Nallani Chakravarthula

2015-01-01

Background The application of antibiotics has been limited due to weak biodistribution and pharmacokinetics. Encapsulation of these drugs in lipid vesicles might be a good solution for obtaining the required properties. Liposomes are one of the most suitable drug-delivery systems to deliver the drug to the target organ and minimize the distribution of the drug to non-target tissues. Objective The study reported here aimed to develop cefditoren pivoxil liposomes by thin-film hydration, characterize them in terms of physical interactions, and undertake in vitro and in vivo release studies. Methodology The pre-formulation studies were carried out using Fourier-transform infrared spectroscopy and differential scanning calorimetry. Cefditoren pivoxil liposomal formulations were formulated by thin-film hydration using biomaterials ie, soya lecithin and cholesterol in different molar ratios. The best molar ratio was determined by in vitro studies such as entrapment efficacy, particle size distribution, and diffusion. Results From the in vitro release studies, it was found that the formulation that contained soya lecithin and cholesterol in a 1.0:0.6 molar ratio gave good entrapment of 72.33% and drug release of 92.5% at 36 hours. Further, the formulation’s zeta potential and surface morphology were examined and stability and in vivo studies were undertaken evaluating the pharmacokinetic parameters, which showed promising results. Conclusion Formulation CPL VI showed the maximum drug-loading capacity of 72.3% with good controlled release and acceptable stability when compared with the other formulations. In vivo studies in rabbits showed that the drug release from the liposomes was successfully retarded with good controlled release behavior which can be used to treat many bacterial infections with a minimal dose. PMID:26491316

Laser based synthesis of nanofunctionalized particulates for pulmonary based controlled drug delivery applications

NASA Astrophysics Data System (ADS)

Singh, R. K.; Kim, W.-S.; Ollinger, M.; Craciun, V.; Coowantwong, I.; Hochhaus, G.; Koshizaki, N.

2002-09-01

There is an urgent need to develop controlled drug release systems for the delivery of drugs via the pulmonary route. A key issue in pulmonary dry delivery systems is to reduce the amount of biodegradable polymers that are added to control the drug release. We have synthesized nanofunctionalized drug particles using the pulsed laser deposition on particles (PLDP) (e.g. budesonide) in an effort to control the architecture and thickness of a nanoscale polymer coating on the drug particles. In vitro studies indicated that the dry half-life release for budesonide can be enhanced from 1.2 to over 60 min by a nanoscale coating on the drug particle. Extensive studies have been conducted to characterize the bonding and composition of the polymer film deposited on drug particles.

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

PubMed Central

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

2017-01-01

To prolong the residence time of dosage forms within the gastrointestinal tract until all drug is released at the desired rate is one of the real challenges for oral controlled-release drug delivery systems. This study was designed to develop a controlled-release floating matrix tablet and floating raft system of Mebeverine HCl (MbH) and evaluate different excipients for their floating behavior and in vitro controlled-release profiles. Oral pharmacokinetics of the optimum matrix tablet, raft system formula, and marketed Duspatalin® 200 mg retard as reference were studied in beagle dogs. The optimized tablet formula (FT-10) and raft system formula (FRS-11) were found to float within 34±5 sec and 15±7 sec, respectively, and both remain buoyant over a period of 12 h in simulated gastric fluid. FT-10 (Compritol/HPMC K100M 1:1) showed the slowest drug release among all prepared tablet formulations, releasing about 80.2% of MbH over 8 h. In contrast, FRS-11 (Sodium alginate 3%/HPMC K100M 1%/Precirol 2%) had the greatest retardation, providing sustained release of 82.1% within 8 h. Compared with the marketed MbH product, the Cmax of FT-10 was almost the same, while FRS-11 maximum concentration was higher. The tmax was 3.33, 2.167, and 3.0 h for marketed MbH product, FT-10, and FRS-11, respectively. In addition, the oral bioavailability experiment showed that the relative bioavailability of the MbH was 104.76 and 116.01% after oral administration of FT-10 and FRS-11, respectively, compared to marketed product. These results demonstrated that both controlled-released floating matrix tablet and raft system would be promising gastroretentive delivery systems for prolonging drug action. PMID:28435220

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

PubMed

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

2017-01-01

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

Electrospinning of PLGA/gum tragacanth nanofibers containing tetracycline hydrochloride for periodontal regeneration.

PubMed

Ranjbar-Mohammadi, Marziyeh; Zamani, M; Prabhakaran, M P; Bahrami, S Hajir; Ramakrishna, S

2016-01-01

Controlled drug release is a process in which a predetermined amount of drug is released for longer period of time, ranging from days to months, in a controlled manner. In this study, novel drug delivery devices were fabricated via blend electrospinning and coaxial electrospinning using poly lactic glycolic acid (PLGA), gum tragacanth (GT) and tetracycline hydrochloride (TCH) as a hydrophilic model drug in different compositions and their performance as a drug carrier scaffold was evaluated. Scanning electron microscopy (SEM) results showed that fabricated PLGA, blend PLGA/GT and core shell PLGA/GT nanofibers had a smooth and bead-less morphology with the diameter ranging from 180 to 460 nm. Drug release studies showed that both the fraction of GT within blend nanofibers and the core-shell structure can effectively control TCH release rate from the nanofibrous membranes. By incorporation of TCH into core-shell nanofibers, drug release was sustained for 75 days with only 19% of burst release within the first 2h. The prolonged drug release, together with proven biocompatibility, antibacterial and mechanical properties of drug loaded core shell nanofibers make them a promising candidate to be used as drug delivery system for periodontal diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

Development of extended release dosage forms using non-uniform drug distribution techniques.

PubMed

Huang, Kuo-Kuang; Wang, Da-Peng; Meng, Chung-Ling

2002-05-01

Development of an extended release oral dosage form for nifedipine using the non-uniform drug distribution matrix method was conducted. The process conducted in a fluid bed processing unit was optimized by controlling the concentration gradient of nifedipine in the coating solution and the spray rate applied to the non-pareil beads. The concentration of nifedipine in the coating was controlled by instantaneous dilutions of coating solution with polymer dispersion transported from another reservoir into the coating solution at a controlled rate. The USP dissolution method equipped with paddles at 100 rpm in 0.1 N hydrochloric acid solution maintained at 37 degrees C was used for the evaluation of release rate characteristics. Results indicated that (1) an increase in the ethyl cellulose content in the coated beads decreased the nifedipine release rate, (2) incorporation of water-soluble sucrose into the formulation increased the release rate of nifedipine, and (3) adjustment of the spray coating solution and the transport rate of polymer dispersion could achieve a dosage form with a zero-order release rate. Since zero-order release rate and constant plasma concentration were achieved in this study using the non-uniform drug distribution technique, further studies to determine in vivo/in vitro correlation with various non-uniform drug distribution dosage forms will be conducted.

An Open-Label Study of Controlled-Release Melatonin in Treatment of Sleep Disorders in Children with Autism

ERIC Educational Resources Information Center

Giannotti, F.; Cortesi, F.; Cerquiglini, A.; Bernabei, P.

2006-01-01

Long-term effectiveness of controlled-release melatonin in 25 children, aged 2.6-9.6 years with autism without other coexistent pathologies was evaluated openly. Sleep patterns were studied using Children's Sleep Habits Questionnaire (CSHQ) and sleep diaries at baseline, after 1-3-6 months melatonin treatment and 1 month after discontinuation.…

Ion-exchange and iontophoresis-controlled delivery of apomorphine.

PubMed

Malinovskaja, Kristina; Laaksonen, Timo; Kontturi, Kyösti; Hirvonen, Jouni

2013-04-01

The objective of this study was to test a drug delivery system that combines iontophoresis and cation-exchange fibers as drug matrices for the controlled transdermal delivery of antiparkinsonian drug apomorphine. Positively charged apomorphine was bound to the ion-exchange groups of the cation-exchange fibers until it was released by mobile counter-ions in the external solution. The release of the drug was controlled by modifying either the fiber type or the ionic composition of the external solution. Due to high affinity of apomorphine toward the ion-exchanger, a clear reduction in the in vitro transdermal fluxes from the fibers was observed compared to the respective fluxes from apomorphine solutions. Changes in the ionic composition of the donor formulations affected both the release and iontophoretic flux of the drug. Upon the application of higher co-ion concentrations or co-ions of higher valence in the donor formulation, the release from the fibers was enhanced, but the iontophoretic steady-state flux was decreased. Overall, the present study has demonstrated a promising approach using ion-exchange fibers for controlling the release and iontophoretic transdermal delivery of apomorphine. Copyright © 2012 Elsevier B.V. All rights reserved.

EVALUATION OF BIOREMEDIATION STRATEGIES OF A CONTROLLED OIL RELEASE IN A WETLAND

EPA Science Inventory

A controlled petroleum release was conducted to evaluate bioremediation in a wetland near Houston, Texas. The 140-day study was conducted using a randomized, complete block design to test three treatments with six replicates per treatment. The three treatment strategies were in...

THE HISTOLOGY OF FITC AND FITC-17B ESTRADIOL IN CUNNER, TAUTOGOLABRUS ADSPERSUS, AFTER SUBCUTANEOUS IMPLANTATION IN A CONTROLLED RELEASE MATRIX

EPA Science Inventory

To mimic environmental exposures in studying the effects of estrogenic chemicals on fish reproduction, a slow-release mechanism is needed to deliver a continuous dosing of chemicals over the course of a long-term study. The effects of slow-release chemical exposures via a subcuta...

The feasibility and efficacy of early-season releases of a generalist predator (Forficula auricularia L.) to control populations of the RAA (Dysaphis plantaginea Passerini) in Southeastern France.

PubMed

Dib, H; Jamont, M; Sauphanor, B; Capowiez, Y

2016-04-01

Augmentative biological control is not commonly used in commercial orchards. We used an exclusion system to evaluate the potential of early-season releases of the European earwig (Forficula auricularia L., Dermaptera: Forficulidae) for control of the rosy apple aphid (Dysaphis plantaginea Passerini, Hemiptera: Aphididae) in the spring of 2009 in two pesticide-free apple orchards. In order to conduct this experiment we successfully reared earwigs with a high survival rate of nymphs (more than 96%) which may have commercial application. There were three treatments in the study: (i) a 'release treatment' where we confined the released earwigs in the canopy by using a barrier system; (ii) an 'exclusion treatment' where we blocked free access of earwigs into the canopy using the same barrier system; and (iii) a 'control treatment' that represented the natural situation. Contrary to expectations, earwig releases did not reduce D. plantaginea populations. In general, the abundance of natural enemies and their groups did not differ significantly among treatments, except for earwigs. We observed that the exclusion systems we used successfully kept both earwigs and ants away from tree canopies; total numbers on trees in the 'exclusion treatment' were significantly lower than on the other two treatments. Due to the complexity and difficulty of evaluating augmentative releases of natural enemies in open orchard conditions, we conclude that new technical approaches to control site conditions are needed when conducting such studies.

Controlled release of silyl ether camptothecin from thiol-ene click chemistry-functionalized mesoporous silica nanoparticles.

PubMed

Yan, Yue; Fu, Jie; Wang, Tianfu; Lu, Xiuyang

2017-03-15

As efficient drug carriers, stimuli-responsive mesoporous silica nanoparticles are at the forefront of research on drug delivery systems. An acid-responsive system based on silyl ether has been applied to deliver a hybrid prodrug. Thiol-ene click chemistry has been successfully utilized for tethering this prodrug to mesoporous silica nanoparticles. Here, by altering the steric bulk of the substituent on the silicon atom, the release rate of a model drug, camptothecin, was controlled. The synthesized drug delivery system was investigated by analytical methods to confirm the functionalization and conjugation of the mesoporous silica nanoparticles. Herein, trimethyl silyl ether and triethyl silyl ether were selected to regulate the release rate. Under normal plasma conditions (pH 7.4), both types of camptothecin-loaded mesoporous silica nanoparticles (i.e., MSN-Me-CPT and MSN-Et-CPT) did not release the model drug. However, under in vitro acidic conditions (pH 4.0), based on a comparison of the release rates, camptothecin was released from MSN-Me-CPT more rapidly than from MSN-Et-CPT. To determine the biocompatibility of the modified mesoporous silica nanoparticles and the in vivo camptothecin uptake behavior, MTT assays with cancer cells and confocal microscopy observations were conducted, with positive results. These functionalized nanoparticles could be useful in clinical treatments requiring controlled drug release. As the release rate of drug from drug-carrier plays important role in therapy effects, trimethyl silyl ether (TMS) and triethyl silyl ether (TES) were selected as acid-sensitive silanes to control the release rates of model drugs conjugated from MSNs by thiol-ene click chemistry. The kinetic profiles of TMS and TES materials have been studied. At pH 4.0, the release of camptothecin from MSN-Et-CPT occurred after 2h, whereas MSN-Me-CPT showed immediate drug release. The results showed that silyl ether could be used to control release rates of drugs from MSNs under acid environment, which could be useful in clinical treatments requiring controlled drug release. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Formulation and evaluation of controlled release antibiotic biodegradable implants for post operative site delivery.

PubMed

Mathur, Vijay; Mudnaik, Rajesh; Barde, Laxmikant; Roy, Arghya; Shivhare, Umesh; Bhusari, Kishore

2010-03-01

Biodegradable implants of ciprofloxacin hydrochloride for post operative site delivery were prepared using glyceryl monostearate and different concentrations of polyethylene glycol (PEG 6000), glycerol and Tween 80 as erosion enhancers by compression and molding technique. Formulations were subjected to in vitro drug release by the USP dissolution method, while promising formulations were subjected to in vitro drug release by the agar gel method and also to stability studies. It was observed that glyceryl monostearate formed hydrophobic matrix and delayed the drug delivery. Antibiotic release profile was controlled by using different combinations of erosion enhancers. The formulation prepared by the compression method showed more delayed release compared to formulations prepared by the molding method.

Utilization of wheat straw for the preparation of coated controlled-release fertilizer with the function of water retention.

PubMed

Xie, Lihua; Liu, Mingzhu; Ni, Boli; Wang, Yanfang

2012-07-18

With the aim of improving fertilizer use efficiency and minimizing the negative impact on the environment, a new coated controlled-release fertilizer with the function of water retention was prepared. A novel low water solubility macromolecular fertilizer, poly(dimethylourea phosphate) (PDUP), was "designed" and formulated from N,N'-dimethylolurea (DMU) and potassium dihydrogen phosphate. Simultaneously, an eco-friendly superabsorbent composite based on wheat straw (WS), acrylic acid (AA), 2-acryloylamino-2-methyl-1-propanesulfonic acid (AMPS), and N-hydroxymethyl acrylamide (NHMAAm) was synthesized and used as the coating to control the release of nutrient. The nitrogen release profile and water retention capacity of the product were also investigated. The degradation of the coating material in soil solution was studied. Meanwhile, the impact of the content of N-hydroxymethyl acrylamide on the degradation extent was examined. The experimental data showed that the product with good water retention and controlled-release capacities, being economical and eco-friendly, could be promising for applications in agriculture and horticulture.

Water-based polyurethane 3D printed scaffolds with controlled release function for customized cartilage tissue engineering.

PubMed

Hung, Kun-Che; Tseng, Ching-Shiow; Dai, Lien-Guo; Hsu, Shan-hui

2016-03-01

Conventional 3D printing may not readily incorporate bioactive ingredients for controlled release because the process often involves the use of heat, organic solvent, or crosslinkers that reduce the bioactivity of the ingredients. Water-based 3D printing materials with controlled bioactivity for customized cartilage tissue engineering is developed in this study. The printing ink contains the water dispersion of synthetic biodegradable polyurethane (PU) elastic nanoparticles, hyaluronan, and bioactive ingredients TGFβ3 or a small molecule drug Y27632 to replace TGFβ3. Compliant scaffolds are printed from the ink at low temperature. These scaffolds promote the self-aggregation of mesenchymal stem cells (MSCs) and, with timely release of the bioactive ingredients, induce the chondrogenic differentiation of MSCs and produce matrix for cartilage repair. Moreover, the growth factor-free controlled release design may prevent cartilage hypertrophy. Rabbit knee implantation supports the potential of the novel 3D printing scaffolds in cartilage regeneration. We consider that the 3D printing composite scaffolds with controlled release bioactivity may have potential in customized tissue engineering. Copyright © 2016 Elsevier Ltd. All rights reserved.

An Exclusion Zone for Ca2+ Channels around Docked Vesicles Explains Release Control by Multiple Channels at a CNS Synapse

PubMed Central

Keller, Daniel; Babai, Norbert; Kochubey, Olexiy; Han, Yunyun; Markram, Henry; Schürmann, Felix; Schneggenburger, Ralf

2015-01-01

The spatial arrangement of Ca2+ channels and vesicles remains unknown for most CNS synapses, despite of the crucial importance of this geometrical parameter for the Ca2+ control of transmitter release. At a large model synapse, the calyx of Held, transmitter release is controlled by several Ca2+ channels in a "domain overlap" mode, at least in young animals. To study the geometrical constraints of Ca2+ channel placement in domain overlap control of release, we used stochastic MCell modelling, at active zones for which the position of docked vesicles was derived from electron microscopy (EM). We found that random placement of Ca2+ channels was unable to produce high slope values between release and presynaptic Ca2+ entry, a hallmark of domain overlap, and yielded excessively large release probabilities. The simple assumption that Ca2+ channels can be located anywhere at active zones, except below a critical distance of ~ 30 nm away from docked vesicles ("exclusion zone"), rescued high slope values and low release probabilities. Alternatively, high slope values can also be obtained by placing all Ca2+ channels into a single supercluster, which however results in significantly higher heterogeneity of release probabilities. We also show experimentally that high slope values, and the sensitivity to the slow Ca2+ chelator EGTA-AM, are maintained with developmental maturation of the calyx synapse. Taken together, domain overlap control of release represents a highly organized active zone architecture in which Ca2+ channels must obey a certain distance to docked vesicles. Furthermore, domain overlap can be employed by near-mature, fast-releasing synapses. PMID:25951120

Influence of surfactants on the release behaviour and structural properties of sol-gel derived silica xerogels embedded with metronidazole.

PubMed

Czarnobaj, Katarzyna; Sawicki, Wiesław

2013-01-01

The aim of this study was to obtain stable and controlled release silica xerogels containing metronidazole (MT) prepared with surfactants with different charges: cetyltrimethylammonium bromide (CTAB), sodium dodecyl sulphate (SDS) and hydroxypropyl cellulose (HPC), which could be the promising carrier materials used as the implantable drug delivery systems. The xerogels were prepared by the sol-gel method. The influence of various formulation precursors on porosity parameters and drug release were investigated. Addition of surfactants showed a promising result in controlling the MT release. Dissolution study revealed increased release of MT from silica modified SDS and CTAB, whereas the release of MT from silica modified HPC considerably decreased, in comparison with unmodified silica. The addition of surfactants showed slight changes in porosity parameters. All xerogels are characterized by a highly developed surface area (701-642 m(2) g(-1)) and mesoporous structure. The correlation between pore size obtained matrices and release rate of drug was also observed. Based on the presented results of this study, it may be stated that applied xerogel matrices: pure silica and surfactants-modified silica could be promising candidates for the formulation in local delivery systems.

Impact of Release Rates on the Effectiveness of Augmentative Biological Control Agents

PubMed Central

Crowder, David W.

2007-01-01

To access the effect of augmentative biological control agents, 31 articles were reviewed that investigated the impact of release rates of 35 augmentative biological control agents on the control of 42 arthropod pests. In 64% of the cases, the release rate of the biological control agent did not significantly affect the density or mortality of the pest insect. Results where similar when parasitoidsor predators were utilized as the natural enemy. Within any order of natural enemy, there were more cases where release rates did not affect augmentative biological control than cases where release rates were significant. There were more cases in which release rates did not affect augmentative biological control when pests were from the orders Hemiptera, Acari, or Diptera, but not with pests from the order Lepidoptera. In most cases, there was an optimal release rate that produced effective control of a pest species. This was especially true when predators were used as a biological control agent. Increasing the release rate above the optimal rate did not improve control of the pest and thus would be economically detrimental. Lower release rates were of ten optimal when biological control was used in conjunction with insecticides. In many cases, the timing and method of biological control applications were more significant factors impacting the effectiveness of biological control than the release rate. Additional factors that may limit the relative impact of release rates include natural enemy fecundity, establishment rates, prey availability, dispersal, and cannibalism. PMID:20307240

[Oral controlled release dosage forms].

PubMed

Mehuys, Els; Vervaet, Chris

2010-06-01

Several technologies to control drug release from oral dosage forms have been developed. Drug release can be regulated in several ways: sustained release, whereby the drug is released slowly over a prolonged period of time, postponed release, whereby drug release is delayed until passage from the stomach into the intestine (via enteric coating), and targeted release, whereby the drug is targeted to a specific location of the gastrointestinal tract. This article reviews the various oral controlled release dosage forms on the market.

Nitric Oxide Releasing Coronary Stent: A New Approach Using Layer-by-Layer Coating and Liposomal Encapsulation.

PubMed

Elnaggar, Mahmoud A; Seo, Seong Ho; Gobaa, Samy; Lim, Kyung Seob; Bae, In-Ho; Jeong, Myung Ho; Han, Dong Keun; Joung, Yoon Ki

2016-11-01

The sustained or controlled release of nitric oxide (NO) can be the most promising approach for the suppression or prevention of restenosis and thrombosis caused by stent implantation. The aim of this study is to investigate the feasibility in the potential use of layer-by-layer (LBL) coating with a NO donor-containing liposomes to control the release rate of NO from a metallic stent. Microscopic observation and surface characterizations of LBL-modified stents demonstrate successful LBL coating with liposomes on a stent. Release profiles of NO show that the release rate is sustained up to 5 d. In vitro cell study demonstrates that NO release significantly enhances endothelial cell proliferation, whereas it markedly inhibits smooth muscle cell proliferation. Finally, in vivo study conducted with a porcine coronary injury model proves the therapeutic efficacy of the NO-releasing stents coated by liposomal LBL technique, supported by improved results in luminal healing, inflammation, and neointimal thickening except thrombo-resistant effect. As a result, all these results demonstrate that highly optimized release rate and therapeutic dose of NO can be achieved by LBL coating and liposomal encapsulation, followed by significantly efficacious outcome in vivo. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

PubMed

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.

In vitro and in vivo study of sustained nitric oxide release coating using diazeniumdiolate-oped poly(vinyl chloride) matrix with poly(lactide-co-glycolide) additive

PubMed Central

Handa, Hitesh; Brisbois, Elizabeth J.; Major, Terry C.; Refahiyat, Lahdan; Amoako, Kagya A.; Annich, Gail M.; Bartlett, Robert H.; Meyerhoff, Mark E.

2013-01-01

Nitric oxide (NO) is an endogenous vasodilator as well as natural inhibitor of platelet adhesion and activation that can be released from a NO donor species, such as diazeniumdiolated dibutylhexanediamine (DBHD/N2O2) within a polymer coating. In this study, various Food and Drug Administration approved poly(lactic-co-glycolic acid) (PLGA) species were evaluated as additives to promote a prolonged NO release from DBHD/N2O2 within a plasticized poly(vinyl chloride) (PVC) matrix. When using an ester-capped PLGA additive with a slow hydrolysis time, the resulting coatings continuously release between 7–18×10-10 mol cm-2 min-1 NO for 14 d at 37°C in PBS buffer. The corresponding pH changes within the polymer films were visualized using pH sensitive indicators and are shown to correlate with the extended NO release pattern. The optimal combined diazeniumdiolate/PLGA-doped NO release (NOrel) PVC coating was evaluated in vitro and its effect on the hemodynamics was also studied within a 4 h in vivo extracorporeal circulation (ECC) rabbit model of thrombogenicity. Four out of 7 control circuits clotted within 3 h, whereas all the NOrel coated circuits were patent after 4 h. Platelet counts on the NOrel ECC were preserved (79 ± 11% compared to 54 ± 6% controls). The NOrel coatings showed a significant decrease in the thrombus area as compared to the controls. Results suggest that by using ester-capped PLGAs as additives to a conventional plasticized PVC material containing a lipophilic diazeniumdiolates, the NO release can be prolonged for up to 2 weeks by controlling the pH within the organic phase of the coating. PMID:23914297

Herbicide-Intercalated Zinc Layered Hydroxide Nanohybrid for a Dual-Guest Controlled Release Formulation

PubMed Central

Hussein, Mohd Zobir; Rahman, Nor Shazlirah Shazlyn Abdul; Sarijo, Siti H.; Zainal, Zulkarnain

2012-01-01

Herbicides, namely 4-(2,4-dichlorophenoxy) butyrate (DPBA) and 2-(3-chlorophenoxy) propionate (CPPA), were intercalated simultaneously into the interlayers of zinc layered hydroxide (ZLH) by direct reaction of zinc oxide with both anions under aqueous environment to form a new nanohybrid containing both herbicides labeled as ZCDX. Successful intercalation of both anions simultaneously into the interlayer gallery space of ZLH was studied by PXRD, with basal spacing of 28.7 Å and supported by FTIR, TGA/DTG and UV-visible studies. Simultaneous release of both CPPA and DPBA anions into the release media was found to be governed by a pseudo second-order equation. The loading and percentage release of the DPBA is higher than the CPPA anion, which indicates that the DPBA anion was preferentially intercalated into and released from the ZLH interlayer galleries. This work shows that layered single metal hydroxide, particularly ZLH, is a suitable host for the controlled release formulation of two herbicides simultaneously. PMID:22837696

Comparative release studies on suppositories using the basket, paddle, dialysis tubing and flow-through cell methods I. Acetaminophen in a lipophilic base suppository.

PubMed

Hori, Seiichi; Kawada, Tsubasa; Kogure, Sanae; Yabu, Shinako; Mori, Kenji; Akimoto, Masayuki

2017-02-01

The release characteristics of lipophilic suppositories containing acetaminophen (AAP) were examined using four types of dissolution methods: the basket, paddle, dialysis tubing (DT) and flow-through cell (FTC) methods. The suitability of each apparatus for quality control in AAP compounded suppositories was evaluated using statistical procedures. More than 80% of the drug was released over 60 min in all the release methods studied, with the exception of the basket method. Reproducible and faster release was achieved using the paddle method at 100 and 200 rpm, whereas poor release occurred with the basket method. The mean dissolution time (MDT), maximum dissolved quantity of AAP at the end of the sampling time (Q) and dissolution efficiency (DE) were calculated by model-independent methods. The FTC method with a single chamber used in this study was also appreciable for AAP suppositories (Q of 100%, MDT of 71-91 min and DE of 75-80%). The DT apparatus is considered similar to the FTC apparatus from a quality control perspective for judging the release properties of lipophilic base suppositories containing AAP. However, even the single chamber FTC used in this study has potential as an in vitro drug release test for suppositories. The comparative dissolution method is expected to become one of the valuable tools for selecting an adequate dissolution test.

Nanoencapsulation of dietary flavonoid fisetin: Formulation and in vitro antioxidant and α-glucosidase inhibition activities.

PubMed

Sechi, Mario; Syed, Deeba N; Pala, Nicolino; Mariani, Alberto; Marceddu, Salvatore; Brunetti, Antonio; Mukhtar, Hasan; Sanna, Vanna

2016-11-01

The bioactive flavonoid fisetin (FS) is a diet-derived antioxidant that is being increasingly investigated for its health-promoting effects. Unfortunately, the poor physicochemical and pharmacokinetic properties affect and limit the clinical application. In this study, novel polymeric nanoparticles (NPs), based on Poly-(ε-caprolactone) (PCL) and PLGA-PEG-COOH, encapsulating FS were formulated as suitable oral controlled release systems. Results showed NPs having a mean diameter of 140-200nm, and a percent loading of FS ranging from 70 to 82%. In vitro release studies revealed that NPs are able to protect and preserve the release of FS in gastric simulated conditions, also controlling the release in the intestinal medium. Moreover, the DPPH and ABTS scavenging capacity of FS, as well as α-glucosidase inhibition activity, that resulted about 20-fold higher than commercial Acarbose, were retained during nanoencapsulation process. In summary, our developed NPs can be proposed as an attractive delivery system to control the release of antioxidant and anti-hyperglycemic FS for nutraceutical and/or therapeutic application. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed

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.

Release behavior and bioefficacy of imazethapyr formulations based on biopolymeric hydrogels.

PubMed

Kumar, Vikas; Singh, Anupama; Das, T K; Sarkar, Dhruba Jyoti; Singh, Shashi Bala; Dhaka, Rashmi; Kumar, Anil

2017-06-03

Controlled release formulations of imazethapyr herbicide have been developed employing guar gum-g-cl-polyacrylate/bentonite clay hydrogel composite (GG-HG) and guar gum-g-cl-PNIPAm nano hydrogel (GG-NHG) as carriers, to assess the suitability of biopolymeric hydrogels as controlled herbicide release devices. The kinetics of imazethapyr release from the developed formulations was studied in water and it revealed that the developed formulations of imazethapyr behaved as slow release formulations as compared to commercial formulation. The calculated diffusion exponent (n) values showed that Fickian diffusion was the predominant mechanism of imazethapyr release from the developed formulations. Time for release of half of the loaded imazethapyr (t 1/2 ) ranged between 0.06 and 4.8 days in case of GG-NHG and 4.4 and 12.6 days for the GG-HG formulations. Weed control index (WCI) of GG-HG and GG-NHG formulations was similar to that of the commercial formulation and the herbicidal effect was observed for relatively longer period. Guar gum-based biopolymeric hydrogels in both macro and nano particle size range can serve as potential carriers in developing slow release herbicide formulations.

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

PubMed

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

2017-07-01

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

Controlled release in transdermal pressure sensitive adhesives using organosilicate nanocomposites.

PubMed

Shaikh, Sohel; Birdi, Anil; Qutubuddin, Syed; Lakatosh, Eric; Baskaran, Harihara

2007-12-01

Polydimethyl siloxane (PDMS) based pressure sensitive adhesives (PSA) incorporating organo-clays at different loadings were fabricated via solution casting. Partially exfoliated nanocomposites were obtained for the hydroxyl terminated PDMS in ethyl acetate solvent as determined by X-ray diffraction and atomic force microscopy. Drug release studies showed that the initial burst release was substantially reduced and the drug release could be controlled by the addition of organo-clay. Shear strength and shear adhesion failure temperature (SAFT) measurements indicated substantial improvement in adhesive properties of the PSA nanocomposite adhesives. Shear strength showed more than 200% improvement at the lower clay loadings and the SAFT increased by about 21% due to the reinforcement provided by the nano-dispersed clay platelets. It was found that by optimizing the level of the organosilicate additive to the polymer matrix, superior control over drug release kinetics and simultaneous improvements in adhesive properties could be attained for a transdermal PSA formulation.

Gum Ghatti--a pharmaceutical excipient: development, evaluation and optimization of sustained release mucoadhesive matrix tablets of domperidone.

PubMed

Gurpreetarora; Malik, Karan; Rana, Vikas; Singh, Inderbir

2012-01-01

The objective of this study was to extend the GI residence time of the dosage form and to control the release of domperidone using directly compressible sustained release mucoadhesive matrix (SRMM) tablets. A 2-factor centre composite design (CCD) was employed to study the influence of independent variables like gum ghatti (GG) (X1) and hydroxylpropylmethyl cellulose K 15M (HPMC K 15M) (X2) on dependent variable like mucoadhesive strength, tensile strength, release exponent (n), t50 (time for 50% drug release), rel(10 h) (release after 10 h) and rel(18 h) (release after 18 h). Tablets were prepared by direct compression technology and evaluated for tablet parametric test (drug assay, diameter, thickness, hardness and tensile strength), mucoadhesive strength (using texture analyzer) and in vitro drug release studies. The tensile strength and mucoadhesive strength were found to be increased from 0.665 +/- 0.1 to 1.591 +/- 0.1 MN/cm2 (Z1 to Z9) and 10.789 +/- 0.985 to 50.924 +/- 1.150 N (Z1 to Z9), respectively. The release kinetics follows first order and Hixson Crowell equation indicating drug release following combination of diffusion and erosion. The n varies between 0.834 and 1.273, indicating release mechanism shifts from non fickian (anomalous release) to super case II, which depict that drug follows multiple drug release mechanism. The t50 time was found to increase from 5 +/- 0.12 to 11.4 +/- 0.14 h (Z1 to Z9) and release after 10 and 18 h decreases with increasing concentration of both polymers concluding with release controlling potential of polymers. The accelerated stability studies were performed on optimized formulation as per ICH guideline and the result showed that there was no significant change in tensile strength, mucoadhesive strength and drug assay.

An open-label study of controlled-release melatonin in treatment of sleep disorders in children with autism.

PubMed

Giannotti, F; Cortesi, F; Cerquiglini, A; Bernabei, P

2006-08-01

Long-term effectiveness of controlled-release melatonin in 25 children, aged 2.6-9.6 years with autism without other coexistent pathologies was evaluated openly. Sleep patterns were studied using Children's Sleep Habits Questionnaire (CSHQ) and sleep diaries at baseline, after 1-3-6 months melatonin treatment and 1 month after discontinuation. Sleep diary and CSHQ showed a more problematic sleep in autistic children compared with controls. During treatment sleep patterns of all children improved. After discontinuation 16 children returned to pre-treatment score, readministration of melatonin was again effective. Treatment gains were maintained at 12 and 24-month follow-ups. No adverse side effects were reported. In conclusion, controlled-release melatonin may provide an effective and well-tolerated treatment for autistic children with chronic sleep disorders.

Optogenetic control of ATP release

NASA Astrophysics Data System (ADS)

Lewis, Matthew A.; Joshi, Bipin; Gu, Ling; Feranchak, Andrew; Mohanty, Samarendra K.

2013-03-01

Controlled release of ATP can be used for understanding extracellular purinergic signaling. While coarse mechanical forces and hypotonic stimulation have been utilized in the past to initiate ATP release from cells, these methods are neither spatially accurate nor temporally precise. Further, these methods cannot be utilized in a highly effective cell-specific manner. To mitigate the uncertainties regarding cellular-specificity and spatio-temporal release of ATP, we herein demonstrate use of optogenetics for ATP release. ATP release in response to optogenetic stimulation was monitored by Luciferin-Luciferase assay (North American firefly, photinus pyralis) using luminometer as well as mesoscopic bioluminescence imaging. Our result demonstrates repetitive release of ATP subsequent to optogenetic stimulation. It is thus feasible that purinergic signaling can be directly detected via imaging if the stimulus can be confined to single cell or in a spatially-defined group of cells. This study opens up new avenue to interrogate the mechanisms of purinergic signaling.

Design of Chronomodulated Drug Delivery System of Valsartan: In Vitro Characterization.

PubMed

Sokar, M; Hanafy, A; Elkamel, A; El-Gamal, S

2015-01-01

The aim of the present study was to design and evaluate a chronomodulated time-clock pulsatile tablets of valsartan to release it after a certain lag time, independent of the gastrointestinal pH, in its absorption window to cope with the circadian rhythm of human body for blood pressure elevation. Core tablets were prepared by direct compression of a homogenous mixture of valsartan, Avicel PH101, croscarmellose sodium, magnesium stearate and Aerosil. The core tablets were then sprayed coated with a sealing layer formed of ethyl cellulose that was subsequently coated with a release-controlling layer. Three different aqueous dispersions namely; carnauba wax or beeswax or a mixture in a ratio of 2.5:1, respectively, were used to form five time-clock tablet formulations having the release controlling layer with different thickness {B5, B10, B20, BW5 and CW5}. Quality control testing were carried out to the core tablets. Differential scanning calorimetry was also performed to detect the possible drug excipient interaction in the core tablet formulation. The release was carried out, for the prepared time-clock tablet formulations, in 0.1 N hydrochloric acid for the first 2 h, followed by phosphate buffer (pH 6.8) for 4.5 h. The effect of pH on valsartan release was studied through a release study in 0.1 N hydrochloric acid for 6.5 h. Two phase dissolution study was performed to the selected time-clock tablet formulation to predict the drug permeation through the gastrointestinal tract. Stability study of the selected formula was performed at 25°/60% RH and at 40°/75% RH for 3 months. Results showed that a release-controlling layer composed of a mixture of carnauba wax and beeswax in a ratio of 2.5:1 showed a reasonable release lag time. The release lag time of the tablets increased with the increase of the coat thickness, thus B20>B10>B5 with corresponding lag time values of 4.5, 3 and 2.5 h, respectively. Selected B5 tablet formula exhibited a reasonable lag time after which the highest, complete % drug release at pH 6.8 was obtained. In addition, a good partitioning of valsartan, between the aqueous and organic phases in a ratio of 1:7, was observed. The selected formula was stable for at least 3 months under standard long-term and accelerated storage conditions. In conclusion, in vitro studies revealed that the novel time-clock system could be used successfully to deliver valsartan in a pulsatile pH-independent manner. It provided a desirable lag time followed by a rapid and complete drug release accompanied by an expected effective permeation through the biological membranes upon release in the duodenum; the window of absorption, as indicated by the two phase release study.

Design of Chronomodulated Drug Delivery System of Valsartan: In Vitro Characterization

PubMed Central

Sokar, M.; Hanafy, A.; Elkamel, A.; El-Gamal, S.

2015-01-01

The aim of the present study was to design and evaluate a chronomodulated time-clock pulsatile tablets of valsartan to release it after a certain lag time, independent of the gastrointestinal pH, in its absorption window to cope with the circadian rhythm of human body for blood pressure elevation. Core tablets were prepared by direct compression of a homogenous mixture of valsartan, Avicel PH101, croscarmellose sodium, magnesium stearate and Aerosil. The core tablets were then sprayed coated with a sealing layer formed of ethyl cellulose that was subsequently coated with a release-controlling layer. Three different aqueous dispersions namely; carnauba wax or beeswax or a mixture in a ratio of 2.5:1, respectively, were used to form five time-clock tablet formulations having the release controlling layer with different thickness {B5, B10, B20, BW5 and CW5}. Quality control testing were carried out to the core tablets. Differential scanning calorimetry was also performed to detect the possible drug excipient interaction in the core tablet formulation. The release was carried out, for the prepared time-clock tablet formulations, in 0.1 N hydrochloric acid for the first 2 h, followed by phosphate buffer (pH 6.8) for 4.5 h. The effect of pH on valsartan release was studied through a release study in 0.1 N hydrochloric acid for 6.5 h. Two phase dissolution study was performed to the selected time-clock tablet formulation to predict the drug permeation through the gastrointestinal tract. Stability study of the selected formula was performed at 25°/60% RH and at 40°/75% RH for 3 months. Results showed that a release-controlling layer composed of a mixture of carnauba wax and beeswax in a ratio of 2.5:1 showed a reasonable release lag time. The release lag time of the tablets increased with the increase of the coat thickness, thus B20>B10>B5 with corresponding lag time values of 4.5, 3 and 2.5 h, respectively. Selected B5 tablet formula exhibited a reasonable lag time after which the highest, complete % drug release at pH 6.8 was obtained. In addition, a good partitioning of valsartan, between the aqueous and organic phases in a ratio of 1:7, was observed. The selected formula was stable for at least 3 months under standard long-term and accelerated storage conditions. In conclusion, in vitro studies revealed that the novel time-clock system could be used successfully to deliver valsartan in a pulsatile pH-independent manner. It provided a desirable lag time followed by a rapid and complete drug release accompanied by an expected effective permeation through the biological membranes upon release in the duodenum; the window of absorption, as indicated by the two phase release study. PMID:26664064

pH dependent silver nanoparticles releasing titanium implant: A novel therapeutic approach to control peri-implant infection.

PubMed

Dong, Yiwen; Ye, Hui; Liu, Yi; Xu, Lihua; Wu, Zuosu; Hu, Xiaohui; Ma, Jianfeng; Pathak, Janak L; Liu, Jinsong; Wu, Gang

2017-10-01

Peri-implant infection control is crucial for implant fixation and durability. Antimicrobial administration approaches to control peri-implant infection are far from satisfactory. During bacterial infection, pH level around the peri-implant surface decreases as low as pH 5.5. This change of pH can be used as a switch to control antimicrobial drug release from the implant surface. Silver nanoparticles (AgNPs) have broad-spectrum antimicrobial properties. In this study, we aimed to design a pH-dependent AgNPs releasing titania nanotube arrays (TNT) implant for peri-implant infection control. The nanotube arrays were fabricated on the surface of titanium implant as containers; AgNPs were grafted on TNT implant surface via a low pH-sensitive acetal linker (TNT-AL-AgNPs). SEM, TEM, AFM, FTIR as well as XPS data showed that AgNPs have been successfully linked to TNT via acetal linker without affecting the physicochemical characteristics of TNT. The pH 5.5 enhanced AgNPs release from TNT-AL-AgNPs implant compared with pH 7.4. AgNPs released at pH 5.5 robustly increased antimicrobial activities against gram-positive and gram-negative bacteria compared with AgNPs released at pH 7.4. TNT-AL-AgNPs implant enhanced osteoblast proliferation, differentiation, and did not affect osteoblast morphology in vitro. In conclusion, incorporation of AgNPs in TNT via acetal linker maintained the surface characteristics of TNT. TNT-AL-AgNPs implant was biocompatible to osteoblasts and showed osteoinductive properties. AgNPs were released from TNT-AL-AgNPs implant in high dose at pH 5.5, and this release showed strong antimicrobial properties in vitro. Therefore, this novel design of low pH-triggered AgNPs releasing TNT-AL-AgNPs could be an infection-triggered antimicrobial releasing implant model to control peri-implant infection. Copyright © 2017 Elsevier B.V. All rights reserved.

Controlled release chamber for dispensing aromatic substances.

PubMed

Cilek, J E; Hallmon, C F

2008-12-01

A novel device for the containment and precise release of aromatic substances is described. The device consists of a threaded-tubular polyvinyl chloride chamber (and screw-top cap) with ports for introduction and release of gaseous compounds. This chamber is inexpensive, easy to assemble, and useful for evaluating the combined release of carbon dioxide and aromatic hygroscopic substances as mosquito attractants in field studies.

Influence of poloxamers on the dissolution performance and stability of controlled-release formulations containing Precirol ATO 5.

PubMed

Jannin, V; Pochard, E; Chambin, O

2006-02-17

Lipid excipients are usually used for the development of sustained-release formulations. When used in relatively high quantities, Precirol ATO 5 imparts sustained-release properties to solid oral dosage forms, by forming a lipid matrix. To control or adjust the drug release kinetics from such lipid matrix however, one must often resort to complementary ingredients or techniques. This study investigates the influence of poloxamers (Lutrol) included in lipid matrices composed of glyceryl palmitostearate (Precirol ATO 5) on their dissolution performance and their stability. The addition of these hydrophilic polymers in the lipid matrix increased the amount of theophylline released thanks to the swelling of the hydrophilic polymer and the creation of a porous network into the inert lipid matrix. The grade and the quantity of Lutrol could modulate the extent of drug release. Theophylline was released mainly by the matrix erosion but also by diffusion through the pores as suggested by the Peppas' model. Moreover, the addition of Lutrol enhanced the stability during storage. The theophylline release was quite steady after 6 months in different conditions (temperature and humidity). Thus, the mixture of glyceryl palmitostearate and poloxamers is an approach with many advantages for the development of controlled-release formulations by capsule molding.

Micro-porous surfaces in controlled drug delivery systems: design and evaluation of diltiazem hydrochloride controlled porosity osmotic pump using non-ionic surfactants as pore-former.

PubMed

Adibkia, Khosro; Ghanbarzadeh, Saeed; Shokri, Mohammad Hosein; Arami, Zahra; Arash, Zeinab; Shokri, Javad

2014-06-01

The major problem associated with conventional drug delivery systems is unpredictable plasma concentrations. The aim of this study was to design a controlled porosity osmotic pump (CPOP) of diltiazem hydrochloride to deliver the drug in a controlled manner. CPOP tablets were prepared by incorporation of drug in the core and subsequent coating with cellulose acetate as semi-permeable membrane. Non-ionic surfactants were applied as pore-formers as well. The effect of pore-formers concentration on the in vitro release of diltiazem was also studied. The formulations were compared based on four comparative parameters, namely, total drug released after 24 h (D24 h), lag-time (tL), squared correlation coefficient of zero order equation (RSQzero) and mean percent deviation from zero order kinetic (MPDzero). Results of scanning electron microscopy studies exhibited formation of pores in the membrane from where the drug release occurred. It was revealed that drug release rate was directly proportional to the concentration of the pore-formers. The value of D24 h in the formulations containing Tween 80 (10%) and Brij 35 (5%) were found to be more than 94.9%, and drug release followed zero order kinetic (RSQzero > 0.99 and MPDzero < 8%) with acceptable tL (lower than 1 h).

Multi-unit dosage formulations of theophylline for controlled release applications.

PubMed

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 corresponding values of m infinity and t infinity for the tablets were (240 mg, 9 h), (180 mg, 11 h) and (128 mg, 12 h) against the set target (200 mg, 12 h). The indication is that tableting rather than encapsulation can more effectively control drug release from the systems.

Evaluation of Calendula mucilage as a mucoadhesive and controlled release component in buccal tablets.

PubMed

Sabale, V; Patel, V; Paranjape, A

2014-01-01

Mucoadhesive drug delivery systems were developed to sustain drug delivery via various mucus membranes for either local or systemic delivery of poorly absorbed drugs such as peptides and proteins as well as drugs that are subjected to high first-pass metabolism. The present study was undertaken to use isolated Calendula mucilage as a mucoadhesive agent and to formulate controlled release buccoadhesive tablets with an intention to avoid hepatic first-pass metabolism as well as to enhance residence time of drug in the buccal cavity. The mucilage was isolated from the Calendula petals by aqueous extraction method and characterized for various physiochemical parameters as well as for its adhesive properties. By using direct compression technique, tablets were prepared containing dried mucilage and chlorpheniramine maleate (CPM) as a model drug. Three batches of tablets were prepared and evaluated containing three mucoadhesive components namely Methocel K4M, Carbopol 974P and isolated Calendula mucilage in 16.66%, 33.33 % and 50 % (1:2:3 ratio) resulting in 9 different formulations. FTIR studies between mucilage and CPM suggested the absence of a chemical interaction between CPM and Calendula mucilage. The results of the study showed that the isolated mucilage had good physicochemical and morphological characteristics and tablets conformed to the pharmacopoeial specifications. Also in vitro release studies showed controlled action of drug with increasing the concentration of the isolated Calendula mucilage as a mucoadhesive agent in the formulations. Permeability studies indicated that permeability behavior was not statistically different (P>0.05) by changing the mucoadhesive component. The formulated mucoadhesive tablets for buccal administration containing 75 mg Calendula mucilage showed controlled drug release. Thus, mucoadhesive natural Calendula mucilage based buccal tablets for controlled release were successfully formulated.

Evaluation of Calendula mucilage as a mucoadhesive and controlled release component in buccal tablets

PubMed Central

Sabale, V.; Patel, V.; Paranjape, A.

2014-01-01

Mucoadhesive drug delivery systems were developed to sustain drug delivery via various mucus membranes for either local or systemic delivery of poorly absorbed drugs such as peptides and proteins as well as drugs that are subjected to high first-pass metabolism. The present study was undertaken to use isolated Calendula mucilage as a mucoadhesive agent and to formulate controlled release buccoadhesive tablets with an intention to avoid hepatic first-pass metabolism as well as to enhance residence time of drug in the buccal cavity. The mucilage was isolated from the Calendula petals by aqueous extraction method and characterized for various physiochemical parameters as well as for its adhesive properties. By using direct compression technique, tablets were prepared containing dried mucilage and chlorpheniramine maleate (CPM) as a model drug. Three batches of tablets were prepared and evaluated containing three mucoadhesive components namely Methocel K4M, Carbopol 974P and isolated Calendula mucilage in 16.66%, 33.33 % and 50 % (1:2:3 ratio) resulting in 9 different formulations. FTIR studies between mucilage and CPM suggested the absence of a chemical interaction between CPM and Calendula mucilage. The results of the study showed that the isolated mucilage had good physicochemical and morphological characteristics and tablets conformed to the pharmacopoeial specifications. Also in vitro release studies showed controlled action of drug with increasing the concentration of the isolated Calendula mucilage as a mucoadhesive agent in the formulations. Permeability studies indicated that permeability behavior was not statistically different (P>0.05) by changing the mucoadhesive component. The formulated mucoadhesive tablets for buccal administration containing 75 mg Calendula mucilage showed controlled drug release. Thus, mucoadhesive natural Calendula mucilage based buccal tablets for controlled release were successfully formulated. PMID:25598798

A controlled release of ibuprofen by systematically tailoring the morphology of mesoporous silica materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qu Fengyu; Chemistry and Pharmaceutical College, Jiamusi University, Jiamusi 154007; Zhu Guangshan

2006-07-15

A series of mesoporous silica materials with similar pore sizes, different morphologies and variable pore geometries were prepared systematically. In order to control drug release, ibuprofen was employed as a model drug and the influence of morphology and pore geometry of mesoporous silica on drug release profiles was extensively studied. The mesoporous silica and drug-loaded samples were characterized by X-ray diffraction, Fourier transform IR spectroscopy, N{sub 2} adsorption and desorption, scanning electron microscopy, and transmission electron microscopy. It was found that the drug-loading amount was directly correlated to the Brunauer-Emmett-Teller surface area, pore geometry, and pore volume; while the drugmore » release profiles could be controlled by tailoring the morphologies of mesoporous silica carriers. - Graphical abstract: The release of ibuprofen is controlled by tailoring the morphologies of mesoporous silica. The mesoporous silica and drug-loaded samples are characterized by powder X-ray diffraction, Fourier transform IR spectroscopy, N{sub 2} adsorption and desorption, scanning electron microscopy, and transmission electron microscopy. The drug-loading amount is directly correlated to the Brunauer-Emmett-Teller surface area, pore geometry, and pore volume; while the drug release profiles can be controlled by tailoring the morphologies of mesoporous silica carriers.« less

Magnetic high throughput screening system for the development of nano-sized molecularly imprinted polymers for controlled delivery of curcumin.

PubMed

Piletska, Elena V; Abd, Bashar H; Krakowiak, Agata S; Parmar, Anitha; Pink, Demi L; Wall, Katie S; Wharton, Luke; Moczko, Ewa; Whitcombe, Michael J; Karim, Kal; Piletsky, Sergey A

2015-05-07

Curcumin is a versatile anti-inflammatory and anti-cancer agent known for its low bioavailability, which could be improved by developing materials capable of binding and releasing drug in a controlled fashion. The present study describes the preparation of magnetic nano-sized Molecularly Imprinted Polymers (nanoMIPs) for the controlled delivery of curcumin and their high throughput characterisation using microtitre plates modified with magnetic inserts. NanoMIPs were synthesised using functional monomers chosen with the aid of molecular modelling. The rate of release of curcumin from five polymers was studied under aqueous conditions and was found to correlate well with the binding energies obtained computationally. The presence of specific monomers was shown to be significant in ensuring effective binding of curcumin and to the rate of release obtained. Characterisation of the polymer particles was carried out using dynamic light scattering (DLS) technique and scanning electron microscopy (SEM) in order to establish the relationship between irradiation time and particle size. The protocols optimised during this study could be used as a blueprint for the development of nanoMIPs capable of the controlled release of potentially any compound of interest.

In Vivo Imaging of the Stability and Sustained Cargo Release of an Injectable Amphipathic Peptide-Based Hydrogel.

PubMed

Oyen, Edith; Martin, Charlotte; Caveliers, Vicky; Madder, Annemieke; Van Mele, Bruno; Hoogenboom, Richard; Hernot, Sophie; Ballet, Steven

2017-03-13

Hydrogels are promising materials for biomedical applications such as tissue engineering and controlled drug release. In the past two decades, the peptide hydrogel subclass has attracted an increasing level of interest from the scientific community because of its numerous advantages, such as biocompatibility, biodegradability, and, most importantly, injectability. Here, we report on a hydrogel consisting of the amphipathic hexapeptide H-FEFQFK-NH 2 , which has previously shown promising in vivo properties in terms of releasing morphine. In this study, the release of a small molecule, a peptide, and a protein cargo as representatives of the three major drug classes is directly visualized by in vivo fluorescence and nuclear imaging. In addition, the in vivo stability of the peptide hydrogel system is investigated through the use of a radiolabeled hydrogelator sequence. Although it is shown that the hydrogel remains present for several days, the largest decrease in volume takes place within the first 12 h of subcutaneous injection, which is also the time frame wherein the cargos are released. Compared to the situation in which the cargos are injected in solution, a prolonged release profile is observed up to 12 h, showing the potential of our hydrogel system as a scaffold for controlled drug delivery. Importantly, this study elucidates the release mechanism of the peptide hydrogel system that seems to be based on erosion of the hydrogel providing a generally applicable controlled release platform for small molecule, peptide, and protein drugs.

Controlled Release of Multiple Therapeutics from Silicone Hydrogel Contact Lenses.

PubMed

White, Charles James; DiPasquale, Stephen Anthony; Byrne, Mark Edward

2016-04-01

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

Controlled Release of Multiple Therapeutics from Silicone Hydrogel Contact Lenses

PubMed Central

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

2016-01-01

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

Extracellular control of intracellular drug release for enhanced safety of anti-cancer chemotherapy

NASA Astrophysics Data System (ADS)

Zhu, Qian; Qi, Haixia; Long, Ziyan; Liu, Shang; Huang, Zhen; Zhang, Junfeng; Wang, Chunming; Dong, Lei

2016-06-01

The difficulty of controlling drug release at an intracellular level remains a key challenge for maximising drug safety and efficacy. We demonstrate herein a new, efficient and convenient approach to extracellularly control the intracellular release of doxorubicin (DOX), by designing a delivery system that harnesses the interactions between the system and a particular set of cellular machinery. By simply adding a small-molecule chemical into the cell medium, we could lower the release rate of DOX in the cytosol, and thereby increase its accumulation in the nuclei while decreasing its presence at mitochondria. Delivery of DOX with this system effectively prevented DOX-induced mitochondria damage that is the main mechanism of its toxicity, while exerting the maximum efficacy of this anti-cancer chemotherapeutic agent. The present study sheds light on the design of drug delivery systems for extracellular control of intracellular drug delivery, with immediate therapeutic implications.

Dual-controlled release system of drugs for bone regeneration.

PubMed

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.

The effect of controlled-release ClO2 on the preservation of grapefruit

USDA-ARS?s Scientific Manuscript database

The effect of controlled-release ClO2 gas on the safety and quality of grapefruit was studied. Three different tests were run: 1) isolated peel tissue with microorganism inoculation in a chamber system; 2) individual fruit with microorganism inoculation in a chamber; and 3) boxed fruit under commerc...

An integrative model of the cardiac ventricular myocyte incorporating local control of Ca2+ release.

PubMed Central

Greenstein, Joseph L; Winslow, Raimond L

2002-01-01

The local control theory of excitation-contraction (EC) coupling in cardiac muscle asserts that L-type Ca(2+) current tightly controls Ca(2+) release from the sarcoplasmic reticulum (SR) via local interaction of closely apposed L-type Ca(2+) channels (LCCs) and ryanodine receptors (RyRs). These local interactions give rise to smoothly graded Ca(2+)-induced Ca(2+) release (CICR), which exhibits high gain. In this study we present a biophysically detailed model of the normal canine ventricular myocyte that conforms to local control theory. The model formulation incorporates details of microscopic EC coupling properties in the form of Ca(2+) release units (CaRUs) in which individual sarcolemmal LCCs interact in a stochastic manner with nearby RyRs in localized regions where junctional SR membrane and transverse-tubular membrane are in close proximity. The CaRUs are embedded within and interact with the global systems of the myocyte describing ionic and membrane pump/exchanger currents, SR Ca(2+) uptake, and time-varying cytosolic ion concentrations to form a model of the cardiac action potential (AP). The model can reproduce both the detailed properties of EC coupling, such as variable gain and graded SR Ca(2+) release, and whole-cell phenomena, such as modulation of AP duration by SR Ca(2+) release. Simulations indicate that the local control paradigm predicts stable APs when the L-type Ca(2+) current is adjusted in accord with the balance between voltage- and Ca(2+)-dependent inactivation processes as measured experimentally, a scenario where common pool models become unstable. The local control myocyte model provides a means for studying the interrelationship between microscopic and macroscopic behaviors in a manner that would not be possible in experiments. PMID:12496068

Novel device for continuous spatial control and temporal delivery of nitric oxide for in vitro cell culture☆

PubMed Central

Romanowicz, Genevieve E.; He, Weilue; Nielsen, Matthew; Frost, Megan C.

2013-01-01

Nitric oxide (NO) is an ubiquitous signaling molecule of intense interest in many physiological processes. Nitric oxide is a highly reactive free radical gas that is difficult to deliver with precise control over the level and timing that cells actually experience. We describe and characterize a device that allows tunable fluxes and patterns of NO to be generated across the surface upon which cells are cultured. The system is based on a quartz microscope slide that allows for controlled light levels to be applied to a previously described photosensitive NO-releasing polydimethylsiloxane (PDMS). Cells are cultured in separate wells that are either NO-releasing or a chemically similar PDMS that does not release NO. Both wells are then top coated with DowCorning RTV-3140 PDMS and a polydopamine/gelatin layer to allow cells to grow in the culture wells. When the waveguide is illuminated, the surface of the quartz slide propagates light such that the photosensitive polymer is evenly irradiated and generates NO across the surface of the cell culture well and no light penetrates into the volume of the wells where cells are growing. Mouse smooth muscle cells (MOVAS) were grown in the system in a proof of principle experiment, whereby 60% of the cells were present in the NO-releasing well compared to control wells after 17 h. The compelling advantage of illuminating the NO-releasing polymers with the waveguide system is that light can be used to tunably control NO release while avoiding exposing cells to optical radiation. This device provides means to quantitatively control the surface flux, timing and duration of NO cells experience and allows for systematic study of cellular response to NO generated at the cell/surface interface in a wide variety of studies. PMID:24024168

Preparation and release characteristics of polymer-coated and blended alginate microspheres.

PubMed

Lee, D W; Hwang, S J; Park, J B; Park, H J

2003-01-01

To prevent a rapid drug release from alginate microspheres in simulated intestinal media, alginate microspheres were coated or blended with polymers. Three polymers were selected and evaluated such as HPMC, Eudragit RS 30D and chitosan, as both coating materials and additive polymers for controlling the drug release. This study focused on the release characteristics of polymer-coated and blended alginate microspheres, varying the type of polymer and its concentration. The alginate microspheres were prepared by dropping the mixture of drug and sodium alginate into CaCl(2) solution using a spray-gun. Polymer-coated microspheres were prepared by adding alginate microspheres into polymer solution with mild stirring. Polymer-blended microspheres were prepared by dropping the mixture of drug, sodium alginate and additive polymer with plasticizer into CaCl(2) solution. In vitro release test was carried out to investigate the release profiles in 500 ml of phosphate buffered saline (PBS, pH 7.4). As the amount of polymer in sodium alginate or coating solution increase, the drug release generally decreased. HPMC-blended microspheres swelled but withstood the disintegration, showing an ideal linear release profiles. Chitosan-coated microspheres showed smooth and round surface and extended the release of drug. In comparison with chitosan-coated microspheres, HPMC-blended alginate microspheres can be easily made and used for controlled drug delivery systems due to convenient process and controlled drug release.

Evaluation of Degradation Properties of Polyglycolide and Its Potential as Delivery Vehicle for Anticancer Agents

NASA Astrophysics Data System (ADS)

Noorsal, K.; Ghani, S. M.; Yunos, D. M.; Mohamed, M. S. W.; Yahya, A. F.

2010-03-01

Biodegradable polymers offer a unique combination of properties that can be tailored to suit nearly any controlled drug delivery application. The most common biodegradable polymers used for biomedical applications are semicrystalline polyesters and polyethers which possess good mechanical properties and have been used in many controlled release applications. Drug release from these polymers may be controlled by several mechanisms and these include diffusion of drug through a matrix, dissolution of polymer matrix and degradation of the polymer. This study aims to investigate the degradation and drug release properties of polyglycolide (1.03 dL/g), in which, cis platin, an anticancer agent was used as the model drug. The degradation behaviour of the chosen polymer is thought to largely govern the release of the anticancer agent in vitro.

Poly (lactic-co-glycolic acid) controlled release systems: experimental and modeling insights

PubMed Central

Hines, Daniel J.; Kaplan, David L.

2013-01-01

Poly-lactic-co-glycolic acid (PLGA) has been the most successful polymeric biomaterial for use in controlled drug delivery systems. There are several different chemical and physical properties of PLGA that impact the release behavior of drugs from PLGA delivery devices. These properties must be considered and optimized in drug release device formulation. Mathematical modeling is a useful tool for identifying, characterizing, and predicting the mechanisms of controlled release. The advantages and limitations of poly (lactic-co-glycolic acid) for controlled release are reviewed, followed by a review of current approaches in controlled release technology that utilize PLGA. Mathematical modeling applied towards controlled release rates from PLGA-based devices will also be discussed to provide a complete picture of state of the art understanding of the control achievable with this polymeric system, as well as the limitations. PMID:23614648

[Neuronal LHRH system activity in an animal model of growth retardation].

PubMed

Compagnucci, Cecilia Vanesa; Compagnucci, Gabriela Edith; Lezón, Christian Esteban; Chiarenza, Ana Patricia; Elverdin, Juan Carlos; Boyer, Patricia Mónica

2010-05-01

Mild and chronic energy restriction results in growth retardation with puberal delay, a nutritional disease known as nutritional dwarfing (ND). The aim of the present study was to assess the profile of hypothalamic luteinizing hormone-releasing hormone (LHRH) release, at baseline and under glutamate stimulation, in ND rats to elucidate gonadotrophic dysfunction. Reproductive ability during refeeding was also studied. At weaning, 60 male rats were assigned to two groups of 30 animals each: a control and an experimental group. Control rats were fed ad libitum with a balanced rodent diet. The experimental group received 80% of the diet consumed by the control group for 4 weeks. After 4 weeks of food restriction, the ND group was fed freely for 8 weeks. Ten rats from each group were sacrificed every 4 weeks for assays. At week 4, body weight and length were significantly diminished in the experimental group vs. the control group (p<0.001). No changes were observed in LHRH baseline release, pulse frequency or amplitude in the experimental group compared with the control group at any time. However, under glutamate stimulation, LHRH release was significantly higher in ND rats than in control rats at week 4 (p<0.05). Refeeding the ND group allowed the rats to reach overall growth and reproductive ability. The results of the present study suggest that the response to the facilitatory effect of glutamate on LHRH release in post-restricted ND rats is probably related to a lesser central nervous system maturation in relation to their chronological age. The adequate somatic growth and normal reproductive ability attained with refeeding suggest the reversibility of the two energetically costly processes compromised by global, mild and chronic food restriction. Copyright (c) 2009 SEEN. Published by Elsevier Espana. All rights reserved.

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

PubMed

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.

Controlled release of basic fibroblast growth factor for angiogenesis using acoustically-responsive scaffolds.

PubMed

Moncion, Alexander; Lin, Melissa; O'Neill, Eric G; Franceschi, Renny T; Kripfgans, Oliver D; Putnam, Andrew J; Fabiilli, Mario L

2017-09-01

The clinical translation of pro-angiogenic growth factors for treatment of vascular disease has remained a challenge due to safety and efficacy concerns. Various approaches have been used to design spatiotemporally-controlled delivery systems for growth factors in order to recapitulate aspects of endogenous signaling and thus assist in translation. We have developed acoustically-responsive scaffolds (ARSs), which are fibrin scaffolds doped with a payload-containing, sonosensitive emulsion. Payload release can be controlled non-invasively and in an on-demand manner using focused, megahertz-range ultrasound (US). In this study, we investigate the in vitro and in vivo release from ARSs containing basic fibroblast growth factor (bFGF) encapsulated in monodispersed emulsions. Emulsions were generated in a two-step process utilizing a microfluidic device with a flow focusing geometry. At 2.5 MHz, controlled release of bFGF was observed for US pressures above 2.2 ± 0.2 MPa peak rarefactional pressure. Superthreshold US yielded a 12.6-fold increase in bFGF release in vitro. The bioactivity of the released bFGF was also characterized. When implanted subcutaneously in mice, ARSs exposed to superthreshold US displayed up to 3.3-fold and 1.7-fold greater perfusion and blood vessel density, respectively, than ARSs without US exposure. Scaffold degradation was not impacted by US. These results highlight the utility of ARSs in both basic and applied studies of therapeutic angiogenesis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of microdialyzed oxotremorine, carbachol, epibatidine, and scopolamine on intraspinal release of acetylcholine in the rat.

PubMed

Höglund, A U; Hamilton, C; Lindblom, L

2000-10-01

Intrathecally administered cholinergic agonists such as oxotremorine (muscarinic), carbachol (mixed nicotinic and muscarinic agonist), and epibatidine (nicotinic) have all been shown to reduce nociception in behavioral studies. Thus, there is substantial evidence for a role of acetylcholine (ACh) in the control of nociception in the spinal cord, but the mechanisms regulating ACh release are not known. The present study was initiated to establish a rat model to study which mechanisms are involved in the control of ACh release. Spinal microdialysis probes were inserted intraspinally at the C1-C5 spinal level in isoflurane-anesthetized rats. The probes were perfused with Ringer's solution containing 10 microM neostigmine to prevent degradation of ACh. Oxotremorine, carbachol, epibatidine, and scopolamine, dissolved in Ringer's solution, were administered intraspinally via dialysis and 30 microliter/10-min samples of dialysate were collected for HPLC analysis of ACh content. The release of ACh was found to be constant in the control (Ringer's only) situation during the experimental period of 150 min. Oxotremorine (100-1000 microM), carbachol (1 mM), and epibatidine (50-5000 microM) enhanced but scopolamine (50-200 nM) decreased the intraspinal release of ACh. Oxotremorine (ED(50) = 118 microM) and epibatidine (ED(50) = 175 microM) were found to produce a dose-dependent increase of ACh release. Cholinergic agonists caused an increase of intraspinal ACh and the antagonist scopolamine caused a decreased release of ACh. The data do not support an autoreceptor function of either nicotinic or muscarinic receptors in the spinal cord, contrary to what has been observed in the brain.

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

PubMed

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.

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

PubMed

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

2014-03-01

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

pH-controlled drug release for dental applications

NASA Astrophysics Data System (ADS)

Wironen, John Francis

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

Glucose release in mantle tissue of Mytilus: regulation by calcium ions.

PubMed

Crespo, C A; Espinosa, J

1990-09-01

Glucose release activity in mantle tissue of Mytilus galloprovincialis was studied. Mantle tissue shows a basal glucose releasing activity. The external Ca2+ absence increases 2 to 3-fold the basal glucose release, and when A23187 (10 microM) was simultaneously present the release doubled that obtained in Ca2(+)-absence. EGTA (2 mM), chlorpromazine (200 microM) and lanthanum (3 mM) decreased the glucose release promoted by external Ca2+ absence. This and other data suggest that glucose release activity in mantle tissue might be controlled by Ca2+ ions.

Development of a novel drug delivery system, time-controlled explosion system (TES). IV. In vivo drug release behavior.

PubMed

Ueda, S; Ibuki, R; Kawamura, A; Murata, S; Takahashi, T; Kimura, S; Hata, T

1994-01-01

Time-Controlled Explosion System (TES) has the time-controlled drug release property with a pre-designed lag time. The drug release from the system is initiated by destruction of the membrane. In this study, metoprolol tartrate was used as a model drug. After five types of TES with different in vitro lag times were orally administrated to dogs, plasma metoprolol concentration was monitored. There existed a good correlation between in vitro and in vivo lag time, while the extent of absorbed metoprolol decreased with prolongation of lag time. Next, the in vivo drug release behavior was directly investigated using five different colored TES with a lag time of two hours. Each TES was consecutively administrated to the fasted dogs at predetermined intervals. The amount of metoprolol released was monitored by recovering the administered TES from the gastrointestinal trace. The in vivo release profile corresponded with the in vitro one. It is demonstrated that TES can release the drug in in vivo conditions similarly to in vitro. Based on these results, the decrease of the absorption is suggested to be caused by increased hepatic first-pass metabolism of the drug due to the retarded release rate with longer lag time.

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

PubMed

Hiremath, Praveen S; Saha, Ranendra N

2008-10-01

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

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

PubMed Central

Arora, Gurpreet; Malik, Karan; Singh, Inderbir; Arora, Sandeep; Rana, Vikas

2011-01-01

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/cm2 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. PMID:22171313

Development of an osmotic pump system for controlled delivery of diclofenac sodium.

PubMed

Emara, L H; Taha, N F; Badr, R M; Mursi, N M

2012-10-01

Based on an elementary osmotic pump, controlled release systems of diclofenac sodium (DS) were designed to deliver the drug in a zero-order release pattern. Osmotic pump tablets containing 100 mg DS were prepared and coated with either semipermeable (SPM) or microporous (PM) membranes. The tablet coats were composed of hydrophobic triacetin (TA) or hydrophilic polyethylene glycol 400 (PEG 400) incorporated in cellulose acetate (CA) solution, for SPM and PM, respectively. Variable tablet core compositions such as swelling polymers (PEO and HPMC) and osmotic agents (lactose, NaCl, and KCl) were studied. An optimized, sensitive and well controlled in vitro release design, based on the flow-through cell (FTC), was utilized to discriminate between preparations. The results revealed that the presence of PEG 400 in the coating membrane accelerated the drug release rate, while TA suppressed the release rate of DS. In the case of SPM, the amount of DS released was inversely proportional to the membrane thickness, where 5% (w/w) weight gain gave a higher DS release rate than 10% (w/w). Results of different tablet core compositions revealed that the release rate of DS decreased as PEO molecular weight increased. HPMC K15M showed the lowest DS release rate. The presence of lactose, KCl, or NaCl pronouncedly affected DS release rate depending on polymer type in the core. Scanning electron microscopy (SEM) confirmed formation of pores in the membrane that accounts for faster DS release rate. These results revealed that DS could be formulated as an osmotic pump system with a prolonged, zero-order release pattern.

Intercalation and controlled release properties of vitamin C intercalated layered double hydroxide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gao, Xiaorui, E-mail: gxr_1320@sina.com; School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189; Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA

Two drug-inorganic composites involving vitamin C (VC) intercalated in Mg–Al and Mg–Fe layered double hydroxides (LDHs) have been synthesized by the calcination–rehydration (reconstruction) method. Powder X-ray diffraction (XRD), Fourier transform infrared (FTIR), and UV–vis absorption spectroscopy indicate a successful intercalation of VC into the interlayer galleries of the LDH host. Studies of VC release from the LDHs in deionised water and in aqueous CO{sub 3}{sup 2−} solutions imply that Mg{sub 3}Al–VC LDH is a better controlled release system than Mg{sub 3}Fe–VC LDH. Analysis of the release profiles using a number of kinetic models suggests a solution-dependent release mechanism, and amore » diffusion-controlled deintercalation mechanism in deionised water, but an ion exchange process in CO{sub 3}{sup 2−} solution. - Graphical abstract: Vitamin C anions have been intercalated in the interlayer space of layered double hydroxide and released in CO{sub 3}{sup 2−} solution and deionised water. - Highlights: • Vitamin C intercalated Mg–Al and Mg–Fe layered double hydroxides were prepared. • Release property of vitamin C in aqueous CO{sub 3}{sup 2−} solution is better. • Avrami-Erofe’ev and first-order models provide better fit for release results. • Diffusion-controlled and ion exchange processes occur in deionised water. • An ion exchange process occurs in CO{sub 3}{sup 2−} solution.« less

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

PubMed

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.

Accelerated dissolution testing for controlled release microspheres using the flow-through dissolution apparatus.

PubMed

Collier, Jarrod W; Thakare, Mohan; Garner, Solomon T; Israel, Bridg'ette; Ahmed, Hisham; Granade, Saundra; Strong, Deborah L; Price, James C; Capomacchia, A C

2009-01-01

Theophylline controlled release capsules (THEO-24 CR) were used as a model system to evaluate accelerated dissolution tests for process and quality control and formulation development of controlled release formulations. Dissolution test acceleration was provided by increasing temperature, pH, flow rate, or adding surfactant. Electron microscope studies on the theophylline microspheres subsequent to each experiment showed that at pH values of 6.6 and 7.6 the microspheres remained intact, but at pH 8.6 they showed deterioration. As temperature was increased from 37-57 degrees C, no change in microsphere integrity was noted. Increased flow rate also showed no detrimental effect on integrity. The effect of increased temperature was determined to be the statistically significant variable.

11th Annual Systems Engineering Conference

DTIC Science & Technology

2008-10-23

effectiveness for force structure architecture studies – Problem of interest was Layered Intelligence, Surveillance and Reconnaissance ( LISR ) with Integrated...Cleared for Public Release, Control No. 08-110, dtd. 10-1-0811 LISR CET Typical Products 1 Satellite_A; 1 Satellite_B; 3 VehA; 1 VehB (50%) 2 VehA; 3...the means to support LISR force structure architecture studies: Stand-alone and as a lead-in to detailed work Cleared for Public Release, Control No

Measuring the Acoustic Release of a Chemotherapeutic Agent from Folate-Targeted Polymeric Micelles.

PubMed

Abusara, Ayah; Abdel-Hafez, Mamoun; Husseini, Ghaleb

2018-08-01

In this paper, we compare the use of Bayesian filters for the estimation of release and re-encapsulation rates of a chemotherapeutic agent (namely Doxorubicin) from nanocarriers in an acoustically activated drug release system. The study is implemented using an advanced kinetic model that takes into account cavitation events causing the antineoplastic agent's release from polymeric micelles upon exposure to ultrasound. This model is an improvement over the previous representations of acoustic release that used simple zero-, first- and second-order release and re-encapsulation kinetics to study acoustically triggered drug release from polymeric micelles. The new model incorporates drug release and micellar reassembly events caused by cavitation allowing for the controlled release of chemotherapeutics specially and temporally. Different Bayesian estimators are tested for this purpose including Kalman filters (KF), Extended Kalman filters (EKF), Particle filters (PF), and multi-model KF and EKF. Simulated and experimental results are used to verify the performance of the above-mentioned estimators. The proposed methods demonstrate the utility and high-accuracy of using estimation methods in modeling this drug delivery technique. The results show that, in both cases (linear and non-linear dynamics), the modeling errors are expensive but can be minimized using a multi-model approach. In addition, particle filters are more flexible filters that perform reasonably well compared to the other two filters. The study improved the accuracy of the kinetic models used to capture acoustically activated drug release from polymeric micelles, which may in turn help in designing hardware and software capable of precisely controlling the delivered amount of chemotherapeutics to cancerous tissue.

Controlled release formulations of risperidone antipsychotic drug in novel aliphatic polyester carriers: Data analysis and modelling.

PubMed

Siafaka, Panoraia I; Barmpalexis, Panagiotis; Lazaridou, Maria; Papageorgiou, George Z; Koutris, Efthimios; Karavas, Evangelos; Kostoglou, Margaritis; Bikiaris, Dimitrios N

2015-08-01

In the present study a series of biodegradable and biocompatible poly(ε-caprolactone)/poly(propylene glutarate) (PCL/PPGlu) polymer blends were investigated as controlled release carriers of Risperidone drug (RISP), appropriate for transdermal drug delivery. The PCL/PPGlu carriers were prepared in different weight ratios. Miscibility studies of blends were evaluated through differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). Hydrolysis studies were performed at 37°C using a phosphate buffered saline solution. The prepared blends have been used for the preparation of RISP patches via solvent evaporation method, containing 5, 10 and 15wt% RISP. These formulations were characterized using FT-IR spectroscopy, DSC and WAXD in order to evaluate interactions taking place between polymer matrix and drug, as well as the dispersion and the physical state of the drug inside the polymer matrix. In vitro drug release studies were performed using as dissolution medium phosphate buffered saline simulating body fluids. It was found that in all cases controlled release formulations were obtained, while the RISP release varies due to the properties of the used polymer blend and the different levels of drug loading. Artificial Neural Networks (ANNs) were used for dissolution behaviour modelling showing increased correlation efficacy compared to Multi-Linear-Regression (MLR). Copyright © 2015 Elsevier B.V. All rights reserved.

Modulating dopamine release by optogenetics in transgenic mice reveals terminal dopaminergic dynamics

PubMed Central

Lu, Yao; Driscoll, Nicolette; Ozden, Ilker; Yu, Zeyang; Nurmikko, Arto V.

2015-01-01

Abstract. Dopamine (DA) release and uptake dynamics in the nucleus accumbens (NAc) have important implications for neurological diseases and mammalian animal behaviors. We demonstrate here the use of cell-type-specific optogenetic targeting in conjunction with fast-scan cyclic voltammetry applied to brain slices prepared from specifically tailored transgenic mice, which conditionally express channelrhodopsin-2 (ChR2) through dopamine transporter (DAT)-Cre. Terminal dopaminergic dynamics and the direct manipulation of induced DA release level by controlling light intensity, pulse width, and the shape of stimulation waveforms were studied. Effective cell terminal-targeting optogenetic induction of DA release at physiological levels in NAc is demonstrated and discussed. It was found that delivering more light energy by increasing stimulation intensity and length is not the only way to control DA release; the temporal shape of the stimulus waveform at light onset is also critically related to induced DA concentrations. In addition, DA uptake dynamics as well as the recovery of the presynaptic releasable DA pool are studied and modeled. More broadly, our experimental findings provide important further evidence for effectively applying optogenetics to induce neurotransmitter release in the behaviorally relevant region of the brain in a highly cell-type selective context. PMID:26171413

Determination of Nitrogen, Phosphorus, and Potassium Release Rates of Slow- and Controlled-Release Fertilizers: Single-Laboratory Validation, First Action 2015.15.

PubMed

Thiex, Nancy

2016-01-01

A previously validated method for the determination of nitrogen release patterns of slow- and controlled-release fertilizers (SRFs and CRFs, respectively) was submitted to the Expert Review Panel (ERP) for Fertilizers for consideration of First Action Official Method(SM) status. The ERP evaluated the single-laboratory validation results and recommended the method for First Action Official Method status and provided recommendations for achieving Final Action. The 180 day soil incubation-column leaching technique was demonstrated to be a robust and reliable method for characterizing N release patterns from SRFs and CRFs. The method was reproducible, and the results were only slightly affected by variations in environmental factors such as microbial activity, soil moisture, temperature, and texture. The release of P and K were also studied, but at fewer replications than for N. Optimization experiments on the accelerated 74 h extraction method indicated that temperature was the only factor found to substantially influence nutrient-release rates from the materials studied, and an optimized extraction profile was established as follows: 2 h at 25°C, 2 h at 50°C, 20 h at 55°C, and 50 h at 60°C.

Biocompatibility and intradiscal application of a thermoreversible celecoxib-loaded poly-N-isopropylacrylamide MgFe-layered double hydroxide hydrogel in a canine model.

PubMed

Willems, Nicole; Yang, Hsiao-Yin; Langelaan, Marloes L P; Tellegen, Anna R; Grinwis, Guy C M; Kranenburg, Hendrik-Jan C; Riemers, Frank M; Plomp, Saskia G M; Craenmehr, Eric G M; Dhert, Wouter J A; Papen-Botterhuis, Nicole E; Meij, Björn P; Creemers, Laura B; Tryfonidou, Marianna A

2015-08-20

Chronic low back pain due to intervertebral disc (IVD) degeneration is associated with increased levels of inflammatory mediators. Current medical treatment consists of oral anti-inflammatory drugs to alleviate pain. In this study, the efficacy and safety of a novel thermoreversible poly-N-isopropylacrylamide MgFe-layered double hydroxide (pNIPAAM MgFe-LDH) hydrogel was evaluated for intradiscal controlled delivery of the selective cyclooxygenase (COX) 2 inhibitor and anti-inflammatory drug celecoxib (CXB). Degradation, release behavior, and the ability of a CXB-loaded pNIPAAM MgFe-LDH hydrogel to suppress prostaglandin E2 (PGE2) levels in a controlled manner in the presence of a proinflammatory stimulus (TNF-α) were evaluated in vitro. Biocompatibility was evaluated histologically after subcutaneous injection in mice. Safety of intradiscal application of the loaded and unloaded hydrogels was studied in a canine model of spontaneous mild IVD degeneration by histological, biomolecular, and biochemical evaluation. After the hydrogel was shown to be biocompatible and safe, an in vivo dose-response study was performed in order to determine safety and efficacy of the pNIPAAM MgFe-LDH hydrogel for intradiscal controlled delivery of CXB. CXB release correlated to hydrogel degradation in vitro. Furthermore, controlled release from CXB-loaded hydrogels was demonstrated to suppress PGE2 levels in the presence of TNF-α. The hydrogel was shown to exhibit a good biocompatibility upon subcutaneous injection in mice. Upon intradiscal injection in a canine model, the hydrogel exhibited excellent biocompatibility based on histological evaluation of the treated IVDs. Gene expression and biochemical analyses supported the finding that no substantial negative effects of the hydrogel were observed. Safety of application was further confirmed by the absence of clinical symptoms, IVD herniation or progression of degeneration. Controlled release of CXB resulted in a nonsignificant maximal inhibition (approximately 35 %) of PGE2 levels in the mildly degenerated canine IVDs. In conclusion, this study showed biocompatibility and safe intradiscal application of an MgFe LDH-pNIPAAM hydrogel. Controlled release of CXB resulted in only limited inhibition of PGE2 in this model with mild IVD degeneration, and further studies should concentrate on application of controlled release from this type of hydrogel in animal models with more severe IVD degeneration.

Injectable visible light-cured glycol chitosan hydrogels with controlled release of anticancer drugs for local cancer therapy in vivo: a feasible study.

PubMed

Hyun, Hoon; Park, Min Ho; Lim, Wonbong; Kim, So Yeon; Jo, Danbi; Jung, Jin Seok; Jo, Gayoung; Um, Sewook; Lee, Deok-Won; Yang, Dae Hyeok

2018-05-11

Currently available chemotherapy is associated with serious side effects, and therefore novel drug delivery systems (DDSs) are required to specifically deliver anticancer drugs to targeted sites. In this study, we evaluated the feasibility of visible light-cured glycol chitosan (GC) hydrogels with controlled release of doxorubicin⋅hydrochloride (DOX⋅HCl) as local DDSs for effective cancer therapy in vivo. The storage modulus of the hydrogel precursor solutions was increased as a function of visible light irradiation time. In addition, the swelling ratio of the hydrogel irradiated for 10 s (GC 10 /DOX) was greater than in 60 s (GC 60 /DOX). In vitro release test showed that DOX was rapidly released in GC 10 /DOX compared with GC 60 /DOX due to the density of cross-linking. In vitro and in vivo tests including cell viability and measurement of tumor volume showed that the local treatment of GC 10 /DOX yielded substantially greater antitumor effect compared with that of GC 60 /DOX. Therefore, the visible light-cured GC hydrogel system may exhibit clinical potential as a local DDS of anticancer drugs with controlled release, by modulating cross-linking density.

Improving the controlled release of water-insoluble emodin from amino-functionalized mesoporous silica

NASA Astrophysics Data System (ADS)

Xu, Yunqiang; Wang, Chunfeng; Zhou, Guowei; Wu, Yue; Chen, Jing

2012-06-01

Several types of amino-functionalized mesoporous silica, including F5-SBA-15, F10-SBA-15, and F15-SBA-15 were prepared through co-condensation of tetraethoxysilane (TEOS) and (3-aminopropyl)triethoxysilane (APTES) in varying molar ratios (5 mol%, 10 mol%, and 15 mol%) via a hydrothermal process. The materials obtained were characterized by means of small-angle X-ray powder diffraction, scanning electron microscopy, transmission electron microscopy, N2 adsorption-desorption, Fourier transformed infrared spectra, and X-ray photoelectron spectroscopy. Increasing APTES molar ratios decreased the degree of orderliness of the functionalized mesoporous silica. Pure and amino-functionalized SBA-15 samples were employed as supports for the controlled release of water-insoluble drug emodin. Loading experiments showed that drug loading capacities mainly depended on the surface areas and pore diameters of the carriers. Controlled release profiles of emodin-loaded samples were studied in phosphate buffered saline (PBS, pH 7.4), and results indicated that the emodin release rate could be controlled by surface amino-functionalized carriers. Emodin loaded on functionalized mesoporous supports exhibited a lower release rate than that of loaded on pure SBA-15, emodin loaded on F10-SBA-15 showed the smallest release amount (71.74 wt%) after stirring in PBS for 60 h. Findings suggest that functionalized mesoporous SBA-15 is a promising carrier for achieving prolonged release time periods.

Controlled-release Hydrogen Peroxide for On-site Treatment of Organic Pollutants in Urban Storm Runoff

NASA Astrophysics Data System (ADS)

Lee, E.; Sun, S.; Kim, Y.

2011-12-01

Nonpoint source (NPS) pollutants are the remaining cause of the environment problems, significantly impairing the hydrologic and biologic function of urban water systems and human health. Managing the NPS loads to urban aquatic systems remains a challenge because of ubiquitous contaminant sources and large pollutants loads in the first flush. Best management practices (BMPs) exist for reducing the NPS pollutants in urban storm waters, but the remedial efficiencies of these passive schemes are unpredictable. This study aims to develop a controlled-release system as part of an in situ chemical oxidation scheme designed for on-site treatment of organic pollutants in urban runoff. Controlled-release hydrogen peroxide (CR-HP) solids were manufactured by dispersing fine sodium percarbonate granules in paraffin wax matrices. Release kinetics and treatment efficiencies of CR-HP for BTEX and MTBE were investigated through a series of column tests. Release data indicated that the CR-HP could continually release hydrogen peroxide (H2O2) in flowing water at controlled rates over 276-1756 days, and the release rates could be adjusted by changing the mixing ratios of sodium percarbonate and wax matrices. Additional column tests and model calculations demonstrated that CR-HP/UV systems can provide low-cost, target-specific, and persistent source of oxidants for efficient treatment of organic compounds in urban storm runoff.

Nanostructured DPA-MPC-DPA triblock copolymer gel for controlled drug release of ketoprofen and spironolactone.

PubMed

Azmy, Bahaa; Standen, Guy; Kristova, Petra; Flint, Andrew; Lewis, Andrew L; Salvage, Jonathan P

2017-08-01

Uncontrolled rapid release of drugs can reduce their therapeutic efficacy and cause undesirable toxicity; however, controlled release from reservoir materials helps overcome this issue. The aims of this study were to determine the release profiles of ketoprofen and spironolactone from a pH-responsive self-assembling DPA-MPC-DPA triblock copolymer gel and elucidate underlying physiochemical properties. Drug release profiles from DPA 50 -MPC 250 -DPA 50 gel (pH 7.5), over 32 h (37 °C), were determined using UV-Vis spectroscopy. Nanoparticle size was measured by dynamic light scattering (DLS) and critical micelle concentration (CMC) by pyrene fluorescence. Polymer gel viscosity was examined via rheology, nanoparticle morphology investigated using scanning transmission electron microscopy (STEM) and the gel matrix observed using cryo-scanning electron microscopy (Cryo-SEM). DPA 50 -MPC 250 -DPA 50 copolymer (15% w/v) formed a free-standing gel (pH 7.5) that controlled drug release relative to free drugs. The copolymer possessed a low CMC, nanoparticle size increased with copolymer concentration, and DLS data were consistent with STEM. The gel displayed thermostable viscosity at physiological temperatures, and the gel matrix was a nanostructured aggregation of smaller nanoparticles. The DPA 50 -MPC 250 -DPA 50 copolymer gel could be used as a drug delivery system to provide the controlled drug release of ketoprofen and spironolactone. © 2017 Royal Pharmaceutical Society.

Layered double hydroxide using hydrothermal treatment: morphology evolution, intercalation and release kinetics of diclofenac sodium

NASA Astrophysics Data System (ADS)

Joy, Mathew; Iyengar, Srividhya J.; Chakraborty, Jui; Ghosh, Swapankumar

2017-12-01

The present work demonstrates the possibilities of hydrothermal transformation of Zn-Al layered double hydroxide (LDH) nanostructure by varying the synthetic conditions. The manipulation in washing step before hydrothermal treatment allows control over crystal morphologies, size and stability of their aqueous solutions. We examined the crystal growth process in the presence and the absence of extra ions during hydrothermal treatment and its dependence on the drug (diclofenac sodium (Dic-Na)) loading and release processes. Hexagonal plate-like crystals show sustained release with ˜90% of the drug from the matrix in a week, suggesting the applicability of LDH nanohybrids in sustained drug delivery systems. The fits to the release kinetics data indicated the drug release as a diffusion-controlled release process. LDH with rod-like morphology shows excellent colloidal stability in aqueous suspension, as studied by photon correlation spectroscopy.

Two release rates from monolithic carboxymethyl starch tablets: formulation, characterization, and in vitro/in vivo evaluation.

PubMed

Le, Tien Canh; Mateescu, Mircea Alexandru

2017-08-01

Most of non-steroidal anti-inflammatory drugs (NSAIDs) including ibuprofen at more than 1200 mg/day may generate gastrointestinal and cardiovascular side effects. Bilayer or multiparticulate devices have been developed for controlled release in order to prevent undesired side effects. A new "two release rate (2RR) monolithic tablets" approach is now proposed for controlled release of poorly soluble drugs, particularly NSAIDs. Ibuprofen was used as model drug. This concept is based on a calcium carboxymethyl-starch (CaCMS) complex as a novel, low-cost excipient for monolithic dosage forms easy to manufacture by direct compaction. The in vitro dissolution from CaCMS formulations (tablets containing 400 or 600 mg active principle) showed two distinct release rates: (i) an initial fast release (for 30 min in simulated gastric fluid) of about 200 mg ibuprofen, an amount similar to the dosage of conventional immediate-release form (Motrin® 200 mg), and (ii) a slow release of remaining about 200 or 400 mg for a period of 12 h. A preliminary in vivo study (beagle dogs) showed pharmacokinetic parameters of one single controlled-release dosage of ibuprofen (400 mg) formulated with CaCMS, near equivalence with multiple doses (three tablets of 200 mg ibuprofen) of conventional Motrin®. A marked reduction (with 33%) of administered dose (400 instead 600 mg) was achieved by the new formulation with equivalent therapeutic effects. This dose reduction may be beneficial and is expected to minimize side damage risks. Although the present study was limited to NSAIDs, the 2RR concept can be applied for other drugs, particularly for subjects unable to follow frequent administrations.

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

PubMed

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

2018-04-25

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

Development of a controlled release formulation of an indigenous insect growth regulator, DPE-28, a substituted diphenylether, for controlling the breeding of Culex quinquefasciatus

PubMed Central

Kalyanasundaram, M.; Mathew, Nisha; Elango, A.; Padmanabhan, V.

2011-01-01

Background & objectives: DPE-28, a substituted diphenyl ether (2,6-ditertiarybutyl phenyl-2’,4’-dinitro phenyl ether) was reported to exhibit promising insect growth regulating activity against Culex quinquefasciatus, the vector of lymphatic filariasis. A controlled release formulation (CRF) of DPE-28 has been developed to control Cx. quinquefasciatus in its breeding habitats. Toxicity of DPE-28, safety to non-target mosquito predators and the release profile of the CRF of DPE-28 are studied and discussed. Methods: The acute oral and dermal toxicity was tested in male and female Wistar rats as per the Organization for Economic Cooperation and Development (OECD) guidelines 425 and 402 respectively. The toxicity of DPE-28 to non-target predators was tested as per the reported procedure from this laboratory. The CRF of DPE-28 was prepared by following the reported procedure developed at this laboratory earlier. The concentration of DPE-28 released from the CRF was monitored by HPLC by constructing a calibration graph by plotting the peak area in the Y-axis and the concentration of DPE-28 in the X-axis. Results: DPE-28 has been tested for acute oral toxicity and found to be moderately toxic with LD50 value of 1098 mg/kg body weight (b.w). The results of the acute dermal toxicity and skin irritation studies reveal that DPE-28 is safe and non-irritant. DPE-28 when tested at 0.4 mg/litre against non-target mosquito predators did not produce any mortality. The release profile of the active ingredient DPE-28 from the CRF by HPLC technique showed that the average daily release (ADR) of DPE-28 ranged from 0.07 to 5.0 mg/litre during first four weeks. Thereafter the matrix started eroding and the ADR ranged from 5 to 11 mg/litre during the remaining 5 wk. The cumulative release of active ingredient showed that > 90 per cent of the active ingredient was released from the matrix. Interpretation & conclusions: The controlled release matrix of DPE-28 was thus found to inhibit the adult emergence (>80%) of Cx. quinquefasciatus for a period of nine weeks. The CRF of DPE-28 may play a useful role in field and may be recommended for mosquito control programme after evaluating the same under field conditions. PMID:21727665

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

PubMed

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.

Porcine malignant hyperthermia susceptibility: hypersensitive calcium-release mechanism of skeletal muscle sarcoplasmic reticulum.

PubMed Central

O'Brien, P J

1986-01-01

This study tested the hypothesis that calcium-release from sarcoplasmic reticulum isolated from malignant hyperthermia swine had abnormal concentration-dependency on release modulators. Halothane stimulated half-maximal calcium-release at similar concentrations for malignant hyperthermia and control sarcoplasmic reticulum (0.10 +/- 0.04 mM). However, concentrations causing half-maximal calcium-release were lower for malignant hyperthermia sarcoplasmic reticulum (P less than 0.001) by an order of magnitude for Ca2+ (28.1 +/- 8.3 versus 1.23 +/- 0.45 nM), adenosine triphosphate (0.33 +/- 0.09 versus 0.023 +/- 0.014 mM) and caffeine (7.79 +/- 1.56 versus 0.80 +/- 0.44 mM). Half-maximal inhibition by Mg2+ occurred at threefold higher concentrations for malignant hyperthermia sarcoplasmic reticulum (0.23 +/- 0.02 versus 0.78 +/- 0.17 mM). The Ca2+-sensitivity curves for calcium-release by sarcoplasmic reticulum isolated from heterozygotes for the malignant hyperthermia-defect were indistinguishable from the averages of the curves for controls and malignant hyperthermia-homozygotes. Results of this study suggest that malignant hyperthermia is initiated due to a hypersensitive calcium-release mechanism which is inherited in an autosomal, codominant pattern and may be diagnosed using calcium-release sensitivity-tests on isolated sarcoplasmic reticulum. Images Fig. 1. PMID:3742367

Characterization of natural polymers from jackfruit pulp, calendula flowers and tara seeds as mucoadhesive and controlled release components in buccal tablets.

PubMed

Sabale, Vidya; Paranjape, Archana; Patel, Vandana; Sabale, Prafulla

2017-02-01

Identification and physiochemical parameters such as solubility, loss on drying, viscosity, pH, swelling index, starch and gum constituents were determined in natural polymers and showed satisfactory results. Spectral studies established the compatibility of natural polymers. The drug release kinetics in preliminary trial batches showed that tablets containing natural mucilages and gum showed a prolonged drug release comparable to Carbopol 974P and Methocel K4M. Also, all tablets showed a satisfactory drug permeability flux. Acute toxicity studies confirmed the safety of natural polymers. Using response surface method supported by 2 3 factorial design, the optimized buccoadhesive tablets (C1) with drug release at 8h (R8h, %) of 53.48±0.048% showed controlled release over ≥8h and followed the Korsmeyer-Peppas model with anomalous (non-Fickian) diffusion mechanism. Mucoadhesive strength was found to be 42.71±0.49g. Comparative dissolution study between prepared and marketed formulation showed that there was no significant difference in drug release profile having similarity factor 82.97. In vivo study for optimized formulation of the buccoadhesive tablets showed the better absolute bioavailability (71.26%) against the oral solution (51.22%). Histological study confirmed non-irritant nature and stability study indicated stability of the formulation. Copyright © 2016 Elsevier B.V. All rights reserved.

Controlled Release in Transdermal Pressure Sensitive Adhesives using Organosilicate Nanocomposites

PubMed Central

Shaikh, Sohel; Birdi, Anil; Qutubuddin, Syed; Lakatosh, Eric; Baskaran, Harihara

2010-01-01

Polydimethyl siloxane (PDMS) based pressure sensitive adhesives (PSA) incorporating organo-clays at different loadings were fabricated via solution casting. Partially exfoliated nanocomposites were obtained for the hydroxyl terminated PDMS in ethyl acetate solvent as determined by X-ray diffraction (XRD) and atomic force microscopy (AFM). Drug release studies showed that the initial burst release was substantially reduced and the drug release could be controlled by the addition of organo-clay. Shear strength and shear adhesion failure temperature (SAFT) measurements indicated substantial improvement in adhesive properties of the PSA nanocomposite adhesives. Shear strength showed more than 200 % improvement at the lower clay loadings and the SAFT increased by about 21% due to the reinforcement provided by the nano-dispersed clay platelets. It was found that by optimizing the level of the organosilicate additive to the polymer matrix, superior control over drug release kinetics and simultaneous improvements in adhesive properties could be attained for a transdermal PSA formulation. PMID:17786555

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

PubMed

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.

Active suppression of vortex-driven combustion instability using controlled liquid-fuel injection

NASA Astrophysics Data System (ADS)

Pang, Bin

Combustion instabilities remain one of the most challenging problems encountered in developing propulsion and power systems. Large amplitude pressure oscillations, driven by unsteady heat release, can produce numerous detrimental effects. Most previous active control studies utilized gaseous fuels to suppress combustion instabilities. However, using liquid fuel to suppress combustion instabilities is more realistic for propulsion applications. Active instability suppression in vortex-driven combustors using a direct liquid fuel injection strategy was theoretically established and experimentally demonstrated in this dissertation work. Droplet size measurements revealed that with pulsed fuel injection management, fuel droplet size could be modulated periodically. Consequently, desired heat release fluctuation could be created. If this oscillatory heat release is coupled with the natural pressure oscillation in an out of phase manner, combustion instabilities can be suppressed. To identify proper locations of supplying additional liquid fuel for the purpose of achieving control, the natural heat release pattern in a vortex-driven combustor was characterized in this study. It was found that at high Damkohler number oscillatory heat release pattern closely followed the evolving vortex front. However, when Damkohler number became close to unity, heat release fluctuation wave no longer coincided with the coherent structures. A heat release deficit area was found near the dump plane when combustor was operated in lean premixed conditions. Active combustion instability suppression experiments were performed in a dump combustor using a controlled liquid fuel injection strategy. High-speed Schlieren results illustrated that vortex shedding plays an important role in maintaining self-sustained combustion instabilities. Complete combustion instability control requires total suppression of these large-scale coherent structures. The sound pressure level at the excited dominant frequency was reduced by more than 20 dB with controlled liquid fuel injection method. Scaling issues were also investigated in this dump combustor to test the effectiveness of using pulsed liquid fuel injection strategies to suppress instabilities at higher power output conditions. With the liquid fuel injection control method, it was possible to suppress strong instabilities with initial amplitude of +/-5 psi down to the background noise level. The stable combustor operating range was also expanded from equivalence ratio of 0.75 to beyond 0.9.

Stimuli sensitive polymethacrylic acid microparticles (PMAA)--oral insulin delivery.

PubMed

Victor, Sunita Prem; Sharma, Chandra P

2002-10-01

This study investigated polymethacrylic acid (PMAA) microparticles for controlled release of Insulin in oral administration. The microparticles were characterised by scanning electron microscopy (SEM) for morphological studies. The swelling behaviour and drug release profile in various pH media were studied. The % swelling of gels was found to be inversely related to the amount of crosslinker added. Inclusion complex of betaCD and Insulin was studied using polyacrylamide gel electrophoresis (PAGE). Optimum complexation was obtained in the ratio 100 mg betaCD: 200 IU Insulin. The release pattern of Insulin from Insulin-betaCD complex encapsulated PMAA microparticles showed release of Insulin for more than seven hours.

MRI as a tool for evaluation of oral controlled release dosage forms.

PubMed

Dorożyński, Przemysław P; Kulinowski, Piotr; Młynarczyk, Anna; Stanisz, Greg J

2012-02-01

The magnetic resonance imaging (MRI) studies of controlled-release (CR) dosage forms can be roughly divided into two groups. The first comprises studies performed in static conditions (small solvent volumes and ambient temperature). Such studies have provided insight into molecular phenomena in hydrating polymeric matrices. The second group covers research performed in dynamic conditions (medium flow or stirring) related to drug dissolution. An important issue is supplementation of the MRI results with data obtained by complementary techniques, such as X-ray microtomography (μCT). As we discuss here, an understanding of the mechanism underlying the release of the drug from the dosage form will lead to the development of detailed, molecularly defined, CR dosage forms. Copyright © 2011 Elsevier Ltd. All rights reserved.

Thermoresponsive magnetic composite nanomaterials for multimodal cancer therapy.

PubMed

Purushotham, S; Ramanujan, R V

2010-02-01

The synthesis, characterization and property evaluation of drug-loaded polymer-coated magnetic nanoparticles (MNPs) relevant to multimodal cancer therapy has been studied. The hyperthermia and controlled drug release characteristics of these particles was examined. Magnetite (Fe(3)O(4))-poly-n-(isopropylacrylamide) (PNIPAM) composite MNPs were synthesized in a core-shell morphology by dispersion polymerization of n-(isopropylacrylamide) chains in the presence of a magnetite ferrofluid. These core-shell composite particles, with a core diameter of approximately 13nm, were loaded with the anti-cancer drug doxorubicin (dox), and the resulting composite nanoparticles (CNPs) exhibit thermoresponsive properties. The magnetic properties of the composite particles are close to those of the uncoated magnetic particles. In an alternating magnetic field (AMF), composite particles loaded with 4.15 wt.% dox exhibit excellent heating properties as well as simultaneous drug release. Drug release testing confirmed that release was much higher above the lower critical solution temperature (LCST) of the CNP, with a release of up to 78.1% of bound dox in 29h. Controlled drug release testing of the particles reveals that the thermoresponsive property can act as an on/off switch by blocking drug release below the LCST. Our work suggests that these dox-loaded polymer-coated MNPs show excellent in vitro hyperthermia and drug release behavior, with the ability to release drugs in the presence of AMF, and the potential to act as agents for combined targeting, hyperthermia and controlled drug release treatment of cancer.

Albumin nanoparticles coated with polysorbate 80 as a novel drug carrier for the delivery of antiretroviral drug—Efavirenz

PubMed Central

Jenita, Josephine Leno; Chocalingam, Vijaya; Wilson, Barnabas

2014-01-01

Purpose of the study: The antiretroviral therapy (ART) has dramatically improved human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) treatment, prevention and also has been found to increase the lifespan of HIV/AIDS patients by providing durable control of the HIV replication in patients. Efavirenz is a non-nucleoside reverse transcriptase inhibitor of HIV-1. The purpose of this study is to formulate efavirenz-loaded bovine serum albumin nanoparticles to improve efavirenz delivery into various organs. Materials and Methods: Nanoparticles were prepared by desolvation technique and coated with polysorbate 80. Ethanol, glutaraldehyde, and mannitol were used as desolvating, cross linking agent, and cryoprotectant, respectively. Drug to polymer ratio was chosen at five levels from 1:2, 1:3, 1:4, 1:5, and 1:6 (by weight). The formulated nanoparticles were characterized for Fourier Transform Infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC) studies, entrapment efficiency, particle size, surface charge, surface morphology, in vitro drug release, release kinetics, stability studies, and biodistribution studies. Results and Major Conclusion: The particle size of the prepared formulations was found below 250nm with narrow size distribution, spherical in shape and showed good entrapment efficiency (45.62-72.49%). The in vitro drug release indicated biphasic release and its data were fitted to release kinetics models and release pattern was Fickian diffusion controlled release profile. The prepared nanoparticles increased efavirenz delivery into various organs by several fold in comparison with the free drug. PMID:25126528

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

PubMed

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.

Modulation of microenvironmental pH for dual release and reduced in vivo gastrointestinal bleeding of aceclofenac using hydroxypropyl methylcellulose-based bilayered matrix tablet.

PubMed

Kang, Won-Ho; Nguyen, Hien Van; Park, Chulhun; Choi, Youn-Woong; Lee, Beom-Jin

2017-05-01

This study was designed to develop a once-daily controlled-release matrix tablet of aceclofenac 200mg (AFC-CR) with dual release characteristics and to investigate the role of an alkalizer in enhancing drug solubility and reducing the occurrence of gastroduodenal mucosal lesions. Two formulation approaches were employed, namely a monolithic matrix tablet and a bilayered tablet. In vitro dissolution studies of AFC-CR tablets were carried out in simulated intestinal fluid (pH6.8 buffer). The in vivo pharmacokinetic studies and drug safety of the immediate-release reference tablet Airtal® 100mg (Daewoong Co., Korea) and the optimized AFC-CR tablet were compared in beagle dogs under fasted condition. The optimally selected AFC-CR formulation displayed the desired dual release characteristics in simulated intestinal fluid with satisfactory micromeritic properties. The swelling action of the optimal matrix tablet, which was visualized by near-infrared (NIR) chemical imaging, occurred rapidly following hydration. Incorporation of sodium carbonate (Na 2 CO 3 ) was found to enhance the release rate of the AFC-CR bilayered tablets at early stages and increase the microenvironmental pH (pH M ). A pharmacokinetic study in beagle dogs indicated a higher drug plasma concentration and a sustained-release pattern for the AFC-CR tablet compared to the Airtal® tablet. AFC-CR was also superior to Airtal® in terms of in vivo drug safety, since no beagle dog receiving AFC-CR experienced gastrointestinal bleeding. The significant enhancement of drug safety was attributed to the size reduction and the increase of pH M of drug particles by means of incorporation of the alkalizer. These findings provide a scientific rationale for developing a novel controlled-release matrix tablet with enhanced patient compliance and better pain control. Copyright © 2017 Elsevier B.V. All rights reserved.

Neutrophils in chronic and aggressive periodontitis in interaction with Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans

PubMed Central

Guentsch, Arndt; Puklo, Magdalena; Preshaw, Philip M.; Glockmann, Eike; Pfister, Wolfgang; Potempa, Jan; Eick, Sigrun

2014-01-01

AIM The aim of this in vitro study was to study phagocytosis and killing of Porphyromonas gingivalis ATCC 33277 and Aggregatibacter actinomycetemcomitans Y4 by peripheral blood PMNs taken from aggressive and chronic periodontitis patients. Also, the release of reactive oxygen species (ROS) and human neutrophil elastase (HNE) upon the interaction of PMNs with bacteria was measured. METHODS Peripheral blood PMNs obtained from 12 chronic periodontitis patients, 6 aggressive periodontitis patients and 12 healthy controls were exposed to Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans following opsonisation of the bacteria using the patient’s own serum. Phagocytosis and killing of the bacteria as well as the extracellular HNE activity were quantified for up to 2 hours. The total amount and the extracellular release of ROS were measured by luminol and isoluminol dependent chemiluminescence. RESULTS PMNs from chronic (62.16 ± 19.39 %) and aggressive periodontitis (43.26 ± 26.63 %) patients phagocytosed more P. gingivalis than the healthy controls (24.43 ± 19.87 %) at 30 mins after exposure to the bacteria (p < 0.05). PMNs from subjects with chronic and aggressive periodontitis released significantly more ROS and demonstrated greater HNE activity in the absence of any stimulus than PMNs from healthy controls (p < 0.05). The total release of ROS increased in chronic periodontitis PMNs and in the control group PMNs after interaction with P. gingivalis. The interaction with A. actinomycetemcomitans resulted in greater total ROS release in chronic periodontitis PMNs and in the control group PMNs than P. gingivalis. CONCLUSION PMNs in aggressive and chronic periodontitis are hyperactive even without any particular stimulus. The extracellular release of ROS and neutrophil elastase by PMNs may not only affect bacterial virulence and/or viability, but also contribute to damage of the surrounding periodontal tissues. PMID:19210340

Bio-composites composed of a solid free-form fabricated polycaprolactone and alginate-releasing bone morphogenic protein and bone formation peptide for bone tissue regeneration.

PubMed

Kim, MinSung; Jung, Won-Kyo; Kim, GeunHyung

2013-11-01

Biomedical scaffolds should be designed with highly porous three-dimensional (3D) structures that have mechanical properties similar to the replaced tissue, biocompatible properties, and biodegradability. Here, we propose a new composite composed of solid free-form fabricated polycaprolactone (PCL), bone morphogenic protein (BMP-2) or bone formation peptide (BFP-1), and alginate for bone tissue regeneration. In this study, PCL was used as a mechanical supporting component to enhance the mechanical properties of the final biocomposite and alginate was used as the deterring material to control the release of BMP-2 and BFP-1. A release test revealed that alginate can act as a good release control material. The in vitro biocompatibilities of the composites were examined using osteoblast-like cells (MG63) and the alkaline phosphatase (ALP) activity and calcium deposition were assessed. The in vitro test results revealed that PCL/BFP-1/Alginate had significantly higher ALP activity and calcium deposition than the PCL/BMP-2/Alginate composite. Based on these findings, release-controlled BFP-1 could be a good growth factor for enhancement of bone tissue growth and the simple-alginate coating method will be a useful tool for fabrication of highly functional biomaterials through release-control supplementation.

Laser-induced disruption of systemically administered liposomes for targeted drug delivery

NASA Astrophysics Data System (ADS)

Mackanos, Mark A.; Larabi, Malika; Shinde, Rajesh; Simanovskii, Dmitrii M.; Guccione, Samira; Contag, Christopher H.

2009-07-01

Liposomal formulations of drugs have been shown to enhance drug efficacy by prolonging circulation time, increasing local concentration and reducing off-target effects. Controlled release from these formulations would increase their utility, and hyperthermia has been explored as a stimulus for targeted delivery of encapsulated drugs. Use of lasers as a thermal source could provide improved control over the release of the drug from the liposomes with minimal collateral tissue damage. Appropriate methods for assessing local release after systemic delivery would aid in testing and development of better formulations. We use in vivo bioluminescence imaging to investigate the spatiotemporal distribution of luciferin, used as a model small molecule, and demonstrate laser-induced release from liposomes in animal models after systemic delivery. These liposomes were tested for luciferin release between 37 and 45 °C in PBS and serum using bioluminescence measurements. In vivo studies were performed on transgenic reporter mice that express luciferase constitutively throughout the body, thus providing a noninvasive readout for controlled release following systemic delivery. An Nd:YLF laser was used (527 nm) to heat tissues and induce rupture of the intravenously delivered liposomes in target tissues. These data demonstrate laser-mediated control of small molecule delivery using thermally sensitive liposomal formulations.

Development and evaluation of accelerated drug release testing methods for a matrix-type intravaginal ring.

PubMed

Externbrink, Anna; Eggenreich, Karin; Eder, Simone; Mohr, Stefan; Nickisch, Klaus; Klein, Sandra

2017-01-01

Accelerated drug release testing is a valuable quality control tool for long-acting non-oral extended release formulations. Currently, several intravaginal ring candidates designed for the long-term delivery of steroids or anti-infective drugs are being in the developing pipeline. The present article addresses the demand for accelerated drug release methods for these formulations. We describe the development and evaluation of accelerated release methods for a steroid releasing matrix-type intravaginal ring. The drug release properties of the formulation were evaluated under real-time and accelerated test conditions. Under real-time test conditions drug release from the intravaginal ring was strongly affected by the steroid solubility in the release medium. Under sufficient sink conditions that were provided in release media containing surfactants drug release was Fickian diffusion driven. Both temperature and hydro-organic dissolution media were successfully employed to accelerate drug release from the formulation. Drug release could be further increased by combining the temperature effect with the application of a hydro-organic release medium. The formulation continued to exhibit a diffusion controlled release kinetic under the investigated accelerated conditions. Moreover, the accelerated methods were able to differentiate between different prototypes of the intravaginal ring that exhibited different release profiles under real-time test conditions. Overall, the results of the present study indicate that both temperature and hydro-organic release media are valid parameters for accelerating drug release from the intravaginal ring. Variation of either a single or both parameters yielded release profiles that correlated well with real-time release. Copyright © 2016 Elsevier B.V. All rights reserved.

Remote modulation of neural activities via near-infrared triggered release of biomolecules.

PubMed

Li, Wei; Luo, Rongcong; Lin, Xudong; Jadhav, Amol D; Zhang, Zicong; Yan, Li; Chan, Chung-Yuan; Chen, Xianfeng; He, Jufang; Chen, Chia-Hung; Shi, Peng

2015-10-01

The capability to remotely control the release of biomolecules provides an unique opportunity to monitor and regulate neural signaling, which spans extraordinary spatial and temporal scales. While various strategies, including local perfusion, molecular "uncaging", or photosensitive polymeric materials, have been applied to achieve controlled releasing of neuro-active substances, it is still challenging to adopt these technologies in many experimental contexts that require a straightforward but versatile loading-releasing mechanism. Here, we develop a synthetic strategy for remotely controllable releasing of neuro-modulating molecules. This platform is based on microscale composite hydrogels that incorporate polypyrrole (PPy) nanoparticles as photo-thermal transducers and is triggered by near-infrared-light (NIR) irradiation. Specifically, we first demonstrate the utility of our technology by recapitulating the "turning assay" and "collapse assay", which involve localized treatment of chemotactic factors (e.g. Netrin or Semaphorin 3A) to subcellular neural elements and have been extensively used in studying axonal pathfinding. On a network scale, the photo-sensitive microgels are also validated for light-controlled releasing of neurotransmitters (e.g. glutamate). A single NIR-triggered release is sufficient to change the dynamics of a cultured hippocampal neuron network. Taking the advantage of NIR's capability to penetrate deep into live tissue, this technology is further shown to work similarly well in vivo, which is evidenced by synchronized spiking activity in response to NIR-triggered delivery of glutamate in rat auditory cortex, demonstrating remote control of brain activity without any genetic modifications. Notably, our nano-composite microgels are capable of delivering various molecules, ranging from small chemicals to large proteins, without involving any crosslinking chemistry. Such great versatility and ease-of-use will likely make our optically-controlled delivery technology a general and important tool in cell biology research. Copyright © 2015 Elsevier Ltd. All rights reserved.

QbD-Oriented Development and Characterization of Effervescent Floating-Bioadhesive Tablets of Cefuroxime Axetil.

PubMed

Bansal, Sanjay; Beg, Sarwar; Garg, Babita; Asthana, Abhay; Asthana, Gyati S; Singh, Bhupinder

2016-10-01

The objective of the present studies was systematic development of floating-bioadhesive gastroretentive tablets of cefuroxime axetil employing rational blend of hydrophilic polymers for attaining controlled release drug delivery. As per the QbD-based approach, the patient-centric target product profile and quality attributes of tablet were earmarked, and preliminary studies were conducted for screening the suitability of type of polymers, polymer ratio, granulation technique, and granulation time for formulation of tablets. A face-centered cubic design (FCCD) was employed for optimization of the critical material attributes, i.e., concentration of release controlling polymers, PEO 303 and HPMC K100 LV CR, and evaluating in vitro buoyancy, drug release, and ex vivo mucoadhesion strength. The optimized formulation was embarked upon through numerical optimization, which yield excellent floatation characteristic with drug release control (i.e., T 60% > 6 h) and bioadhesion strength. Drug-excipient compatibility studies through FTIR and P-XRD revealed the absence of any interaction between the drug and polymers. In vivo evaluation of the gastroretentive characteristics through X-ray imaging and in vivo pharmacokinetic studies in rabbits revealed significant extension in the rate of drug absorption (i.e., T max, K a, and MRT) from the optimized tablet formulation as compared to the marketed formulation. Successful establishment of various levels of in vitro/in vivo correlations (IVIVC) substantiated high degree of prognostic ability of in vitro dissolution conditions in predicting the in vivo performance. In a nutshell, the studies demonstrate successful development of the once-a-day gastroretentive formulations of cefuroxime axetil with controlled drug release profile and improved compliance.

A Systematic Review of Randomized Controlled Trials of Interventions to Improve the Health of Persons During Imprisonment and in the Year After Release

PubMed Central

McIsaac, Kathryn E.; Liauw, Jessica; Green, Samantha; Karachiwalla, Fareen; Siu, Winnie; Burkholder, Kaite; Binswanger, Ingrid; Kiefer, Lori; Kinner, Stuart A.; Korchinski, Mo; Matheson, Flora I.; Young, Pam; Hwang, Stephen W.

2015-01-01

We systematically reviewed randomized controlled trials of interventions to improve the health of people during imprisonment or in the year after release. We searched 14 biomedical and social science databases in 2014, and identified 95 studies. Most studies involved only men or a majority of men (70/83 studies in which gender was specified); only 16 studies focused on adolescents. Most studies were conducted in the United States (n = 57). The risk of bias for outcomes in almost all studies was unclear or high (n = 91). In 59 studies, interventions led to improved mental health, substance use, infectious diseases, or health service utilization outcomes; in 42 of these studies, outcomes were measured in the community after release. Improving the health of people who experience imprisonment requires knowledge generation and knowledge translation, including implementation of effective interventions. PMID:25713970

Contamination delays the release of Laricobius osakensis for biological control of hemlock woolly adelgid: cryptic diversity in Japanese Laricobius spp

Treesearch

Melissa J. Fischer; Nathan P. Havill; Carrie S. Jubb; Sean W. Prosser; Brent D. Opell; Scott M. Salom; Loke T. Kok

2014-01-01

Laricobius osakensis (Coleoptera: Derodontidae) was imported from Japan to the United States in 2006 for study in quarantine facilities as a potential biological control of Hemlock Woolly Adelgid. Laricobius osakensis was released from quarantine in 2010, but it was soon discovered that the colony also contained a cryptic species...

Fusion pores and their control of neurotransmitter and hormone release

PubMed Central

Chang, Che-Wei; Chiang, Chung-Wei

2017-01-01

Ca2+-triggered exocytosis functions broadly in the secretion of chemical signals, enabling neurons to release neurotransmitters and endocrine cells to release hormones. The biological demands on this process can vary enormously. Although synapses often release neurotransmitter in a small fraction of a millisecond, hormone release can be orders of magnitude slower. Vesicles usually contain multiple signaling molecules that can be released selectively and conditionally. Cells are able to control the speed, concentration profile, and content selectivity of release by tuning and tailoring exocytosis to meet different biological demands. Much of this regulation depends on the fusion pore—the aqueous pathway by which molecules leave a vesicle and move out into the surrounding extracellular space. Studies of fusion pores have illuminated how cells regulate secretion. Furthermore, the formation and growth of fusion pores serve as a readout for the progress of exocytosis, thus revealing key kinetic stages that provide clues about the underlying mechanisms. Herein, we review the structure, composition, and dynamics of fusion pores and discuss the implications for molecular mechanisms as well as for the cellular regulation of neurotransmitter and hormone release. PMID:28167663

Novel Starch-PVA Polymer for Microparticle Preparation and Optimization Using Factorial Design Study

PubMed Central

Chattopadhyay, Helen; De, Amit Kumar; Datta, Sriparna

2015-01-01

The aim of our present work was to optimize the ratio of a very novel polymer, starch-polyvinyl alcohol (PVA), for controlled delivery of Ornidazole. Polymer-coated drug microparticles were prepared by emulsion method. Microscopic study, scanning electron microscopic study, and atomic force microscopic study revealed that the microparticles were within 10 micrometers of size with smooth spherical shape. The Fourier transform infrared spectroscopy showed absence of drug polymer interaction. A statistical 32 full factorial design was used to study the effect of different concentration of starch and PVA on the drug release profile. The three-dimensional plots gave us an idea about the contribution of each factor on the release kinetics. Hence this novel polymer of starch and polyvinyl alcohol can be utilized for control release of the drug from a targeted delivery device. PMID:27347511

EFFECTS OF MEDIAL SEPTAL LESION ON HIPPOCAMPAL EXTRACELLULAR GLUTAMATE AND GABA LEVELS DURING SPATIAL ALTERNATION TESTING.

PubMed

Mataradze, S; Naneishvili, T; Sephashvili, M; Mikeladze, D; Dashniani, M

2016-10-01

The present study investigated spatial working memory assessed in spontaneous alternation (SA) task and hippocampal glutamate and GABA release prior to, during, and after SA test in sham-operated and electrolytic medial septal (MS) lesioned rats. Also, have been investigated the effects of MS lesion on KCl-stimulated release of glutamate and GABA in the hippocampus. Behavioral study showed that electrolytic lesion of MS significantly impaired SA performance. Although both groups of animals had an insignificant rise in their respective hippocampal glutamate efflux during the SA, the rise of MS lesioned animals was blunted when compared with control animals. Hippocampal GABA levels did not change during behavioral testing in both groups. Most of control animals showed increase in KCl-stimulated glutamate release. By contrast, only one MS lesioned rat showed increase in glutamate release in response to KCl stimulation. Most of control and MS lesioned rats were non-responders in GABA release in response to KCl stimulation. Decreased glutamate release (upon stimulation) in the MS lesioned rats may contribute to spatial working memory impairment in these animals. We propose that SA testing coupled with in vivo microdialysis sampling represents a suitable approach to revealing the neurochemical correlates of hippocampal-dependent memory function, and thus could be a useful tool for better understanding of the neurochemical basis of cognitive decline associated with various disorders and neurodegenerative diseases.

[Mitigation effect of several controlled-release N fertilizers on ammonia volatilization and related affecting factors].

PubMed

Sun, Kejun; Mao, Xiaoyun; Lu, Qiming; Jia, Aiping; Liao, Zongwen

2004-12-01

By using static absorption and soil column leaching methods, this paper studied the behaviors of several controlled-release N fertilizers in soil under laboratory conditions. The results showed that under the application rate of 450 mg x kg(-1), total ammonia volatilization from three controlled-release fertilizers decreased by 49.7%, 28.0% and 71.2%, respectively, in comparing with common urea. When the application rate was 600 mg x kg(-1), total ammonia volatilization decreased by 34.6%, 12.3%, 69.9%, respectively. Controlled-release fertilizers could markedly reduce total ammonia volatilization from soil and decrease environment pollution via fertilization. The results also indicated that total ammonia volatilization correlated significantly with soil urease activity, pH value and N leaching rate. The correlation coefficient between total ammonia volatilization and accumulated N leaching rate was 0.9533, and that between total ammonia volatilization and soil urease activity and pH value was 0.9533 and 0.9908, respectively.

Three-year bole response of white oak (Quercus alba L.) crop trees to fertilizer and crown release on a Tennessee upland site

Treesearch

G. Richard Schaertl; Allan E. Houston; Edward R. Buckner; James S. Meadows

1997-01-01

Bole diameter responses to fertilization, crown release, and fertilization x release treatments with untreated controls and treatment-by-year interactions were studied in pole-sized (approx. 43 years old) white oak (Quercus alba L.) crop trees. In the main study, fertilizer was applied by broadcast to plots at a rate of 150 lbs N and 35 lbs P

Fluid flow releases fibroblast growth factor-2 from human aortic smooth muscle cells

NASA Technical Reports Server (NTRS)

Rhoads, D. N.; Eskin, S. G.; McIntire, L. V.

2000-01-01

This study tested the hypothesis that fluid shear stress regulates the release of fibroblast growth factor (FGF)-2 from human aortic smooth muscle cells. FGF-2 is a potent mitogen that is involved in the response to vascular injury and is expressed in a wide variety of cell types. FGF-2 is found in the cytoplasm of cells and outside cells, where it associates with extracellular proteoglycans. To test the hypothesis that shear stress regulates FGF-2 release, cells were exposed to flow, and FGF-2 amounts were measured from the conditioned medium, pericellular fraction (extracted by heparin treatment), and cell lysate. Results from the present study show that after 15 minutes of shear stress at 25 dyne/cm(2) in a parallel-plate flow system, a small but significant fraction (17%) of the total FGF-2 was released from human aortic smooth muscle cells. FGF-2 levels in the circulating medium increased 10-fold over medium from static controls (P<0.01). A 50% increase in FGF-2 content versus control (P<0.01) was found in the pericellular fraction (extracted by heparin treatment). Furthermore, a significant decrease in FGF-2 was detected in the cell lysate, indicating that FGF-2 was released from inside the cell. Cell permeability studies with fluorescent dextran were performed to examine whether transient membrane disruption caused FGF-2 release. Flow cytometry detected a 50% increase in mean fluorescence of cells exposed to 25 dyne/cm(2) versus control cells. This indicates that the observed FGF-2 release from human aortic smooth muscle cells is likely due to transient membrane disruption on initiation of flow.

Investigating the feasibility of temperature-controlled accelerated drug release testing for an intravaginal ring.

PubMed

Externbrink, Anna; Clark, Meredith R; Friend, David R; Klein, Sandra

2013-11-01

The objective of the present study was to investigate if temperature can be utilized to accelerate drug release from Nuvaring®, a reservoir type intravaginal ring based on polyethylene vinyl acetate copolymer that releases a constant dose of contraceptive steroids over a duration of 3 weeks. The reciprocating holder apparatus (USP 7) was utilized to determine real-time and accelerated etonogestrel release from ring segments. It was demonstrated that drug release increased with increasing temperature which can be attributed to enhanced drug diffusion. An Arrhenius relationship of the zero-order release constants was established, indicating that temperature is a valid parameter to accelerate drug release from this dosage form and that the release mechanism is maintained under these accelerated test conditions. Accelerated release tests are particularly useful for routine quality control to assist during batch release of extended release formulations that typically release the active over several weeks, months or even years, since they can increase the product shelf life. The accelerated method should therefore be able to discriminate between formulations with different release characteristics that can result from normal manufacturing variance. In the case of Nuvaring®, it is well known that the process parameters during the extrusion process strongly influence the polymeric structure. These changes in the polymeric structure can affect the permeability which, in turn, is reflected in the release properties. Results from this study indicate that changes in the polymeric structure can lead to a different temperature dependence of the release rate, and as a consequence, the accelerated method can become less sensitive to detect changes in the release properties. When the accelerated method is utilized during batch release, it is therefore important to take this possible restriction into account and to evaluate the accelerated method with samples from non-conforming batches that are explicitly "out of specification" under real-time test conditions. Copyright © 2013 Elsevier B.V. All rights reserved.

Nanostructured aligned CNT platforms enhance the controlled release of a neurotrophic protein from polypyrrole

NASA Astrophysics Data System (ADS)

Thompson, Brianna C.; Chen, Jun; Moulton, Simon E.; Wallace, Gordon G.

2010-04-01

An aligned CNT array membrane electrode has been used as a nanostructured supporting platform for polypyrrole (PPy) films, exhibiting significant improvement in the controlled release of neurotrophin. In terms of linearity of release, stimulated to unstimulated control of NT-3 release and increased mass and % release of incorporated NT-3, the nanostructured material performed more favourably than the flat PPy film.

Oil and drug control the release rate from lyotropic liquid crystals.

PubMed

Martiel, Isabelle; Baumann, Nicole; Vallooran, Jijo J; Bergfreund, Jotam; Sagalowicz, Laurent; Mezzenga, Raffaele

2015-04-28

The control of the diffusion coefficient by the dimensionality d of the structure appears as a most promising lever to efficiently tune the release rate from lyotropic liquid crystalline (LLC) phases and dispersed particles towards sustained, controlled and targeted release. By using phosphatidylcholine (PC)- and monolinoleine (MLO)-based mesophases with various apolar structural modifiers and water-soluble drugs, we present a comprehensive study of the dimensional structural control of hydrophilic drug release, including 3-d bicontinuous cubic, 2-d lamellar, 1-d hexagonal and 0-d micellar cubic phases in excess water. We investigate how the surfactant, the oil properties and the drug hydrophilicity mitigate or even cancel the effect of structure variation on the drug release rate. Unexpectedly, the observed behavior cannot be fully explained by the thermodynamic partition of the drug into the lipid matrix, which points out to previously overlooked kinetic effects. We therefore interpret our results by discussing the mechanism of structural control of the diffusion rate in terms of drug permeation through the lipid membrane, which includes exchange kinetics. A wide range of implications follow regarding formulation and future developments, both for dispersed LLC delivery systems and topical applications in bulk phase. Copyright © 2015 Elsevier B.V. All rights reserved.

Motor control differs for increasing and releasing force

PubMed Central

Park, Seoung Hoon; Kwon, MinHyuk; Solis, Danielle; Lodha, Neha

2016-01-01

Control of the motor output depends on our ability to precisely increase and release force. However, the influence of aging on force increase and release remains unknown. The purpose of this study, therefore, was to determine whether force control differs while increasing and releasing force in young and older adults. Sixteen young adults (22.5 ± 4 yr, 8 females) and 16 older adults (75.7 ± 6.4 yr, 8 females) increased and released force at a constant rate (10% maximum voluntary contraction force/s) during an ankle dorsiflexion isometric task. We recorded the force output and multiple motor unit activity from the tibialis anterior (TA) muscle and quantified the following outcomes: 1) variability of force using the SD of force; 2) mean discharge rate and variability of discharge rate of multiple motor units; and 3) power spectrum of the multiple motor units from 0–4, 4–10, 10–35, and 35–60 Hz. Participants exhibited greater force variability while releasing force, independent of age (P < 0.001). Increased force variability during force release was associated with decreased modulation of multiple motor units from 35 to 60 Hz (R2 = 0.38). Modulation of multiple motor units from 35 to 60 Hz was further correlated to the change in mean discharge rate of multiple motor units (r = 0.66) and modulation from 0 to 4 Hz (r = −0.64). In conclusion, these findings suggest that force control is altered while releasing due to an altered modulation of the motor units. PMID:26961104

Controlled Release System for Localized and Sustained Drug Delivery Applications

NASA Astrophysics Data System (ADS)

Rodriguez, Lidia Betsabe

Current controlled release formulations has many drawbacks such as excess of initial burst release, low drug efficiency, non-degradability of the system and low reproducibility. The present project aims to offer an alternative by developing a technique to prepare uniform, biodegradable particles ( ˜19 mum ) that can sustainably release a drug for a specific period of time. Chitosan is a natural polysaccharide that has many characteristics to be used for biomedical applications. In the last two decades, there have been a considerable number of studies affirming that chitosan could be used for pharmaceutical applications. However, chitosan suffers from inherent weaknesses such as low mechanical stability and dissolution of the system in acidic media. In the present study, chitosan microparticles were prepared by emulsification process. The model drug chosen was acetylsalicylic acid as it is a small and challenging molecule. The maximum loading capacity obtained for the microparticles was approximately 96%. The parameters for the preparation of uniform particles with a narrow size distribution were identified in a triangular phase diagram. Moreover, chitosan particles were successfully coated with thin layers of poly lactic-coglycolic acid (PLGA) and poly lactic acid (PLA). The performance of different layerswas tested for in vitro drug release and degradation studies. Additionally, the degradability of the system was evaluated by measuring the weight loss of the system when exposed to enzyme and without enzyme. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM) and inductively coupled plasma optical emission spectrometry (ICP-OES) were used to characterize the controlled release system. Additionally, the in vitro drug release was monitored by ultraviolet-visible spectrophotometry (UV-Vis) and liquid chromatography mass spectrometry (LC-MS). The results obtained from this project showed that it is possible to prepare biodegradable microparticles with a uniform size distribution and high drug loading efficiency. However, this could only be achieved with a hybrid system consisting of chitosan matrix interior and then exterior coating of PLGA or PLA. A two layer coating of PLGA 50:50 was shown to be optimal with sustainable controlled drug release for almost 5 days and with 91% of degradation (weight loss) in 8 weeks.

Preparation of Porous γ-Fe2O3@mWO3 Multifunctional Nanoparticles for Drug Loading and Controlled Release.

PubMed

Peng, Hongxia; Huang, Qin; Wu, Tengyan; Wen, Jin; He, Hengping

2018-02-14

The use of chemotherapy drug is hindered by relatively low selectivity toward cancer cells and severe side effects from uptake by noncancerous cells and tissue. Thus, targeted drug delivery systems are preferred to increase the efficiency of drug delivery to specific tissues as well as to decrease its side effects. The aims of this paper are develop microwave-triggered controlled-release drug delivery systems using porous γ-Fe2O3@mWO3 multifunctional core-shell nanoparticles. We also studied its magnetic- microwave to heat responsive properties and large specific surface area. We chose ibuprofen (IBU) as a model drug to evaluate the loading and release function of the γ- Fe2O3@mWO3 nanoparticles. We used a direct precipitation method and thermal decomposition of CTAB template method to synthesize core-shell structured γ-Fe2O3@mWO3 nanoparticles. The specific surface areas were calculated by the Brunauer-Emmett-Teller (BET) method. The load drug and controlled release of the γ-Fe2O3@mWO3 triggered by microwave was determined with ultraviolet-visible spectroscopic analysis. The γ-Fe2O3@mWO3 nanoparticles possesses high surface area of 100.09 m2/g, provides large accessible pore diameter of 6.0 nm for adsorption of drug molecules, high magnetization saturation value of 43.6 emu/g for drug targeting under foreign magnetic fields, quickly convert electromagnetic energy into thermal energy for controlled release by microwave-triggered which was caused by mWO3 shell. The IBU release of over 78% under microwave discontinuous irradiation out classes the 0.15% within 20s only stirring release. This multifunctional material shows good performance for targeting delivery and mWO3 microwave controlled release of anticancer drugs based on all the properties they possess. The porous shell and the introduction of absorbing material not only increased the drug loading efficiency of the nanoparticles but also realized the microwave-stimulated anticancer drug controlled release. The nanoparticles would be very promising for microwave-induced controlled drug release, targeted drug delivery and hyperthermia therapy using microwave. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Tailorable drug capacity of dexamethasone-loaded conducting polymer matrix

NASA Astrophysics Data System (ADS)

Krukiewicz, K.

2018-05-01

The unique properties of conducting polymers, which are in the same time biocompatible and electrically responsive materials, make them perfect candidates for controlled drug release systems. In this study, the electrically-triggered controlled release system based on dexamethasone-loaded poly (3, 4-ethylenedioxypyrrole) (PEDOP) matrix is described. It is shown that the electropolymerization conditions can facilitate or suppress the formation of PEDOP/Dex matrix, as well as they can have the effect on its electrochemical performance. The release experiments performed in three different modes show that the drug capacity of PEDOP matrix increases with the increase in Dex concentration in the step of matrix synthesis, and higher Dex concentrations make it easier to control the amount of Dex released in an electrically-triggered mode. These results confirm the importance of the careful optimization of immobilization conditions to maximize drug capacity of matrix and maintain its electrochemical properties.

Smart Porous Silicon Nanoparticles with Polymeric Coatings for Sequential Combination Therapy.

PubMed

Xu, Wujun; Thapa, Rinez; Liu, Dongfei; Nissinen, Tuomo; Granroth, Sari; Närvänen, Ale; Suvanto, Mika; Santos, Hélder A; Lehto, Vesa-Pekka

2015-11-02

In spite of the advances in drug delivery, the preparation of smart nanocomposites capable of precisely controlled release of multiple drugs for sequential combination therapy is still challenging. Here, a novel drug delivery nanocomposite was prepared by coating porous silicon (PSi) nanoparticles with poly(beta-amino ester) (PAE) and Pluronic F-127, respectively. Two anticancer drugs, doxorubicin (DOX) and paclitaxel (PTX), were separately loaded into the core of PSi and the shell of F127. The nanocomposite displayed enhanced colloidal stability and good cytocompatibility. Moreover, a spatiotemporal drug release was achieved for sequential combination therapy by precisely controlling the release kinetics of the two tested drugs. The release of PTX and DOX occurred in a time-staggered manner; PTX was released much faster and earlier than DOX at pH 7.0. The grafted PAE on the external surface of PSi acted as a pH-responsive nanovalve for the site-specific release of DOX. In vitro cytotoxicity tests demonstrated that the DOX and PTX coloaded nanoparticles exhibited a better synergistic effect than the free drugs in inducing cellular apoptosis. Therefore, the present study demonstrates a promising strategy to enhance the efficiency of combination cancer therapies by precisely controlling the release kinetics of different drugs.

The Effect of Formulation Excipients and Thermal Treatment on the Release Properties of Lisinopril Spheres and Tablets.

PubMed

Amador Ríos, Zoriely; Ghaly, Evone Shehata

2015-01-01

Multiparticulate systems are used in the development of controlled release systems. The objective of this study was to determine the effect of the wax level, the type of excipient, and the exposure of the tablets to thermal treatment on drug release. Spheres from multiparticulate system with different wax levels and excipients were developed using the drug Lisinopril and compressed into tablets; these tablets were analyzed to determine the drug release. All tablets contained constant level of Lisinopril (10% w/w) and Compritol (30% and 50% w/w). Also, as a diluent, all of them contained 30% w/w Avicel and 30% w/w dibasic calcium phosphate or lactose, or 60% Avicel. Tablets compacted from spheres prepared by extruder/marumerizer and using 30% w/w lipid and 60% Avicel released 84% of drug at six hours of dissolution testing, while tablets of the same composition but prepared using 30% dibasic calcium phosphate and 30% Avicel released 101%. When the tablets were thermally treated, the drug release reduced. As the percent of lipid increased in the formulation, the drug release decreased. Compaction of tablets prepared from spheres with wax has potential for controlling the drug release.

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

NASA Astrophysics Data System (ADS)

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.

To share or not to share: a randomized trial of consent for data sharing in genome research.

PubMed

McGuire, Amy L; Oliver, Jill M; Slashinski, Melody J; Graves, Jennifer L; Wang, Tao; Kelly, P Adam; Fisher, William; Lau, Ching C; Goss, John; Okcu, Mehmet; Treadwell-Deering, Diane; Goldman, Alica M; Noebels, Jeffrey L; Hilsenbeck, Susan G

2011-11-01

Despite growing concerns toward maintaining participants' privacy, individual investigators collecting tissue and other biological specimens for genomic analysis are encouraged to obtain informed consent for broad data sharing. Our purpose was to assess the effect on research enrollment and data sharing decisions of three different consent types (traditional, binary, or tiered) with varying levels of control and choices regarding data sharing. A single-blinded, randomized controlled trial was conducted with 323 eligible adult participants being recruited into one of six genome studies at Baylor College of Medicine in Houston, Texas, between January 2008 and August 2009. Participants were randomly assigned to one of three experimental consent documents (traditional, n = 110; binary, n = 103; and tiered, n = 110). Debriefing in follow-up visits provided participants a detailed review of all consent types and the chance to change data sharing choices or decline genome study participation. Before debriefing, 83.9% of participants chose public data release. After debriefing, 53.1% chose public data release, 33.1% chose restricted (controlled access database) release, and 13.7% opted out of data sharing. Only one participant declined genome study participation due to data sharing concerns. Our findings indicate that most participants are willing to publicly release their genomic data; however, a significant portion prefers restricted release. These results suggest discordance between existing data sharing policies and participants' judgments and desires.

Ristocetin induces phosphorylated-HSP27 (HSPB1) release from the platelets of type 2 DM patients: Anti-platelet agent-effect on the release.

PubMed

Tokuda, Haruhiko; Kuroyanagi, Gen; Onuma, Takashi; Enomoto, Yukiko; Doi, Tomoaki; Iida, Hiroki; Otsuka, Takanobu; Ogura, Shinji; Iwama, Toru; Kojima, Kumi; Kozawa, Osamu

2018-04-01

It has been previously reported that HSP27 is released from platelets in type 2 diabetes mellitus (DM) patients according to phosphorylation. In the present study, we investigated the effect of ristocetin, a glycoprotein (GP)Ib/IX/V activator, on the release of HSP27 and the effect of anti-platelet agents, such as acetylsalicylic acid (ASA), on this release. Forty-six patients with type 2 DM were recruited, and classified into two groups depending on administration of anti-platelet agents, resulting in 31 patients without these agents (control group) and 15 patients with them (anti-platelet group). Ristocetin potently induced the aggregation of platelets in the two groups. Ristocetin-induced changes of the area under the curve of light transmittance and the ratio of the size of platelet aggregates in the anti-platelet group were slightly different from those in the control group. On the other hand, the levels of phosphorylated-HSP27 induced by ristocetin in the platelets from a patient of the anti-platelet group taking ASA were significantly lower than those from a patient of the control group. The levels of HSP27 release from the ristocetin-stimulated platelets were significantly correlated with the levels of phosphorylated-HSP27 in the platelets from patients in the two groups. The levels of HSP27 release and those of platelet-derived growth factor-AB (PDGF-AB) secretion stimulated by ristocetin in the anti-platelet group were lower than those in the control group. In addition, the levels of HSP27 release and those of PDGF-AB secretion stimulated by ADP in the anti-platelet group were lower than those in the control group. These results strongly suggest that anti-platelet agents inhibit the HSP27 release from platelets stimulated by ristocetin but not the aggregation in type 2 DM patients.

Controlled nerve growth factor release from multi-ply alginate/chitosan-based nerve conduits.

PubMed

Pfister, Lukas A; Alther, Eva; Papaloïzos, Michaël; Merkle, Hans P; Gander, Bruno

2008-06-01

The delivery kinetics of growth factors has been suggested to play an important role in the regeneration of peripheral nerves following axotomy. In this context, we designed a nerve conduit (NC) with adjustable release kinetics of nerve growth factor (NGF). A multi-ply system was designed where NC consisting of a polyelectrolyte alginate/chitosan complex was coated with layers of poly(lactide-co-glycolide) (PLGA) to control the release of embedded NGF. Prior to assessing the in vitro NGF release from NC, various release test media, with and without stabilizers for NGF, were evaluated to ensure adequate quantification of NGF by ELISA. Citrate (pH 5.0) and acetate (pH 5.5) buffered saline solutions containing 0.05% Tween 20 yielded the most reliable results for ELISA active NGF. The in vitro release experiments revealed that the best results in terms of reproducibility and release control were achieved when the NGF was embedded between two PLGA layers and the ends of the NC tightly sealed by the PLGA coatings. The release kinetics could be efficiently adjusted by accommodating NGF at different radial locations within the NC. A sustained release of bioactive NGF in the low nanogram per day range was obtained for at least 15days. In conclusion, the developed multi-ply NGF loaded NC is considered a suitable candidate for future implantation studies to gain insight into the relationship between local growth factor availability and nerve regeneration.

Modulating drug release from gastric-floating microcapsules through spray-coating layers.

PubMed

Lee, Wei Li; Tan, Jun Wei Melvin; Tan, Chaoyang Nicholas; Loo, Say Chye Joachim

2014-01-01

Floating dosage forms with prolonged gastric residence time have garnered much interest in the field of oral delivery. However, studies had shown that slow and incomplete release of hydrophobic drugs during gastric residence period would reduce drug absorption and cause drug wastage. Herein, a spray-coated floating microcapsule system was developed to encapsulate fenofibrate and piroxicam, as model hydrophobic drugs, into the coating layers with the aim of enhancing and tuning drug release rates. Incorporating fenofibrate into rubbery poly(caprolactone) (PCL) coating layer resulted in a complete and sustained release for up to 8 h, with outermost non-drug-holding PCL coating layer serving as a rate-controlling membrane. To realize a multidrug-loaded system, both hydrophilic metformin HCl and hydrophobic fenofibrate were simultaneously incorporated into these spray-coated microcapsules, with metformin HCl and fenofibrate localized within the hollow cavity of the capsule and coating layer, respectively. Both drugs were observed to be completely released from these coated microcapsules in a sustained manner. Through specific tailoring of coating polymers and their configurations, piroxicam loaded in both the outer polyethylene glycol and inner PCL coating layers was released in a double-profile manner (i.e. an immediate burst release as the loading dose, followed by a sustained release as the maintenance dose). The fabricated microcapsules exhibited excellent buoyancy in simulated gastric fluid, and provided controlled and sustained release, thus revealing its potential as a rate-controlled oral drug delivery system.

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

PubMed

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.

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

PubMed Central

Kim, Ju-Young; Lee, Sung-Hoon; Park, Chun-Woong; Rhee, Yun-Seok; Kim, Dong-Wook; Park, Junsang; Lee, Moonseok; Seo, Jeong-Woong; Park, Eun-Seok

2015-01-01

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. PMID:25678774

Drug Release Studies from Caesalpinia pulcherrima Seed Polysaccharide.

PubMed

Jeevanandham, Somasundaram; Dhachinamoorthi, Duraiswamy; Bannoth Chandra Sekhar, Kothapalli

2011-01-01

This study examines the controlled release behavior of both water-soluble (acetaminophen, caffeine, theophylline and salicylic acid) and water insoluble (indomethacin) drugs derived from Caesalpinia pulcherrima seed Gum isolated from Caesalpinia pulcherrima kernel powder. It further investigates the effect of incorporating diluents such as microcrystalline cellulose and lactose on caffeine release. In addition the effect the gum's (polysaccharide) partial cross-linking had on release of acetaminophen was examined. Applying the exponential equation, the soluble drugs mechanism of release was found to be anomalous. The insoluble drugs showed a near case II or zero order release mechanism. The rate of release in descending order was caffeine, acetaminophen, theophylline, salicylic acid and indomethacin. An increase in the release kinetics of the drug was observed on blending with diluents. However, the rate of release varied with the type and amount of blend within the matrix. The mechanism of release due to effect of diluents was found to be anomalous. The rate of drug release decreased upon partial cross-linking and the mechanism of release was found to be of super case II.

Release characteristics and bioactivity of gelatin-tricalcium phosphate membranes covalently immobilized with nerve growth factors.

PubMed

Chen, Pei-Ru; Chen, Ming-Hong; Lin, Feng-Huei; Su, Wen-Yu

2005-11-01

The gelatin-tricalcium phosphate membranes were cross-linking with low concentration glutaraldehyde solution (GTG). This material has good mechanical property, biocompatibility, and is feasible for surgical manipulation. For axonal regeneration, nerve growth factors (NGF) were immobilized onto the composite (GTG) with carbodiimide. The purpose of this study was to evaluate the release characteristics and bioactivity of NGF after covalent immobilization onto the GTG membranes (GEN). NGF immobilized onto and released from the composite was quantified using ELISA method. PC 12 cells were cultured on the GTG and GEN composites. Cell survival, cytotoxicity, and cellular activity were evaluated by total protein content, LDH activity, and MTT assay respectively. Neurite outgrowth assay was used to evaluate the biological activity of NGF released from GEN composite. From ELISA measurement, the releasing curve for NGF showing two distinctive parts with different slopes indicated that NGF were released from the composite in diffusion-controlled mechanism and degradation-controlled mechanism respectively. While culturing with PC 12 cells, LDH leakage results implied that whether GTG composite cross-linked with NGF or not showed little cytotoxicity. The total protein content and cellular activity of PC 12 cells were lower on GTG and GEN membranes than control group. However, 56%+/-3.98 of PC 12 cells showed significant neurite outgrowth on GEN membranes which was statistically higher than GTG without NGF immobilization. In addition, sustained release of bioactive NGF for two months had been demonstrated by neurite outgrowth assay. From these experiments, it can be concluded that the technique used in the present study is capable of immobilizing NGF onto GTG membranes covalently and remaining the bioactivity of NGF. Therefore, GEN composite can be materials for sustained release of bioactive NGF and a candidate for future therapeutic application in nerve repair.

Tetracycline-Containing MCM-41 Mesoporous Silica Nanoparticles for the Treatment of Escherichia coli.

PubMed

Koneru, Bhuvaneswari; Shi, Yi; Wang, Yu-Chieh; Chavala, Sai H; Miller, Michael L; Holbert, Brittany; Conson, Maricar; Ni, Aiguo; Di Pasqua, Anthony J

2015-10-30

Tetracycline (TC) is a well-known broad spectrum antibiotic, which is effective against many Gram positive and Gram negative bacteria. Controlled release nanoparticle formulations of TC have been reported, and could be beneficial for application in the treatment of periodontitis and dental bone infections. Furthermore, TC-controlled transcriptional regulation systems (Tet-on and Tet-off) are useful for controlling transgene expression in vitro and in vivo for biomedical research purposes; controlled TC release systems could be useful here, as well. Mesoporous silica nanomaterials (MSNs) are widely studied for drug delivery applications; Mobile crystalline material 41 (MCM-41), a type of MSN, has a mesoporous structure with pores forming channels in a hexagonal fashion. We prepared 41 ± 4 and 406 ± 55 nm MCM-41 mesoporous silica nanoparticles and loaded TC for controlled dug release; TC content in the TC-MCM-41 nanoparticles was 18.7% and 17.7% w/w, respectively. Release of TC from TC-MCM-41 nanoparticles was then measured in phosphate-buffered saline (PBS), pH 7.2, at 37 °C over a period of 5 h. Most antibiotic was released from both over this observation period; however, the majority of TC was released over the first hour. Efficacy of the TC-MCM-41 nanoparticles was then shown to be superior to free TC against Escherichia coli (E. coli) in culture over a 24 h period, while blank nanoparticles had no effect.

Antibacterial, anti-inflammatory and neuroprotective layer-by-layer coatings for neural implants.

PubMed

Zhang, Zhiling; Nong, Jia; Zhong, Yinghui

2015-08-01

Infection, inflammation, and neuronal loss are common issues that seriously affect the functionality and longevity of chronically implanted neural prostheses. Minocycline hydrochloride (MH) is a broad-spectrum antibiotic and effective anti-inflammatory drug that also exhibits potent neuroprotective activities. In this study, we investigated the development of biocompatible thin film coatings capable of sustained release of MH for improving the long term performance of implanted neural electrodes. We developed a novel magnesium binding-mediated drug delivery mechanism for controlled and sustained release of MH from an ultrathin hydrophilic layer-by-layer (LbL) coating and characterized the parameters that control MH loading and release. The anti-biofilm, anti-inflammatory and neuroprotective potencies of the LbL coating and released MH were also examined. Sustained release of physiologically relevant amount of MH for 46 days was achieved from the Mg(2+)-based LbL coating at a thickness of 1.25 μm. In addition, MH release from the LbL coating is pH-sensitive. The coating and released MH demonstrated strong anti-biofilm, anti-inflammatory, and neuroprotective potencies. This study reports, for the first time, the development of a bioactive coating that can target infection, inflammation, and neuroprotection simultaneously, which may facilitate the translation of neural interfaces to clinical applications.

Antibacterial, anti-inflammatory and neuroprotective layer-by-layer coatings for neural implants

NASA Astrophysics Data System (ADS)

Zhang, Zhiling; Nong, Jia; Zhong, Yinghui

2015-08-01

Objective. Infection, inflammation, and neuronal loss are common issues that seriously affect the functionality and longevity of chronically implanted neural prostheses. Minocycline hydrochloride (MH) is a broad-spectrum antibiotic and effective anti-inflammatory drug that also exhibits potent neuroprotective activities. In this study, we investigated the development of biocompatible thin film coatings capable of sustained release of MH for improving the long term performance of implanted neural electrodes. Approach. We developed a novel magnesium binding-mediated drug delivery mechanism for controlled and sustained release of MH from an ultrathin hydrophilic layer-by-layer (LbL) coating and characterized the parameters that control MH loading and release. The anti-biofilm, anti-inflammatory and neuroprotective potencies of the LbL coating and released MH were also examined. Main results. Sustained release of physiologically relevant amount of MH for 46 days was achieved from the Mg2+-based LbL coating at a thickness of 1.25 μm. In addition, MH release from the LbL coating is pH-sensitive. The coating and released MH demonstrated strong anti-biofilm, anti-inflammatory, and neuroprotective potencies. Significance. This study reports, for the first time, the development of a bioactive coating that can target infection, inflammation, and neuroprotection simultaneously, which may facilitate the translation of neural interfaces to clinical applications.

An Algorithmic, Pie-Crusting Medial Soft Tissue Release Reduces the Need for Constrained Inserts Patients With Severe Varus Deformity Undergoing Total Knee Arthroplasty.

PubMed

Goudarz Mehdikhani, Kaveh; Morales Moreno, Beatriz; Reid, Jeremy J; de Paz Nieves, Ana; Lee, Yuo-Yu; González Della Valle, Alejandro

2016-07-01

We studied the need to use a constrained insert for residual intraoperative instability and the 1-year result of patients undergoing total knee arthroplasty (TKA) for a varus deformity. In a control group, a "classic" subperiosteal release of the medial soft tissue sleeve was performed as popularized by pioneers of TKA. In the study group, an algorithmic approach that selectively releases and pie-crusts posteromedial structures in extension and anteromedial structures in flexion was used. All surgeries were performed by a single surgeon using measured resection technique, and posterior-stabilized, cemented implants. There were 228 TKAs in the control group and 188 in the study group. Outcome variables included the use of a constrained insert, and the Knee Society Score at 6 weeks, 4 months, and 1 year postoperatively. The effect of the release technique on use of constrained inserts and clinical outcomes were analyzed in a multivariate model controlling for age, sex, body mass index, and severity of deformity. The use of constrained inserts was significantly lower in study than in control patients (8% vs 18%; P = .002). There was no difference in the Knee Society Score and range of motion between the groups at last follow-up. No patient developed postoperative medial instability. This algorithmic, pie-crusting release technique resulted in a significant reduction in the use of constrained inserts with no detrimental effects in clinical results, joint function, and stability. As constrained TKA implants are more costly than nonconstrained ones, if the adopted technique proves to be safe in the long term, it may cause a positive shift in value for hospitals and cost savings in the health care system. Copyright © 2016 Elsevier Inc. All rights reserved.

Free-standing few-layered graphene oxide films: selective, steady and lasting permeation of organic molecules with adjustable speeds

NASA Astrophysics Data System (ADS)

Huang, Tao; An, Qi; Luan, Xinglong; Zhang, Qian; Zhang, Yihe

2016-01-01

A variety of small molecules with diameters around 1 nm possess a range of functions, such as antibiotic, antimicrobic, anticoagulant, pesticidal and chemotherapy effects, making these molecules especially useful in various applications ranging from medical treatment to environmental microbiological control. However, the long-term steady delivery (release or permeation) of these small molecules with adjustable and controllable speeds has remained an especially challenging task. In this study, we prepared covalently cross-linked free-standing few-layered GO films using a layer-by-layer technique in combination with photochemical cross-linkages, and achieved a controlled release of positively charged, negatively charged, and zwitterionic small molecules with adjustable and controllable speeds. The steady delivery of the small molecule lasted up to 9 days. Other functionalities, such as graphene-enhanced Raman spectra and electrochemical properties that could also be integrated or employed in delivery systems, were also studied for our films. We expect the special molecular delivery properties of our films to lead to new possibilities in drug/fertilizer delivery and environmental microbiological control applications.A variety of small molecules with diameters around 1 nm possess a range of functions, such as antibiotic, antimicrobic, anticoagulant, pesticidal and chemotherapy effects, making these molecules especially useful in various applications ranging from medical treatment to environmental microbiological control. However, the long-term steady delivery (release or permeation) of these small molecules with adjustable and controllable speeds has remained an especially challenging task. In this study, we prepared covalently cross-linked free-standing few-layered GO films using a layer-by-layer technique in combination with photochemical cross-linkages, and achieved a controlled release of positively charged, negatively charged, and zwitterionic small molecules with adjustable and controllable speeds. The steady delivery of the small molecule lasted up to 9 days. Other functionalities, such as graphene-enhanced Raman spectra and electrochemical properties that could also be integrated or employed in delivery systems, were also studied for our films. We expect the special molecular delivery properties of our films to lead to new possibilities in drug/fertilizer delivery and environmental microbiological control applications. Electronic supplementary information (ESI) available: AFM images of GO and GO films, UV-vis spectra of delayed release, and permeation fidelities. See DOI: 10.1039/c5nr08129g

Sintering of wax for controlling release from pellets.

PubMed

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.

PREVENTION REFERENCE MANUAL: CONTROL TECHNOLOGIES, VOL. 2. POST-RELEASE MITIGATION MEASURES FOR CONTROLLING ACCIDENTAL RELEASES OF AIR TOXICS

EPA Science Inventory

The volume discusses prevention and protection measures for controlling accidental releases of air toxics. The probability of accidental releases depends on the extent to which deviations (in magnitude and duration) in the process can be tolerated before a loss of chemical contai...

How controlled release technology can aid gene delivery.

PubMed

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.

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

PubMed

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

2016-09-10

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

Kinetics and mechanism of release from glyceryl monostearate-based implants: evaluation of release in a gel simulating in vivo implantation.

PubMed

Allababidi, S; Shah, J C

1998-06-01

The overall objective of the study was to design an implantable delivery system based on glyceryl monostearate (GMS) for the site-specific delivery of antibiotics for the prevention of surgical wound infection. To design the implant, a release method had to be developed that simulate the in vivo implantation conditions to be able to predict the release characteristics from the implants when they are actually used in vivo. Also, identifying the release kinetics and mechanism and evaluating the factors that influence the release of drugs from the GMS-based matrix were necessary to allow further design of implants that could yield a desired release rate. The release of cefazolin was monitored from GMS matrixes implanted into agar gel, simulating subcutaneous tissues with respect to viscosity and water content. The gel method resulted in observation of spatial and temporal concentration profiles in the immediate vicinity of the implants, indicating the benefits of local drug delivery; however, there was no significant difference between the cumulative release profiles by the gel method or the vial release method. The release of cefazolin from the GMS-based matrix with the vial method followed Higuchi's square root of time kinetics. The release rate was found to be directly proportional to cefazolin load (A) and the surface area (SA) of the matrix as expressed by the following equation: = 0.24ASA. On the basis of this equation, one can design a variety of GMS matrixes that would result in a desired release rate or release duration. This also indicated that cefazolin release followed the release kinetics of a freely soluble drug from an insoluble matrix and hence it is a diffusion-controlled process. The effect of drug solubility on the release kinetics was determined by comparing the release kinetics of the poorly water soluble ciprofloxacin (0.16 mg/mL) to that of the highly water soluble cefazolin (325 mg/mL). The release duration of ciprofloxacin (80 h) was longer than that of cefazolin (25 h) from identical GMS matrixes. Although ciprofloxacin release was initially controlled by the matrix, agitation accelerated disintegration of the matrix and release due to its poor solubility, and ciprofloxacin release appeared to be a dissolution-controlled process following zero-order release kinetics.

Low-intensity case management increases contact with primary care in recently released prisoners: a single-blinded, multisite, randomised controlled trial

PubMed Central

Alati, Rosa; Longo, Marie; Spittal, Matthew J; Boyle, Frances M; Williams, Gail M; Lennox, Nicholas G

2016-01-01

Background The world prison population is large and growing. Poor health outcomes after release from prison are common, but few programmes to improve health outcomes for ex-prisoners have been rigorously evaluated. The aim of this study was to evaluate the impact of individualised case management on contact with health services during the first 6 months post-release. Methods Single-blinded, randomised, controlled trial. Baseline assessment with N=1325 adult prisoners in Queensland, Australia, within 6 weeks of expected release; follow-up interviews 1, 3 and 6 months post-release. The intervention consisted of provision of a personalised booklet (‘Passport’) at the time of release, plus up to four brief telephone contacts in the first 4 weeks post-release. Results Of 1179 eligible participants, 1003 (85%) completed ≥1 follow-up interview. In intention-to-treat analyses, 53% of the intervention group and 41% of the control group reported contacting a general practitioner (GP) at 1 month post-release (difference=12%, 95% CI 5% to 19%). Similar effects were observed for GP contact at 3 months (difference=9%, 95% CI 2% to 16%) and 6 months (difference=8%, 95% CI 1% to 15%), and for mental health (MH) service contact at 6 months post release (difference=8%, 95% CI 3% to 14%). Conclusions Individualised case management in the month after release from prison increases usage of primary care and MH services in adult ex-prisoners for at least 6 months post-release. Given the poor health profile of ex-prisoners, there remains an urgent need to develop and rigorously evaluate interventions to increase health service contact in this profoundly marginalised population. Trial registration number ACTRN12608000232336. PMID:26787201

Effect of decrease in both postprandial blood glucose (PBG) and fasting blood glucose (FBG) levels in normal beagle dogs with nateglinide enteric coated granules and immediate release tablets.

PubMed

Makino, Chisato; Ninomiya, Nobutaka; Sakai, Hidetoshi; Orita, Haruo; Okano, Akira; Yabuki, Akira

2006-04-01

Nateglinide is a new quick action/short duration (QRSD) type of oral blood glucose regulator, and nateglinide immediate release tablets are used for patients with mild diabetes under the trade name of Fastic((R)) tablets. In this study, we attempted to determine if it was possible to control both post-prandial blood glucose level (PBG) and fasting blood glucose level (FBG) for moderate or severe diabetes through controlled release of nateglinide. Enteric coated granules were selected for the administration form for controlled release of nateglinide, and three types of enteric coated granules were prepared having dissolution pH values of 5.5, 6.5 and 7.2. The three types of enteric coated granules were each administered separately or the enteric coated granules having an dissolution pH of 6.5 were administered simultaneous to administration of nateglinide immediate release tablets to normal beagle dogs just before feeding followed by measurement of plasma nateglinide concentration, plasma insulin concentration and blood glucose level. In the case of administering enteric coated granules alone (nateglinide: 9 mg/kg), the absorption of nateglinide was confirmed to tend to be delayed as the dissolution pH increased. In the case of an dissolution pH of 5.5, decreases in both PBG and FBG were observed. In the case of dissolution pH values of 6.5 and 7.2, only decrease in FBG was observed. In case of nateglinide immediate release tablets (nateglinide: 9 mg/kg), only decrease in PBG was observed. Decreases in both PBG and FBG were observed in the case of simultaneous administration of dissolution pH 6.5 enteric coated granules and nateglinide immediate release tablets just before feeding (nateglinide: 90 mg/head+60 mg/head). A correlation was observed between plasma nateglinide concentrations and blood glucose levels. On the other hand, there were no correlations observed between changes in plasma insulin concentrations and blood glucose levels. In case of nateglinide immediate release tablets (nateglinide: 150 mg/head), Decreases in both PBG and FBG were observed. However, the nateglinide controlled release formulation is more useful than the nateglinide immediate release tablets from the view point of avoidance of side effect, or of easy control of both PBG and FBG. On the basis of these results, the design of a controlled release formulation that contains nateglinide was suggested to enable control of both PBG and FBG for moderate and severe diabetes patients.

Biodegradable poly(L-lactic acid)-lavender nanocapsules: synthesis, controlled release, and application in remedy of sleep disorder.

PubMed

Daoud, Walid A; Ngan, Mandy; Cheuk, Kevin

2010-02-01

In this study, nanocapsules of poly(L-lactic acid) (PLLA) containing lavender oil were synthesized by solvent evaporation emulsion. Poly(L-lactic acid) is a biodegradable aliphatic polyester derived from lactic acid formed by bacterial fermentation of glucose-rich substances. Lavender oil is a plant extract that finds uses in phytotherapy. It is reputed as anti-septic, anti-depressant and sleep promoter. Encapsulation is a technique used to encase tiny oil droplets with a thin and permeable coating that allows for a controlled release of the volatile oil. The size and morphology of the nanocapsules were characterized by scanning electron microscope. The particle size and distribution were measured by photon correlation spectroscopy. The time-controlled release of the lavender oil was studied and the use of the lavender capsules in the remedy of sleep disorder was investigated.

Cost-effectiveness analysis of hypertension treatment: controlled release nifedipine and candesartan low-dose combination therapy in patients with essential hypertension--the Nifedipine and Candesartan Combination (NICE-Combi) Study.

PubMed

Fujikawa, Keita; Hasebe, Naoyuki; Kikuchi, Kenjiro

2005-07-01

Societal interest in pharmaco-economic analysis is increasing in Japan. In this study, the cost-effectiveness of low-dose combination therapy with controlled release nifedipine plus candesartan and up-titrated monotherapy with candesartan was estimated, based on the results of the NICE-Combi study. The NICE-Combi study was a double-blind, parallel arm, randomized clinical trial to compare the efficacy of low-dose combination therapy of controlled release nifedipine (20 mg/day) plus candesartan (8 mg/day) vs. up-titrated monotherapy of candesartan (12 mg/day) on blood pressure control in Japanese patients with mild to severe essential hypertension who were not sufficiently controlled by the conventional dose of candesartan (8 mg/ day). The incremental cost effectiveness of each cohort during the 8-week randomization period was compared, from the perspective of a third-party payer (i.e., insurers). The average total cost per patient was 29,943 Japanese yen for the combination therapy group and 33,182 Japanese yen for the candesartan monotherapy group, while the rate of achievement of the target blood pressure was significantly higher in the combination therapy group than in the up-titrated monotherapy group. In the combination therapy group, higher efficacy and lower incremental treatment cost ("Dominance") were observed when compared to the monotherapy group. The sensitivity analyses also supported the results. In conclusion, these results suggest that combination therapy with controlled release nifedipine and low-dose candesartan (8 mg) is "dominant" to up-titrated candesartan monotherapy for the management of essential hypertension. This conclusion was robust to sensitivity analysis.

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

NASA Astrophysics Data System (ADS)

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.

Development of a poly (ether urethane) system for the controlled release of two novel anti-biofilm agents based on gallium or zinc and its efficacy to prevent bacterial biofilm formation

PubMed Central

Ma, Hongyan; Darmawan, Erica T.; Zhang, Min; Zhange, Lei; Bryers, James D.

2013-01-01

Traditional antibiotic therapy to control medical device-based infections typically fails to clear biofilm infections and may even promote the evolution of antibiotic resistant species. We report here the development of two novel antibiofilm agents; gallium (Ga) or zinc (Zn) complexed with protoporphyrin IX (PP) or mesoprotoporphyrin IX (MP) that are both highly effective in negating suspended bacterial growth and biofilm formation. These chelated gallium or zinc complexes act as iron siderophore analogs, surplanting the natural iron uptake of most bacteria. Poly (ether urethane) (PEU; Biospan®) polymer films were fabricated for the controlled sustained release of the Ga- or Zn-complexes, using an incorporated pore-forming agent, poly (ethylene glycol) (PEG). An optimum formulation containing 8% PEG (MW=1450) in the PEU polymer effectively sustained drug release for at least 3 months. All drug-loaded PEU films exhibited in vitro ≥ 90% reduction of Gram-positive (Staphylococcus epidermidis) and Gram-negative (Pseudomonas aeruginosa) bacteria in both suspended and biofilm culture versus the negative control PEU films releasing nothing. Cytotoxicity and endotoxin evaluation demonstrated no adverse responses to the Ga- or Zn-complex releasing PEU films. Finally, in vivo studies further substantiate the anti-biofilm efficacy of the PEU films releasing Ga- or Zn- complexes. PMID:24140747

Development of a poly(ether urethane) system for the controlled release of two novel anti-biofilm agents based on gallium or zinc and its efficacy to prevent bacterial biofilm formation.

PubMed

Ma, Hongyan; Darmawan, Erica T; Zhang, Min; Zhang, Lei; Bryers, James D

2013-12-28

Traditional antibiotic therapy to control medical device-based infections typically fails to clear biofilm infections and may even promote the evolution of antibiotic resistant species. We report here the development of two novel antibiofilm agents; gallium (Ga) or zinc (Zn) complexed with protoporphyrin IX (PP) or mesoprotoporphyrin IX (MP) that are both highly effective in negating suspended bacterial growth and biofilm formation. These chelated gallium or zinc complexes act as iron siderophore analogs, supplanting the natural iron uptake of most bacteria. Poly (ether urethane) (PEU; Biospan®) polymer films were fabricated for the controlled sustained release of the Ga- or Zn-complexes, using an incorporated pore-forming agent, poly(ethylene glycol) (PEG). An optimum formulation containing 8% PEG (MW=1450) in the PEU polymer effectively sustained drug release for at least 3months. All drug-loaded PEU films exhibited in vitro ≥ 90% reduction of Gram-positive (Staphylococcus epidermidis) and Gram-negative (Pseudomonas aeruginosa) bacteria in both suspended and biofilm culture versus the negative control PEU films releasing nothing. Cytotoxicity and endotoxin evaluation demonstrated no adverse responses to the Ga- or Zn-complex releasing PEU films. Finally, in vivo studies further substantiate the anti-biofilm efficacy of the PEU films releasing Ga- or Zn- complexes. © 2013.

Acute effects of nitrogen dioxide after accidental release.

PubMed

Bauer, U; Berg, D; Kohn, M A; Meriwether, R A; Nickle, R A

1998-01-01

Following an accidental release of nitrogen dioxide from a railroad tank car containing nitrous tetroxide, the authors undertook a study of the health effects of the release, measuring the association between acute low level exposure and pulmonary symptoms. The authors reviewed the records of three emergency departments, surveyed 80 emergency department patients, 552 community residents, 21 chemical plant workers, and 29 emergency workers, and conducted a case-control study. Pulmonary case status was defined as having an objective pulmonary finding noted on the emergency department record, reporting that the onset of symptoms was subsequent to the release, and being within the city limits at the time of the release. Self-reported case status was defined as reporting one or more symptoms consistent with exposure to nitrogen dioxide in the week after the release and having been within the city limits at the time of the release. Control subjects were survey respondents who reported no symptoms in the week after the release and had been within the city limits at the time of the release. Chemical exposure was characterized by proximity to, direction from, and being outdoors within one hour after the release. Duration of potential exposure was not measured. Logistic regression was used to estimate odds ratios and 95% confidence interval for symptoms by exposure level, adjusted for age, sex, smoking, and preexisting pulmonary conditions. Local emergency department visits increased fivefold in the week after the release. The most common complaints recorded in a systematic sample of 528 visits in the first 30 hours after the release were headache (31%), burning eyes (30%), and sore throat (24%). Objective pulmonary findings were recorded for 41 (5%) patients in the week before and 165 (4%) in the week after the release. The odds of being a pulmonary case increased by 40% for each quarter-mile increment in proximity to the release (odds ratio [OR] 1.4; 95% confidence interval [CI] 1.1, 1.7), while the odds of being a self-reported case increased by 20% for each quarter-mile increment in proximity (OR 1.2, 95% CI 1.1, 1.4). People who met the pulmonary case definition were 2.5 times (CI 1.3, 4.8) more likely than control subjects to have been outdoors and 6.4 times (CI 3.2, 12.6) more likely to report a preexisting pulmonary condition. Self-reported cases were 2.6 times (95% CI 1.8, 3.8) more likely than control subjects to have been outdoors and 1.9 times (95% CI 1.1, 3.1) more likely to report a preexisting pulmonary condition. Emergency department visits increased five-fold, but serious acute health effects were uncommon. People who met the pulmonary case definition were six times more likely to report pulmonary symptoms than those without preexisting conditions. This study was not designed to determine any potential long-term effects of exposure.

Influence of Scaffold Size on Bactericidal Activity of Nitric Oxide Releasing Silica Nanoparticles

PubMed Central

Carpenter, Alexis W.; Slomberg, Danielle L.; Rao, Kavitha S.; Schoenfisch, Mark H.

2011-01-01

A reverse microemulsion synthesis was used to prepare amine functionalized silica nanoparticles of three distinct sizes (i.e., 50, 100, and 200 nm) with identical amine concentrations. The resulting hybrid nanoparticles, consisting of N-(6 aminohexyl) aminopropyltrimethoxysilane and tetraethoxysilane, were highly monodisperse in size. N-diazeniumdiolate nitric oxide (NO) donors were subsequently formed on secondary amines while controlling reaction conditions to keep the total amount of nitric oxide (NO) released constant for each particle size. The bactericidal efficacy of the NO releasing nanoparticles against Pseudomonas aeruginosa increased with decreasing particle size. Additionally, smaller diameter nanoparticles were found to associate with the bacteria at a faster rate and to a greater extent than larger particles. Neither control (non-NO-releasing) nor NO releasing particles exhibited toxicity towards L929 mouse fibroblasts at concentrations above their respective minimum bactericidal concentrations. This study represents the first investigation of the bactericidal efficacy of NO-releasing silica nanoparticles as a function of particle size. PMID:21842899

Controlled Release Applications of Organometals.

ERIC Educational Resources Information Center

Thayer, John S.

1981-01-01

Reviews two classes of controlled release organometals: (1) distributional, to distribute bioactive materials to control a certain target organism; and (2) protective, to protect surface or interior of some structure from attach by organisms. Specific examples are given including a discussion of controlled release for schistosomiasis. (SK)

CRRES combined radiation and release effects satellite program

NASA Technical Reports Server (NTRS)

Giles, B. L. (Compiler); Mccook, M. A. (Compiler); Mccook, M. W. (Compiler); Miller, G. P. (Compiler)

1995-01-01

The various regions of the magnetosphere-ionosphere system are coupled by flows of charged particle beams and electromagnetic waves. This coupling gives rise to processes that affect both technical and non-technical aspects of life on Earth. The CRRES Program sponsored experiments which were designed to produce controlled and known input to the space environment and the effects were measured with arrays of diagnostic instruments. Large amounts of material were used to modify and perturb the environment in a controlled manner, and response to this was studied. The CRRES and PEGSAT satellites were dual-mission spacecraft with a NASA mission to perform active chemical-release experiments, grouped into categories of tracer, modification, and simulation experiments. Two sounding rocket chemical release campaigns completed the study.

28 CFR 541.50 - Release from a control unit.

Code of Federal Regulations, 2010 CFR

2010-07-01

... general population of the institution which has a control unit. [49 FR 32991, Aug. 17, 1984, as amended at... 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...

28 CFR 541.50 - Release from a control unit.

Code of Federal Regulations, 2013 CFR

2013-07-01

... general population of the institution which has a control unit. [49 FR 32991, Aug. 17, 1984, as amended at... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Release from a control unit. 541.50... INMATE DISCIPLINE AND SPECIAL HOUSING UNITS Control Unit Programs § 541.50 Release from a control unit...

28 CFR 541.50 - Release from a control unit.

Code of Federal Regulations, 2012 CFR

2012-07-01

... general population of the institution which has a control unit. [49 FR 32991, Aug. 17, 1984, as amended at... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Release from a control unit. 541.50... INMATE DISCIPLINE AND SPECIAL HOUSING UNITS Control Unit Programs § 541.50 Release from a control unit...

28 CFR 541.50 - Release from a control unit.

Code of Federal Regulations, 2011 CFR

2011-07-01

... general population of the institution which has a control unit. [49 FR 32991, Aug. 17, 1984, as amended at... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Release from a control unit. 541.50... INMATE DISCIPLINE AND SPECIAL HOUSING UNITS Control Unit Programs § 541.50 Release from a control unit...

28 CFR 541.50 - Release from a control unit.

Code of Federal Regulations, 2014 CFR

2014-07-01

... general population of the institution which has a control unit. [49 FR 32991, Aug. 17, 1984, as amended at... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Release from a control unit. 541.50... INMATE DISCIPLINE AND SPECIAL HOUSING UNITS Control Unit Programs § 541.50 Release from a control unit...

Natural gum-type biopolymers as potential modified nonpolar drug release systems.

PubMed

Salamanca, Constain H; Yarce, Cristhian J; Moreno, Roger A; Prieto, Vanessa; Recalde, Juanita

2018-06-01

In this work, the relationship between surface properties and drug release mechanism from binary composition tablets formed by quetiapine fumarate and biopolymer materials was studied. The biopolymers correspond to xanthan and tragacanth gums, which are projected as modified drug release systems. The surface studies were carried out by the sessile drop method, while the surface free energy (SFE) was determinate through Young-Dupree and OWRK semi-empirical models. On the other hand, the drug release studies were performed by in vitro dissolution tests, where the data were analyzed through kinetic models of zero order, first order, Higuchi, and Korsmeyer-Peppas. The results showed that depending on the type and the proportion of biopolymer, surface properties, and the drug release processes are significantly affected, wherein tragacanth gum present a usual erosion mechanism, while xanthan gum describes a swelling mechanism that controls the release of the drug. Copyright © 2018 Elsevier Ltd. All rights reserved.

Gold and Iron Oxide Nanoparticle-Based Ethylcellulose Nanocapsules for Cisplatin Drug Delivery

PubMed Central

Sathish Kumar, Kannaiyan; Jaikumar, Vasudevan

2011-01-01

The present study is aimed at the overall improvement in the efficacy, reduced toxicity and enhancement of therapeutic index of cisplatin. Nanocapsules of cisplatin containing ethylcellulose have been prepared using solvent evaporation technique under ambient conditions. The prepared nanocapsules were used for controlled drug release of anticancer agents with gold and iron oxide nanoparticles. The drug-entrapped nanocapsules were characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Fourier transform infrared (FTIR) studies indicated the absence of chemical interactions between the drug, polymer and metal nanoparticles. The drug loaded nanoparticles are spherical in shape and had average diameter in the range of 100-300 nm. Drug release study showed that the acidic media provided a faster release than the phosphate buffer media. These findings were also compared statistically through calculating mean, standard deviation and coefficient of variation for various polymer nanocapsules. However, the drug release for gold nanoparticles/anticancer drug (Au-cis) incorporated ethylcellulose nanocapsules was controlled and slow compared to iron oxide nanoparticles-cisplatin incorporated ethylcellulose nanocapsules. Hence, gold nanoparticles act as good trapping agents which slow down the rate of drug release from nanocapsules. PMID:24250373

The Relationship Between the Evolution of an Internal Structure and Drug Dissolution from Controlled-Release Matrix Tablets.

PubMed

Kulinowski, Piotr; Hudy, Wiktor; Mendyk, Aleksander; Juszczyk, Ewelina; Węglarz, Władysław P; Jachowicz, Renata; Dorożyński, Przemysław

2016-06-01

In the last decade, imaging has been introduced as a supplementary method to the dissolution tests, but a direct relationship of dissolution and imaging data has been almost completely overlooked. The purpose of this study was to assess the feasibility of relating magnetic resonance imaging (MRI) and dissolution data to elucidate dissolution profile features (i.e., kinetics, kinetics changes, and variability). Commercial, hydroxypropylmethyl cellulose-based quetiapine fumarate controlled-release matrix tablets were studied using the following two methods: (i) MRI inside the USP4 apparatus with subsequent machine learning-based image segmentation and (ii) dissolution testing with piecewise dissolution modeling. Obtained data were analyzed together using statistical data processing methods, including multiple linear regression. As a result, in this case, zeroth order release was found to be a consequence of internal structure evolution (interplay between region's areas-e.g., linear relationship between interface and core), which eventually resulted in core disappearance. Dry core disappearance had an impact on (i) changes in dissolution kinetics (from zeroth order to nonlinear) and (ii) an increase in variability of drug dissolution results. It can be concluded that it is feasible to parameterize changes in micro/meso morphology of hydrated, controlled release, swellable matrices using MRI to establish a causal relationship between the changes in morphology and drug dissolution. Presented results open new perspectives in practical application of combined MRI/dissolution to controlled-release drug products.

Drug release characteristics of quercetin-loaded TiO2 nanotubes coated with chitosan.

PubMed

Mohan, L; Anandan, C; Rajendran, N

2016-12-01

TiO 2 nanotubes formed by anodic oxidation of Ti-6Al-7Nb were loaded with quercetin (TNTQ) and chitosan was coated on the top of the quercetin (TNTQC) to various thicknesses. Field emission scanning electron microscopy (FESEM), 3D and 2D analyses were used to characterize the samples. The drug release studies of TNTQ and TNTQC were studied in Hanks' solution for 192h. The studies showed that the native oxide on the sample is substituted by self assembled nanotube arrays by anodisation. FESEM images of chitosan-loaded TNT samples showed that filling of chitosan takes place in inter-tubular space and pores. Drug release studies revealed that the release of drug into the local environment during that duration was constant. The local concentration of the drug can be controlled and tuned by controlling the thickness of the chitosan (0.6, 1 and 3μm) to fit into an optimal therapeutic window in order to treat postoperative infections, inflammation and for quick healing with better osseointegration of the titanium implants. Copyright © 2016 Elsevier B.V. All rights reserved.

Design of eudragit RL nanoparticles by nanoemulsion method as carriers for ophthalmic drug delivery of ketotifen fumarate

PubMed Central

Soltani, Saieede; Zakeri-Milani, Parvin; Barzegar-Jalali, Mohammad; Jelvehgari, Mitra

2016-01-01

Objective(s): Ketotifen fumarate (KF) is a selective and noncompetitive histamine antagonist (H1-receptor) that is used topically in the treatment of allergic conditions of rhinitis and conjunctivitis. The aim of this study was to formulate and improve an ophthalmic delivery system of KF. Ocular nanoparticles were prepared with the objective of reducing the frequency of administration and obtaining controlled release to improve the anti-inflammatory drug delivery. Materials and Methods: In the present study, ocular KF loaded Eudragit RL 100 nanoparticles were prepared using O/W solvent diffusion method. The nanoparticles were evaluated for particle size, entrapment efficiency, surface morphology, X-ray diffraction (XRD), Fourier transform spectroscopy (FTIR), and differential scanning calorimetry (DSC). In vitro release and permeation studies were also carried out on nanoparticles. Results: An average size range of 182 to 314.30 nm in diameter was obtained and encapsulation efficiency up to 95.0% was observed for all the formulations. Drug release for all formulations after 24 hr was between 65.51% and 88.82% indicating effective controlled release property of KF. The mechanism of drug release for best formulation was found to be fickian diffusion mechanism. KF nanoparticles containing high polymer concentration (1:15) presented a faster drug release and a higher drug penetration; on the contrary, nanoparticles containing low polymer concentration (1:7.5) were able to give a more sustained release of the drug and thus a slower KF permeation through the cornea. Conclusion: The study revealed that KF NPs were capable of releasing the drug for a prolonged period of time and increasing the ocular bioavailability. PMID:27403262

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

PubMed

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.

Breast feeding increases vasoconstriction induced by electrical field stimulation in rat mesenteric artery. Role of neuronal nitric oxide and ATP.

PubMed

Blanco-Rivero, Javier; Sastre, Esther; Caracuel, Laura; Granado, Miriam; Balfagón, Gloria

2013-01-01

The aim of this study was to investigate in rat mesenteric artery whether breast feeding (BF) affects the vasomotor response induced by electrical field stimulation (EFS), participation by different innervations in the EFS-induced response and the mechanism/s underlying these possible modifications. Experiments were performed in female Sprague-Dawley rats (3 months old), divided into three groups: Control (in oestrous phase), mothers after 21 days of BF, and mothers that had recovered their oestral cycle (After BF, in oestrous phase). Vasomotor response to EFS, noradrenaline (NA) and nitric oxide (NO) donor DEA-NO were studied. Neuronal NO synthase (nNOS) and phosphorylated nNOS (P-nNOS) protein expression were analysed and NO, superoxide anion (O(2)(.-)), NA and ATP releases were also determined. EFS-induced contraction was higher in the BF group, and was recovered after BF. 1 µmol/L phentolamine decreased the response to EFS similarly in control and BF rats. NA vasoconstriction and release were similar in both experimental groups. ATP release was higher in segments from BF rats. 0.1 mmol/L L-NAME increased the response to EFS in both control and BF rats, but more so in control animals. BF decreased NO release and did not modify O(2)(.-) production. Vasodilator response to DEA-NO was similar in both groups, while nNOS and P-nNOS expressions were decreased in segments from BF animals. Breast feeding increases EFS-induced contraction in mesenteric arteries, mainly through the decrease of neuronal NO release mediated by decreased nNOS and P-nNOS expression. Sympathetic function is increased through the increased ATP release in BF rats.

Breast Feeding Increases Vasoconstriction Induced by Electrical Field Stimulation in Rat Mesenteric Artery. Role of Neuronal Nitric Oxide and ATP

PubMed Central

Caracuel, Laura; Granado, Miriam; Balfagón, Gloria

2013-01-01

Objectives The aim of this study was to investigate in rat mesenteric artery whether breast feeding (BF) affects the vasomotor response induced by electrical field stimulation (EFS), participation by different innervations in the EFS-induced response and the mechanism/s underlying these possible modifications. Methods Experiments were performed in female Sprague-Dawley rats (3 months old), divided into three groups: Control (in oestrous phase), mothers after 21 days of BF, and mothers that had recovered their oestral cycle (After BF, in oestrous phase). Vasomotor response to EFS, noradrenaline (NA) and nitric oxide (NO) donor DEA-NO were studied. Neuronal NO synthase (nNOS) and phosphorylated nNOS (P-nNOS) protein expression were analysed and NO, superoxide anion (O2 .–), NA and ATP releases were also determined. Results EFS-induced contraction was higher in the BF group, and was recovered after BF. 1 µmol/L phentolamine decreased the response to EFS similarly in control and BF rats. NA vasoconstriction and release were similar in both experimental groups. ATP release was higher in segments from BF rats. 0.1 mmol/L L-NAME increased the response to EFS in both control and BF rats, but more so in control animals. BF decreased NO release and did not modify O2 .– production. Vasodilator response to DEA-NO was similar in both groups, while nNOS and P-nNOS expressions were decreased in segments from BF animals. Conclusion Breast feeding increases EFS-induced contraction in mesenteric arteries, mainly through the decrease of neuronal NO release mediated by decreased nNOS and P-nNOS expression. Sympathetic function is increased through the increased ATP release in BF rats. PMID:23342008

Transport mechanism of L-[14C]glutamate in cortical slices and synaptosomes of rabbits exposed to brain ischemia and reperfusion.

PubMed

Solyakov, L; Dobrota, D; Drany, O; Vachova, M; Machac, S; Mezesova, V; Bachurin, S; Lombardi, V

1995-01-01

Changes in the functioning of the glutamatergic system in rabbit brain were studied after partial brain ischemia and reperfusion. In vitro studies were conducted relating to the release of L-[14C]glutamate from cortical brain slices, L-[14C]glutamate uptake in synaptosomes, and 45Ca uptake in synaptosomes. It was found that basal release of L-[14C]glutamate from rabbit brain cortical slices after 30 min of partial ischemia and 1 d of reperfusion was essentially without change compared to the control values. After 3 d of reperfusion, there was an increase in basal release of L-[14C]glutamate from rabbit brain cortical slices. K+ stimulated release of L-[14C]glutamate in normal Krebs-Ringer medium was essentially the same in the control group and in the experimental group after 30 min of ischemia. The K+ stimulated release of L-[14C]glutamate independent of calcium was increased to 145% after 30 min of ischemia and 1 d of reperfusion. The decreased Km value at the glutamate transporter may have contributed to this difference. Kinetic parameters of the L-[14C]glutamate uptake (Km and Vmax) in synaptosomes from rabbit brain were significantly lower after 30 min of ischemia. The authors discovered that during the reperfusion period, Vmax was almost the same as in the control group. The activity of the Na+/Ca2+ exchanger in synaptosomes of rat brain was about 70% of the control values after 30 min of ischemia and 72 h of reperfusion. According to our results, increased L-[14C]glutamate release after 30 min of ischemia appears to be the result of higher intracellular calcium concentration and possibly also of a higher uptake of glutamate.

Controlled release of functional proteins through designer self-assembling peptide nanofiber hydrogel scaffold

PubMed Central

Koutsopoulos, Sotirios; Unsworth, Larry D.; Nagai, Yusuke; Zhang, Shuguang

2009-01-01

The release kinetics for a variety of proteins of a wide range of molecular mass, hydrodynamic radii, and isoelectric points through a nanofiber hydrogel scaffold consisting of designer self-assembling peptides were studied by using single-molecule fluorescence correlation spectroscopy (FCS). In contrast to classical diffusion experiments, the single-molecule approach allowed for the direct determination of diffusion coefficients for lysozyme, trypsin inhibitor, BSA, and IgG both inside the hydrogel and after being released into the solution. The results of the FCS analyses and the calculated pristine in-gel diffusion coefficients were compared with the values obtained from the Stokes–Einstein equation, Fickian diffusion models, and the literature. The release kinetics suggested that protein diffusion through nanofiber hydrogels depended primarily on the size of the protein. Protein diffusivities decreased, with increasing hydrogel nanofiber density providing a means of controlling the release kinetics. Secondary and tertiary structure analyses and biological assays of the released proteins showed that encapsulation and release did not affect the protein conformation and functionality. Our results show that this biocompatible and injectable designer self-assembling peptide hydrogel system may be useful as a carrier for therapeutic proteins for sustained release applications. PMID:19273853

Influence of Volatile Anesthesia on the Release of Glutamate and other Amino Acids in the Nucleus Accumbens in a Rat Model of Alcohol Withdrawal: A Pilot Study

PubMed Central

Seidemann, Thomas; Spies, Claudia; Morgenstern, Rudolf; Wernecke, Klaus-Dieter; Netzhammer, Nicolai

2017-01-01

Background Alcohol withdrawal syndrome is a potentially life-threatening condition, which can occur when patients with alcohol use disorders undergo general anesthesia. Excitatory amino acids, such as glutamate, act as neurotransmitters and are known to play a key role in alcohol withdrawal syndrome. To understand this process better, we investigated the influence of isoflurane, sevoflurane, and desflurane anesthesia on the profile of excitatory and inhibitory amino acids in the nucleus accumbens (NAcc) of alcohol-withdrawn rats (AWR). Methods Eighty Wistar rats were randomized into two groups of 40, pair-fed with alcoholic or non-alcoholic nutrition. Nutrition was withdrawn and microdialysis was performed to measure the activity of amino acids in the NAcc. The onset time of the withdrawal syndrome was first determined in an experiment with 20 rats. Sixty rats then received isoflurane, sevoflurane, or desflurane anesthesia for three hours during the withdrawal period, followed by one hour of elimination. Amino acid concentrations were measured using chromatography and results were compared to baseline levels measured prior to induction of anesthesia. Results Glutamate release increased in the alcohol group at five hours after the last alcohol intake (p = 0.002). After 140 min, desflurane anesthesia led to a lower release of glutamate (p < 0.001) and aspartate (p = 0.0007) in AWR compared to controls. GABA release under and after desflurane anesthesia was also significantly lower in AWR than controls (p = 0.023). Over the course of isoflurane anesthesia, arginine release decreased in AWR compared to controls (p < 0.001), and aspartate release increased after induction relative to controls (p20min = 0.015 and p40min = 0.006). However, amino acid levels did not differ between the groups as a result of sevoflurane anesthesia. Conclusions Each of three volatile anesthetics we studied showed different effects on excitatory and inhibitory amino acid concentrations. Under desflurane anesthesia, both glutamate and aspartate showed a tendency to be lower in AWR than controls over the whole timecourse. The inhibitory amino acid arginine increased in AWR compared to controls, whereas GABA levels decreased. However, there were no significant differences in amino acid concentrations under or after sevoflurane anesthesia. Under isoflurane, aspartate release increased in AWR following induction, and from 40 min to 140 min arginine release in controls was elevated. The precise mechanisms through which each of the volatile anesthetics affected amino acid concentrations are still unclear and further experimental research is required to draw reliable conclusions. PMID:28045949

Influence of Volatile Anesthesia on the Release of Glutamate and other Amino Acids in the Nucleus Accumbens in a Rat Model of Alcohol Withdrawal: A Pilot Study.

PubMed

Seidemann, Thomas; Spies, Claudia; Morgenstern, Rudolf; Wernecke, Klaus-Dieter; Netzhammer, Nicolai

2017-01-01

Alcohol withdrawal syndrome is a potentially life-threatening condition, which can occur when patients with alcohol use disorders undergo general anesthesia. Excitatory amino acids, such as glutamate, act as neurotransmitters and are known to play a key role in alcohol withdrawal syndrome. To understand this process better, we investigated the influence of isoflurane, sevoflurane, and desflurane anesthesia on the profile of excitatory and inhibitory amino acids in the nucleus accumbens (NAcc) of alcohol-withdrawn rats (AWR). Eighty Wistar rats were randomized into two groups of 40, pair-fed with alcoholic or non-alcoholic nutrition. Nutrition was withdrawn and microdialysis was performed to measure the activity of amino acids in the NAcc. The onset time of the withdrawal syndrome was first determined in an experiment with 20 rats. Sixty rats then received isoflurane, sevoflurane, or desflurane anesthesia for three hours during the withdrawal period, followed by one hour of elimination. Amino acid concentrations were measured using chromatography and results were compared to baseline levels measured prior to induction of anesthesia. Glutamate release increased in the alcohol group at five hours after the last alcohol intake (p = 0.002). After 140 min, desflurane anesthesia led to a lower release of glutamate (p < 0.001) and aspartate (p = 0.0007) in AWR compared to controls. GABA release under and after desflurane anesthesia was also significantly lower in AWR than controls (p = 0.023). Over the course of isoflurane anesthesia, arginine release decreased in AWR compared to controls (p < 0.001), and aspartate release increased after induction relative to controls (p20min = 0.015 and p40min = 0.006). However, amino acid levels did not differ between the groups as a result of sevoflurane anesthesia. Each of three volatile anesthetics we studied showed different effects on excitatory and inhibitory amino acid concentrations. Under desflurane anesthesia, both glutamate and aspartate showed a tendency to be lower in AWR than controls over the whole timecourse. The inhibitory amino acid arginine increased in AWR compared to controls, whereas GABA levels decreased. However, there were no significant differences in amino acid concentrations under or after sevoflurane anesthesia. Under isoflurane, aspartate release increased in AWR following induction, and from 40 min to 140 min arginine release in controls was elevated. The precise mechanisms through which each of the volatile anesthetics affected amino acid concentrations are still unclear and further experimental research is required to draw reliable conclusions.

Injectable nanocomposite cryogels for versatile protein drug delivery.

PubMed

Koshy, Sandeep T; Zhang, David K Y; Grolman, Joshua M; Stafford, Alexander G; Mooney, David J

2018-01-01

Sustained, localized protein delivery can enhance the safety and activity of protein drugs in diverse disease settings. While hydrogel systems are widely studied as vehicles for protein delivery, they often suffer from rapid release of encapsulated cargo, leading to a narrow duration of therapy, and protein cargo can be denatured by incompatibility with the hydrogel crosslinking chemistry. In this work, we describe injectable nanocomposite hydrogels that are capable of sustained, bioactive, release of a variety of encapsulated proteins. Injectable and porous cryogels were formed by bio-orthogonal crosslinking of alginate using tetrazine-norbornene coupling. To provide sustained release from these hydrogels, protein cargo was pre-adsorbed to charged Laponite nanoparticles that were incorporated within the walls of the cryogels. The presence of Laponite particles substantially hindered the release of a number of proteins that otherwise showed burst release from these hydrogels. By modifying the Laponite content within the hydrogels, the kinetics of protein release could be precisely tuned. This versatile strategy to control protein release simplifies the design of hydrogel drug delivery systems. Here we present an injectable nanocomposite hydrogel for simple and versatile controlled release of therapeutic proteins. Protein release from hydrogels often requires first entrapping the protein in particles and embedding these particles within the hydrogel to allow controlled protein release. This pre-encapsulation process can be cumbersome, can damage the protein's activity, and must be optimized for each protein of interest. The strategy presented in this work simply premixes the protein with charged nanoparticles that bind strongly with the protein. These protein-laden particles are then placed within a hydrogel and slowly release the protein into the surrounding environment. Using this method, tunable release from an injectable hydrogel can be achieved for a variety of proteins. This strategy greatly simplifies the design of hydrogel systems for therapeutic protein release applications. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Encapsulation of Naproxen in Lipid-Based Matrix Microspheres: Characterization and Release Kinetics

PubMed Central

Bhoyar, PK; Morani, DO; Biyani, DM; Umekar, MJ; Mahure, JG; Amgaonkar, YM

2011-01-01

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. PMID:21731354

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

PubMed

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.

Effects of artemisinin sustained-release granules on mixed alga growth and microcystins production and release.

PubMed

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

2015-12-01

To safely and effectively apply artemisinin sustained-release granules to control and prevent algal water-blooms, the effects of artemisinin and its sustained-release granules on freshwater alga (Scenedesmus obliquus (S. obliquus) and Microcystis aeruginosa (M. aeruginosa)), as well as the production and release of microcystins (MCs) were studied. The results showed that artemisinin sustained-release granules inhibited the growth of M. aeruginosa (above 95% IR) and S. obliquus (about 90% IR), with M. aeruginosa more sensitive. The artemisinin sustained-release granules had a longer inhibition effect on growth of pure algae and algal coexistence than direct artemisinin dosing. The artemisinin sustained-release granules could decrease the production and release of algal toxins due to the continued stress of artemisinin released from artemisinin sustained-release granules. There was no increase in the total amount of MC-LR in the algal cell culture medium.

Modeling CICR in rat ventricular myocytes: voltage clamp studies

PubMed Central

2010-01-01

Background The past thirty-five years have seen an intense search for the molecular mechanisms underlying calcium-induced calcium-release (CICR) in cardiac myocytes, with voltage clamp (VC) studies being the leading tool employed. Several VC protocols including lowering of extracellular calcium to affect Ca2+ loading of the sarcoplasmic reticulum (SR), and administration of blockers caffeine and thapsigargin have been utilized to probe the phenomena surrounding SR Ca2+ release. Here, we develop a deterministic mathematical model of a rat ventricular myocyte under VC conditions, to better understand mechanisms underlying the response of an isolated cell to calcium perturbation. Motivation for the study was to pinpoint key control variables influencing CICR and examine the role of CICR in the context of a physiological control system regulating cytosolic Ca2+ concentration ([Ca2+]myo). Methods The cell model consists of an electrical-equivalent model for the cell membrane and a fluid-compartment model describing the flux of ionic species between the extracellular and several intracellular compartments (cell cytosol, SR and the dyadic coupling unit (DCU), in which resides the mechanistic basis of CICR). The DCU is described as a controller-actuator mechanism, internally stabilized by negative feedback control of the unit's two diametrically-opposed Ca2+ channels (trigger-channel and release-channel). It releases Ca2+ flux into the cyto-plasm and is in turn enclosed within a negative feedback loop involving the SERCA pump, regulating[Ca2+]myo. Results Our model reproduces measured VC data published by several laboratories, and generates graded Ca2+ release at high Ca2+ gain in a homeostatically-controlled environment where [Ca2+]myo is precisely regulated. We elucidate the importance of the DCU elements in this process, particularly the role of the ryanodine receptor in controlling SR Ca2+ release, its activation by trigger Ca2+, and its refractory characteristics mediated by the luminal SR Ca2+ sensor. Proper functioning of the DCU, sodium-calcium exchangers and SERCA pump are important in achieving negative feedback control and hence Ca2+ homeostasis. Conclusions We examine the role of the above Ca2+ regulating mechanisms in handling various types of induced disturbances in Ca2+ levels by quantifying cellular Ca2+ balance. Our model provides biophysically-based explanations of phenomena associated with CICR generating useful and testable hypotheses. PMID:21062495

Impact of early salmon louse, Lepeophtheirus salmonis, infestation and differences in survival and marine growth of sea-ranched Atlantic salmon, Salmo salar L., smolts 1997–2009

PubMed Central

Skilbrei, O T; Finstad, B; Urdal, K; Bakke, G; Kroglund, F; Strand, R

2013-01-01

The impact of salmon lice on the survival of migrating Atlantic salmon smolts was studied by comparing the adult returns of sea-ranched smolts treated for sea lice using emamectin benzoate or substance EX with untreated control groups in the River Dale in western Norway. A total of 143 500 smolts were released in 35 release groups in freshwater from 1997 to 2009 and in the fjord system from 2007 to 2009. The adult recaptures declined gradually with release year and reached minimum levels in 2007. This development corresponded with poor marine growth and increased age at maturity of ranched salmon and in three monitored salmon populations and indicated unfavourable conditions in the Norwegian Sea. The recapture rate of treated smolts was significantly higher than the controls in three of the releases performed: the only release in 1997, one of three in 2002 and the only group released in sea water in 2007. The effect of treating the smolts against salmon lice was smaller than the variability in return rates between release groups, and much smaller that variability between release years, but its overall contribution was still significant (P < 0.05) and equivalent to an odds ratio of the probability of being recaptured of 1.17 in favour of the treated smolts. Control fish also tended to be smaller as grilse (P = 0.057), possibly due to a sublethal effect of salmon lice. PMID:23311746

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

NASA Astrophysics Data System (ADS)

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.

Bioinspired nanovalves with selective permeability and pH sensitivity

NASA Astrophysics Data System (ADS)

Zheng, Z.; Huang, X.; Schenderlein, M.; Moehwald, H.; Xu, G.-K.; Shchukin, D. G.

2015-01-01

Biological systems with controlled permeability and release functionality, which are among the successful examples of living beings to survive in evolution, have attracted intensive investigation and have been mimicked due to their broad spectrum of applications. We present in this work, for the first time, an example of nuclear pore complexes (NPCs)-inspired controlled release system that exhibits on-demand release of angstrom-sized molecules. We do so in a cost-effective way by stabilizing porous cobalt basic carbonates as nanovalves and realizing pH-sensitive release of entrapped subnano cargo. The proof-of-concept work also consists of the establishment of two mathematical models to explain the selective permeability of the nanovalves. Finally, gram-sized (or larger) quantities of the bio-inspired controlled release system can be synthesized through a scaling-up strategy, which opens up opportunities for controlled release of functional molecules in wider practical applications.Biological systems with controlled permeability and release functionality, which are among the successful examples of living beings to survive in evolution, have attracted intensive investigation and have been mimicked due to their broad spectrum of applications. We present in this work, for the first time, an example of nuclear pore complexes (NPCs)-inspired controlled release system that exhibits on-demand release of angstrom-sized molecules. We do so in a cost-effective way by stabilizing porous cobalt basic carbonates as nanovalves and realizing pH-sensitive release of entrapped subnano cargo. The proof-of-concept work also consists of the establishment of two mathematical models to explain the selective permeability of the nanovalves. Finally, gram-sized (or larger) quantities of the bio-inspired controlled release system can be synthesized through a scaling-up strategy, which opens up opportunities for controlled release of functional molecules in wider practical applications. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr06378c

Preparation and characterization of metoprolol tartrate containing matrix type transdermal drug delivery system.

PubMed

Malipeddi, Venkata Ramana; Awasthi, Rajendra; Ghisleni, Daniela Dal Molim; de Souza Braga, Marina; Kikuchi, Irene Satiko; de Jesus Andreoli Pinto, Terezinha; Dua, Kamal

2017-02-01

The present study aimed to develop matrix-type transdermal drug delivery system (TDDS) of metoprolol tartrate using polyvinyl pyrrolidone (PVP) and polyvinyl alcohol (PVA). The transdermal films were evaluated for physical parameters, Fourier transform infrared spectroscopy analysis (FTIR), differential scanning calorimetry (DSC), in vitro drug release, in vitro skin permeability, skin irritation test and stability studies. The films were found to be tough, non-sticky, easily moldable and possess good tensile strength. As the concentration of PVA was increased, the tensile strength of the films was also increased. Results of FTIR spectroscopy and DSC revealed the absence of any drug-polymer interactions. In vitro release of metoprolol followed zero-order kinetics and the mechanism of release was found to be diffusion rate controlled. In vitro release studies of metoprolol using Keshary-Chein (vertical diffusion cell) indicated 65.5 % drug was released in 24 h. In vitro skin permeation of metoprolol transdermal films showed 58.13 % of the drug was released after 24 h. In vitro skin permeation of metoprolol followed zero-order kinetics in selected formulations. The mechanism of release was found to be diffusion rate controlled. In a 22-day skin irritation test, tested formulation of transdermal films did not exhibit any allergic reactions, inflammation, or contact dermatitis. The transdermal films showed good stability in the 180-day stability study. It can be concluded that the TDDS of MPT can help in bypassing the first-pass effect and will provide patient improved compliance, without sacrificing the therapeutic advantages of the drugs.

Microgels produced using microfluidic on-chip polymer blending for controlled released of VEGF encoding lentivectors.

PubMed

Madrigal, Justin L; Sharma, Shonit N; Campbell, Kevin T; Stilhano, Roberta S; Gijsbers, Rik; Silva, Eduardo A

2018-03-15

Alginate hydrogels are widely used as delivery vehicles due to their ability to encapsulate and release a wide range of cargos in a gentle and biocompatible manner. The release of encapsulated therapeutic cargos can be promoted or stunted by adjusting the hydrogel physiochemical properties. However, the release from such systems is often skewed towards burst-release or lengthy retention. To address this, we hypothesized that the overall magnitude of burst release could be adjusted by combining microgels with distinct properties and release behavior. Microgel suspensions were generated using a process we have termed on-chip polymer blending to yield composite suspensions of a range of microgel formulations. In this manner, we studied how alginate percentage and degradation relate to the release of lentivectors. Whereas changes in alginate percentage had a minimal impact on lentivector release, microgel degradation led to a 3-fold increase, and near complete release, over 10 days. Furthermore, by controlling the amount of degradable alginate present within microgels the relative rate of release can be adjusted. A degradable formulation of microgels was used to deliver vascular endothelial growth factor (VEGF)-encoding lentivectors in the chick chorioallantoic membrane (CAM) assay and yielded a proangiogenic response in comparison to the same lentivectors delivered in suspension. The utility of blended microgel suspensions may provide an especially appealing platform for the delivery of lentivectors or similarly sized therapeutics. Genetic therapeutics hold considerable potential for the treatment of diseases and disorders including ischemic cardiovascular diseases. To realize this potential, genetic vectors must be precisely and efficiently delivered to targeted regions of the body. However, conventional methods of delivery do not provide sufficient spatial and temporal control. Here, we demonstrate how alginate microgels provide a basis for developing systems for controlled genetic vector release. We adjust the physiochemical properties of alginate for quicker or slower release, and we demonstrate how combining distinct formulations of microgels can tune the release of the overall composite microgel suspension. These composite suspensions are generated using a straightforward and powerful application of droplet microfluidics which allows for the real-time generation of a composite suspension. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Development and experimental design of a novel controlled-release matrix tablet formulation for indapamide hemihydrate.

PubMed

Antovska, Packa; Ugarkovic, Sonja; Petruševski, Gjorgji; Stefanova, Bosilka; Manchevska, Blagica; Petkovska, Rumenka; Makreski, Petre

2017-11-01

Development, experimental design and in vitro in vivo correlation (IVIVC) of controlled-release matrix formulation. Development of novel oral controlled delivery system for indapamide hemihydrate, optimization of the formulation by experimental design and evaluation regarding IVIVC on a pilot scale batch as a confirmation of a well-established formulation. In vitro dissolution profiles of controlled-release tablets of indapamide hemihydrate from four different matrices had been evaluated in comparison to the originator's product Natrilix (Servier) as a direction for further development and optimization of a hydroxyethylcellulose-based matrix controlled-release formulation. A central composite factorial design had been applied for the optimization of a chosen controlled-release tablet formulation. The controlled-release tablets with appropriate physical and technological properties had been obtained with a matrix: binder concentration variations in the range: 20-40w/w% for the matrix and 1-3w/w% for the binder. The experimental design had defined the design space for the formulation and was prerequisite for extraction of a particular formulation that would be a subject for transfer on pilot scale and IVIV correlation. The release model of the optimized formulation has shown best fit to the zero order kinetics depicted with the Hixson-Crowell erosion-dependent mechanism of release. Level A correlation was obtained.

An integrated system for dissolution studies and magnetic resonance imaging of controlled release, polymer-based dosage forms-a tool for quantitative assessment of hydrogel formation processes.

PubMed

Kulinowski, Piotr; Dorozyński, Przemysław; Jachowicz, Renata; Weglarz, Władysław P

2008-11-04

Controlled release (CR) dosage forms are often based on polymeric matrices, e.g., sustained-release tablets and capsules. It is crucial to visualise and quantify processes of the hydrogel formation during the standard dissolution study. A method for imaging of CR, polymer-based dosage forms during dissolution study in vitro is presented. Imaging was performed in a non-invasive way by means of the magnetic resonance imaging (MRI). This study was designed to simulate in vivo conditions regarding temperature, volume, state and composition of dissolution media. Two formulations of hydrodynamically balanced systems (HBS) were chosen as model CR dosage forms. HBS release active substance in stomach while floating on the surface of the gastric content. Time evolutions of the diffusion region, hydrogel formation region and "dry core" region were obtained during a dissolution study of L-dopa as a model drug in two simulated gastric fluids (i.e. in fed and fasted state). This method seems to be a very promising tool for examining properties of new formulations of CR, polymer-based dosage forms or for comparison of generic and originator dosage forms before carrying out bioequivalence studies.

Design of a long-term antipsychotic in situ forming implant and its release control method and mechanism.

PubMed

Wang, Lexi; Wang, Aiping; Zhao, Xiaolei; Liu, Ximing; Wang, Dan; Sun, Fengying; Li, Youxin

2012-05-10

Two kinds of in situ forming implants (ISFIs) of atypical antipsychotics, risperidone and its 9-hydroxy active metabolite, paliperidone, using poly(lactide-co-glycolide)(PLGA) as carrier, were investigated. Significant difference was observed in the solution-gel transition mechanism of the two systems: homogeneous system of N-methyl-2-pyrrolidone (NMP) ISFI, in which drug was dissolved, and heterogeneous system of dimethyl sulfoxide (DMSO) ISFI, in which drug was dispersed. Fast solvent extractions were found in both systems, but in comparison with the high drug release rate from homogeneous system of drug/polymer/NMP, a fast solvent extraction from the heterogeneous system of drug/polymer/DMSO was not accompanied by a high drug release rate but a rapid solidification of the implant, which resulted in a high drug retention, well-controlled initial burst and slow release of the drug. In vivo study on beagle dogs showed a more than 3-week sustained release with limited initial burst. Pharmacologic evaluation on optimized paliperidone ISFIs presented a sustained-suppressing effect from 1 day to 38 day on the MK-801 induced schizophrenic behavior mice model. A long sustained-release antipsychotic ISFI of 50% drug loading and controlled burst release was achieved, which indicated a good potential in clinic application. Copyright © 2012 Elsevier B.V. All rights reserved.

Tabletted microspheres containing Cynara scolymus (var. Spinoso sardo) extract for the preparation of controlled release nutraceutical matrices.

PubMed

Gavini, E; Alamanni, M C; Cossu, M; Giunchedi, P

2005-08-01

Controlled release dosage forms based on tabletted microspheres containing fresh artichoke Cynara scolymus extract were performed for the oral administration of a nutritional supplement. Microspheres were prepared using a spray-drying technique; lactose or hypromellose have been chosen as excipients. Microspheres were characterized in terms of encapsulated extract content, size and morphology. Qualitative and quantitative composition of the extract before and after the spray process was determined. Compressed matrices (tablets) were prepared by direct compression of the spray-dried microspheres. In vitro release tests of microparticles and tablets prepared were carried out in both acidic and neutral media. Spray-drying is a good method to prepare microspheres containing the artichoke extract. The microspheres encapsulate an amount of extract close to the theoretical value. Particle size analyses indicate that the microparticles have dvs of approximately 6-7 microm. Electronic microscopy observations reveal that particles based on lactose have spherical shape and particles containing hypromellose are almost collapsed. The hydroalcoholic extract is stable to the microsphere production process: its polyphenolic composition (qualitative and quantitative) did not change after spraying. In vitro release studies show that microparticles characterized by a quick polyphenolic release both in acidic and neutral media due to the high water solubility of the carrier lactose. On the contrary, microspheres based hypromellose release only 20% of the loaded extract at pH 1.2 in 2 h and the total amount of polyphenols is released only after about further 6 h at pH 6.8. Matrices prepared tabletting lactose microspheres and hypromellose microparticles in the weight ratio 1:1 show a slow release rate, that lasts approximately 24 h. This one-a-day sustained release formulation containing Cynara scolymus extract could be proposed as a nutraceutical controlled release dosage form for oral administration.

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

PubMed

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 release from aspirin based linear biodegradable poly(anhydride esters) for anti-inflammatory activity.

PubMed

Dasgupta, Queeny; Movva, Sahitya; Chatterjee, Kaushik; Madras, Giridhar

2017-08-07

This work reports the synthesis of a novel, aspirin-loaded, linear poly (anhydride ester) and provides mechanistic insights into the release of aspirin from this polymer for anti-inflammatory activity. As compared to conventional drug delivery systems that rely on diffusion based release, incorporation of bioactives in the polymer backbone is challenging and high loading is difficult to achieve. In the present study, we exploit the pentafunctional sugar alcohol (xylitol) to provide sites for drug (aspirin) attachment at its non-terminal OH groups. The terminal OH groups are polymerized with a diacid anhydride. The hydrolysis of the anhydride and ester bonds under physiological conditions release aspirin from the matrix. The resulting poly(anhydride ester) has high drug loading (53%) and displays controlled release kinetics of aspirin. The polymer releases 8.5 % and 20%, of the loaded drug in one and four weeks, respectively and has a release rate constant of 0.0035h -0.61 . The release rate is suitable for its use as an anti-inflammatory agent without being cytotoxic. The polymer exhibits good cytocompatibility and anti-inflammatory properties and may find applications as injectable or as an implantable bioactive material. The physical insights into the release mechanism can provide development of other drug loaded polymers. Copyright © 2017 Elsevier B.V. All rights reserved.

In situ monitoring of intracellular controlled drug release from mesoporous silica nanoparticles coated with pH-responsive charge-reversal polymer.

PubMed

Zhang, Peng; Wu, Tong; Kong, Ji-Lie

2014-10-22

Therapeutic platforms such as chemotherapy that respond to physical and biological stimuli are highly desirable for effective cancer therapy. In this study, pH-responsive charge-reversal, polymer-coated mesoporous silica nanoparticles [PAH-cit/APTES-MSNs; PAH-cit refers to poly(allylamine)-citraconic anhydride; APTES refers to (3-aminopropyl)triethoxysilane] were synthesized for application as drug-delivery systems for the treatment of malignant cells. Confocal laser scanning microscopy (CLSM) revealed that the PAH-cit/APTES-MSNs nanocomposite effectively delivered and released doxorubicin hydrochloride to the nucleus of HeLa (human cervical carcinoma) cells. Additionally, the real-time dynamic drug-release process was monitored by CLSM. The current pH-controlled-smart-release platform holds promise in drug-delivery and cancer therapy-related applications.

PHYSICAL AND CHEMICAL CONTROL OF RELEASED MICROORGANISMS AT FIELD SITES

EPA Science Inventory

An important consideration in the environmental release of a genetically engineered microorganism (GEM) is the capability for reduction or elimination of GEM populations once their function is completed or if adverse environmental effects are observed. In this study the decontami...

Chitosan-starch beads prepared by ionotropic gelation as potential matrices for controlled release of fertilizers.

PubMed

Perez, Jonas J; Francois, Nora J

2016-09-05

The present study examines the agrochemical application of macrospheres prepared with chitosan and chitosan-starch blends by an easy dripping technique, using a sodium tripolyphosphate aqueous solution as the crosslinking agent. These biopolymers form hydrogels that could be a viable alternative method to obtain controlled-release fertilizers (CRFs). Three different concentrations (ranging from 20 to 100wt/wt% of chitosan) and two crosslinking times (2 or 4h) were used. The resulting polymeric matrices were examined by scanning electron microscopy coupled with energy dispersive X-ray, X-ray diffraction, Fourier transform infrared spectroscopy, solid-state nuclear magnetic resonance, thermogravimetric analysis and differential scanning calorimetry. Ionotropic gelation and neutralization induced the formation of the macrospheres. The crosslinking time and the composition of the polymeric hydrogel controlled the crosslinking degree, the swelling behavior and the fertilizer loading capability. Potassium nitrate-loaded beads were shown to be useful as a controlled-release fertilizer. After 14days of continuous release into distilled water, the cumulative concentration in the release medium reached between 70 and 93% of the initially loaded salt, depending on the matrix used. The prepared beads showed properties that make them suitable for use in the agrochemical industry as CRFs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Controlled drug delivery systems: past forward and future back.

PubMed

Park, Kinam

2014-09-28

Controlled drug delivery technology has progressed over the last six decades. This progression began in 1952 with the introduction of the first sustained release formulation. The 1st generation of drug delivery (1950-1980) focused on developing oral and transdermal sustained release systems and establishing controlled drug release mechanisms. The 2nd generation (1980-2010) was dedicated to the development of zero-order release systems, self-regulated drug delivery systems, long-term depot formulations, and nanotechnology-based delivery systems. The latter part of the 2nd generation was largely focused on studying nanoparticle formulations. The Journal of Controlled Release (JCR) has played a pivotal role in the 2nd generation of drug delivery technologies, and it will continue playing a leading role in the next generation. The best path towards a productive 3rd generation of drug delivery technology requires an honest, open dialog without any preconceived ideas of the past. The drug delivery field needs to take a bold approach to designing future drug delivery formulations primarily based on today's necessities, to produce the necessary innovations. The JCR provides a forum for sharing the new ideas that will shape the 3rd generation of drug delivery technology. Copyright © 2014 Elsevier B.V. All rights reserved.

Evaluation of urinary catheters coated with sustained-release varnish of chlorhexidine in mitigating biofilm formation on urinary catheters in dogs.

PubMed

Segev, G; Bankirer, T; Steinberg, D; Duvdevani, M; Shapur, N K; Friedman, M; Lavy, E

2013-01-01

Biofilm formation occurs commonly on urinary catheters. To assess the efficacy of urinary catheters coated with sustained-release varnish of chlorhexidine in decreasing catheter-associated biofilm formation in dogs. Thirty client-owned dogs. Prospective study. Thirteen dogs were catheterized with urinary catheters coated with sustained-release varnish of chlorhexidine (study group), and 13 dogs were catheterized with an untreated urinary catheter (control group). Presence and intensity of biofilm formation on the urinary catheters were assessed and compared between the groups by evaluating colony-forming units (CFU) of biofilm bacteria, and semiquantitatively, using confocal laser scanning microscopy and electron microscopy. None of the dogs experienced adverse effects associated with the presence of the urinary catheters. Median CFU count of biofilm bacteria at all portions of the urinary catheter was significantly (P < .001) lower in the study compared with the control group. The degree of biofilm formation on the urinary catheters, as evaluated by confocal laser scanning microscopy and electron microscopy, was significantly lower in the study compared with the control group. Electron microscopy examination identified crystals on some of the urinary catheters. The proportion of catheters on which crystals were observed was significantly lower on the distal part of the urinary catheter in the study group compared with the control group (16.7% versus 66.7%, respectively; P = .04). Chlorhexidine sustained-release varnish-coated urinary catheters effectively decrease urinary catheter-associated biofilm formation in dogs. Copyright © 2012 by the American College of Veterinary Internal Medicine.

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

PubMed Central

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

2010-01-01

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

Cyclodextrin controlled release of poorly water-soluble drugs from hydrogels.

PubMed

Woldum, Henriette Sie; Larsen, Kim Lambertsen; Madsen, Flemming

2008-01-01

The effect of 2-hydroxypropyl-beta-cyclodextrin and gamma-cyclodextrin on the release of ibuprofen, ketoprofen and prednisolone was studied. Stability constants calculated for inclusion complexes show size dependence for complexes with both cyclodextrins. Hydrogels were prepared by ultraviolet irradiation and release of each model drug was studied. For drugs formulated using cyclodextrins an increase in the achievable concentration and in the release from hydrogels was obtained due to increased solubility, although the solubility of all gamma-cyclodextrin complexes was limited. The load also was increased by adjusting pH for the acidic drugs and this exceeds the increase obtained with gamma-cyclodextrin addition.

PELA microspheres with encapsulated arginine-chitosan/pBMP-2 nanoparticles induce pBMP-2 controlled-release, transfected osteoblastic progenitor cells, and promoted osteogenic differentiation.

PubMed

Xu, Xiaolong; Qiu, Sujun; Zhang, Yuxian; Yin, Jie; Min, Shaoxiong

2017-03-01

Repair of the bone injury remains a challenge in clinical practices. Recent progress in tissue engineering and therapeutic gene delivery systems have led to promising new strategies for successful acceleration of bone repair process. The aim of this study was to create a controlled-release system to slowly release the arginine-chitosan/plasmid DNA nanoparticles encoding BMP-2 gene (Arg-CS/pBMP-2 NPs), efficiently transfect osteoblastic progenitor cells, secrete functional BMP-2 protein, and promote osteogenic differentiation. In this study, chitosan was conjugated with arginine to generate arginine-chitosan polymer (Arg-CS) for gene delivery. Mix the Arg-CS with pBMP-2 to condense pBMP-2 into nano-sized particles. In vitro transfection assays demonstrated that the transfection efficiency of Arg-CS/pBMP-2 nanoparticles and the expression level of BMP-2 was obviously exceed control groups. Further, PELA microspheres as the controlled-release carrier for the nanoparticles were used to encapsulate Arg-CS/pBMP-2 NPs. We demonstrated that the Arg-CS/pBMP-2 NPs could slowly release from the PELA microspheres at least for 42 d. During the co-culture with the PELA microspheres, the content of BMP-2 protein secreted by MC3T3-E1 reached the peak at 7 d. After 21d, the secretion of BMP-2 protein still maintain a higher level. The alkaline phosphatase activity, alizarin red staining, and osteogenesis-related gene expression by real-time quantitative PCR analysis all showed the PELA microspheres entrapping with Arg-CS/pBMP-2 NPs can obviously induce the osteogenic differentiation. The results indicated that the Arg-CS is a suitable gene vector which can promote the gene transfection. And the novel PELA microspheres-nanoparticle controlled-release system has potential clinical application in the future after further research.

pH-sensitive inulin-based nanomicelles for intestinal site-specific and controlled release of celecoxib.

PubMed

Mandracchia, Delia; Trapani, Adriana; Perteghella, Sara; Sorrenti, Milena; Catenacci, Laura; Torre, Maria Luisa; Trapani, Giuseppe; Tripodo, Giuseppe

2018-02-01

Aiming at a site-specific drug release in the lower intestinal tract, this paper deals with the synthesis and physicochemical/biological characterization of pH-sensitive nanomicelles from an inulin (INU) amphiphilic derivative. To allow an intestinal site specific release of the payload, INU-Vitamin E (INVITE) bioconjugates were functionalized with succinic anhydride to provide the system with pH-sensitive groups preventing a premature release of the payload into the stomach. The obtained INVITESA micelles resulted nanosized, with a low critical aggregation concentration and the release studies showed a marked pH-dependent release. The drug loading stabilized the micelles against the acidic hydrolysis. From transport studies on Caco-2 cells, resulted that INVITESA nanomicelles cross the cellular monolayer but are actively re-transported in the secretory (basolateral-apical) direction when loaded in apical side. It suggests that the entrapped drug could not be absorbed before the release from the micelles, enabling so a local release of the active. Copyright © 2017 Elsevier Ltd. All rights reserved.

Monoamine Release during Unihemispheric Sleep and Unihemispheric Waking in the Fur Seal

PubMed Central

Lyamin, Oleg I.; Lapierre, Jennifer L.; Kosenko, Peter O.; Kodama, Tohru; Bhagwandin, Adhil; Korneva, Svetlana M.; Peever, John H.; Mukhametov, Lev M.; Siegel, Jerome M.

2016-01-01

Study Objectives: Our understanding of the role of neurotransmitters in the control of the electroencephalogram (EEG) has been entirely based on studies of animals with bilateral sleep. The study of animals with unihemispheric sleep presents the opportunity of separating the neurochemical substrates of waking and sleep EEG from the systemic, bilateral correlates of sleep and waking states. Methods: The release of histamine (HI), norepinephrine (NE), and serotonin (5HT) in cortical and subcortical areas (hypothalamus, thalamus and caudate nucleus) was measured in unrestrained northern fur seals (Callorhinus ursinus) using in vivo microdialysis, in combination with, polygraphic recording of EEG, electrooculogram, and neck electromyogram. Results: The pattern of cortical and subcortical HI, NE, and 5HT release in fur seals is similar during bilaterally symmetrical states: highest in active waking, reduced in quiet waking and bilateral slow wave sleep, and lowest in rapid eye movement (REM) sleep. Cortical and subcortical HI, NE, and 5HT release in seals is highly elevated during certain waking stimuli and behaviors, such as being sprayed with water and feeding. However, in contrast to acetylcholine (ACh), which we have previously studied, the release of HI, NE, and 5HT during unihemispheric sleep is not lateralized in the fur seal. Conclusions: Among the studied neurotransmitters most strongly implicated in waking control, only ACh release is asymmetric in unihemispheric sleep and waking, being greatly increased on the activated side of the brain. Commentary: A commentary on this article appears in this issue on page 491. Citation: Lyamin OI, Lapierre JL, Kosenko PO, Kodama T, Bhagwandin A, Korneva SM, Peever JH, Mukhametov LM, Siegel JM. Monoamine release during unihemispheric sleep and unihemispheric waking in the fur seal. SLEEP 2016;39(3):625–636. PMID:26715233

Synthesis and characterization of pharmaceutical surfactant templated mesoporous silica: Its application to controlled delivery of duloxetine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mani, Ganesh; Pushparaj, Hemalatha; Peng, Mei Mei

2014-03-01

Graphical abstract: - Highlights: • Usefulness of dual pharmaceutical surfactants in silica synthesis was evaluated. • Effects of concentration of secondary template (Tween-40) were studied. • Effects of fixed solvothermal condition on mesostructure formation were studied. • Duloxetine drug loading capability was studied. • Sustained release of duloxetine was evaluated. - Abstract: A new group of mesoporous silica nanoparticles (MSNs) were synthesized using combination pharmaceutical surfactants, Triton X-100 and Tween-40 as template and loaded with duloxetine hydrochloride (DX), for improving the sustained release of DX and patterns with high drug loading. Agglomerated spherical silica MSNs were synthesized by sol–gel andmore » solvothermal methods. The calcined and drug loaded MSNs were characterized using X-ray diffraction (XRD), Braunner–Emmett–Teller (BET), thermogravimetric analysis (TGA), Fourier-transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), diffuse reflectance ultraviolet–visible (DRS-UV–vis) spectroscopy. MSNs with high surface area and pore volume were selected and studied for their DX loading and release. The selected MSNs can accommodate a maximum of 34% DX within it. About 90% was released at 200 h and hence, the synthesized MSNs were capable of engulfing DX and sustain its release. Further form the Ritger and Peppas, Higuchi model for mechanism drug release from all the MSN matrices follows anomalous transport or Non-Fickian diffusion with the ‘r’ and ‘n’ value 0.9 and 0.45 < n < 1, respectively. So, from this study it could be concluded that the MSNs synthesized using pharmaceutical templates were better choice of reservoir for the controlled delivery of drug which requires sustained release.« less

A novel solubility-modulated granules through porosity osmotic pump for controlled carvedilol delivery.

PubMed

Song, Qun-Li; Li, Ping; Li, Yu-Min

2012-01-01

A method for the preparation of porosity osmotic pump granules was obtained by modulating carvedilol solubility with tartaric acid. Controlled porosity of the membrane was accomplished by the use of pore-forming agent in the coating. In this study, carvedilol was chosen as a model drug with an aim to develop a zero-order release system; tartaric acid was used as the solubility promoter; NaCl was used as the osmotic agent; cellulose acetate (CA) was used as the materials of semipermeable membrane; and PEG-400 was used as the pore-forming agent in the semipermeable membrane. The influence of different factors or levels on the in vitro release was studied. In order to simulate the gastrointestinal tract environments, two kinds of pH media (pH 1.5 and 6.8) on drug release were studied in this research, respectively. This porosity osmotic pump was optimized by single factor design experiments, and it was found to deliver carvedilol at a zero-order rate within 12 h and controlled release for 24 h. We drew a conclusion that the solubility-modulated porosity osmotic pump system is simple to prepare and might be used for the preparation of osmotic pump system of other poorly water-soluble drugs with alkaline or acid groups.

Luteinising hormone releasing hormone for incomplete descent of the testis.

PubMed

Klidjian, A M; Swift, P G; Johnstone, J M

1985-06-01

Forty boys with 54 incompletely descended testes took part in a double blind, controlled trial of intranasal luteinising hormone releasing hormone. In the control (placebo) group of 18 boys there was no significant change in testicular descent and all required orchidopexy; in the 22 treated boys, however, 12 of 29 testes (42%) were found in a lower position. This study supports the idea that a trial of intranasal luteinising hormone releasing hormone (1200 micrograms/day for 28 days) will help clarify the need for orchidopexy in at least 30% of boys with incomplete descent of the testis, particularly those in whom the testes have emerged from the inguinal canal.

Doxorubicin Release Controlled by Induced Phase Separation and Use of a Co-Solvent.

PubMed

Park, Seok Chan; Yuan, Yue; Choi, Kyoungju; Choi, Seong-O; Kim, Jooyoun

2018-04-26

Electrospun-based drug delivery is emerging as a versatile means of localized therapy; however, controlling the release rates of active agents still remains as a key question. We propose a facile strategy to control the drug release behavior from electrospun fibers by a simple modification of polymer matrices. Polylactic acid (PLA) was used as a major component of the drug-carrier, and doxorubicin hydrochloride (Dox) was used as a model drug. The influences of a polar co-solvent, dimethyl sulfoxide (DMSO), and a hydrophilic polymer additive, polyvinylpyrrolidone (PVP), on the drug miscibility, loading efficiency and release behavior were investigated. The use of DMSO enabled the homogeneous internalization of the drug as well as higher drug loading efficiency within the electrospun fibers. The PVP additive induced phase separation in the PLA matrix and acted as a porogen. Preferable partitioning of Dox into the PVP domain resulted in increased drug loading efficiency in the PLA/PVP fiber. Fast dissolution of PVP domains created pores in the fibers, facilitating the release of internalized Dox. The novelty of this study lies in the detailed experimental investigation of the effect of additives in pre-spinning formulations, such as co-solvents and polymeric porogens, on the drug release behavior of nanofibers.

Doxorubicin Release Controlled by Induced Phase Separation and Use of a Co-Solvent

PubMed Central

Park, Seok Chan; Choi, Kyoungju; Choi, Seong-O

2018-01-01

Electrospun-based drug delivery is emerging as a versatile means of localized therapy; however, controlling the release rates of active agents still remains as a key question. We propose a facile strategy to control the drug release behavior from electrospun fibers by a simple modification of polymer matrices. Polylactic acid (PLA) was used as a major component of the drug-carrier, and doxorubicin hydrochloride (Dox) was used as a model drug. The influences of a polar co-solvent, dimethyl sulfoxide (DMSO), and a hydrophilic polymer additive, polyvinylpyrrolidone (PVP), on the drug miscibility, loading efficiency and release behavior were investigated. The use of DMSO enabled the homogeneous internalization of the drug as well as higher drug loading efficiency within the electrospun fibers. The PVP additive induced phase separation in the PLA matrix and acted as a porogen. Preferable partitioning of Dox into the PVP domain resulted in increased drug loading efficiency in the PLA/PVP fiber. Fast dissolution of PVP domains created pores in the fibers, facilitating the release of internalized Dox. The novelty of this study lies in the detailed experimental investigation of the effect of additives in pre-spinning formulations, such as co-solvents and polymeric porogens, on the drug release behavior of nanofibers. PMID:29701714

A study on maize proteins as a potential new tablet excipient.

PubMed

Georget, Dominique M R; Barker, Susan A; Belton, Peter S

2008-06-01

This investigation has examined the use of zein proteins from maize as the major component in oral controlled-release tablets, such formulations often being required to improve patient compliance. Tablets containing ground zein proteins, calcium hydrogen orthophosphate, polyvinyl pyrrolidone, theophylline and magnesium stearate were produced by wet granulation and compression on a single station tablet press and were compared to directly compressed tablets based on zein proteins, calcium hydrogen orthophosphate and theophylline. Non invasive techniques such as Fourier Transform infrared spectroscopy and Fourier Transform Raman spectroscopy were employed to investigate any changes in the secondary structure of zein proteins during tablet production. Random coils, alpha helices and beta sheets predominated and their relative content remained unaffected during grinding, wet granulation and compression, indicating that formulations based on zeins will be robust, i.e. insensitive to minor changes in the production conditions. Drug release from the tablets was studied using a standard pharmacopoeial dissolution test. Dissolution profiles in water, 0.1M HCl (pH=1) and phosphate buffer (pH=6.8) show that only a limited amount of theophylline was released after 4.5h, suggesting that zein proteins could act as a potential vehicle for oral controlled drug release. Analysis of the theophylline release profiles using the Peppas and Sahlin model reveals that diffusion and polymer relaxation occurred in acidic (pH=1) and buffered (pH=6.8) conditions for wet granulated tablets, whereas diffusion was predominant in directly compressed tablets. In conclusion, the present study has shown that zeins can be successfully used as a pharmaceutical excipient, and in particular as a matrix in monolithic controlled release tablets.

Chemical release module facility

NASA Technical Reports Server (NTRS)

Reasoner, D. L.

1980-01-01

The chemical release module provides the capability to conduct: (1) thermite based metal vapor releases; (2) pressurized gas releases; (3) dispersed liquid releases; (4) shaped charge releases from ejected submodules; and (5) diagnostic measurements with pi supplied instruments. It also provides a basic R-F and electrical system for: (1) receiving and executing commands; (2) telemetering housekeeping data; (3) tracking; (4) monitoring housekeeping and control units; and (5) ultrasafe disarming and control monitoring.

Poly(ethylene glycol) (PEG)-lactic acid nanocarrier-based degradable hydrogels for restoring the vaginal microenvironment

PubMed Central

Rajan, Sujata Sundara; Turovskiy, Yevgeniy; Singh, Yashveer; Chikindas, Michael L.; Sinko, Patrick J.

2014-01-01

Women with bacterial vaginosis (BV) display reduced vaginal acidity, which make them susceptible to associated infections such as HIV. In the current study, poly(ethylene glycol) (PEG) nanocarrier-based degradable hydrogels were developed for the controlled release of lactic acid in the vagina of BV-infected women. PEG-lactic acid (PEG-LA) nanocarriers were prepared by covalently attaching lactic acid to 8-arm PEG-SH via cleavable thioester bonds. PEG-LA nanocarriers with 4 copies of lactic acid per molecule provided controlled release of lactic acid with a maximum release of 23% and 47% bound lactic acid in phosphate buffered saline (PBS, pH 7.4) and acetate buffer (AB, pH 4.3), respectively. The PEG nanocarrier-based hydrogels were formed by cross-linking the PEG-LA nanocarriers with 4-arm PEG-NHS via degradable thioester bonds. The nanocarrier-based hydrogels formed within 20 min under ambient conditions and exhibited an elastic modulus that was 100-fold higher than the viscous modulus. The nanocarrier-based degradable hydrogels provided controlled release of lactic acid for several hours; however, a maximum release of only 10%–14% bound lactic acid was observed possibly due to steric hindrance of the polymer chains in the cross-linked hydrogel. In contrast, hydrogels with passively entrapped lactic acid showed burst release with complete release within 30 min. Lactic acid showed antimicrobial activity against the primary BV pathogen Gardnerella vaginalis with a minimum inhibitory concentration (MIC) of 3.6 mg/ml. In addition, the hydrogels with passively entrapped lactic acid showed retained antimicrobial activity with complete inhibition G. vaginalis growth within 48 h. The results of the current study collectively demonstrate the potential of PEG nanocarrier-based hydrogels for vaginal administration of lactic acid for preventing and treating BV. PMID:25223229

Nanostructural control of the release of macromolecules from silica sol–gels

PubMed Central

Radin, Shula; Bhattacharyya, Sanjib; Ducheyne, Paul

2013-01-01

The therapeutic use of biological molecules such as growth factors and monoclonal antibodies is challenging in view of their limited half-life in vivo. This has elicited the interest in delivery materials that can protect these molecules until released over extended periods of time. Although previous studies have shown controlled release of biologically functional BMP-2 and TGF-β from silica sol–gels, more versatile release conditions are desirable. This study focuses on the relationship between room temperature processed silica sol–gel synthesis conditions and the nanopore size and size distribution of the sol–gels. Furthermore, the effect on release of large molecules with a size up to 70 kDa is determined. Dextran, a hydrophilic polysaccharide, was selected as a large model molecule at molecular sizes of 10, 40 and 70 kDa, as it enabled us to determine a size effect uniquely without possible confounding chemical effects arising from the various molecules used. Previously, acid catalysis was performed at a pH value of 1.8 below the isoelectric point of silica. Herein the silica synthesis was pursued using acid catalysis at either pH 1.8 or 3.05 first, followed by catalysis at higher values by adding base. This results in a mesoporous structure with an abundance of pores around 3.5 nm. The data show that all molecular sizes can be released in a controlled manner. The data also reveal a unique in vivo approach to enable release of large biological molecules: the use more labile sol–gel structures by acid catalyzing above the pH value of the isoelectric point of silica; upon immersion in a physiological fluid the pores expand to reach an average size of 3.5 nm, thereby facilitating molecular out-diffusion. PMID:23643607

Formulation and in-vitro evaluation of floating bilayer tablet of lisinopril maleate and metoprolol tartrate.

PubMed

Ijaz, Hira; Qureshi, Junaid; Danish, Zeeshan; Zaman, Muhammad; Abdel-Daim, Mohamed; Hanif, Muhammad; Waheed, Imran; Mohammad, Imran Shair

2015-11-01

The purpose of this study was to introduce the technology for the development of rate-controlled oral drug delivery system to overcome various physiological problems. Several approaches are being used for the purpose of increasing the gastric retentive time, including floating drug delivery system. Gastric floating lisinopril maleate and metoprolol tartrate bilayer tablets were formulated by direct compression method using the sodium starch glycolate, crosscarmellose sodium for IR layer. Eudragit L100, pectin, acacia as sustained release polymers in different ratios for SR metoprolol tartrate layer and sodium bicarbonate, citric acid as gas generating agents for the floating extended release layer. The floating bilayer tablets of lisinopril maleate and metoprolol tartrate were designed to overcome the various problems associated with conventional oral dosage form. Floating tablets were evaluated for floating lag time, drug contents and in-vitro dissolution profile and different kinetic release models were applied. It was clear that the different ratios of polymers affected the drug release and floating time. L2 and M4 showed good drug release profile and floating behavior. The linear regression and model fitting showed that all formulation followed Higuchi model of drug release model except M4 that followed zero order kinetic. From the study it is evident that a promising controlled release by floating bilyer tablets of lisinopril maleate and metoprolol tartrate can be developed successfully.

Programming of Multicomponent Temporal Release Profiles in 3D Printed Polypills via Core-Shell, Multilayer, and Gradient Concentration Profiles.

PubMed

Haring, Alexander P; Tong, Yuxin; Halper, Justin; Johnson, Blake N

2018-06-10

Additive manufacturing (AM) appears poised to provide novel pharmaceutical technology and controlled release systems, yet understanding the effects of processing and post-processing operations on pill design, quality, and performance remains a significant barrier. This paper reports a study of the relationship between programmed concentration profile and resultant temporal release profile using a 3D printed polypill system consisting of a Food and Drug Administration (FDA) approved excipient (Pluronic F-127) and therapeutically relevant dosages of three commonly used oral agents for treatment of type 2 diabetes (300-500 mg per pill). A dual-extrusion hydrogel microextrusion process enables the programming of three unique concentration profiles, including core-shell, multilayer, and gradient structures. Experimental and computational studies of diffusive mass transfer processes reveal that programmed concentration profiles are dynamic throughout both pill 3D printing and solidification. Spectrophotometric assays show that the temporal release profiles could be selectively programmed to exhibit delayed, pulsed, or constant profiles over a 5 h release period by utilizing the core-shell, multilayer, and gradient distributions, respectively. Ultimately, this work provides new insights into the mass transfer processes that affect design, quality, and performance of spatially graded controlled release systems, as well as demonstrating the potential to create disease-specific polypill technology with programmable temporal release profiles. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Injectable, in situ forming poly(propylene fumarate)-based ocular drug delivery systems.

PubMed

Ueda, H; Hacker, M C; Haesslein, A; Jo, S; Ammon, D M; Borazjani, R N; Kunzler, J F; Salamone, J C; Mikos, A G

2007-12-01

This study sought to develop an injectable formulation for long-term ocular delivery of fluocinolone acetonide (FA) by dissolving the anti-inflammatory drug and the biodegradable polymer poly(propylene fumarate) (PPF) in the biocompatible, water-miscible, organic solvent N-methyl-2-pyrrolidone (NMP). Upon injection of the solution into an aqueous environment, a FA-loaded PPF matrix is precipitated in situ through the diffusion/extraction of NMP into surrounding aqueous fluids. Fabrication of the matrices and in vitro release studies were performed in phosphate buffered saline at 37 degrees C. Drug loadings up to 5% were achieved. High performance liquid chromatography was employed to determine the released amount of FA. The effects of drug loading, PPF content of the injectable formulation, and additional photo-crosslinking of the matrix surface were investigated. Overall, FA release was sustained in vitro over up to 400 days. After an initial burst release of 22 to 68% of initial FA loading, controlled drug release driven by diffusion and bulk erosion was observed. Drug release rates in a therapeutic range were demonstrated. Release kinetics were found to be dependent on drug loading, formulation PPF content, and extent of surface crosslinking. The results suggest that injectable, in situ formed PPF matrices are promising candidates for the formulation of long-term, controlled delivery devices for intraocular drug delivery. Copyright 2007 Wiley Periodicals, Inc.

Suicide after release from prison - a population-based cohort study from Sweden

PubMed Central

Haglund, Axel; Tidemalm, Dag; Jokinen, Jussi; Långström, Niklas; Liechtenstein, Paul; Fazel, Seena; Runeson, Bo

2015-01-01

Objective Released prisoners have high suicide rates compared with the general population, but little is known about risk factors and possible causal pathways. We conducted a population-based cohort study to investigate rates and risk factors for suicide in people previously imprisoned. Methods We identified individuals released from prison in Sweden between January 1, 2005 and December 31, 2009 through linkage of national population-based registers. Released prisoners were followed from the day of release until death, emigration, new incarceration, or December 31, 2009. Survival analyses were conducted to compare incidence rates and psychiatric morbidity with non-convicted population controls matched on gender and year of birth. Results We identified 38,995 releases among 26,953 prisoners (7.6% females) during 2005-2009. Overall, 127 suicides occurred, accounting for 14% of all deaths after release (n=920). The mean suicide rate was 204 per 100,000 person years yielding an incidence rate ratio of 18.2 (95% CI 13.9-23.8) compared with general population controls. Previous substance use disorder (Hazard Ratio [HR]=2.1, 1.4-3.2), suicide attempt (HR=2.5, 1.7-3.7), and being born in Sweden vs. abroad (HR=2.1, 1.2-3.6) were independent risk factors for suicide after release. Conclusions Released prisoners are at high suicide risk and with a slightly different pattern of psychiatric risk factors for suicide compared with the general population. Results suggest appropriate allocation of resources to facilitate transition to life outside prison and increased attention to prisoners with both a previous suicide attempt and substance use disorder. PMID:25373114

Enhancement of wound closure by modifying dual release patterns of stromal-derived cell factor-1 and a macrophage recruitment agent from gelatin hydrogels.

PubMed

Kim, Yang-Hee; Tabata, Yasuhiko

2017-11-01

The objective of the present study is to evaluate the effects of the release patterns of stromal derived factor (SDF)-1 and sphingosine-1 phosphate agonist (SEW2871), used as MSC and macrophage recruitment agents, on the wound closure of diabetic mouse skin defects. To achieve different release patterns, hydrogels were prepared using two types of gelatin with isoelectric points (IEP) of 5 and 9, into which SDF-1 and SEW2871 were then incorporated in various combinations. When the hydrogels incorporating SDF-1 and SEW2871 were applied into wound defects of diabetic mice, the number of MSCs and macrophages recruited to the defects and the levels of pro- and anti- inflammatory cytokines were found to be dependent on the release profiles of SDF-1 and SEW2871. Of particular interest was the case of a rapid release of SDF-1 combined with a controlled release of SEW2871. This resulted in a higher number of M2 macrophages and gene expression levels of anti-inflammatory cytokines 3 days after implantation and faster wound closure than when pairing the controlled release of SDF-1 with a rapid release of SEW2871. Therefore, the present study demonstrates that different release patterns of SDF-1 and SEW2871 can enhance the in vivo recruitment of MSCs and macrophages, and can promote skin wound closure through the modulation of inflammation. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Design and characterization of Amoitone B-loaded nanostructured lipid carriers for controlled drug release.

PubMed

Luan, Jingjing; Zhang, Dianrui; Hao, Leilei; Li, Caiyun; Qi, Lisi; Guo, Hejian; Liu, Xinquan; Zhang, Qiang

2013-11-01

Amoitone B, a novel compound chemically synthesized as the analogue of cytosporone B, has been proved to own superior affinity with Nur77 than its parent compound and exhibit notable anticancer activity. However, its application is seriously restricted due to the water-insolubility and short biological half-time. The aim of this study was to construct an effective delivery system for Amoitone B to realize sustained release, thus prolong drug circulation time in body and improve the bioavailability. Nanostructured lipid carriers (NLC) act as a new type of colloidal drug delivery system, which offer the advantages of improved drug loading and sustained release. Amoitone B-loaded NLC (AmB-NLC) containing glyceryl monostearate (GMS) and various amounts of medium chain triglycerides (MCT) were successfully prepared by emulsion-evaporation and low temperature-solidification technology with a particle size of about 200 nm and a zeta potential value of about -20 mV. The results of X-ray diffraction and DSC analysis showed amorphous crystalline state of Amoitone B in NLC. Furthermore, the drug entrapment efficacy (EE) was improved compared with solid lipid nanoparticles (SLN). The EE range was from 71.1% to 84.7%, enhanced with the increase of liquid lipid. In vitro drug release studies revealed biphasic drug release patterns with burst release initially and prolonged release afterwards and the release was accelerated with augment of liquid lipid. These results demonstrated that AmB-NLC could be a promising delivery system to control drug release and improve loading capacity, thus prolong drug action time in body and enhance the bioavailability.

pH-controlled drug loading and release from biodegradable microcapsules.

PubMed

Zhao, Qinghe; Li, Bingyun

2008-12-01

Microcapsules made of biopolymers are of both scientific and technological interest and have many potential applications in medicine, including their use as controlled drug delivery devices. The present study makes use of the electrostatic interaction between polycations and polyanions to form a multilayered microcapsule shell and also to control the loading and release of charged drug molecules inside the microcapsule. Micron-sized calcium carbonate (CaCO3) particles were synthesized and integrated with chondroitin sulfate (CS) through a reaction between sodium carbonate and calcium nitrate tetrahydrate solutions suspended with CS macromolecules. Oppositely charged biopolymers were alternately deposited onto the synthesized particles using electrostatic layer-by-layer self-assembly, and glutaraldehyde was introduced to cross-link the multilayered shell structure. Microcapsules integrated with CS inside the multilayered shells were obtained after decomposition of the CaCO3 templates. The integration of a matrix (i.e., CS) permitted the subsequent selective control of drug loading and release. The CS-integrated microcapsules were loaded with a model drug, bovine serum albumin labeled with fluorescein isothiocyanate (FITC-BSA), and it was shown that pH was an effective means of controlling the loading and release of FITC-BSA. Such CS-integrated microcapsules may be used for controlled localized drug delivery as biodegradable devices, which have advantages in reducing systemic side effects and increasing drug efficacy.

Encapsulation of an adamantane-doxorubicin prodrug in pH-responsive polysaccharide capsules for controlled release.

PubMed

Luo, Guo-Feng; Xu, Xiao-Ding; Zhang, Jing; Yang, Juan; Gong, Yu-Hui; Lei, Qi; Jia, Hui-Zhen; Li, Cao; Zhuo, Ren-Xi; Zhang, Xian-Zheng

2012-10-24

Supramolecular microcapsules (SMCs) with the drug-loaded wall layers for pH-controlled drug delivery were designed and prepared. By using layer-by-layer (LbL) technique, the SMCs were constructed based on the self-assembly between polyaldenhyde dextran-graft-adamantane (PAD-g-AD) and carboxymethyl dextran-graft-β-CD (CMD-g-β-CD) on CaCO(3) particles via host-guest interaction. Simultaneously, adamantine-modified doxorubicin (AD-Dox) was also loaded on the LbL wall via host-guest interaction. The in vitro drug release study was carried out at different pHs. Because the AD groups were linked with PAD (PAD-g-AD) or Dox (AD-Dox) by pH-cleavable hydrazone bonds, AD moieties can be removed under the weak acidic condition, leading to destruction of SMCs and release of Dox. The pH-controlled drug release can enhance the uptake by tumor cells and thus achieve improved cancer therapy efficiency.

Materials for pharmaceutical dosage forms: molecular pharmaceutics and controlled release drug delivery aspects.

PubMed

Mansour, Heidi M; Sohn, Minji; Al-Ghananeem, Abeer; Deluca, Patrick P

2010-09-15

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

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

PubMed Central

Mansour, Heidi M.; Sohn, MinJi; Al-Ghananeem, Abeer; DeLuca, Patrick P.

2010-01-01

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. PMID:20957095

In silico study on the effects of matrix structure in controlled drug release

NASA Astrophysics Data System (ADS)

Villalobos, Rafael; Cordero, Salomón; Maria Vidales, Ana; Domínguez, Armando

2006-07-01

Purpose: To study the effects of drug concentration and spatial distribution of the medicament, in porous solid dosage forms, on the kinetics and total yield of drug release. Methods: Cubic networks are used as models of drug release systems. They were constructed by means of the dual site-bond model framework, which allows a substrate to have adequate geometrical and topological distribution of its pore elements. Drug particles can move inside the networks by following a random walk model with excluded volume interactions between the particles. The drug release time evolution for different drug concentration and different initial drug spatial distribution has been monitored. Results: The numerical results show that in all the studied cases, drug release presents an anomalous behavior, and the consequences of the matrix structural properties, i.e., drug spatial distribution and drug concentration, on the drug release profile have been quantified. Conclusions: The Weibull function provides a simple connection between the model parameters and the microstructure of the drug release device. A critical modeling of drug release from matrix-type delivery systems is important in order to understand the transport mechanisms that are implicated, and to predict the effect of the device design parameters on the release rate.

PLA/PEG-PPG-PEG/dexamethasone implant prepared by hot-melt extrusion for controlled release of immunosuppressive drug to implantable medical devices, Part 2: in vivo evaluation.

PubMed

Li, DeXia; Guo, Gang; Deng, Xin; Fan, RangRang; Guo, QingFa; Fan, Min; Liang, Jian; Luo, Feng; Qian, ZhiYong

2013-01-01

Hot-melt extrusion (HME) plays an important role in preparing implants as local drug delivery systems in pharmaceutical fields. Here, a new PLA/PEG-PPG-PEG/Dexamethasone (PLA/F68/Dex) implant prepared by HME has been developed. Importantly, the implant was successfully achieved to control release of immunosuppressive drug to an implanted device. In particular, this implant has not been reported previously in pharmaceutical fields. FTIR and XRD were adopted to investigate the properties of the samples. The in vivo release study showed that the maximum value of Dex release from the implants was approximately 50% at 1 month. The in vivo degradation behavior was determined by UV spectrophotometer and scanning electron microscopy studies, and the weight loss rate of the implants were up to 25% at 1 month. Furthermore, complete blood count (CBC) test, serum chemistry and major organs were performed, and there is no significant lesion and side effects observed in these results. Therefore, the results elucidated that the new PLA/F68/Dex implant prepared by HME could deliver an immunosuppressive drug to control the inflammatory reaction at the implant site.

Development of controlled drug release systems based on thiolated polymers.

PubMed

Bernkop-Schnürch, A; Scholler, S; Biebel, R G

2000-05-03

The purpose of the present study was to generate mucoadhesive matrix-tablets based on thiolated polymers. Mediated by a carbodiimide, L-cysteine was thereby covalently linked to polycarbophil (PCP) and sodium carboxymethylcellulose (CMC). The resulting thiolated polymers displayed 100+/-8 and 1280+/-84 micromol thiol groups per gram, respectively (means+/-S.D.; n=6-8). In aqueous solutions these modified polymers were capable of forming inter- and/or intramolecular disulfide bonds. The velocity of this process augmented with increase of the polymer- and decrease of the proton-concentration. The oxidation proceeded more rapidly within thiolated PCP than within thiolated CMC. Due to the formation of disulfide bonds within thiol-containing polymers, the stability of matrix-tablets based on such polymers could be strongly improved. Whereas tablets based on the corresponding unmodified polymer disintegrated within 2 h, the swollen carrier matrix of thiolated CMC and PCP remained stable for 6.2 h (mean, n=4) and more than 48 h, respectively. Release studies of the model drug rifampicin demonstrated that a controlled release can be provided by thiolated polymer tablets. The combination of high stability, controlled drug release and mucoadhesive properties renders matrix-tablets based on thiolated polymers useful as novel drug delivery systems.

PLGA-Mesoporous Silicon Microspheres for the in Vivo Controlled Temporospatial Delivery of Proteins.

PubMed

Minardi, Silvia; Pandolfi, Laura; Taraballi, Francesca; De Rosa, Enrica; Yazdi, Iman K; Liu, Xeuwu; Ferrari, Mauro; Tasciotti, Ennio

2015-08-05

In regenerative medicine, the temporospatially controlled delivery of growth factors (GFs) is crucial to trigger the desired healing mechanisms in the target tissues. The uncontrolled release of GFs has been demonstrated to cause severe side effects in the surrounding tissues. The aim of this study was to optimize a translational approach for the fine temporal and spatial control over the release of proteins, in vivo. Hence, we proposed a newly developed multiscale composite microsphere based on a core consisting of the nanostructured silicon multistage vector (MSV) and a poly(dl-lactide-co-glycolide) acid (PLGA) outer shell. Both of the two components of the resulting composite microspheres (PLGA-MSV) can be independently tailored to achieve multiple release kinetics contributing to the control of the release profile of a reporter protein in vitro. The influence of MSV shape (hemispherical or discoidal) and size (1, 3, or 7 μm) on PLGA-MSV's morphology and size distribution was investigated. Second, the copolymer ratio of the PLGA used to fabricate the outer shell of PLGA-MSV was varied. The composites were fully characterized by optical microscopy, scanning electron microscopy, ζ potential, Fourier transform infrared spectroscopy, and thermogravimetric analysis-differential scanning calorimetry, and their release kinetics over 30 days. PLGA-MSV's biocompatibility was assessed in vitro with J774 macrophages. Finally, the formulation of PLGA-MSV was selected, which concurrently provided the most consistent microsphere size and allowed for a zero-order release kinetic. The selected PLGA-MSVs were injected in a subcutaneous model in mice, and the in vivo release of the reporter protein was followed over 2 weeks by intravital microscopy, to assess if the zero-order release was preserved. PLGA-MSV was able to retain the payload over 2 weeks, avoiding the initial burst release typical of most drug delivery systems. Finally, histological evaluation assessed the biocompatibility of the platform in vivo.

Release of betaine and dexpanthenol from vitamin E modified silicone-hydrogel contact lenses.

PubMed

Hsu, Kuan-Hui; de la Jara, Percy Lazon; Ariyavidana, Amali; Watling, Jason; Holden, Brien; Garrett, Qian; Chauhan, Anuj

2015-03-01

To develop a contact lens system that will control the release of an osmoprotectant and a moisturizing agent with the aim to reduce symptoms of ocular dryness. Profiles of the release of osmoprotectant betaine and moisturizing agent dexpanthenol from senofilcon A and narafilcon B contact lenses were determined in vitro under sink conditions. Both types of lenses were also infused with vitamin E to increase the duration of drug release due to the formation of the vitamin E diffusion barriers in the lenses. The release profiles from vitamin E-infused lenses were compared with those from the control lenses. Both dexpanthenol and betaine are released from commercial silicone hydrogel lenses for only about 10 min. Vitamin E loadings into contact lenses at about 20-23% can increase the release times to about 10 h, which is about 60 times larger compared to the control unmodified lenses. Vitamin E-loaded silicone hydrogel contact lenses released betaine and dexpanthenol in a controlled fashion.

Development and evaluation of controlled porosity osmotic pump for Nifedipine and Metoprolol combination

PubMed Central

2011-01-01

Background A system that can deliver multi-drug at a prolonged rate is very important for the treatment of various chronic diseases such as diabetes, asthma and heart disease. Controlled porosity osmotic pump tablet (CPOP) system was designed to deliver Nifedipine (NP) and Metoprolol (MP) in a controlled manner up to 12 h. It was prepared by incorporating drugs in the core and coated with various types (PVP, PEG-400 and HPMC) and levels (30, 40 and 50% w/w of polymer) of pore former at a weight gain of 8, 12 & 15%. Results Formulation variables like type and level of pore former and percent weight gain of membrane was found to affect the drug release from the developed formulations. Drug release was inversely proportional to the membrane weight but directly related to the level of pore former. Burst strength of the exhausted shell was inversely proportional to the level of pore former, but directly affected by the membrane weight. Results of scanning electron microscopy (SEM) studies showed the formation of pores in the membrane from where the drug release occurred. Dissolution models were applied to drug release data in order to establish the mechanism of drug release kinetics. In vitro release kinetics was subjected to superposition method to predict in vivo performance of the developed formulation. Conclusion The developed osmotic system is effective in the multi-drug therapy of hypertension by delivering both drugs in a controlled manner. PMID:21477386

Polymer grafted-magnetic halloysite nanotube for controlled and sustained release of cationic drug.

PubMed

Fizir, Meriem; Dramou, Pierre; Zhang, Kai; Sun, Cheng; Pham-Huy, Chuong; He, Hua

2017-11-01

In this research, novel polymer grafted-magnetic halloysite nanotubes with norfloxacin loaded (NOR-MHNTs) and controlled-release, was achieved by surface-initiated precipitation polymerization. The magnetic halloysite nanotubes exhibited better adsorption of NOR (72.10mgg -1 ) compared with the pristine HNTs (30.80mgg -1 ). Various parameters influencing the drug adsorption of the MHNTs for NOR were studied. Polymer grafted NOR-MHNTs has been designed using flexible docking in computer simulation to choose optimal monomers. NOR-MHNTs/poly (methacrylic acid or acrylamide-co-ethylene glycol dimethacrylate) nanocomposite were synthesized using NOR-MHNTs, methacrylic acid (MAA) or acrylamide (AM), ethylene glycol dimethacrylate (EGDMA) and AIBN as nanotemplate, monomers, cross linker and initiator, respectively. The magnetic nanocomposites were characterized by FTIR, TEM, XRD and VSM. The magnetic nanocomposites show superparamagnetic property and fast magnetic response (12.09emug -1 ). The copolymerization of monomers and cross linker led to a better sustained release of norfloxacin (>60h) due to the strong interaction formed between monomers and this cationic drug. The cumulative release rate of NOR is closely related to the cross linker amount. In conclusion, combining the advantages of the high adsorption capacity and magnetic proprieties of this biocompatible clay nanotube and the advantages of polymer shell in the enhancement of controlled-sustained release of cationic drug, a novel formulation for the sustained-controlled release of bioactive agents is developed and may have considerable potential application in targeting drug delivery system. Copyright © 2017. Published by Elsevier Inc.

Construction and characterization of curcumin nanoparticles system

NASA Astrophysics Data System (ADS)

Sun, Weitong; Zou, Yu; Guo, Yaping; Wang, Lu; Xiao, Xue; Sun, Rui; Zhao, Kun

2014-03-01

This study was aimed at developing a nanoparticles system for curcumin, a widely used traditional Chinese medicine, but with the disadvantage of poor aqueous solubility. The objective was intended to improve in vitro release characteristics, enhance blood and gastrointestinal stability, increase bioavailability and pharmacological activities. Curcumin nanoparticles system (Cur-NS) was prepared by ionotropic gelation technique. Cur-NS was characterized by particle size, zeta potential, drug entrapment efficiency, drug loading, and physical stability, respectively. Cur-NS presented controlled release properties, and the release properties of Cur from NS were fit non-Fickian mechanism, controlled by the expected diffusional release and the erosion or solubilization from the crosslink layer of polymer carrier. In addition, the pharmacokinetic study in rats revealed a notable improved oral bioavailability of Cur, and the anti-tumor activity in vivo of Cur-NS on tumor growth was investigated. Cur-NS significantly inhibited tumor effect compared with non-vehicle group, thus making it a potential candidate for cancer therapy.

Model studies of diffusion-controlled (2-hydroxyethyl methacrylate) HEMA hydrogel membranes for controlled release of proteins

NASA Astrophysics Data System (ADS)

Appawu, Jennifer A. M.

This thesis project consisted of three main components that were connected by roots in chemical analysis for studies in tissue engineering. The first part focused on characterizing the structural parameters of synthetic cross-linked poly (2-hydroxyethyl methacrylate) (Poly(HEMA) hydrogel membranes to determine optimal formulations for clinical studies. Poly(HEMA) membranes were loaded with Keratincocyte Growth Factor (KGF) for controlled release studies. Protein loading and release kinetics were determined with fluorescence spectroscopy. The spatial distribution of a protein in the membrane was determined using Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS). The last part of the project focused on determining the biological effects of the polymer membranes in-vitro with a model cell line and a pilot in-vivo animal study. Based on the components completed in this project, five chapters are included in this dissertation document and are summarized below. A new protocol was developed using fluorescence spectroscopy that measured the rate of protein diffusion into cross-linked polymer membranes by measuring the change in the fluorescence intensity of the protein solution. This technique was also able to detect a conformational change that occurs within protein when KGF was imbibed within these cross-linked polymer membranes. ToF-SIMS chemical imaging and 3D depth profiling was used to determine the spatial distribution of KGF protein in frozen-hydrated HEMA hydrogel membranes. The 3D depth profiles showed that the KGF protein was aggregated in bright spots that indicated that KGF was not spatially homogenous on the surface and through the depth profiles. 3D depth profiles of the membranes studied at various times during release studies show that areas with aggregated proteins were retained during release, and at times with maximum release. The interpretation of the bright regions is that the KGf protein interacted with the cross-linked network of the hydrogel membranes, making it not available for release. The in-vitro biological experiments with the HaCaT cell line showed that the HEMA hydrogels were capable of sustaining cell viability, proliferation, and adhesion through cell adhesion and wounding experiments. The pilot in-vivo animal study also revealed that KGF protein had retained its pharmacological activity. The study also showed that the KGF protein enhanced the rate of wound closure.

Conductive polymer nanotube patch for fast and controlled in vivo transdermal drug delivery

NASA Astrophysics Data System (ADS)

Nguyen, Thao M.

Transdermal drug delivery has created new applications for existing therapies and offered an alternative to the traditional oral route where drugs can prematurely metabolize in the liver causing adverse side effects. Opening the transdermal delivery route to large hydrophilic drugs is one of the greatest challenges due to the hydrophobicity of the skin. However, the ability to deliver hydrophilic drugs using a transdermal patch would provide a solution to problems of other delivery methods for hydrophilic drugs. The switching of conductive polymers (CP) between redox states cause simultaneous changes in the polymer charge, conductivity, and volume—properties that can all be exploited in the biomedical field of controlled drug delivery. Using the template synthesis method, poly(3,4-ethylenedioxythiophene (PEDOT) nanotubes were synthesized electrochemically and a transdermal drug delivery patch was successfully designed and developed. In vitro and in vivo uptake and release of hydrophilic drugs were investigated. The relationship between the strength of the applied potential and rate of drug release were also investigated. Results revealed that the strength of the applied potential is proportional to the rate of drug release; therefore one can control the rate of drug release by controlling the applied potential. The in vitro studies focused on the kinetics of the drug delivery system. It was determined that the drug released mainly followed zero-order kinetics. In addition, it was determined that applying a releasing potential to the transdermal drug delivery system lead to a higher release rate constant (up to 7 times greater) over an extended period of time (˜24h). In addition, over 24 hours, an average of 80% more model drug molecules were released with an applied potential than without. The in vivo study showed that the drug delivery system was capable of delivering model hydrophilic drugs molecules through the dermis layer of the skin within 30 minutes, while the control showed no visible drugs at the same depth. Most importantly, it was determined that the delivery of drugs into the blood stream was stable within 20 minutes. The functionalization of CP was also studied in order to enhance the properties and drug loading capabilities of the polymers. The co-polymerization of poly(3,4-(2-methylene)propylenedioxythiophene) (PMProDot) with polystyrene (PS) and polyvinylcarbazole (PVK) through the highly reactive methylene group was achieved. The modified PMProDot nanotubes demonstrated response times that were two times faster than without modification. The modification of PEDOT nanotubes with polydopamine, a biocompatible polymer, was also investigated and achieved. In depth characterization of functionalized CP demonstrate the ability to fine tune the properties of the polymer in order to achieve the required therapeutic drug release profile.

Diclofenac salts, part 6: release from lipid microspheres.

PubMed

Fini, Adamo; Cavallari, Cristina; Rabasco Alvarez, Antonio M; Rodriguez, Marisa Gonzalez

2011-08-01

The release of diclofenac (20%, w/w) was studied from lipidic solid dispersions using three different chemical forms (acid, sodium salt, and pyrrolidine ethanol salt) and two different lipid carriers (Compritol 888 ATO or Carnauba wax) either free or together with varying amounts (10%-30%, w/w) of stearic acid. Microspheres were prepared by ultrasound-assisted atomization of the molten dispersions and analyzed by scanning electron microscopy, differential scanning calorimetry, and hot stage microscopy. The effects of different formulations on the resulting drug release profiles as a function of pH were studied and the results were discussed. The formulation of the 18 systems and the chemical form of the drug were found to strongly affect the mode of the drug release. The solubility of the chemical forms in the lipid mixture is in the following order: pyrrolidine ethanol salt ≫ acid > sodium salt (according to the solubility parameters), and the nature of the systems thus obtained ranges from a matrix, for mutually soluble drug/carrier pairs, to a microcapsule, for pairs wherein mutual solubility is poor. Drug release from microspheres prepared by pure lipids was primarily controlled by diffusion, whereas the release from microspheres containing stearic acid was diffusion/erosion controlled at pH 7.4. Copyright © 2011 Wiley-Liss, Inc.

Pore structures in an implantable sol gel titania ceramic device used in controlled drug release applications: A modeling study

NASA Astrophysics Data System (ADS)

Peterson, Aaron; Lopez, Tessy; Islas, Emma Ortiz; Gonzalez, Richard D.

2007-04-01

Several process variables, which may be helpful in optimizing the rate at which drugs are released from implantable, sol-gel titania devices have been identified in this study. The controlled rate of drug release is compared for two different anticonvulsant drugs, valproic acid and sodic phenytoin. Contrary to what one might expect, when the concentration is increased in the titania reservoir the rate of initial drug delivery decreases. This is a desirable result, because it may reduce the danger of a high initial discharge, which may harm the epileptic rat. The structure of the porous structure within the titania network has been studied using a generalized form of the BET equation which considers only n layers. In general, following an initial discharge, the rate at which the drug is released will increase with the increasing concentration. Pore mouth blocking can present a problem. However, this problem tends to disappear following the initial discharge. The extent of drug loading is a useful variable parameter, which can be adjusted in order to deliver the amount of drug required in a given application.

Postoperative maintenance levonorgestrel-releasing intrauterine system and endometrioma recurrence: a randomized controlled study.

PubMed

Chen, Yi-Jen; Hsu, Teh-Fu; Huang, Ben-Shian; Tsai, Hsiao-Wen; Chang, Yen-Hou; Wang, Peng-Hui

2017-06-01

According to 3 randomized trials, the levonorgestrel-releasing intrauterine system significantly reduced recurrent endometriosis-related pelvic pain at postoperative year 1. Only a few studies have evaluated the long-term effectiveness of the device for preventing endometrioma recurrence, and the effects of a levonorgestrel-releasing intrauterine system as a maintenance therapy remain unclear. The objective of the study was to evaluate whether a maintenance levonorgestrel-releasing intrauterine system is effective for preventing postoperative endometrioma recurrence. From May 2011 through March 2012, a randomized controlled trial including 80 patients with endometriomas undergoing laparoscopic cystectomy followed by six cycles of gonadotropin-releasing hormone agonist treatment was conducted. After surgery, the patients were randomized to groups that did or did not receive a levonorgestrel-releasing intrauterine system (intervention group, n = 40, vs control group, n = 40). The primary outcome was endometrioma recurrence 30 months after surgery. The secondary outcomes included dysmenorrhea, CA125 levels, noncyclic pelvic pain, and side effects. Endometrioma recurrence at 30 months did not significantly differ between the 2 groups (the intervention group, 10 of 40, 25% vs the control group 15 of 40, 37.5%; hazard ratio, 0.60, 95% confidence interval, 0.27-1.33, P = .209). The intervention group exhibited a lower dysmenorrhea recurrence rate, with an estimated hazard ratio of 0.32 (95% confidence interval, 0.12-0.83, P = .019). Over a 30 month follow-up, the intervention group exhibited a greater reduction in dysmenorrhea as assessed with a visual analog scale score (mean ± SD, 60.8 ± 25.5 vs 38.7 ± 25.9, P < .001, 95% confidence interval, 10.7-33.5), noncyclic pelvic pain visual analog scale score (39.1 ± 10.9 vs 30.1 ± 14.7, P = .014, 95% confidence interval, 1.9-16.1), and CA125 (median [interquartile range], -32.1 [-59.1 to 14.9], vs -15.6 [-33.0 to 5.0], P = .001) compared with the control group. The number-needed-to-treat benefit for dysmenorrhea recurrence at 30 months was 5. The number of recurrent cases requiring further surgical or hormone treatment in the intervention group (1 of 40, 2.5%, 95% confidence interval, -2.3% to 7.3%) was significantly lower than that in the control group (8 of 40, 20%, 95% confidence interval, 7.6-32.4%; P = .031). Long-term maintenance therapy using a levonorgestrel-releasing intrauterine system is not effective for preventing endometrioma recurrence. Copyright © 2017 Elsevier Inc. All rights reserved.

Drug release and swelling kinetics of directly compressed glipizide sustained-release matrices: establishment of level A IVIVC.

PubMed

Sankalia, Jolly M; Sankalia, Mayur G; Mashru, Rajashree C

2008-07-02

The purpose of this study was to examine a level A in vitro-in vivo correlation (IVIVC) for glipizide hydrophilic sustained-release matrices, with an acceptable internal predictability, in the presence of a range of formulation/manufacturing changes. The effect of polymeric blends of ethylcellulose, microcrystalline cellulose, hydroxypropylmethylcellulose, xanthan gum, guar gum, Starch 1500, and lactose on in vitro release profiles was studied and fitted to various release kinetics models. Water uptake kinetics with scanning electron microscopy (SEM) was carried out to support the drug release mechanism. An IVIVC was established by comparing the pharmacokinetic parameters of optimized (M-24) and marketed (Glytop-2.5 SR) formulations after single oral dose studies on white albino rabbits. The matrix M-19 (xanthan:MCC PH301 at 70:40) and M-24 (xanthan:HPMC K4M:Starch 1500 at 70:25:15) showed the glipizide release within the predetermined constraints at all time points with Korsmeyer-Peppas' and zero-order release mechanism, respectively. Kopcha model revealed that the xanthan gum is the major excipient responsible for the diffusional release profile and was further supported by SEM and swelling studies. A significant level A IVIVC with acceptable limits of prediction errors (below 15%) enables the prediction of in vivo performance from their in vitro release profile. It was concluded that proper selection of rate-controlling polymers with release rate modifier excipients will determine overall release profile, duration and mechanism from directly compressed matrices.

Suitability Screening Test for Marine Corps Air Traffic Controllers

DTIC Science & Technology

2012-12-01

Approved for public release; distribution is unlimited. Navy Personnel Research, Studies, and Technology 5720 Integrity Drive  Millington...Karen M. Walker, Ph.D. William L. Farmer, Ph.D. Rebecca C. Roberts, MS Navy Personnel Research, Studies, and Technology NPRST-TR-13-1...Roberts, MS Navy Personnel Research, Studies, and Technology Reviewed by David Alderton, Ph.D. Approved and released by D. M. Cashbaugh Assistant

Photoresponsive lipid-polymer hybrid nanoparticles for controlled doxorubicin release

NASA Astrophysics Data System (ADS)

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.

Simultaneously Load and Extended Release of Betamethasone and Ciprofloxacin from Vitamin E-Loaded Silicone-Based Soft Contact Lenses.

PubMed

Rad, Maryam Shayani; Mohajeri, Seyed Ahmad

2016-09-01

The purpose of the present study was to evaluate the efficacy of commercial soft contact lenses, loaded with vitamin E, as ocular drug delivery systems for simultaneous loading and release of ciprofloxacin (Cipro) and betamethasone (BMZ) in artificial tears. In this study, we applied vitamin E as a barrier to increase BMZ-Cipro loading into three commercial silicone-based soft contact lenses and control their simultaneous release into the artificial lachrymal fluid. Two different concentrations of vitamin E solution (0.1 and 0.2 g/ml) were used, and various parameters including changes in lens diameter, water content, ultraviolet-visible light (UV-Vis) transmittance, drug-binding properties, and drug release profile were investigated. The obtained results indicated that vitamin E significantly reduced the swelling properties of contact lenses in aqueous media, while it enhanced the lens diameter in both dry and hydrated states. Vitamin E had no significant effects on visible transmittance, while it blocked UV radiation, which could be harmful for the eye surface. Our findings revealed that vitamin E improved the simultaneous loading amount of BMZ-Cipro into soft contact lenses. Additionally, BMZ and Cipro release rates significantly reduced after using vitamin E as a hydrophobic diffusion barrier. After soaking the lenses in 0.1 and 0.2 g/ml of vitamin E solution, BMZ release time increased by 28.8-81.6 and 182.4-201 folds, respectively. Moreover, Cipro release time increased by 12-18 and 1152-2313 folds, respectively. The results of the present study indicated the efficacy of vitamin E as a diffusion barrier in developing a controlled drug delivery system for the simultaneous loading of BMZ and Cipro and sustaining their release from soft contact lenses.

Development of KMnO(4)-releasing composites for in situ chemical oxidation of TCE-contaminated groundwater.

PubMed

Liang, S H; Chen, K F; Wu, C S; Lin, Y H; Kao, C M

2014-05-01

The objective of this study was to develop a controlled-oxidant-release technology combining in situ chemical oxidation (ISCO) and permeable reactive barrier (PRB) concepts to remediate trichloroethene (TCE)-contaminated groundwater. In this study, a potassium permanganate (KMnO4)-releasing composite (PRC) was designed for KMnO4 release. The components of this PRC included polycaprolactone (PCL), KMnO4, and starch with a weight ratio of 1.14:2:0.96. Approximately 64% (w/w) of the KMnO4 was released from the PRC after 76 days of operation in a batch system. The results indicate that the released KMnO4 could oxidize TCE effectively. The results from a column study show that the KMnO4 released from 200 g of PRC could effectively remediate 101 pore volumes (PV) of TCE-contaminated groundwater (initial TCE concentration = 0.5 mg/L) and achieve up to 95% TCE removal. The effectiveness of the PRC system was verified by the following characteristics of the effluents collected after the PRC columns (barrier): (1) decreased TCE concentrations, (2) increased ORP and pH values, and (3) increased MnO2 and KMnO4 concentrations. The results of environmental scanning electron microscope (ESEM) analysis show that the PCL and starch completely filled up the pore spaces of the PRC, creating a composite with low porosity. Secondary micro-scale capillary permeability causes the KMnO4 release, mainly through a reaction-diffusion mechanism. The PRC developed could be used as an ISCO-based passive barrier system for plume control, and it has the potential to become a cost-effective alternative for the remediation of chlorinated solvent-contaminated groundwater. Copyright © 2014 Elsevier Ltd. All rights reserved.

Preliminary evaluation of an aqueous wax emulsion for controlled-release coating.

PubMed

Walia, P S; Stout, P J; Turton, R

1998-02-01

The purpose of this work was to evaluate the use of an aqueous carnauba wax emulsion (Primafresh HS, Johnson Wax) in a spray-coating process. This involved assessing the effectiveness of the wax in sustaining the release of the drug, theophylline. Second, the process by which the drug was released from the wax-coated pellets was modeled. Finally, a method to determine the optimum blend of pellets with different wax thicknesses, in order to yield a zero-order release profile of the drug, was addressed. Nonpareil pellets were loaded with theophylline using a novel powder coating technique. These drug-loaded pellets were then coated with different levels of carnauba wax in a 6-in. diameter Plexiglas fluid bed with a 3.5-in. diameter Wurster partition. Drug release was measured using a spin-filter dissolution device. The study resulted in continuous carnauba wax coatings which showed sustained drug release profile characteristics typical of a barrier-type, diffusion-controlled system. The effect of varying wax thickness on the release profiles was investigated. It was observed that very high wax loadings would be required to achieve long sustained-release times. The diffusion model, developed to predict the release of the drug, showed good agreement with the experimental data. However, the data exhibited an initial lag-time for drug release which could not be predicted a priori based on the wax coating thickness. A method of mixing pellets with different wax thicknesses was proposed as a way to approximate zero-order release.

Alveolar macrophage release of tumor necrosis factor-alpha in chronic alcoholics without liver disease.

PubMed

Omidvari, K; Casey, R; Nelson, S; Olariu, R; Shellito, J E

1998-05-01

Alcohol is an immunosuppressive drug, and chronic abuse has been associated with increased susceptibility to a variety of infections, including bacterial pneumonia and tuberculosis. Alveolar macrophages are the resident phagocytes of the lung and play a central role in lung host defenses against infection ranging from direct antibacterial activity to the release of proinflammatory cytokines such as tumor necrosis factor-alpha (TNFalpha). TNFalpha, in particular, plays a key role in the development of the early inflammatory response. In this study, we investigated the effects of chronic alcohol consumption on alveolar macrophage release of TNFalpha in vitro. We prospectively studied lipopolysaccharide (LPS)-stimulated release of TNFalpha from alveolar macrophages obtained from bronchoalveolar lavage fluid (BALF) in 22 alcoholic (18 smokers, 4 nonsmokers) and 7 nondrinking healthy volunteers (3 smokers, 4 nonsmokers). The total number of cells recovered by bronchoalveolar lavage (BAL) and their differential distribution were not significantly different in alcoholics versus controls (43 +/- 8 x 10(6) and 39 +/- 13 x 10(6), respectively). However, the total number of cells recovered from BALF was significantly higher in smokers (51 +/- 8 x 10(6)) than in nonsmokers (19 +/- 5 x 10(6)). Spontaneous (basal) release of TNFalpha by alveolar macrophages was the same in alcoholics and controls. In contrast, LPS-stimulated release of TNFalpha was significantly suppressed in alcoholics compared with that of controls (1343 +/- 271 vs. 3806 +/- 926 U TNF/ml/10(6) cells, respectively, p < 0.015). When controlled for smoking, LPS-stimulated TNFalpha production was suppressed in alcoholic nonsmokers (563 +/- 413 U TNF/ml/10(6)) compared with control nonsmokers (5113 +/- 1264 U TNF/ml/10(6)). LPS-stimulated TNFalpha production was also less in control smokers (2063 +/- 386 U TNF/ml/10(6) cells) than in control nonsmokers (5113 +/- 1264 U TNF/ml/10(6) cells). There was no difference in TNFalpha production between smoking alcoholics and smoking control subjects. We conclude that chronic alcohol consumption significantly suppresses LPS-stimulated alveolar macrophage production of TNFalpha. This effect is obscured if the subject also smokes. Because TNFalpha production is an important element in host defense, this may explain, in part, the susceptibility of chronic alcohol abusers to a variety of infections.

Thermoplastic polyurethanes for the manufacturing of highly dosed oral sustained release matrices via hot melt extrusion and injection molding.

PubMed

Claeys, Bart; Vervaeck, Anouk; Hillewaere, Xander K D; Possemiers, Sam; Hansen, Laurent; De Beer, Thomas; Remon, Jean Paul; Vervaet, Chris

2015-02-01

This study evaluated thermoplastic polyurethanes (TPUR) as matrix excipients for the production of oral solid dosage forms via hot melt extrusion (HME) in combination with injection molding (IM). We demonstrated that TPURs enable the production of solid dispersions - crystalline API in a crystalline carrier - at an extrusion temperature below the drug melting temperature (Tm) with a drug content up to 65% (wt.%). The release of metoprolol tartrate was controlled over 24h, whereas a complete release of diprophylline was only possible in combination with a drug release modifier: polyethylene glycol 4000 (PEG 4000) or Tween 80. No burst release nor a change in tablet size and geometry was detected for any of the formulations after dissolution testing. The total matrix porosity increased gradually upon drug release. Oral administration of TPUR did not affect the GI ecosystem (pH, bacterial count, short chain fatty acids), monitored via the Simulator of the Human Intestinal Microbial Ecosystem (SHIME). The high drug load (65 wt.%) in combination with (in vitro and in vivo) controlled release capacity of the formulations, is noteworthy in the field of formulations produced via HME/IM. Copyright © 2014 Elsevier B.V. All rights reserved.

Formulation and evaluation of diclofenac controlled release matrix tablets made of HPMC and Poloxamer 188 polymer: An assessment on mechanism of drug release.

PubMed

Al-Hanbali, Othman A; Hamed, Rania; Arafat, Mosab; Bakkour, Youssef; Al-Matubsi, Hisham; Mansour, Randa; Al-Bataineh, Yazan; Aldhoun, Mohammad; Sarfraz, Muhammad; Dardas, Abdel Khaleq Yousef

2018-01-01

In this study, hydrophilic hydroxypropyl methylcellulose matrices with various concentrations of Poloxamer 188 were used in the development of oral controlled release tablets containing diclofenac sodium. Four formulations of hydrophilic matrix tablets containing 16.7% w/w HPMC and 0, 6.7, 16.7 and 25.0% w/w Poloxamer 188, respectively, were developed. Tablets were prepared by direct compression and characterized for diameter, hardness, thickness, weight and uniformity of content. The influence of various blends of hydroxypropyl methylcellulose and Poloxamer 188 on the in vitro dissolution profile and mechanism of drug release of was investigated. In the four formulations, the rate of drug release decreased with increasing the concentration of Poloxamer 188 at the initial dissolution stages due to the increase in the apparent viscosity of the gel diffusion layer. However, in the late dissolution stages, the rate of drug release increased with increasing Poloxamer 188 concentration due to the increase in wettability and dissolution of the matrix. The kinetic of drug release from the tablets followed non-Fickian mechanism, as predicted by Korsmeyer-Peppas model, which involves diffusion through the gel layer and erosion of the matrix system.

Development of a sustained fluoride delivery system.

PubMed

Baturina, Olga; Tufekci, Eser; Guney-Altay, Ozge; Khan, Shadeed M; Wnek, Gary E; Lindauer, Steven J

2010-11-01

To develop a novel delivery system by which fluoride incorporated into elastomeric rings, such as those used to ligate orthodontic wires, will be released in a controlled and constant manner. Polyethylene co-vinyl acetate (PEVA) was used as the model elastomer. Samples (N = 3) were prepared by incorporating 0.02 to 0.4 g of sodium fluoride (NaF) into previously prepared PEVA solution. Another group of samples prepared in the same manner were additionally dip-coated in PEVA to create an overcoat. Fluoride release studies were conducted in vitro using an ion selective electrode over a period of 45 days. The amount of fluoride released was compared to the optimal therapeutic dose of 0.7 microg F(-)/ring/d. Only coated samples with the highest fluoride content (group D, 0.4 g of NaF) were able to release fluoride at therapeutic levels. When fluoride release from coated and uncoated samples with the same amount of NaF were compared, it was shown that the dip-coating technique resulted in a fluoride release in a controlled manner while eliminating the initial burst effect. This novel fluoride delivery matrix provided fluoride release at a therapeutically effective rate and profile.

Controlled release of paclitaxel from a self-assembling peptide hydrogel formed in situ and antitumor study in vitro

PubMed Central

Liu, Jingping; Zhang, Lanlan; Yang, Zehong; Zhao, Xiaojun

2011-01-01

Background A nanoscale injectable in situ-forming hydrogel drug delivery system was developed in this study. The system was based on a self-assembling peptide RADA16 solution, which can spontaneously form a hydrogel rapidly under physiological conditions. We used the RADA16 hydrogel for the controlled release of paclitaxel (PTX), a hydrophobic antitumor drug. Methods The RADA16-PTX suspension was prepared simply by magnetic stirring, followed by atomic force microscopy, circular dichroism analysis, dynamic light scattering, rheological analysis, an in vitro release assay, and a cell viability test. Results The results indicated that RADA16 and PTX can interact with each other and that the amphiphilic peptide was able to stabilize hydrophobic drugs in aqueous solution. The particle size of PTX was markedly decreased in the RADA16 solution compared with its size in water. The RADA16-PTX suspension could form a hydrogel in culture medium, and the elasticity of the hydrogel showed a positive correlation with peptide concentration. In vitro release measurements indicated that hydrogels with a higher peptide concentration had a longer half-release time. The RADA16-PTX hydrogel could effectively inhibit the growth of the breast cancer cell line, MDA-MB-435S, in vitro, and hydrogels with higher peptide concentrations were more effective at inhibiting tumor cell proliferation. The RADA16-PTX hydrogel was effective at controlling the release of PTX and inhibiting tumor cell growth in vitro. Conclusion Self-assembling peptide hydrogels may work well as a system for drug delivery. PMID:22114478

Diisocyanate mediated polyether modified gelatin drug carrier for controlled release

PubMed Central

Vijayakumar, Vediappan; Subramanian, Kaliappagounder

2013-01-01

Gelatin is an extensively studied biopolymer hydrogel drug carrier due to its biocompatibility, biodegradability and non-toxicity of its biodegraded products formed in vivo. But with the pristine gelatin it is difficult to achieve a controlled and desirable drug release characteristics due to its structural and thermal lability and high solubility in aqueous biofluids. Hence it is necessary to modify its solubility and structural stability in biofluids to achieve controlled release features with improved drug efficacy and broader carrier applications. In the present explorations an effort is made in this direction by cross linking gelatin to different extents using hitherto not studied isocyanate terminated poly(ether) as a macrocrosslinker prepared from poly(ethylene glycol) and isophorone diisocyanate in dimethyl sulfoxide. The crosslinked samples were analyzed for structure by Fourier transform-infrared spectroscopy, thermal behavior through thermogravimetric analysis and differential scanning calorimetry. The cross linked gelatins were biodegradable, insoluble and swellable in biofluids. They were evaluated as a carrier for in vitro drug delivery taking theophylline as a model drug used in asthma therapy. The crosslinking of gelatin decreased the drug release rate by 10–20% depending upon the extent of crosslinking. The modeled drug release characteristics revealed an anomalous transport mechanism. The release rates for ampicillin sodium, 5-fluorouracil and theophylline drugs in a typical crosslinked gelatin carrier were found to depend on the solubility and hydrophobicity of the drugs, and the pH of the fluid. The observed results indicated that this material can prove its mettle as a viable carrier matrix in drug delivery applications. PMID:24493973

Responsive copolymer–graphene oxide hybrid microspheres with enhanced drug release properties

DOE PAGES

Dong, Fuping; Firkowska-Boden, Izabela; Arras, Matthias M. L.; ...

2017-01-13

Here, the ability to integrate both high encapsulation efficiency and controlled release in a drug delivery system (DDS) is a highly sought solution to cure major diseases. However, creation of such a system is challenging. This study was aimed at constructing a new delivery system based on thermoresponsive poly(N-isopropylacrylamide-co-styrene) (PNIPAAm-co-PS) hollow microspheres prepared via two-step precipitation polymerization. To control the diffusion-driven drug release, the PNIPAAm-co-PS spheres were electrostatically coated with graphene oxide (GO) nanosheets. As a result of the coating the permeability of such copolymer-GO hybrid microspheres was reduced to the extent that suppressed the initial burst release and enabledmore » sustained drug release in in vitro testing. The hybrid microspheres showed improved drug encapsulation by 46.4% which was attributed to the diffusion barrier properties and -conjugated structure of GO. The system presented here is promising to advance, e.g., the anticancer drug delivery technologies by enabling sustained drug release and thus minimizing local and systemic side effects.« less

Responsive copolymer–graphene oxide hybrid microspheres with enhanced drug release properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dong, Fuping; Firkowska-Boden, Izabela; Arras, Matthias M. L.

Here, the ability to integrate both high encapsulation efficiency and controlled release in a drug delivery system (DDS) is a highly sought solution to cure major diseases. However, creation of such a system is challenging. This study was aimed at constructing a new delivery system based on thermoresponsive poly(N-isopropylacrylamide-co-styrene) (PNIPAAm-co-PS) hollow microspheres prepared via two-step precipitation polymerization. To control the diffusion-driven drug release, the PNIPAAm-co-PS spheres were electrostatically coated with graphene oxide (GO) nanosheets. As a result of the coating the permeability of such copolymer-GO hybrid microspheres was reduced to the extent that suppressed the initial burst release and enabledmore » sustained drug release in in vitro testing. The hybrid microspheres showed improved drug encapsulation by 46.4% which was attributed to the diffusion barrier properties and -conjugated structure of GO. The system presented here is promising to advance, e.g., the anticancer drug delivery technologies by enabling sustained drug release and thus minimizing local and systemic side effects.« less

Fabrication of core-shell micro/nanoparticles for programmable dual drug release by emulsion electrospraying

NASA Astrophysics Data System (ADS)

Wang, Yazhou; Zhang, Yiqiong; Wang, Bochu; Cao, Yang; Yu, Qingsong; Yin, Tieying

2013-06-01

The study aimed at constructing a novel drug delivery system for programmable multiple drug release controlled with core-shell structure. The core-shell structure consisted of chitosan nanoparticles as core and polyvinylpyrrolidone micro/nanocoating as shell to form core-shell micro/nanoparticles, which was fabricated by ionic gelation and emulsion electrospray methods. As model drug agents, Naproxen and rhodamine B were encapsulated in the core and shell regions, respectively. The core-shell micro/nanoparticles thus fabricated were characterized and confirmed by scanning electron microscope, transmission electron microscope, and fluorescence optical microscope. The core-shell micro/nanoparticles showed good release controllability through drug release experiment in vitro. It was noted that a programmable release pattern for dual drug agents was also achieved by adjusting their loading regions in the core-shell structures. The results indicate that emulsion electrospraying technology is a promising approach in fabrication of core-shell micro/nanoparticles for programmable dual drug release. Such a novel multi-drug delivery system has a potential application for the clinical treatment of cancer, tuberculosis, and tissue engineering.

Near-Infrared-Induced Heating of Confined Water in Polymeric Particles for Efficient Payload Release

PubMed Central

2015-01-01

Near-infrared (NIR) light-triggered release from polymeric capsules could make a major impact on biological research by enabling remote and spatiotemporal control over the release of encapsulated cargo. The few existing mechanisms for NIR-triggered release have not been widely applied because they require custom synthesis of designer polymers, high-powered lasers to drive inefficient two-photon processes, and/or coencapsulation of bulky inorganic particles. In search of a simpler mechanism, we found that exposure to laser light resonant with the vibrational absorption of water (980 nm) in the NIR region can induce release of payloads encapsulated in particles made from inherently non-photo-responsive polymers. We hypothesize that confined water pockets present in hydrated polymer particles absorb electromagnetic energy and transfer it to the polymer matrix, inducing a thermal phase change. In this study, we show that this simple and highly universal strategy enables instantaneous and controlled release of payloads in aqueous environments as well as in living cells using both pulsed and continuous wavelength lasers without significant heating of the surrounding aqueous solution. PMID:24717072

Near-infrared-induced heating of confined water in polymeric particles for efficient payload release.

PubMed

Viger, Mathieu L; Sheng, Wangzhong; Doré, Kim; Alhasan, Ali H; Carling, Carl-Johan; Lux, Jacques; de Gracia Lux, Caroline; Grossman, Madeleine; Malinow, Roberto; Almutairi, Adah

2014-05-27

Near-infrared (NIR) light-triggered release from polymeric capsules could make a major impact on biological research by enabling remote and spatiotemporal control over the release of encapsulated cargo. The few existing mechanisms for NIR-triggered release have not been widely applied because they require custom synthesis of designer polymers, high-powered lasers to drive inefficient two-photon processes, and/or coencapsulation of bulky inorganic particles. In search of a simpler mechanism, we found that exposure to laser light resonant with the vibrational absorption of water (980 nm) in the NIR region can induce release of payloads encapsulated in particles made from inherently non-photo-responsive polymers. We hypothesize that confined water pockets present in hydrated polymer particles absorb electromagnetic energy and transfer it to the polymer matrix, inducing a thermal phase change. In this study, we show that this simple and highly universal strategy enables instantaneous and controlled release of payloads in aqueous environments as well as in living cells using both pulsed and continuous wavelength lasers without significant heating of the surrounding aqueous solution.

Synthetic Geopolymers for Controlled Delivery of Oxycodone: Adjustable and Nanostructured Porosity Enables Tunable and Sustained Drug Release

PubMed Central

Forsgren, Johan; Pedersen, Christian; Strømme, Maria; Engqvist, Håkan

2011-01-01

In this article we for the first time present a fully synthetic mesoporous geopolymer drug carrier for controlled release of opioids. Nanoparticulate precursor powders with different Al/Si-ratios were synthesized by a sol-gel route and used in the preparation of different geopolymers, which could be structurally tailored by adjusting the Al/Si-ratio and the curing temperatures. In particular, it was shown that the pore sizes of the geopolymers decreased with increasing Al/Si ratio and that completely mesoporous geopolymers could be produced from precursor particles with the Al/Si ratio 2∶1. The mesoporosity was shown to be associated with a sustained and linear in vitro release profile of the opioid oxycodone. A clinically relevant release period of about 12 h was obtained by adjusting the size of the pellets. The easily fabricated and tunable geopolymers presented in this study constitute a novel approach in the development of controlled release formulations, not only for opioids, but whenever the clinical indication is best treated with a constant supply of drugs and when the mechanical stability of the delivery vehicle is crucial. PMID:21423616

Controlled release of agrochemicals intercalated into montmorillonite interlayer space.

PubMed

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.

Controlled Release of Agrochemicals Intercalated into Montmorillonite Interlayer Space

PubMed Central

2014-01-01

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

Establishing the environmental risk of metal contaminated river bank sediments

NASA Astrophysics Data System (ADS)

Lynch, Sarah; Batty, Lesley; Byrne, Patrick

2016-04-01

Climate change predictions indicate an increase in the frequency and duration of flood events along with longer dry antecedent conditions, which could alter patterns of trace metal release from contaminated river bank sediments. This study took a laboratory mesocosm approach. Chemical analysis of water and sediment samples allowed the patterns of Pb and Zn release and key mechanisms controlling Pb and Zn mobility to be determined. Trace metal contaminants Pb and Zn were released throughout flooded periods. The highest concentrations of dissolved Pb were observed at the end of the longest flood period and high concentrations of dissolved Zn were released at the start of a flood. These concentrations were found to exceed environmental quality standards. Key mechanisms controlling mobility were (i) evaporation, precipitation and dissolution of Zn sulphate salts, (ii) anglesite solubility control of dissolved Pb, (iii) oxidation of galena and sphalerite, (iv) reductive dissolution of Mn/Fe hydroxides and co-precipitation/adsorption with Zn. In light of climate change predictions these results indicate future scenarios may include larger or more frequent transient 'pulses' of dissolved Pb and Zn released to river systems. These short lived pollution episodes could act as a significant barrier to achieving the EU Water Framework Directive objectives.

Facile preparation and characterization of pH sensitive Mt/CMC nanocomposite hydrogel beads for propranolol controlled release.

PubMed

Farhadnejad, Hassan; Mortazavi, Seyed Alireza; Erfan, Mohammad; Darbasizadeh, Behzad; Motasadizadeh, Hamidreza; Fatahi, Yousef

2018-05-01

The main aim of the present study was to design pH-sensitive nanocomposite hydrogel beads, based on carboxymethyl cellulose (CMC) and montmorillonite (Mt)-propranolol (PPN) nanohybrid, and evaluate whether the prepared nanocomposite beads could potentially be used as oral drug delivery systems. PPN-as a model drug-was intercalated into the interlayer space of Mt clay mineral via the ion exchange procedure. The resultant nanohybrid (Mt-PPN) was applied to fabricate nanocomposite hydrogel beads by association with carboxymethyl cellulose. The characterization of test samples was performed using different techniques: X-Ray Diffraction (XRD), IR spectroscopy (FT-IR), thermal gravity analysis (TGA), and scanning electron microscopy (SEM). The drug encapsulation efficiency was evaluated by UV-vis spectroscopy, and was found to be high for Mt/CMC beads. In vitro drug release test was performed in the simulated gastrointestinal conditions to evaluate the efficiency of Mt-PPN/CMC nanocomposite beads as a controlled-release drug carrier. The drug release profiles indicated that the Mt-PPN/CMC nanocomposite beads had high stability against stomach acid and a sustained- and controlled-release profile for PPN under the simulated intestinal conditions. Copyright © 2018 Elsevier B.V. All rights reserved.

21 CFR 1312.29 - Domestic release prohibited.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Domestic release prohibited. 1312.29 Section 1312... OF CONTROLLED SUBSTANCES Exportation of Controlled Substances § 1312.29 Domestic release prohibited. An exporter or a forwarding agent acting for an exporter must either deliver the controlled...

Flavonoids preservation and release by methacrylic acid-grafted (N-vinyl-pyrrolidone).

PubMed

Parisi, Ortensia Ilaria; Puoci, Francesco; Iemma, Francesca; Curcio, Manuela; Cirillo, Giuseppe; Spizzirri, Umile Gianfranco; Picci, Nevio

2013-01-01

Flavonoids preservation and release. Synthesis of a polymeric material able to prevent thermal and photo degradation of a flavonoid model compound, such as (+)-catechin, and suitable for a controlled/sustained delivery of this molecule in gastro-intestinal simulating fluids. Methacrylic acid (MAA) was grafted onto poly(N-vinyl-pyrrolidone) (PVP) by a free radical grafting procedure involving a single-step reaction at room temperature. For this purpose, hydrogen peroxide/ascorbic acid redox pair was employed as water-soluble and biocompatible initiator system. FT-IR spectra confirmed the insertion of MAA onto the polymeric chain. Stability studies, performed under various conditions, such as freeze-thaw cycles, exposure to strong light, thermal stability studies under constant humidity and with light protection at different temperatures, showed the preservative properties of the polymeric material towards flavonoids. Furthermore, the biocompatibility was highlighted by Hen's Egg Test-Chorioallantoic Membrane assay and in vitro release studies demonstrated the possibility to employ PVP-MAA copolymer as a device for gastro-intestinal release of flavonoids. The coupling of good preservative properties together with biocompatibility and the usefulness as carrier in controlled release make this kind of material very interesting from an industrial point of view for different applications in food, pharmaceutical, and cosmetic fields.

A stimuli responsive liposome loaded hydrogel provides flexible on-demand release of therapeutic agents.

PubMed

O'Neill, Hugh S; Herron, Caroline C; Hastings, Conn L; Deckers, Roel; Lopez Noriega, Adolfo; Kelly, Helena M; Hennink, Wim E; McDonnell, Ciarán O; O'Brien, Fergal J; Ruiz-Hernández, Eduardo; Duffy, Garry P

2017-01-15

Lysolipid-based thermosensitive liposomes (LTSL) embedded in a chitosan-based thermoresponsive hydrogel matrix (denoted Lipogel) represents a novel approach for the spatiotemporal release of therapeutic agents. The entrapment of drug-loaded liposomes in an injectable hydrogel permits local liposome retention, thus providing a prolonged release in target tissues. Moreover, release can be controlled through the use of a minimally invasive external hyperthermic stimulus. Temporal control of release is particularly important for complex multi-step physiological processes, such as angiogenesis, in which different signals are required at different times in order to produce a robust vasculature. In the present work, we demonstrate the ability of Lipogel to provide a flexible, easily modifiable release platform. It is possible to tune the release kinetics of different drugs providing a passive release of one therapeutic agent loaded within the gel and activating the release of a second LTSL encapsulated agent via a hyperthermic stimulus. In addition, it was possible to modify the drug dosage within Lipogel by varying the duration of hyperthermia. This can allow for adaption of drug dosing in real time. As an in vitro proof of concept with this system, we investigated Lipogels ability to recruit stem cells and then elevate their production of vascular endothelial growth factor (VEGF) by controlling the release of a pro-angiogenic drug, desferroxamine (DFO) with an external hyperthermic stimulus. Initial cell recruitment was accomplished by the passive release of hepatocyte growth factor (HGF) from the hydrogel, inducing a migratory response in cells, followed by the delayed release of DFO from thermosensitive liposomes, resulting in a significant increase in VEGF expression. This delayed release could be controlled up to 14days. Moreover, by changing the duration of the hyperthermic pulse, a fine control over the amount of DFO released was achieved. The ability to trigger the release of therapeutic agents at a specific timepoint and control dosing level through changes in duration of hyperthermia enables sequential multi-dose profiles. This paper details the development of a heat responsive liposome loaded hydrogel for the controlled release of pro-angiogenic therapeutics. Lysolipid-based thermosensitive liposomes (LTSLs) embedded in a chitosan-based thermoresponsive hydrogel matrix represents a novel approach for the spatiotemporal release of therapeutic agents. This hydrogel platform demonstrates remarkable flexibility in terms of drug scheduling and sequencing, enabling the release of multiple agents and the ability to control drug dosing in a minimally invasive fashion. The possibility to tune the release kinetics of different drugs independently represents an innovative platform to utilise for a variety of treatments. This approach allows a significant degree of flexibility in achieving a desired release profile via a minimally invasive stimulus, enabling treatments to be tuned in response to changing symptoms and complications. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Evaluation of Matrix Tablets Based on Eudragit®E100/Carbopol®971P Combinations for Controlled Release and Improved Compaction Properties of Water Soluble Model Drug Paracetamol.

PubMed

Obeidat, Wasfy M; Nokhodchi, Ali; Alkhatib, Hatim

2015-10-01

The purpose of this work was to investigate the influence of Eudragit®E100 polymer in modifying the release rates and compaction properties of water soluble model drug paracetamol from Carbopol®971P NF polymer matrix tablets prepared by direct compression. The effects of the ratio of the two polymers, the total polymeric content, and the tablets mechanical strength on paracetamol release rates were investigated. Dissolution studies were conducted using USP XX Π rotating paddle apparatus at 50 rpm and 37°C at three different stages (pH 1.2, 4.8, and 6.8). Results showed that the polymers combination improved significantly the compaction properties of paracetamol tablets as evident by the higher crushing strengths (8.3 ± 0.4 Kp) compared to polymer-free tablets (3.4 ± 0.2 Kp) at intermediate compression pressure of 490 MPa. When combined with Carbopol®971P NF, Eudragit®E100 was found to be capable of extending paracetamol release for more than 12 h compared to 1 h for polymers-free tablets. The combined polymers were able to control paracetamol release in a pH independent pattern. The f2 (similarity factor) analysis showed that the ratio between the polymers and the total polymer concentration exhibited significant impact on drug release rates. In conclusion, Eudragit®E100 when combined with Carbopol®971P NF was capable of improving the compaction and sustained release properties of paracetamol. Korsmeyer-Peppas model was found to be the most suitable for fitting drug release data. The polymer combinations can potentially be used to control the release rates of highly water soluble drugs.

Interaction between fed gastric media (Ensure Plus®) and different hypromellose based caffeine controlled release tablets: comparison and mechanistic study of caffeine release in fed and fasted media versus water using the USP dissolution apparatus 3.

PubMed

Franek, Frans; Holm, Per; Larsen, Frank; Steffansen, Bente

2014-01-30

The aim of the study was to investigate caffeine release in fed and fasted state media from three controlled release matrix tablets containing different HPMC viscosity grades. The biorelevant in vitro dissolution methods utilize the USP 3 dissolution apparatus and biorelevant media to simulate fed and fasted gastro-intestinal dissolution conditions. The effect of tablet reciprocation rate (dip speed) in dissolution media (10 and 15 dips per minute) and media (water, fed and fasted) on caffeine release rate from - and erosion rate of - 100, 4000 and 15,000 mPa s HPMC viscosity tablets was investigated using factorial designed experiments. Furthermore, the mechanism of release in Ensure Plus(®), a nutrition drink similar in composition to the FDA standard meal, was investigated by studying tablet swelling using texture analysis. Altering dip speed has negligible effect on release and erosion rates. Using fasted media instead of water slightly decreases caffeine release from 100 and 4000 mPa s HPMC viscosity tablets as well as erosion rates, while 15,000 mPa s tablets remain unaffected. Fed compared to fasted media decreases caffeine release rate, and the food effect is greater for the 100 mPa s viscosity tablets compared to the 4000 and 15,000 mPa s viscosity tablets. The investigation using texture analysis indicates that Ensure Plus(®) becomes rate-limiting for caffeine release from HPMC tablets by forming a hydrophobic barrier around the tablets. The barrier decreases tablet water permeation, which decreases erosion rate in 100 mPa s viscosity tablets, swelling in 15,000 mPa s viscosity tablets and caffeine release from both tablets. This observed interaction between Ensure Plus(®) and the HPMC tablets may translate into decreased drug release rate in the fed stomach, which may decrease the amount of drug available for absorption in the small intestine and thus reduce systemic drug exposure and maximum plasma concentration. Copyright © 2013 Elsevier B.V. All rights reserved.

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

PubMed

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.

Ultrasound Stimulation of Insulin Release from Pancreatic Beta Cells

NASA Astrophysics Data System (ADS)

Suarez Castellanos, Ivan M.

Type 2 diabetes (T2D) mellitus is a complex metabolic disease that has reached epidemic proportions in the United States and around the world. Controlling T2D is often difficult as pharmacological management routinely requires complex therapy with multiple medications, and loses its effectiveness over time. The objective of this dissertation was to explore a novel, non-pharmacological approach that utilizes the application of ultrasound energy to stimulate insulin release. Our experiments have focused on determination of effectiveness and safety of ultrasound application in stimulation of insulin release from the pancreatic beta cells. Our results showed that ultrasound treatment, applied at frequencies of 800 kHz and 1 MHz and intensities of 0.5 W/cm2 and 1 W/cm2, did not produce any significant effects on cell viability compared to sham group as assessed with trypan blue dye exclusion test and MTT cytotoxicity assay. ELISA quantification of insulin release from beta cells resulting from ultrasound treatment showed clinically-significant amounts of released insulin as compared to sham-treated beta cells. Carbon fiber amperometry detection of secretory events from dopamine-loaded beta cells treated with ultrasound showed that release of secretory content could be temporally controlled by careful selection of ultrasound parameters. Both ELISA and amperometry experiments demonstrated that ultrasound-stimulated insulin release is a calcium-dependent process, potentially mediated by the mechanical effects of ultrasound. This study demonstrated that therapeutic ultrasound is a technique capable of stimulating the release of insulin from pancreatic beta cells in a safe, effective and controlled manner.

Pharmaceutical quality of "party pills" raises additional safety concerns in the use of illicit recreational drugs.

PubMed

Young, Simon A; Thrimawithana, Thilini R; Antia, Ushtana; Fredatovich, John D; Na, Yonky; Neale, Peter T; Roberts, Amy F; Zhou, Huanyi; Russell, Bruce

2013-06-14

To determine the content and release kinetics of 1-benzylpiperazine (BZP) and 1-(3-trifluoromethyl-phenyl)piperazine (TFMPP) from "party pill" formulations. From these data, the possible impact of pharmaceutical quality upon the safety of such illicit formulations may be inferred. The amount of BZP and TFMPP in party pill formulations was determined using a validated HPLC method. The in-vitro release kinetics of selected party pill brands were determined using a USP dissolution apparatus (75 rpm, 37.5 degrees Celsius). The release data were then fitted to a first order release model using PLOT software and the time taken to achieve 90% release reported. Many of the tested party pill brands contained amounts of BZP and TFMPP that varied considerably from that stated on the packaging; including considerable TFMPP content in some brands not labelled to contain this drug. Dissolution studies revealed that there was considerable variability in the release kinetics between brands; in one case 90% release required >30 minutes. Lack of quality control in party pill manufacture may have led to the toxic effects reported by users unaware of the true content and release of drug from pills. More stringent regulation in the manufacture and quality control of "new generation party pills" is essential to the harm reduction campaign.

Controlling insulin release from reverse hexagonal (HII) liquid crystalline mesophase by enzymatic lipolysis.

PubMed

Mishraki-Berkowitz, Tehila; Cohen, Guy; Aserin, Abraham; Garti, Nissim

2018-01-01

In the present study we aimed to control insulin release from the reverse hexagonal (H II ) mesophase using Thermomyces lanuginosa lipase (TLL) in the environment (outer TLL) or within the H II cylinders (inner TLL). Two insulin-loaded systems differing by the presence (or absence) of phosphatidylcholine (PC) were examined. In general, incorporation of PC into the H II interface (without TLL) increased insulin release, as a more cooperative system was formed. Addition of TLL to the systems' environments resulted in lipolysis of the H II structure. In the absence of PC, the lipolysis was more dominant and led to a significant increase in insulin release (50% after 8h). However, the presence of PC stabilized the interface, hindering the lipolysis, and therefore no impact on the release profile was detected during the first 8h. Entrapment of TLL within the H II cylinders (with and without PC) drastically increased insulin release in both systems up to 100%. In the presence of PC insulin released faster and the structure was more stable. Consequently, the presence of lipases (inner or outer) both enhanced the destruction of the carrier, and provided sustained release of the entrapped insulin. Copyright © 2017 Elsevier B.V. All rights reserved.

Eradication of Helicobacter pylori restores the inhibitory effect of cholecystokinin on postprandial gastrin release in duodenal ulcer patients.

PubMed Central

Konturek, J W; Gillessen, A; Konturek, S J; Domschke, W

1995-01-01

Helicobacter pylori infection may be associated with duodenal ulcer (DU) and accompanied by enhanced gastrin release but the mechanism of this H pylori related hypergastrinaemia in DU patients is unclear. Cholecystokinin (CCK) has been implicated in the feedback control of gastrin release and gastric acid secretion in healthy subjects. This study therefore investigated if CCK participates in the impairment of postprandial gastrin release and gastric secretion in six DU patients. Tests were undertaken with and without elimination of endogenous CCK by loxiglumide, a selective CCK-A receptors antagonist, before and after eradication of H pylori with triple therapy (omeprazole, amoxicyllin, bismuth). In H pylori positive DU patients, the post-prandial decline in pH (with median pH 3.5) was accompanied by a pronounced increment in plasma gastrin but the administration of loxiglumide did not affect significantly this postprandial rise in plasma gastrin and gastric pH profile. After eradication of H pylori, the plasma gastrin concentration was reduced while the median postprandial pH was significantly increased (median pH 4.3). The administration of loxiglumide resulted in significantly greater increase in postprandial plasma gastrin and greater decrease in pH (median pH 3.1) in these patients. This study shows that (a) infection with H pylori is accompanied by an enhanced gastrin release and gastric acidity in DU patients, (b) the failure of loxiglumide to affect plasma gastrin or gastric acid secretion in H pylori infected DU patients could be attributed, at least in part, to the failure of endogenous CCK to control gastrin release and gastric secretion by releasing somatostatin, and (c) the test with loxiglumide may be useful in the identification of patients with impaired feedback control of gastrin release and gastric secretion resulting from infection with H pylori. PMID:7489932

Combustion instability and active control: Alternative fuels, augmentors, and modeling heat release

NASA Astrophysics Data System (ADS)

Park, Sammy Ace

Experimental and analytical studies were conducted to explore thermo-acoustic coupling during the onset of combustion instability in various air-breathing combustor configurations. These include a laboratory-scale 200-kW dump combustor and a 100-kW augmentor featuring a v-gutter flame holder. They were used to simulate main combustion chambers and afterburners in aero engines, respectively. The three primary themes of this work includes: 1) modeling heat release fluctuations for stability analysis, 2) conducting active combustion control with alternative fuels, and 3) demonstrating practical active control for augmentor instability suppression. The phenomenon of combustion instabilities remains an unsolved problem in propulsion engines, mainly because of the difficulty in predicting the fluctuating component of heat release without extensive testing. A hybrid model was developed to describe both the temporal and spatial variations in dynamic heat release, using a separation of variables approach that requires only a limited amount of experimental data. The use of sinusoidal basis functions further reduced the amount of data required. When the mean heat release behavior is known, the only experimental data needed for detailed stability analysis is one instantaneous picture of heat release at the peak pressure phase. This model was successfully tested in the dump combustor experiments, reproducing the correct sign of the overall Rayleigh index as well as the remarkably accurate spatial distribution pattern of fluctuating heat release. Active combustion control was explored for fuel-flexible combustor operation using twelve different jet fuels including bio-synthetic and Fischer-Tropsch types. Analysis done using an actuated spray combustion model revealed that the combustion response times of these fuels were similar. Combined with experimental spray characterizations, this suggested that controller performance should remain effective with various alternative fuels. Active control experiments validated this analysis while demonstrating 50-70% reduction in the peak spectral amplitude. A new model augmentor was built and tested for combustion dynamics using schlieren and chemiluminescence techniques. Novel active control techniques including pulsed air injection were implemented and the results were compared with the pulsed fuel injection approach. The pulsed injection of secondary air worked just as effectively for suppressing the augmentor instability, setting up the possibility of more efficient actuation strategy.

Effects of Lidocaine, Bupivacaine, and Ropivacaine on Calcitonin Gene-Related Peptide and Substance P Levels in the Incised Rat Skin.

PubMed

Lapin, Guilherme A F; Hochman, Bernardo; Maximino, Jessica R; Chadi, Gerson; Ferreira, Lydia M

2016-04-01

To evaluate the effect of 2% lidocaine, 0.5% bupivacaine, and 0.75% ropivacaine on the release of substance P (SP) and calcitonin gene-related peptide (CGRP) in skin wounds. A primary, experimental, analytical, prospective, self-controlled, blinded study. The study is set in a university research center. Twenty-eight Wistar rats were randomly divided into 4 groups: lidocaine, bupivacaine, ropivacaine, and the control. After general anesthesia, a local anesthetic or 0.9% saline (control) was injected subdermally along a 2-cm line on the dorsal midline of each rat; 30 minutes later, an incision (nociceptive stimulus) was made along this line. The animals were euthanized, and skin samples were collected from the center of the incision line and sent for CGRP and SP quantification. Quantification of CGRP and SP by Western blotting. Substance P levels were similar in the lidocaine and ropivacaine groups but were significantly lower than those of the control group (P = .002); no significant difference in SP levels was found between the bupivacaine and control groups. Procalcitonin gene-related peptide levels were significantly lower in the experimental groups than those in control subjects (P = .009), with no significant differences among the experimental groups. No significant differences in CGRP levels were found among all groups. Lidocaine and ropivacaine inhibited SP release. All 3 local anesthetics inhibited the release of procalcitonin gene-related peptide, but not the release of CGRP in rat skin. Lidocaine and ropivacaine may inhibit neurogenic inflammation by biochemical pathways activated by SP, whereas bupivacaine seems to have no influence on this process.

Control of arachidonic acid release in chick muscle cultures

NASA Technical Reports Server (NTRS)

Templeton, G. H.; Padalino, M.; Wright, W.

1985-01-01

Cultures from thigh muscles of 12 day old embryonic chicks are utilized to examine arachidonic release, prostaglandin (PG) biosynthesis, and protein synthesis. The preparation of the cultures is described. It is observed that exogenous arachidonic acid is formed into photsphatidylethanolamine and phosphatidylcholine, is released by a calcium ionosphere or phospholiphase simulator, and is the substrate for the biosynthesis of PG; the epidermal growth factor and PGF do not stimulate protein synthesis over the basal levels. The relationship between arachidonate release and melittin is studied. The data reveal that a change in intracellular calcium stimulates phospholiphase activity, arachidonate release, and PG synthesis in chick muscle culture.

Development of electrospun beaded fibers from Thai silk fibroin and gelatin for controlled release application.

PubMed

Somvipart, Siraporn; Kanokpanont, Sorada; Rangkupan, Rattapol; Ratanavaraporn, Juthamas; Damrongsakkul, Siriporn

2013-04-01

Thai silk fibroin and gelatin are attractive biomaterials for tissue engineering and controlled release applications due to their biocompatibility, biodegradability, and bioactive properties. The development of electrospun fiber mats from silk fibroin and gelatin were reported previously. However, burst drug release from such fiber mats remained the problem. In this study, the formation of beads on the fibers aiming to be used for the sustained release of drug was of our interest. The beaded fiber mats were fabricated using electrospinning technique by controlling the solution concentration, weight blending ratio of Thai silk fibroin/gelatin blend, and applied voltage. It was found that the optimal conditions including the solution concentration and the weight blending ratio of Thai silk fibroin/gelatin at 8-10% (w/v) and 70/30, respectively, with the applied voltage at 18 kV provided the fibers with homogeneous formation of beads. Then, the beaded fiber mats obtained were crosslinked by the reaction of carbodiimide hydrochloride (EDC)/N-hydroxysuccinimide (NHS). Methylene blue as a model active compound was loaded on the fiber mats. The release test of methylene blue from the beaded fiber mats was carried out in comparison to that of the smooth fiber mats without beads. It was found that the beaded fiber mats could prolong the release of methylene blue, comparing to the smooth fiber mats without beads. This was possibly due to the beaded fiber mats that would absorb and retain higher amount of methylene blue than the fiber mats without beads. Thai silk fibroin/gelatin beaded fiber mats were established as an effective carrier for the controlled release applications. Copyright © 2013 Elsevier B.V. All rights reserved.

Dietary uridine-5'-monophosphate supplementation increases potassium-evoked dopamine release and promotes neurite outgrowth in aged rats.

PubMed

Wang, Lei; Pooler, Amy M; Albrecht, Meredith A; Wurtman, Richard J

2005-01-01

Membrane phospholipids like phosphatidylcholine (PC) are required for cellular growth and repair, and specifically for synaptic function. PC synthesis is controlled by cellular levels of its precursor, cytidine-5'-diphosphate choline (CDP-choline), which is produced from cytidine triphosphate (CTP) and phosphocholine. In rat PC12 cells exogenous uridine was shown to elevate intracellular CDP-choline levels, by promoting the synthesis of uridine triphosphate (UTP), which was partly converted to CTP. In such cells uridine also enhanced the neurite outgrowth produced by nerve growth factor (NGF). The present study assessed the effect of dietary supplementation with uridine-5'-monophosphate disodium (UMP-2Na+, an additive in infant milk formulas) on striatal dopamine (DA) release in aged rats. Male Fischer 344 rats consumed either a control diet or one fortified with 2.5% UMP for 6 wk, ad libitum. In vivo microdialysis was then used to measure spontaneous and potassium (K+)-evoked DA release in the right striatum. Potassium (K+)-evoked DA release was significantly greater among UMP-treated rats, i.e., 341+/-21% of basal levels vs. 283+/-9% of basal levels in control rats (p<0.05); basal DA release was unchanged. In general, each animal's K+-evoked DA release correlated with its striatal DA content, measured postmortem. The levels of neurofilament-70 and neurofilament-M proteins, biomarkers of neurite outgrowth, increased to 182+/-25% (p<0.05) and 221+/-34% (p<0.01) of control values, respectively, with UMP consumption. Hence, UMP treatment not only enhances membrane phosphatide production but also can modulate two membrane-dependent processes, neurotransmitter release and neurite outgrowth, in vivo.

49 CFR 236.506 - Release of brakes after automatic application.

Code of Federal Regulations, 2010 CFR

2010-10-01

... INSTALLATION, INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Automatic Train Stop, Train Control and Cab Signal Systems Standards § 236.506 Release of brakes after automatic application. The automatic train stop or train control apparatus shall prevent release of the...

49 CFR 236.506 - Release of brakes after automatic application.

Code of Federal Regulations, 2011 CFR

2011-10-01

... INSTALLATION, INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Automatic Train Stop, Train Control and Cab Signal Systems Standards § 236.506 Release of brakes after automatic application. The automatic train stop or train control apparatus shall prevent release of the...

Applied dendroecology and environmental forensics. Characterizing and age dating environmental releases: fundamentals and case studies

Treesearch

Jean-Christophe Balouet; Gil Oudijk; Kevin T. Smith; Ioana Petrisor; Hakan Grudd; Bengt Stocklassa

2007-01-01

Dendroecology, or the use of ring patterns to assess the age of trees and environmental factors controlling their growth, is a well-developed method in climatologic studies. This method holds great potential as a forensic tool for age dating, contamination assessment, and characterization of releases. Moreover, the method is independent of the physical presence of...

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

PubMed Central

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

Controlled release of betamethasone from vitamin E-loaded silicone-based soft contact lenses.

PubMed

Rad, Maryam Shayani; Sajadi Tabassi, Sayyed Abolghasem; Moghadam, Maryam Hassanpour; Mohajeri, Seyed Ahmad

2016-11-01

Betamethasone (BMZ) is an effective drug which is commonly used as an eye drop for the management of ophthalmic inflammations. Due to low ocular bioavailability, it is necessary to prepare and optimize an ocular drug delivery system for BMZ. In this study we tried to use vitamin E diffusion barrier for sustaining BMZ release. Three commercial contact lenses were soaked in vitamin E solutions and swelling percentage, diameter, transmittance, binding capacity and release amount and time were evaluated in comparison with non-vitamin E-loaded pure lenses. The results showed that vitamin E significantly decreased water content of contact lenses whereas, increased the lens diameter in both dry and wet states. It effectively blocked UV radiation which is harmful for the eye surface while had no significant effect on visible transmittance. BMZ loading capacity enhanced and release rate remarkably decreased after using vitamin E as a hydrophobic diffusion barrier. This study revealed that vitamin E can be applied as a hydrophobic diffusion barrier for controlling and sustaining BMZ release from silicone-based soft contact lenses into the lachrymal fluid. It can also protect eye tissues as an antioxidant by blocking the UV radiation.

Electrosprayed nanoparticle delivery system for controlled release.

PubMed

Eltayeb, Megdi; Stride, Eleanor; Edirisinghe, Mohan; Harker, Anthony

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 70nm at the rate of 1.37×10(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. Copyright © 2016 Elsevier B.V. All rights reserved.

MMC controlled-release membranes attenuate epidural scar formation in rat models after laminectomy.

PubMed

Xie, Hao; Wang, Binbin; Shen, Xun; Qin, Jian; Jiang, Longhai; Yu, Chen; Geng, Dawei; Yuan, Tangbo; Wu, Tao; Cao, Xiaojian; Liu, Jun

2017-06-01

Epidural scar formation after laminectomy impede surgical outcomes of decompression. Mitomycin C (MMC) has been demonstrated to have significant inhibitory effects on epidural scar. This study was undertaken to develop an effective MMC controlled‑release membrane and to investigate its effects on epidural scar in rat models of laminectomy. A total of 72 rats that underwent laminectomy were divided into three groups. Among them, 24 were treated with mitomycin C‑polylactic acid (MMC-PLA) controlled‑release membrane, 24 with mitomycin C-polyethylene glycol (MMC-PEG) controlled-release membrane, and no treatment was performed for the remaining 24 rats (control group). In the following 4 weeks, magnetic resonance image (MRI), macroscopic observation, histology and hydroxyproline (Hyp) concentration analysis were performed to explore the effects of these three therapies on epidural scar. MRI revealed a significant reduction of epidural fibrosis in MMC-PLA and MMC-PEG treatment groups, compared with the control group. Histological results also showed that collagen deposition was significantly reduced after being treated with MMC-PLA or MMC-PEG membranes. Likewise, Hyp concentrations of the epidural scar tissue in MMC-PLA and MMC-PEG groups were markedly lower than those in the control group. However, regarding the effects on reducing epidural scar, no significant difference was found between the MMC-PLA and MMC-PEG groups. In conclusion, MMC-PLA and MMC-PEG membranes are safe and effective in reducing fibrosis. Thus, MMC-controlled-release membranes promises to be a potential therapeutic in preventing epidural scar formation after laminectomy.

Control of Alginate Core Size in Alginate-Poly (Lactic-Co-Glycolic) Acid Microparticles

NASA Astrophysics Data System (ADS)

Lio, Daniel; Yeo, David; Xu, Chenjie

2016-01-01

Core-shell alginate-poly (lactic-co-glycolic) acid (PLGA) microparticles are potential candidates to improve hydrophilic drug loading while facilitating controlled release. This report studies the influence of the alginate core size on the drug release profile of alginate-PLGA microparticles and its size. Microparticles are synthesized through double-emulsion fabrication via a concurrent ionotropic gelation and solvent extraction. The size of alginate core ranges from approximately 10, 50, to 100 μm when the emulsification method at the first step is homogenization, vortexing, or magnetic stirring, respectively. The second step emulsification for all three conditions is performed with magnetic stirring. Interestingly, although the alginate core has different sizes, alginate-PLGA microparticle diameter does not change. However, drug release profiles are dramatically different for microparticles comprising different-sized alginate cores. Specifically, taking calcein as a model drug, microparticles containing the smallest alginate core (10 μm) show the slowest release over a period of 26 days with burst release less than 1 %.

Preparation and evaluation of a controlled drug release of repaglinide through matrix pellets: in vitro and in vivo studies.

PubMed

Tavakoli, Naser; Minaiyan, Mohsen; Tabbakhian, Majid; Pendar, Yaqub

2014-01-01

Repaglinide, an oral antidiabetic agent, has a rapid onset of action and short half-life of approximately 1 h. Designing a controlled release dosage form of the drug is required to maintain its therapeutic blood level and to eliminate its adverse effects, particularly the hypoglycaemia. Repaglinide sustained release matrix pellets consisting of Avicel, lactose and different polymers were prepared using extrusion-spheronisation method. The effect of different formulation components on in vitro drug release were evaluated using USP apparatus (paddle) for 12 h in phosphate buffer. The optimised formulation was orally administrated to normal and STZ induced diabetic rats. Most pellet formulations had acceptable physical properties with regard to size distribution, flowability and friability. Repaglinide pellets comprising Avicel 50%, lactose 47% and SLS 1% were released 94% of its drug content after 12 h. The optimised formulation was able to decrease blood glucose level in normal rats and those with diabetes throughout 8-12 h.

Synthetic Zeolites as Controlled-Release Delivery Systems for Anti-Inflammatory Drugs.

PubMed

Khodaverdi, Elham; Soleimani, Hossein Ali; Mohammadpour, Fatemeh; Hadizadeh, Farzin

2016-06-01

Scientists have always been trying to use artificial zeolites to make modified-release drug delivery systems in the gastrointestinal tract. An ideal carrier should have the capability to release the drug in the intestine, which is the main area of absorption. Zeolites are mineral aluminosilicate compounds with regular structure and huge porosity, which are available in natural and artificial forms. In this study, soaking, filtration and solvent evaporation methods were used to load the drugs after activation of the zeolites. Weight measurement, spectroscopy FTIR, thermogravimetry and scanning electronic microscope were used to determine drug loading on the systems. Finally, consideration of drug release was made in a simulated gastric fluid and a simulated intestinal fluid for all matrixes (zeolites containing drugs) and drugs without zeolites. Diclofenac sodium (D) and piroxicam (P) were used as the drug models, and zeolites X and Y as the carriers. Drug loading percentage showed that over 90% of drugs were loaded on zeolites. Dissolution tests in stomach pH environment showed that the control samples (drug without zeolite) released considerable amount of drugs (about 90%) within first 15 min when it was about 10-20% for the matrixes. These results are favorable as NSAIDs irritate the stomach wall and it is ideal not to release much drugs in the stomach. Furthermore, release rate of drugs from matrixes has shown slower rate in comparison with control samples in intestine pH environment. © 2016 John Wiley & Sons A/S.

Water conditioning and whooping crane survival after release in Florida

USGS Publications Warehouse

Gee, G.F.; Nicolich, Jane M.; Nesbitt, S.A.; Hatfield, J.S.; Ellis, D.H.; Olsen, Glenn H.

2001-01-01

About 50% of the whooping cranes (Grus americana) released in Florida die within the first year of release. Most of these deaths and those in subsequent years result from bobcat (Lynx rufus) predation. Choosing release sites in open marshes away from bobcat habitat has improved survival. We hypothesized that exposure to ponds (water conditioning) at the rearing site would encourage birds to roost in deeper water marshes after release and such exposure would thereby reduce bobcat predation. In this study, we moved young birds (ca 50 days of age) to netted pens with large (15-m diameter), deep 30-60 cm) naturally vegetated ponds. We randomly assigned the costume-reared whooping cranes into 2 equal-sized groups at fledging. Some groups were placed in pens with a pond (experimental or ponded groups) and the others we reared without additional water exposure (control groups). All birds in the pens with ponds used the water. At night, they roosted at a depth of 36-46 cm. During the day, the birds used the ponds as well as other areas of the pen. We released 3 pairs of water-conditioned and control cohorts, 1 set in 1995 and 2 in 1996. No obvious behavioral differences were noted between the cohorts released in those years. Controls survived as expected (about 60% first year survival). The water-conditioned birds had much higher survival the first year (85%) and continued to survive better for the next 3 years.

Preparation and Characterization of Azadirachtin Alginate-Biosorbent Based Formulations: Water Release Kinetics and Photodegradation Study.

PubMed

Flores-Céspedes, Francisco; Martínez-Domínguez, Gerardo P; Villafranca-Sánchez, Matilde; Fernández-Pérez, Manuel

2015-09-30

The botanical insecticide azadirachtin was incorporated in alginate-based granules to obtain controlled release formulations (CRFs). The basic formulation [sodium alginate (1.47%) - azadirachtin (0.28%) - water] was modified by the addition of biosorbents, obtaining homogeneous hybrid hydrogels with high azadirachtin entrapment efficiency. The effect on azadirachtin release rate caused by the incorporation of biosorbents such as lignin, humic acid, and olive pomace in alginate formulation was studied by immersion of the granules in water under static conditions. The addition of the biosorbents to the basic alginate formulation reduces the rate of release because the lignin-based formulation produces a slower release. Photodegradation experiments showed the potential of the prepared formulations in protecting azadirachtin against simulated sunlight, thus improving its stability. The results showed that formulation prepared with lignin provided extended protection. Therefore, this study provides a new procedure to encapsulate the botanical insecticide azadirachtin, improving its delivery and photostability.

The evaluation of doxycycline controlled release gel versus doxycycline controlled release implant in the management of periodontitis

PubMed Central

Chadha, Vandana Srikrishna; Bhat, Khandige Mahalinga

2012-01-01

Background: Investigators have sought different methods to deliver antimicrobials to periodontal pockets. This study was designed to assess the efficacy of locally made doxycycline gel versus locally made doxycycline implant as biodegradable controlled local delivery systems, by evaluating the pharmacological drug release and improvement in gingival status, gain in attachment, and reduction in pocket depth. Materials and Methods: Thirty patients with localized periodontal pockets ≥5 mm were randomly divided into three groups. The first group received the doxycycline gel, the second the doxycycline implant, and the third received only scaling and root planing (the control group). The patients in the first two groups were selected for the drug release. Clinical parameters such as gingival index, plaque index, probing depth, and attachment levels were recorded at baseline and the 90th day. Gingival crevicular fluid (GCF) and saliva samples were collected 1 hour following gel and implant placement and then on the 10th, 30th, and 60th days. Results: There was a statistically significant difference in the release of doxycycline from the gel when compared with the implant in the GCF and saliva on the 10th and 30th days. All the three groups showed improvement in clinical parameters. The improvements in both gel and implant groups were greater when compared with the control group with no statistically significant difference between the implant and gel systems. Conclusion: The use of local delivery of doxycycline through gel and Implant media further enhances the positive changes obtained following scaling and root planing. The release of doxycycline from the implant and the gel was comparable. PMID:23055585

Exposure Assessment of a High-energy Tensile Test With Large Carbon Fiber Reinforced Polymer Cables.

PubMed

Schlagenhauf, Lukas; Kuo, Yu-Ying; Michel, Silvain; Terrasi, Giovanni; Wang, Jing

2015-01-01

This study investigated the particle and fiber release from two carbon fiber reinforced polymer cables that underwent high-energy tensile tests until rupture. The failing event was the source of a large amount of dust whereof a part was suspected to be containing possibly respirable fibers that could cause adverse health effects. The released fibers were suspected to migrate through small openings to the experiment control room and also to an adjacent machine hall where workers were active. To investigate the fiber release and exposure risk of the affected workers, the generated particles were measured with aerosol devices to obtain the particle size and particle concentrations. Furthermore, particles were collected on filter samples to investigate the particle shape and the fiber concentration. Three situations were monitored for the control room and the machine hall: the background concentrations, the impact of the cable failure, and the venting of the exposed rooms afterward. The results showed four important findings: The cable failure caused the release of respirable fibers with diameters below 3 μm and an average length of 13.9 μm; the released particles did migrate to the control room and to the machine hall; the measured peak fiber concentration of 0.76 fibers/cm(3) and the overall fiber concentration of 0.07 fibers/cm(3) in the control room were below the Permissible Exposure Limit (PEL) for fibers without indication of carcinogenicity; and the venting of the rooms was fast and effective. Even though respirable fibers were released, the low fiber concentration and effective venting indicated that the suspected health risks from the experiment on the affected workers was low. However, the effect of long-term exposure is not known therefore additional control measures are recommended.

What factors are related to success on conditional release/discharge? Findings from the New Orleans forensic aftercare clinic: 2002-2013.

PubMed

Manguno-Mire, Gina M; Coffman, Kelly L; DeLand, Sarah M; Thompson, John W; Myers, Leann

2014-09-01

The present study investigated the empirically based factors that predicted success on conditional release among a sample of individuals conditionally discharged in Louisiana. Not guilty by reason of insanity acquittees and individuals on conditional release/discharge for incompetency to stand trial were included in the study. Success on conditional release was defined as maintenance of conditional release during the study period. Recidivism (arrest on new charges) and incidents were empirically evaluated. Success on conditional release was maintained in over 70% of individuals. Recidivism was low, with only five arrests on new charges. Success on conditional release was predicted by financial resources, not having a personality disorder, and having fewer total incidents in the program. After controlling for the influence of other variables, having an incident on conditional release was predicted by a substance use diagnosis and being released from jail. Individuals conditionally released from jail showed fewer number of days to first incident (67 vs. 575 days) compared with individuals discharged from the hospital. These data provide support for the successful management of forensic patients in the community via conditional release, although they highlight specific factors that should be considered when developing community-based release programming. Conditional release programs should consider empirical factors in the development of risk assessment and risk management approaches to improve successful maintenance of community-based forensic treatment alternatives. Copyright © 2014 John Wiley & Sons, Ltd.

Double loaded self-decomposable SiO2 nanoparticles for sustained drug release

NASA Astrophysics Data System (ADS)

Zhao, Saisai; Zhang, Silu; Ma, Jiang; Fan, Li; Yin, Chun; Lin, Ge; Li, Quan

2015-10-01

Sustained drug release for a long duration is a desired feature of modern drugs. Using double-loaded self-decomposable SiO2 nanoparticles, we demonstrated sustained drug release in a controllable manner. The double loading of the drugs was achieved using two different mechanisms--the first one via a co-growth mechanism, and the second one by absorption. A two-phase sustained drug release was firstly revealed in an in vitro system, and then further demonstrated in mice. After a single intravenous injection, the drug was controllably released from the nanoparticles into blood circulation with a Tmax of about 8 h, afterwards a long lasting release pattern was achieved to maintain drug systemic exposure with a plasma elimination half-life of approximately 28 h. We disclosed that the absorbed drug molecules contributed to the initial fast release for quickly reaching the therapeutic level with relatively higher plasma concentrations, while the ``grown-in'' drugs were responsible for maintaining the therapeutic level via the later controlled slow and sustained release. The present nanoparticle carrier drug configuration and the loading/maintenance release mechanisms provide a promising platform that ensures a prolonged therapeutic effect by controlling drug concentrations within the therapeutic window--a sustained drug delivery system with a great impact on improving the management of chronic diseases.Sustained drug release for a long duration is a desired feature of modern drugs. Using double-loaded self-decomposable SiO2 nanoparticles, we demonstrated sustained drug release in a controllable manner. The double loading of the drugs was achieved using two different mechanisms--the first one via a co-growth mechanism, and the second one by absorption. A two-phase sustained drug release was firstly revealed in an in vitro system, and then further demonstrated in mice. After a single intravenous injection, the drug was controllably released from the nanoparticles into blood circulation with a Tmax of about 8 h, afterwards a long lasting release pattern was achieved to maintain drug systemic exposure with a plasma elimination half-life of approximately 28 h. We disclosed that the absorbed drug molecules contributed to the initial fast release for quickly reaching the therapeutic level with relatively higher plasma concentrations, while the ``grown-in'' drugs were responsible for maintaining the therapeutic level via the later controlled slow and sustained release. The present nanoparticle carrier drug configuration and the loading/maintenance release mechanisms provide a promising platform that ensures a prolonged therapeutic effect by controlling drug concentrations within the therapeutic window--a sustained drug delivery system with a great impact on improving the management of chronic diseases. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr03029c

Reconviction and revocation rates in Flanders after medium security treatment.

PubMed

Jeandarme, Inge; Habets, Petra; Oei, T I; Bogaerts, Stefan

2016-01-01

To examine the criminal outcome of Flemish forensic psychiatric patients ('internees') after medium security treatment. Also, the effect of conditional release on recidivism of two subgroups (internees under conditional release and internees who received unconditional release) was examined. Reconviction rates and revocation rates were collected for all participants. Kaplan-Meier survival analyses were used to investigate recidivism rates while controlling for time at risk. During the 10-year period, 502 offenders were discharged from medium security treatment. Over a follow-up period averaging 3.6years, 7.4% of discharged patients were reconvicted or received a new 'not guilty by reason of insanity' (NGRI) verdict for a violent offence. One-quarter of the population had their conditional release revoked. Part of the study population was granted unconditional release. Reconviction rates were higher after unconditional release in comparison to conditional release. The results of this study suggest that the court supervision of NGRI patients in Flanders is effective in protecting the community from further offending. Copyright © 2016 Elsevier Ltd. All rights reserved.

Encapsulation and release studies of strawberry polyphenols in biodegradable chitosan nanoformulation.

PubMed

Pulicharla, Rama; Marques, Caroline; Das, Ratul Kumar; Rouissi, Tarek; Brar, Satinder Kaur

2016-07-01

Polyphenols (negative groups) of strawberry extract interacts with positively protonated amino groups of chitosan which helps in maximum encapsulation. This approach can improve the bioavailability and sustained release of phytochemicals having lower bioavailability. The optimum mass ratio of chitosan-tripolyphosphate and polyphenols (PPs) loading was investigated to be 3:1 and 0.5mg/ml of strawberry extract, respectively. Prepared nanoformulation were characterized by UV-vis spectroscopy, Fourier transform infrared spectroscopy and scanning electron microscopy. The formed particles size ranged between 300 and 600nm and polydispersity index (PDI) of≈0.5. The optimized formulation showed encapsulation efficiency of 58.09% at 36.47% of polyphenols loading. Initial burst and continuous release of PPs was observed at pH 7.4 of in vitro release studies. PPs release profile at this pH was found to be non-Fickian analomous diffusion and the release was followed first order kinetics. And at pH 1.4, diffusion-controlled Fickian release of PPs was observed. Copyright © 2016 Elsevier B.V. All rights reserved.

ATP release from freshly isolated guinea-pig bladder urothelial cells: a quantification and study of the mechanisms involved.

PubMed

McLatchie, Linda M; Fry, Christopher H

2015-06-01

To quantify the amount of ATP released from freshly isolated bladder urothelial cells, study its control by intracellular and extracellular calcium and identify the pathways responsible for its release. Urothelial cells were isolated from male guinea-pig urinary bladders and stimulated to release ATP by imposition of drag forces by repeated pipetting. ATP was measured using a luciferin-luciferase assay and the effects of modifying internal and external calcium concentration and blockers of potential release pathways studied. Freshly isolated guinea-pig urothelial cells released ATP at a mean (sem) rate of 1.9 (0.1) pmoles/mm(2) cell membrane, corresponding to about 700 pmoles/g of tissue, and about half [49 (6)%, n = 9) of the available cell ATP. This release was reduced to a mean (sem) of 0.46 (0.08) pmoles/mm(2) (160 pmoles/g) with 1.8 mm external calcium, and was increased about two-fold by increasing intracellular calcium. The release from umbrella cells was not significantly different from a mixed intermediate and basal cell population, suggesting that all three groups of cells release a similar amount of ATP per unit area. ATP release was reduced by ≈ 50% by agents that block pannexin and connexin hemichannels. It is suggested that the remainder may involve vesicular release. A significant fraction of cellular ATP is released from isolated urothelial cells by imposing drag forces that cause minimal loss of cell viability. This release involves multiple release pathways, including hemichannels and vesicular release. © 2014 The Authors BJU International © 2014 BJU International.

Amphiphilic polymer based on fluoroalkyl and PEG side chains for fouling release coating

NASA Astrophysics Data System (ADS)

Cong, W. W.; Wang, K.; Yu, X. Y.; Zhang, H. Q.; Lv, Z.; Gui, T. J.

2017-12-01

Under static conditions, fouling release coating could not express good release property to marine organisms. Amphiphilic polymer with mixture of fluorinated monomer and short side group of polyethylene glycol (PEG) was synthesized. And also we studied the ability of amphiphilic polymer to influence the surface properties and how it controlled the adhesion of marine organisms to coated surfaces. By incorporating fluorinated monomer and PEG side chain into the polymer, the effect of incorporating both polar and non-polar groups on fouling-release coating could be studied. The dry surface was characterized by three-dimensional digital microscopy and scanning electron microscopy (SEM), and the morphology of the amphiphilic fouling release coating showed just like flaky petal. The amphiphilic polymer in fouling release coating tended to reconstruct in water, and the ability was examined by static contact angle, which was smaller than the PDMS (polydimethylsiloxane) fouling release coating. Also surface energy was calculated by three solvents, and surface energy of amphiphilic fouling release coating was higher than that of the PDMS fouling release coating. To understand more about its fouling release property, seawater exposure method was adopted in gulf of Qingdao port. Fewer diatoms Navicula were found in biofilm after using amphiphilic fouling release coating. In general, coating containing both PEG and fluorinated side chain possessed certain fouling release property.

Biodegradable nano-micro carrier systems for sustained pulmonary drug delivery: (I) Self-assembled nanoparticles encapsulated in respirable/swellable semi-IPN microspheres

PubMed Central

El-Sherbiny, I. M.; Smyth, H. D. C.

2012-01-01

Design of appropriate inhaled carriers with adequate aerodynamic properties, drug release, biodegradation and evasion of macrophage uptake is a major challenge for controlled release pulmonary drug delivery. In this study, PEG graft copolymerized onto N-phthaloyl chitosan (NPHCs) was synthesized then characterized using FTIR, EA, DSC and 2D-XRD. The resulting PEG-g-NPHCs copolymers were self-assembled into drug loaded nanoparticles and encapsulated in respirable/swellable sodium alginate semi-IPN hydrogel microspheres as novel biodegradable carriers for controlled release pulmonary drug delivery. The developed nano-/microspheres carrier systems were formed via spray drying followed by ionotropic crosslinking in mild aqueous medium. The size of the developed self-assembled nanoparticles and the microspheres was measured using dynamic light scattering and laser diffraction, respectively. Morphology, moisture content, in-vitro biodegradation and dynamic swelling studies were also investigated for the developed carriers. A model protein was entrapped and the in-vitro release profiles were determined in PBS, pH 7.4 at 37°C. A dry powder aerosolization study was conducted using a Next Generation Impactor (NGI). The developed microspheres had suitable aerodynamic diameters (1.02–2.63 μm) and an excellent fine particle fraction, FPF of 31.52%. The microspheres showed also a very fast initial swelling within the first 2 min and started to enzymatically degrade within the first two hours. Moreover, the microspheres entrapped up 90% of the model drug and showed promising in-vitro sustained release profiles as compared to the control formulation. PMID:20580794

The Effects of Angiotensin II and Angiotensin-(1–7) in the Rostral Ventrolateral Medulla of Rats on Stress-Induced Hypertension

PubMed Central

Du, Dongshu; Chen, Jun; Liu, Min; Zhu, Minxia; Jing, Haojia; Fang, Jie; Shen, Linlin; Zhu, Danian; Yu, Jerry; Wang, Jin

2013-01-01

We have shown that angiotensin II (Ang II) and angiotensin-(1–7) [Ang-(1–7)] increased arterial blood pressure (BP) via glutamate release when microinjected into the rostral ventrolateral medulla (RVLM) in normotensive rats (control). In the present study, we tested the hypothesis that Ang II and Ang-(1–7) in the RVLM are differentially activated in stress-induced hypertension (SIH) by comparing the effects of microinjection of Ang II, Ang-(1–7), and their receptor antagonists on BP and amino acid release in SIH and control rats. We found that Ang II had greater pressor effect, and more excitatory (glutamate) and less inhibitory (taurine and γ-aminobutyric acid) amino acid release in SIH than in control animals. Losartan, a selective AT1 receptor (AT1R) antagonist, decreased mean BP in SIH but not in control rats. PD123319, a selective AT2 receptor (AT2R) antagonist, increased mean BP in control but not in SIH rats. However, Ang-(1–7) and its selective Mas receptor antagonist Ang779 evoked similar effects on BP and amino acid release in both SIH and control rats. Furthermore, we found that in the RVLM, AT1R, ACE protein expression (western blot) and ACE mRNA (real-time PCR) were significantly higher, whereas AT2R protein, ACE2 mRNA and protein expression were significantly lower in SIH than in control rats. Mas receptor expression was similar in the two groups. The results support our hypothesis and demonstrate that upregulation of Ang II by AT1R, not Ang-(1–7), system in the RVLM causes hypertension in SIH rats by increasing excitatory and suppressing inhibitory amino acid release. PMID:23967142

Luteinising hormone releasing hormone for incomplete descent of the testis.

PubMed Central

Klidjian, A M; Swift, P G; Johnstone, J M

1985-01-01

Forty boys with 54 incompletely descended testes took part in a double blind, controlled trial of intranasal luteinising hormone releasing hormone. In the control (placebo) group of 18 boys there was no significant change in testicular descent and all required orchidopexy; in the 22 treated boys, however, 12 of 29 testes (42%) were found in a lower position. This study supports the idea that a trial of intranasal luteinising hormone releasing hormone (1200 micrograms/day for 28 days) will help clarify the need for orchidopexy in at least 30% of boys with incomplete descent of the testis, particularly those in whom the testes have emerged from the inguinal canal. PMID:2861791

Acid-Labile Acyclic Cucurbit[n]uril Molecular Containers for Controlled Release.

PubMed

Mao, Dake; Liang, Yajun; Liu, Yamin; Zhou, Xianhao; Ma, Jiaqi; Jiang, Biao; Liu, Jia; Ma, Da

2017-10-02

Stimuli-responsive molecular containers are of great importance for controlled drug delivery and other biomedical applications. A new type of acid labile acyclic cucurbit[n]uril (CB[n]) molecular containers is presented that can degrade and release the encapsulated cargo at accelerated rates under mildly acidic conditions (pH 5.5-6.5). These containers retain the excellent recognition properties of CB[n]-type hosts. A cell culture study demonstrated that the cellular uptake of cargos could be fine-tuned by complexation with different containers. The release and cell uptake of cargo dye was promoted by acidic pH. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

TiO2 nanocomposite for the controlled release of drugs against pathogens causing wound infections

NASA Astrophysics Data System (ADS)

Devanand Venkatasubbu, G.; Nagamuthu, S.; Anusuya, T.; Kumar, J.; Chelliah, Ramachandran; Rani Ramakrishnan, Sudha; Antony, Usha; Khan, Imran; Oh, Deog-Hwan

2018-02-01

Chitosan titanium dioxide nanocomposite has been used for wound healing. Titanium dioxide (TiO2) nanoparticles are synthesised and made in to nanocomposite along with chitosan. Curcumin nanoparticles are synthesised. Three different drugs with antimicrobial activity are incorporated into the chitosan/TiO2nanocomposite. Ciprofloxacin, amoxicillin and curcumin nanoparticles are incorporated within the chitosan/TiO2 nanoparticles. The nanoparticles and nanocomposite are characterized with XRD, FTIR, TEM and SEM. Drug loading was found to be around 45% for all the three drug molecules. The drug release profile shows a controlled release of drug molecules from the nanocomposite. Antibacterial studies shows a good inhibition of bacterial species by the nanocomposites.

Identification of conditions for successful aphid control by ladybirds in greenhouses

USDA-ARS?s Scientific Manuscript database

As part of my research on the mass production and augmentative release of ladybirds, I reviewed the primary research literature to test the prediction that ladybirds are effective aphid predators in greenhouses. Aphid population reduction exceeded 50% in most studies and ladybird release rates usual...

Relative benefits of stimulant therapy with OROS methylphenidate versus mixed amphetamine salts extended release in improving the driving performance of adolescent drivers with attention-deficit/hyperactivity disorder.

PubMed

Cox, Daniel J; Merkel, R Lawrence; Moore, Melissa; Thorndike, Frances; Muller, Carrie; Kovatchev, Boris

2006-09-01

Automobile accidents are the leading cause of death among adolescents, and collisions are 2 to 4 times more likely to occur among adolescents with attention-deficit/hyperactivity disorder. Studies have demonstrated that stimulants improve driving performance. This study compared 2 long-acting stimulant medications during daytime and evening driving evaluations. Adolescent drivers with attention-deficit/hyperactivity disorder were compared on a driving simulator after taking 72 mg of OROS methylphenidate, 30 mg of mixed amphetamine salts extended release, or placebo in a randomized, double-blind, placebo-controlled, crossover study design. During laboratory testing, adolescents drove a driving simulator at 5:00 pm, 8:00 pm, and 11:00 pm. Driving performance was rated by adolescents and investigators. The study included 35 adolescent drivers with attention-deficit/hyperactivity disorder (19 boys/16 girls). The mean age was 17.8 years. The overall Impaired Driving Score demonstrated that OROS methylphenidate led to better driving performance compared with placebo and mixed amphetamine salts extended release, whereas mixed amphetamine salts extended release demonstrated no statistical improvement over placebo. Specifically, relative to placebo, OROS methylphenidate resulted in less time driving off the road, fewer instances of speeding, less erratic speed control, more time executing left turns, and less inappropriate use of brakes. OROS methylphenidate and mixed amphetamine salts extended release worked equally well for male and female adolescents and equally as well with teenagers who have combined and inattentive subtypes of attention-deficit/hyperactivity disorder. This study validates the use of stimulants to improve driving performance in adolescents with attention-deficit/hyperactivity disorder. In the study, OROS methylphenidate promoted significantly improved driving performance compared with placebo and mixed amphetamine salts extended release.

Mutational Analysis of Rab3 Function for Controlling Active Zone Protein Composition at the Drosophila Neuromuscular Junction

PubMed Central

Roche, John P.; Alsharif, Peter; Graf, Ethan R.

2015-01-01

At synapses, the release of neurotransmitter is regulated by molecular machinery that aggregates at specialized presynaptic release sites termed active zones. The complement of active zone proteins at each site is a determinant of release efficacy and can be remodeled to alter synapse function. The small GTPase Rab3 was previously identified as playing a novel role that controls the distribution of active zone proteins to individual release sites at the Drosophila neuromuscular junction. Rab3 has been extensively studied for its role in the synaptic vesicle cycle; however, the mechanism by which Rab3 controls active zone development remains unknown. To explore this mechanism, we conducted a mutational analysis to determine the molecular and structural requirements of Rab3 function at Drosophila synapses. We find that GTP-binding is required for Rab3 to traffick to synapses and distribute active zone components across release sites. Conversely, the hydrolytic activity of Rab3 is unnecessary for this function. Through a structure-function analysis we identify specific residues within the effector-binding switch regions that are required for Rab3 function and determine that membrane attachment is essential. Our findings suggest that Rab3 controls the distribution of active zone components via a vesicle docking mechanism that is consistent with standard Rab protein function. PMID:26317909

[Effect on iron release in drinking water distribution systems].

PubMed

Niu, Zhang-bin; Wang, Yang; Zhang, Xiao-jian; Chen, Chao; Wang, Sheng-hui

2007-10-01

Batch-scale experiments were done to quantitatively study the effect of inorganic chemical parameters on iron release in drinking water distribution systems. The parameters include acid-base condition, oxidation-reduction condition, and neutral ion condition. It was found that the iron release rate decreased with pH, alkalinity, the concentration of dissolved oxygen increasing, and the iron release rate increased with the concentration of chloride increasing. The theoretical critical formula of iron release rate was elucidated. According to the formula, the necessary condition for controlling iron release is that pH is above 7.6, the concentration of alkalinity and dissolved oxygen is more than 150 mg/L and 2 mg/L, and the concentration of chloride is less than 150 mg/L of distributed water.

Habituation of adult sea lamprey repeatedly exposed to damage-released alarm and predator cues

USGS Publications Warehouse

Imre, Istvan; Di Rocco, Richard T.; Brown, Grant E.; Johnson, Nicholas

2016-01-01

Predation is an unforgiving selective pressure affecting the life history, morphology and behaviour of prey organisms. Selection should favour organisms that have the ability to correctly assess the information content of alarm cues. This study investigated whether adult sea lamprey Petromyzon marinus habituate to conspecific damage-released alarm cues (fresh and decayed sea lamprey extract), a heterospecific damage-released alarm cue (white sucker Catostomus commersoniiextract), predator cues (Northern water snake Nerodia sipedon washing, human saliva and 2-phenylethylamine hydrochloride (PEA HCl)) and a conspecific damage-released alarm cue and predator cue combination (fresh sea lamprey extract and human saliva) after they were pre-exposed 4 times or 8 times, respectively, to a given stimulus the previous night. Consistent with our prediction, adult sea lamprey maintained an avoidance response to conspecific damage-released alarm cues (fresh and decayed sea lamprey extract), a predator cue presented at high relative concentration (PEA HCl) and a conspecific damage-released alarm cue and predator cue combination (fresh sea lamprey extract plus human saliva), irrespective of previous exposure level. As expected, adult sea lamprey habituated to a sympatric heterospecific damage-released alarm cue (white sucker extract) and a predator cue presented at lower relative concentration (human saliva). Adult sea lamprey did not show any avoidance of the Northern water snake washing and the Amazon sailfin catfish extract (heterospecific control). This study suggests that conspecific damage-released alarm cues and PEA HCl present the best options as natural repellents in an integrated management program aimed at controlling the abundance of sea lamprey in the Laurentian Great Lakes.

Enzymatically cross-linked injectable alginate-g-pyrrole hydrogels for neovascularization.

PubMed

Devolder, Ross; Antoniadou, Eleni; Kong, Hyunjoon

2013-11-28

Microparticles capable of releasing protein drugs are often incorporated into injectable hydrogels to minimize their displacement at an implantation site, reduce initial drug burst, and further control drug release rates over a broader range. However, there is still a need to develop methods for releasing drug molecules over extended periods of time, in order to sustain the bioactivity of drug molecules at an implantation site. In this study, we hypothesized that a hydrogel formed through the cross-linking of pyrrole units linked to a hydrophilic polymer would release protein drugs in a more sustained manner, because of an enhanced association between cross-linked pyrrole groups and the drug molecules. To examine this hypothesis, we prepared hydrogels of alginate substituted with pyrrole groups, alginate-g-pyrrole, through a horse-radish peroxidase (HRP)-activated cross-linking of the pyrrole groups. The hydrogels were encapsulated with poly(lactic-co-glycolic acid) (PLGA) microparticles loaded with vascular endothelial growth factor (VEGF). The resulting hydrogel system released VEGF in a more sustained manner than Ca(2+) alginate or Ca(2+) alginate-g-pyrrole gel systems. Finally, implantations of the VEGF-releasing HRP-activated alginate-g-pyrrole hydrogel system on chicken chorioallantoic membranes resulted in the formation of blood vessels in higher densities and with larger diameters, compared to other control conditions. Overall, the drug releasing system developed in this study will be broadly useful for regulating release rates of a wide array of protein drugs, and further enhance the quality of protein drug-based therapies. © 2013 Elsevier B.V. All rights reserved.

The influence of Surelease and sodium alginate on the in-vitro release of tamsulosin hydrochloride in pellet dosage form.

PubMed

Kim, Min-Soo; Jun, Seoung Wook; Lee, Sibeum; Lee, Tae Wan; Park, Jeong-Sook; Hwang, Sung-Joo

2005-06-01

The objective of this study was to prepare controlled-release pellets containing 0.2 mg tamsulosin hydrochloride using a pelletizer-equipped piston extruder and double-arm counter-rotating rollers with Surelease and sodium alginate. The release of tamsulosin HCl from pellets coated with the commercial aqueous ethylcellulose dispersion (Surelease) was investigated at different coating loads. In addition, the effect of sodium alginate on drug release was investigated by varying the ratio of sodium alginate to microcrystalline cellulose (MCC). Dissolution studies were first performed in 500 mL simulated gastric fluid (pH 1.2) containing 0.003% (w/w) polysorbate 80 and then in simulated intestinal fluids (pH 7.2). The morphology of pellet surfaces and cross sections were examined by scanning electron microscopy (SEM). Apparently, the spherical pellets were prepared using a pelletizer-equipped piston extruder and double-arm counter-rotating rollers. The release profiles of tamsulosin HCl from Surelease-coated pellets were significantly affected by changing the content of Surelease, the pH of the dissolution medium and the ratio of sodium alginate to MCC. The drug release rates not only decreased with increase in the coating load, but also increased when the pH of the dissolution medium was increased from 1.2 to 7.2 regardless of the sodium alginate-to-MCC ratio. Moreover, the drug release rate at pH 7.2 was gradually increased by increasing the ratio of sodium alginate to MCC. SEM showed smooth surfaces of Surelease-coated pellets. These results suggest that Surelease and sodium alginate would be useful excipients in the preparation of controlled-release pellets with the desired release profiles.

Clinical translation of controlled protein delivery systems for tissue engineering.

PubMed

Spiller, Kara L; Vunjak-Novakovic, Gordana

2015-04-01

Strategies that utilize controlled release of drugs and proteins for tissue engineering have enormous potential to regenerate damaged organs and tissues. The multiple advantages of controlled release strategies merit overcoming the significant challenges to translation, including high costs and long, difficult regulatory pathways. This review highlights the potential of controlled release of proteins for tissue engineering and regenerative medicine. We specifically discuss treatment modalities that have reached preclinical and clinical trials, with emphasis on controlled release systems for bone tissue engineering, the most advanced application with several products already in clinic. Possible strategies to address translational and regulatory concerns are also discussed.

Clinical translation of controlled protein delivery systems for tissue engineering

PubMed Central

Spiller, Kara L.; Vunjak-Novakovic, Gordana

2013-01-01

Strategies that utilize controlled release of drugs and proteins for tissue engineering have enormous potential to regenerate damaged organs and tissues. The multiple advantages of controlled release strategies merit overcoming the significant challenges to translation, including high costs and long, difficult regulatory pathways. This review highlights the potential of controlled release of proteins for tissue engineering and regenerative medicine. We specifically discuss treatment modalities that have reached preclinical and clinical trials, with emphasis on controlled release systems for bone tissue engineering, the most advanced application with several products already in clinic. Possible strategies to address translational and regulatory concerns are also discussed. PMID:25787736

[Effects of mechanical transplanting of rice with controlled release bulk blending fertilizer on rice yield and soil fertility].

PubMed

Zhang, Xuan; Ding, Jun-Shan; Liu, Yan-Ling; Gu, Yan; Han, Ke-Feng; Wu, Liang-Huan

2014-03-01

Abstract: A 2-year field experiment with a yellow-clay paddy soil in Zhejiang Province was conducted to study the effects of different planting measures combined with different fertilization practices on rice yield, soil nutrients, microbial biomass C and N and activities of urease, phosphatase, sucrase and hydrogen peroxidase at the maturity stage. Results showed that mechanical transplanting of rice with controlled release bulk blending (BB) fertilizer (BBMT) could achieve a significantly higher mean yield than traditional manual transplanting with traditional fertilizer (TFTM) and direct seeding with controlled release BB fertilizer (BBDS) by 16.3% and 27.0%, respectively. The yield by BBMT was similar to that by traditional manual transplanting with controlled release BB fertilizer (BBTM). Compared with TFTM, BBMT increased the contents of soil total-N, available N, available P and microbial biomass C, and the activities of urease, sucrase and hydrogen peroxidase by 21.5%, 13.6%, 41.2%, 27.1%, 50.0%, 22.5% and 46.2%, respectively. Therefore, BBMT, a simple high-efficiency rice cultivation method with use of a light-weighted mechanical transplanter, should be widely promoted and adopted.

[Effects of applying controlled-release fertilizer blended with conventional nitrogen fertilizer on Chinese cabbage yield and quality as well as nitrogen losses].

PubMed

Yang, Jun-gang; Xu, Kai; Tong, Er-jian; Cao, Bing; Ni, Xiao-hui; Xu, Jun-xiang

2010-12-01

An open field experiment was conducted to study the effects of applying controlled-release fertilizer blended with rapidly available chemical N fertilizer on Chinese cabbage yield and quality as well as nitrogen losses, including ammonia volatilization and NO3- -N accumulation and leaching in Beijing suburb. The results showed that a combined application of 2:1 controlled-release fertilizer and urea fertilizer (total N rate 150 kg x hm(-2)) did not induce the reduction of Chinese cabbage yield, and decreased the leaf nitrate and organic acid contents significantly, compared with conventional urea N application (300 kg x hm(-2)), and had no significant difference in the cabbage yield and leaf nitrate content, compared with applying 150 kg x hm(-2) of urea N. The combined application of 2:1 controlled-release fertilizer and urea fertilizer improved the N use efficiency of Chinese cabbage, and reduced the ammonia volatilization and NO3- -N leaching. At harvest, the NO3- -N concentrations in 20-40, 60-80 and 80-100 cm soil layers were significantly lower in the combined application treatment than in urea N treatment.

Inocluative release of an exotic predator for the biological control of the black turpentine beetle

Treesearch

John C. Moser

1989-01-01

An inoculative release of the Eurasian predatorial beetle, Rhizophagus grandis, was made for control of the black turpentine beetle, Dendroctonus terebrans Olivier, a prominent native pest of southern pines. If this central Louisiana release proves successful, and rearing programs are prefectied, further releases should expand the...

Use of natural and biobased materials for controlled-release of urea in water: Environmental applications

USDA-ARS?s Scientific Manuscript database

Urea pearls were encapsulated in cloisite-based matrices using different natural materials (lignin, beeswax and latex) to control the release of urea over time. It was found that all cloisite-based fertilizer tablets showed better release profiles than neat urea tablets. The best release profile was...

Nano-suspension coating as a technique to modulate the drug release from controlled porosity osmotic pumps for a soluble agent.

PubMed

Bahari, Leila Azharshekoufeh; Javadzadeh, Yousef; Jalali, Mohammad Barzegar; Johari, Peyvand; Nokhodchi, Ali; Shokri, Javad

2017-05-01

In controlled porosity osmotic pumps (CPOP), usually finding a single solvent with a capability to dissolve both film former (hydrophobic) and pore former (hydrophilic) is extremely challenging. Therefore, the aim of the present investigation was to tackle the issue associated with controlled porosity osmotic pump (CPOP) system using nano-suspension coating method. In the present study 4-Amino pyridine was used as a highly water soluble drug. In this method, a hydrophilic pore former (sucrose or mannitol) in nano range was suspended in polymeric coating solution using ball-mill. The performance of the prepared formulations was assessed in terms of D 12h (cumulative release percent after 12h), Dev zero (mean percent deviation of drug release from zero order kinetic), t L (lag time of the drug release) and RSQ zero . The results revealed that gelling agent amount (HPMC E 15LV ) in core and pore former concentration in SPM had crucial effect on SPM integrity. All the optimised formulations showed a burst drug release due to fast dissolving nature of the pore formers. Results obtained from scanning electron microscopy demonstrated the formation of nanopores in the membrane where the drug release takes place via these nanopores. Nano suspension coating method can be introduced as novel method in formulation of CPOPs. Copyright © 2017 Elsevier B.V. All rights reserved.

Striatal dopamine release codes uncertainty in pathological gambling.

PubMed

Linnet, Jakob; Mouridsen, Kim; Peterson, Ericka; Møller, Arne; Doudet, Doris Jeanne; Gjedde, Albert

2012-10-30

Two mechanisms of midbrain and striatal dopaminergic projections may be involved in pathological gambling: hypersensitivity to reward and sustained activation toward uncertainty. The midbrain-striatal dopamine system distinctly codes reward and uncertainty, where dopaminergic activation is a linear function of expected reward and an inverse U-shaped function of uncertainty. In this study, we investigated the dopaminergic coding of reward and uncertainty in 18 pathological gambling sufferers and 16 healthy controls. We used positron emission tomography (PET) with the tracer [(11)C]raclopride to measure dopamine release, and we used performance on the Iowa Gambling Task (IGT) to determine overall reward and uncertainty. We hypothesized that we would find a linear function between dopamine release and IGT performance, if dopamine release coded reward in pathological gambling. If, on the other hand, dopamine release coded uncertainty, we would find an inversely U-shaped function. The data supported an inverse U-shaped relation between striatal dopamine release and IGT performance if the pathological gambling group, but not in the healthy control group. These results are consistent with the hypothesis of dopaminergic sensitivity toward uncertainty, and suggest that dopaminergic sensitivity to uncertainty is pronounced in pathological gambling, but not among non-gambling healthy controls. The findings have implications for understanding dopamine dysfunctions in pathological gambling and addictive behaviors. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Controlled-release formulation of antihistamine based on cetirizine zinc-layered hydroxide nanocomposites and its effect on histamine release from basophilic leukemia (RBL-2H3) cells

PubMed Central

Hasan, Samer; Ali, Hussein Al; Al-Qubaisi, Mothanna; Hussein, Mohd Zobir; Ismail, Maznah; Zainal, Zulkarnain; Hakim, Muhammad Nazrul

2012-01-01

A controlled-release formulation of an antihistamine, cetirizine, was synthesized using zinc-layered hydroxide as the host and cetirizine as the guest. The resulting well-ordered nanolayered structure, a cetirizine nanocomposite “CETN,” had a basal spacing of 33.9 Å, averaged from six harmonics observed from X-ray diffraction. The guest, cetirizine, was arranged in a horizontal bilayer between the zinc-layered hydroxide (ZLH) inorganic interlayers. Fourier transform infrared spectroscopy studies indicated that the intercalation takes place without major change in the structure of the guest and that the thermal stability of the guest in the nanocomposites is markedly enhanced. The loading of the guest in the nanocomposites was estimated to be about 49.4% (w/w). The release study showed that about 96% of the guest could be released in 80 hours by phosphate buffer solution at pH 7.4 compared with about 97% in 73 hours at pH 4.8. It was found that release was governed by pseudo-second order kinetics. Release of histamine from rat basophilic leukemia cells was found to be more sensitive to the intercalated cetirizine in the CETN compared with its free counterpart, with inhibition of 56% and 29%, respectively, at 62.5 ng/mL. The cytotoxicity assay toward Chang liver cells line show the IC50 for CETN and ZLH are 617 and 670 μg/mL, respectively. PMID:22848164

Gelatin-based hydrogel for vascular endothelial growth factor release in peripheral nerve tissue engineering.

PubMed

Gnavi, S; di Blasio, L; Tonda-Turo, C; Mancardi, A; Primo, L; Ciardelli, G; Gambarotta, G; Geuna, S; Perroteau, I

2017-02-01

Hydrogels are promising materials in regenerative medicine applications, due to their hydrophilicity, biocompatibility and capacity to release drugs and growth factors in a controlled manner. In this study, biocompatible and biodegradable hydrogels based on blends of natural polymers were used in in vitro and ex vivo experiments as a tool for VEGF-controlled release to accelerate the nerve regeneration process. Among different candidates, the angiogenic factor VEGF was selected, since angiogenesis has been long recognized as an important and necessary step during tissue repair. Recent studies have pointed out that VEGF has a beneficial effect on motor neuron survival and Schwann cell vitality and proliferation. Moreover, VEGF administration can sustain and enhance the growth of regenerating peripheral nerve fibres. The hydrogel preparation process was optimized to allow functional incorporation of VEGF, while preventing its degradation and denaturation. VEGF release was quantified through ELISA assay, whereas released VEGF bioactivity was validated in human umbilical vein endothelial cells (HUVECs) and in a Schwann cell line (RT4-D6P2T) by assessing VEGFR-2 and downstream effectors Akt and Erk1/2 phosphorylation. Moreover, dorsal root ganglia explants cultured on VEGF-releasing hydrogels displayed increased neurite outgrowth, providing confirmation that released VEGF maintained its effect, as also confirmed in a tubulogenesis assay. In conclusion, a gelatin-based hydrogel system for bioactive VEGF delivery was developed and characterized for its applicability in neural tissue engineering. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

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

PubMed

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.

Influence of some formulation variables on the optimization of pH-dependent, colon-targeted, sustained-release mesalamine microspheres.

PubMed

El-Bary, Ahmed Abd; Aboelwafa, Ahmed A; Al Sharabi, Ibrahim M

2012-03-01

The aim of this work was to understand the influence of different formulation variables on the optimization of pH-dependent, colon-targeted, sustained-release mesalamine microspheres prepared by O/O emulsion solvent evaporation method, employing pH-dependent Eudragit S and hydrophobic pH-independent ethylcellulose polymers. Formulation variables studied included concentration of Eudragit S in the internal phase and the ratios between; internal to external phase, drug to Eudragit S and Eudragit S to ethylcellulose to mesalamine. Prepared microspheres were evaluated by carrying out in vitro release studies and determination of particle size, production yield, and encapsulation efficiency. In addition, morphology of microspheres was examined using optical and scanning electron microscopy. Emulsion solvent evaporation method was found to be sensitive to the studied formulation variables. Particle size and encapsulation efficiency increased by increasing Eudragit S concentration in the internal phase, ratio of internal to external phase, and ratio of Eudragit S to the drug. Employing Eudragit S alone in preparation of the microspheres is only successful in forming acid-resistant microspheres with pulsatile release pattern at high pH. Eudragit S and ethylcellulose blend microspheres were able to control release under acidic condition and to extend drug release at high pH. The stability studies carried out at 40°C/75% RH for 6 months proved the stability of the optimized formulation. From the results of this investigation, microencapsulation of mesalamine in microspheres using blend of Eudragit S and ethylcellulose could constitute a promising approach for site-specific and controlled delivery of drug in colon.

75 FR 2845 - ArborGen, LLC; Availability of an Environmental Assessment for Controlled Release of a...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-19

... Engineered Eucalyptus Hybrid AGENCY: Animal and Plant Health Inspection Service, USDA. ACTION: Notice... for a proposed controlled field release of a genetically engineered clone of a Eucalyptus hybrid. This... proposed controlled field release of a genetically engineered clone of a Eucalyptus hybrid. \\1\\ To view the...

Improving release completeness from PLGA-based implants for the acid-labile model protein ovalbumin.

PubMed

Duque, Luisa; Körber, Martin; Bodmeier, Roland

2018-03-01

The objectives of this study were to assess the feasibility of hot melt extrusion (HME) for the preparation of PLGA-based ovalbumin-loaded implants as well as to characterize and improve protein release from the implants. Ovalbumin (OVA) was stable during extrusion, which was attributed to a protective effect of the biodegradable matrix. OVA release was characterized by a low burst, a slow release up to day 21, which plateaued thereafter resulting in incomplete release for all evaluated protein loadings. Release incompleteness was accompanied by the formation of an insoluble residual mass. Further characterization of this mass indicated that it consisted of non-covalent protein aggregates and polymer, where ovalbumin was ionically bound as the pH inside the degrading matrix decreased below the pI of the protein. Although higher protein release was obtained with the inclusion of weak bases because of their neutralizing effect, OVA aggregation and release incompleteness were not fully avoided. With the use of shellac, a well-known enteric and biocompatible polymer, as protective excipient, a distinct late release phase occurred and release completeness was increased to more than 75% cumulative release. Shellac apparently protected the protein against the acidic microclimate due to its low solubility at low pH. Protected OVA was thus released once the pH increased due to a declining PLGA-oligomer formation. The result was a triphasic release profile consisting of an initial burst, a slow diffusion phase over about 7 weeks, and an erosion-controlled dissolution phase over the next 3 weeks. An acid-labile protein like OVA was thus feasibly protected from interactions with PLGA and its degradation products, resulting in a controlled delivery of more than 85% of the original payload. Copyright © 2018 Elsevier B.V. All rights reserved.

The Smart Aerial Release Machine, a Universal System for Applying the Sterile Insect Technique

PubMed Central

Mubarqui, Ruben Leal; Perez, Rene Cano; Kladt, Roberto Angulo; Lopez, Jose Luis Zavala; Parker, Andrew; Seck, Momar Talla; Sall, Baba; Bouyer, Jérémy

2014-01-01

Background Beyond insecticides, alternative methods to control insect pests for agriculture and vectors of diseases are needed. Management strategies involving the mass-release of living control agents have been developed, including genetic control with sterile insects and biological control with parasitoids, for which aerial release of insects is often required. Aerial release in genetic control programmes often involves the use of chilled sterile insects, which can improve dispersal, survival and competitiveness of sterile males. Currently available means of aerially releasing chilled fruit flies are however insufficiently precise to ensure homogeneous distribution at low release rates and no device is available for tsetse. Methodology/Principal Findings Here we present the smart aerial release machine, a new design by the Mubarqui Company, based on the use of vibrating conveyors. The machine is controlled through Bluetooth by a tablet with Android Operating System including a completely automatic guidance and navigation system (MaxNav software). The tablet is also connected to an online relational database facilitating the preparation of flight schedules and automatic storage of flight reports. The new machine was compared with a conveyor release machine in Mexico using two fruit flies species (Anastrepha ludens and Ceratitis capitata) and we obtained better dispersal homogeneity (% of positive traps, p<0.001) for both species and better recapture rates for Anastrepha ludens (p<0.001), especially at low release densities (<1500 per ha). We also demonstrated that the machine can replace paper boxes for aerial release of tsetse in Senegal. Conclusions/Significance This technology limits damages to insects and allows a large range of release rates from 10 flies/km2 for tsetse flies up to 600 000 flies/km2 for fruit flies. The potential of this machine to release other species like mosquitoes is discussed. Plans and operating of the machine are provided to allow its use worldwide. PMID:25036274

The smart aerial release machine, a universal system for applying the sterile insect technique.

PubMed

Leal Mubarqui, Ruben; Perez, Rene Cano; Kladt, Roberto Angulo; Lopez, Jose Luis Zavala; Parker, Andrew; Seck, Momar Talla; Sall, Baba; Bouyer, Jérémy

2014-01-01

Beyond insecticides, alternative methods to control insect pests for agriculture and vectors of diseases are needed. Management strategies involving the mass-release of living control agents have been developed, including genetic control with sterile insects and biological control with parasitoids, for which aerial release of insects is often required. Aerial release in genetic control programmes often involves the use of chilled sterile insects, which can improve dispersal, survival and competitiveness of sterile males. Currently available means of aerially releasing chilled fruit flies are however insufficiently precise to ensure homogeneous distribution at low release rates and no device is available for tsetse. Here we present the smart aerial release machine, a new design by the Mubarqui Company, based on the use of vibrating conveyors. The machine is controlled through Bluetooth by a tablet with Android Operating System including a completely automatic guidance and navigation system (MaxNav software). The tablet is also connected to an online relational database facilitating the preparation of flight schedules and automatic storage of flight reports. The new machine was compared with a conveyor release machine in Mexico using two fruit flies species (Anastrepha ludens and Ceratitis capitata) and we obtained better dispersal homogeneity (% of positive traps, p<0.001) for both species and better recapture rates for Anastrepha ludens (p<0.001), especially at low release densities (<1500 per ha). We also demonstrated that the machine can replace paper boxes for aerial release of tsetse in Senegal. This technology limits damages to insects and allows a large range of release rates from 10 flies/km2 for tsetse flies up to 600,000 flies/km2 for fruit flies. The potential of this machine to release other species like mosquitoes is discussed. Plans and operating of the machine are provided to allow its use worldwide.

Programming the composition of polymer blend particles for controlled immunity towards individual protein antigens.

PubMed

Zhan, Xi; Shen, Hong

2015-05-28

In order for a more precise control over the quality and quantity of immune responses stimulated by synthetic particle-based vaccines, it is critical to control the colloidal stability of particles and the release of protein antigens in both extracellular space and intracellular compartments. Different proteins exhibit different sizes, charges and solubilities. This study focused on modulating the release and colloidal stability of proteins with varied isoelectric points. A polymer particle delivery platform made from the blend of three polymers, poly(lactic-co-glycolic acid) (PLGA) and two random pH-sensitive copolymers, were developed. Our study demonstrated its programmability with respective to individual proteins. We showed the colloidal stability of particles at neutral environment and the release of each individual protein at different pH environments were dependent on the ratio of two charge polymers. Subsequently, two antigenic proteins, ovalbumin (OVA) and Type 2 Herpes Simplex Virus (HSV-2) glycoprotein D (gD) protein, were incorporated into particles with systematically varied compositions. We demonstrated that the level of in vitro CD8(+) T cell and in vivo immune responses were dependent on the ratio of two charged polymers, which correlated well with the release of proteins. This study provided a promising design framework of pH-responsive synthetic vaccines for protein antigens of interest. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of Disinfectant Exposure on Legionella pneumophila Associated with Simulated Drinking Water Biofilms: Release, Inactivation, and Infectivity.

PubMed

Shen, Yun; Huang, Conghui; Lin, Jie; Wu, Wenjing; Ashbolt, Nicholas J; Liu, Wen-Tso; Nguyen, Thanh H

2017-02-21

Legionella pneumophila, the most commonly identified causative agent in drinking water associated with disease outbreaks, can be harbored by and released from drinking water biofilms. In this study, the release of biofilm-associated L. pneumophila under simulated drinking water flow containing a disinfectant residual was examined. Meanwhile, the inactivation and infectivity (to amoebae) of the released L. pneumophila were studied. To simulate drinking water system conditions, biofilms were prepared under either disinfectant exposure (predisinfected biofilms) or disinfectant-free (untreated biofilms) conditions, respectively. For experiments with water flow containing a disinfectant to release the biofilm-associated L. pneumophila from these two types of biofilms, the L. pneumophila release kinetics values from predisinfected and untreated biofilms under flow condition were not statistically different (one-way ANOVA, p > 0.05). However, inactivation of the L. pneumophila released from predisinfected biofilms was 1-2 times higher and amoeba infectivity was 2-29 times lower than that from untreated biofilms. The higher disinfectant resistance of L. pneumophila released from untreated biofilms was presumably influenced by the detachment of a larger amount of biofilm material (determined by 16S rRNA qPCR) surrounding the released L. pneumophila. This study highlights the interaction among disinfectant residual, biofilms, and L. pneumophila, which provides guidelines to assess and control pathogen risk.

pH-controlled drug loading and release from biodegradable microcapsules

PubMed Central

Zhao, Qinghe; Li, Bingyun

2013-01-01

Microcapsules made of biopolymers are of both scientific and technological interest and have many potential applications in medicine including their use as controlled drug delivery devices. The present study employs the electrostatic interaction between polycations and polyanions to form a multilayered microcapsule shell and also to control the loading and release of charged drug molecules inside the microcapsule. Micron-sized CaCO3 particles were synthesized and integrated with chondroitin sulfate (CS) through a reaction between Na2CO3 and Ca(NO3)2 solutions suspended with CS macromolecules. Oppositely-charged biopolymers were alternately deposited onto the synthesized particles using electrostatic layer-by-layer self-assembly, and glutaraldehyde was introduced to crosslink the multilayered shell structure. Microcapsules integrated with CS inside the multilayered shells were obtained after decomposition of the CaCO3 templates. The integration of a matrix, i.e. CS, enabled the subsequent selective control of drug loading and release. The CS integrated microcapsules were loaded with a model drug, i.e. bovine serum albumin labeled with fluorescein isothiocyanate (FITC-BSA), and it was shown that pH was an effective means of controlling the loading and release of FITC-BSA. Such CS integrated microcapsules may be used for controlled localized drug delivery as biodegradable devices, which have advantages in reducing systemic side effects and increasing drug efficacy. PMID:18657478

Passage and survival probabilities of juvenile Chinook salmon at Cougar Dam, Oregon, 2012

USGS Publications Warehouse

Beeman, John W.; Evans, Scott D.; Haner, Philip V.; Hansel, Hal C.; Hansen, Amy C.; Smith, Collin D.; Sprando, Jamie M.

2014-01-01

This report describes studies of juvenile-salmon dam passage and apparent survival at Cougar Dam, Oregon, during two operating conditions in 2012. Cougar Dam is a 158-meter tall rock-fill dam used primarily for flood control, and passes water through a temperature control tower to either a powerhouse penstock or to a regulating outlet (RO). The temperature control tower has moveable weir gates to enable water of different elevations and temperatures to be drawn through the dam to control water temperatures downstream. A series of studies of downstream dam passage of juvenile salmonids were begun after the National Oceanic and Atmospheric Administration determined that Cougar Dam was impacting the viability of anadromous fish stocks. The primary objectives of the studies described in this report were to estimate the route-specific fish passage probabilities at the dam and to estimate the survival probabilities of fish passing through the RO. The first set of dam operating conditions, studied in November, consisted of (1) a mean reservoir elevation of 1,589 feet, (2) water entering the temperature control tower through the weir gates, (3) most water routed through the turbines during the day and through the RO during the night, and (4) mean RO gate openings of 1.2 feet during the day and 3.2 feet during the night. The second set of dam operating conditions, studied in December, consisted of (1) a mean reservoir elevation of 1,507 ft, (2) water entering the temperature control tower through the RO bypass, (3) all water passing through the RO, and (4) mean RO gate openings of 7.3 feet during the day and 7.5 feet during the night. The studies were based on juvenile Chinook salmon (Oncorhynchus tshawytscha) surgically implanted with radio transmitters and passive integrated transponder (PIT) tags. Inferences about general dam passage percentage and timing of volitional migrants were based on surface-acclimated fish released in the reservoir. Dam passage and apparent survival probabilities were estimated using the Route-Specific-Survival Model with data from surface-acclimated fish released near the water surface directly upstream of the temperature control tower (treatment group) and slightly downstream of the dam (control group). In this study, apparent survival is the joint probability of surviving and migrating through the study area during the life of the transmitters. Two rearing groups were used to enable sufficient sample sizes for the studies. The groups differed in feed type, and for the December study only, the rearing location. Fish from each group were divided nearly equally among all combinations of release sites, release times, and surgeons. The sizes, travel times, and survivals of the two rearing groups were similar. There were statistical differences in fish lengths and travel times of the two groups, but they were small and likely were not biologically meaningful. There also was evidence of a difference in single-release estimates of survival between the rearing groups during the December study, but the differences had little effect on the relative survival estimates so the analyses of passage and survival were based on data from the rearing groups pooled. Conditions during the December study were more conducive to passing volitionally migrating fish than conditions during the November study. The passage percentage of the fish released in the reservoir was similar between studies (about 70 percent), but the passage occurred in a median of 1.0 day during the December study and a median of 9.3 days during the November study. More than 93 percent of the dam passage of volitionally migrating fish occurred at night during each study. This finding corroborates results of previous studies at Cougar Dam and suggests that the operating conditions at night are most important to volitionally migrating fish, given the current configuration of the dam. Most fish released near the temperature control tower passed through the RO. A total of 92.2 percent of the treatment group passed through the RO during the November study and the RO was the only route open during the December study. The assumptions of the survival model were either met or adjusted for during each study. There was little evidence that tagger skill or premature failure of radio transmitters had an effect on survival estimates. There were statistically significant differences in travel times between treatment and control groups through several of the river reaches they had in common, but the differences were typically only a few hours, and the two groups likely experienced the same in-river conditions. There was direct evidence of bias due to detection of euthanized fish with live transmitters released as part of the study design. The bias was ameliorated by adjusting the survival estimates for the probability of detecting dead fish with live transmitters, which reduced the estimated survival probabilities by about 0.02. The data and models indicated that the treatment effect was not fully expressed until the study reach terminating with Marshall Island Park on the Willamette River, a distance of 105.8 kilometers downstream of Cougar Dam. This was the first reach in which the 95-percent confidence interval of the estimated reach-specific relative survival overlapped 1.0, indicating similar survival of treatment and control groups. The median travel time of the treatment group from release to Marshall Island Park was 1.64 days during the November study and 1.36 days during the December study. The survival probability of fish that passed into the RO was greater during the December study than during the November study. The relative survival probability of fish passing through the RO was 0.4594 (standard error [SE] 0.0543) during the November study and 0.7389 (SE 0.1160) during the December study. These estimates represent relative survival probabilities from release near Cougar Dam to the Marshall Island site. The estimated survival probability of RO passage was lower than previous studies based on balloon and PIT tags, but higher than a similar study based on radio transmitters. We suggest that, apart from dam operations, the differences in survival primarily are due to the release location. We hypothesize that the balloon- and PIT-tagged fish released through a hose at a point near the RO gate opening experienced more benign conditions than the radio-tagged fish passing the RO volitionally. This hypothesis could be tested with further study. An alternative hypothesis is that some live fish remained within the study area beyond the life of their radio transmitter. The results from these and previous studies indicate that entrainment and survival of juvenile salmonids passing Cougar Dam varies with dam operating conditions. The condition most conducive to dam passage has been the discharge and low pool elevation condition tested during December 2012. That condition included large RO gate openings and was the condition with the highest dam passage survival.

Bionomics of Asian Citrus Psyllid (Hemiptera: Liviidae) Associated with Orange Jasmine Hedges in Southeast Central Florida, with Special Reference to Biological Control by Tamarixia radiata.

PubMed

Hall, David G; Rohrig, Eric

2015-06-01

The Asian citrus psyllid, Diaphorina citri Kuwayama, is an important pest in Florida because it transmits bacteria responsible for citrus huanglongbing disease. In addition to infesting citrus, orange jasmine (Murraya exotica L.) is one of Asian citrus psyllid's preferred host plants and is widely grown as an ornamental hedge. We report on Asian citrus psyllid bionomics over three years at five urban plantings of orange jasmine and on biological control of Asian citrus psyllid by a parasitoid Tamarixia radiata (Waterston). T. radiata had been released in Florida shortly after Asian citrus psyllid was first found, and the parasitoid was known to be established at each planting. Additionally, three new T. radiata haplotypes were released every 3 wk at three plantings during the first study year (one haplotype per planting, over all releases an average of 17 parasitoids per linear meter of hedge); all three haplotypes were released at a fourth planting beginning midway through the study (over all releases, an average combined total of 202 parasitoids per linear meter of hedge). Asian citrus psyllid populations were present year-round at each planting, often at large levels. Such plantings may pose risk to commercial citrus as Asian citrus psyllid reservoirs. Releases of the new haplotypes did not cause any measurable reduction in Asian citrus psyllid population levels during the study, and ironically percentage parasitism was generally highest at a planting where no releases were made. Higher release rates might have been more effective. The probability is discussed that repetitive pruning of orange jasmine reduced the full potential of T. radiata against Asian citrus psyllid in this study. Published by Oxford University Press on behalf of Entomological Society of America 2015. This work is written by US Government employees and is in the public domain in the US.

Antifouling composites with self-adaptive controlled release based on an active compound intercalated into layered double hydroxides

NASA Astrophysics Data System (ADS)

Yang, Miaosen; Gu, Lianghua; Yang, Bin; Wang, Li; Sun, Zhiyong; Zheng, Jiyong; Zhang, Jinwei; Hou, Jian; Lin, Cunguo

2017-12-01

This paper reports a novel method to prepare the antifouling composites with properties of self-adaptive controlled release (defined as control the release rate autonomously and adaptively according to the change of environmental conditions) by intercalation of sodium paeonolsilate (PAS) into MgAl and ZnAl layered double hydroxide (LDH) with the molar ratio (M2+/M3+) of 2:1 and 3:1, respectively. The powder X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR) confirm the intercalation of PAS into the galleries of LDH. The controlled release behavior triggered by temperature for the PAS-LDH composites has been investigated, and the results show that the release rate of all PAS-LDH composites increases as the increase of temperature. However, the MgAl-PAS-LDH composites (Mg2Al-PAS-LDH and Mg3Al-PAS-LDH) exhibit the increased release rate of 0.21 ppm/°C from 15 to 30 °C in 3.5% NaCl solution, more than three times of the ZnAl-PAS-LDH composites (0.06 ppm/°C), owing to the confined microenvironment influenced by metal types in LDH layers. In addition, a possible diffusion-controlled process with surface diffusion, bulk diffusion and heterogeneous flat surface diffusion has been revealed via fitting four kinetic equations. Moreover, to verify the practical application of the PAS-LDH composites, a model coating denoted as Mg2Al-PAS-LDH coating was fabricated. The release result displays that the release rate increases or decreases as temperature altered at 15 and 25 °C alternately, indicating its self-adaptive controlled release behavior with temperature. Moreover, the superior resistance to the settlement of Ulva spores at 15 and 25 °C was observed for the Mg2Al-PAS-LDH coating, as a result of the controllable release of antifoulant. Therefore, this work provides a facile and effective method for the fabrication of antifouling composites with self-adaptive controlled release behavior in response to temperature, which can be used to prolong the lifetime of antifouling coatings.

Drug-eluting coating of ginsenoside Rg1 and Re incorporated poly(lactic-co-glycolic acid) on stainless steel 316L: Physicochemical and drug release analyses.

PubMed

Miswan, Zulaika; Lukman, Siti Khadijah; Abd Majid, Fadzilah Adibah; Loke, Mun Fai; Saidin, Syafiqah; Hermawan, Hendra

2016-12-30

Active ingredients of ginsenoside, Rg1 and Re, are able to inhibit the proliferation of vascular smooth muscle cells and promote the growth of vascular endothelial cells. These capabilities are of interest for developing a novel drug-eluting stent to potentially solve the current problem of late-stent thrombosis and poor endotheliazation. Therefore, this study was aimed to incorporate ginsenoside into degradable coating of poly(lactic-co-glycolic acid) (PLGA). Drug mixture composed of ginseng extract and 10% to 50% of PLGA (xPLGA/g) was coated on electropolished stainless steel 316L substrate by using a dip coating technique. The coating was characterized principally by using attenuated total reflectance-Fourier transform infrared spectroscopy, scanning electron microscopy and contact angle analysis, while the drug release profile of ginsenosides Rg1 and Re was determined by using mass spectrometry at a one month immersion period. Full and homogenous coating coverage with acceptable wettability was found on the 30PLGA/g specimen. All specimens underwent initial burst release dependent on their composition. The 30PLGA/g and 50PLGA/g specimens demonstrated a controlled drug release profile having a combination of diffusion- and swelling-controlled mechanisms of PLGA. The study suggests that the 30PLGA/g coated specimen expresses an optimum composition which is seen as practicable for developing a controlled release drug-eluting stent. Copyright © 2016 Elsevier B.V. All rights reserved.

In vitro release of adenosine triphosphate from the urothelium of human bladders with detrusor overactivity, both neurogenic and idiopathic.

PubMed

Kumar, Vivek; Chapple, Christopher R; Rosario, Derek; Tophill, Paul R; Chess-Williams, Russell

2010-06-01

There is increased evidence to suggest a role for nonadrenergic-noncholinergic neurotransmission in the pathogenesis of bladder dysfunction. In this set of experiments, we have assessed the contribution of the urothelium to purinergic activity by quantifying the amount of adenosine triphosphate (ATP) released from the urothelium of patients with idiopathic detrusor overactivity (IDO) and with neurogenic detrusor overactivity (NDO) and comparing these releases to those of controls. Bladder tissue with urodynamically and clinically proven NDO (n=8) and IDO (n=8) were included in this study. The carefully dissected urothelium was stimulated by mechanically stretching as well as electrically stimulating and the ATP; thus, release was quantified. We used a Lucy Anthos 1 luminometre (Anthos Labtec Instruments GmBH, Wals, Austria) to perform the assay. The results were analysed using Stingray software (Dazdaq Ltd, Brighton, UK). Both mechanical stretch and electric field stimulation (EFS) led to increased ATP release in both sets of tissues with overactivity compared to the controls; this rise was even more significant for the IDO urothelium (2416.7±479.8 pmol/g [p<0.005]) than for the NDO urothelium (133.1±22.4 pmol/g [p<0.01]); values for the controls were 77.6±16.2 pmol/g. ATP release following mechanical stretch was more sensitive to tetrodotoxin in bladders with NDO compared to those with IDO as well as to the controls, with ATP levels falling from 233.5±20.7 pmol/g to 107.2±11.6 pmol/g, expressed as percentage of basal levels (p<0.002). The experiments were performed in vitro, and the female patients were a mix of peri- and postmenopausal states. These experiments suggested a significant rise in ATP release from the urothelium of bladders with NDO as well as those with IDO in comparison to controls. Most of the ATP released from bladders with NDO is primarily from neuronal sources. Copyright © 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Highly Effective Birth Control Use Before and After Women's Incarceration

PubMed Central

Chen, Hsiang-Feng; Cropsey, Karen L.; Clarke, Jennifer G.; Kelly, Patricia J.

2015-01-01

Abstract Background: We examined factors associated with women's use of highly effective birth control before and after incarceration, since women with ongoing criminal justice involvement bear a disproportionate burden of sexual and reproductive health problems, including high rates of unintended pregnancy and inconsistent contraceptive use. Methods: Using a longitudinal study design, we conducted surveys with 102 women in an urban midwestern jail and then followed up with 66 of them 6 months after incarceration. We used stepwise logistic regression to assess individual, interpersonal, resource-based, organizational, and environmental factors associated with utilizing highly effective birth control. Results: Forty-two percent of women reported utilizing highly effective birth control (e.g., sterilization or other highly effective reversible methods) prior to incarceration, and 54% reported using these methods after release from jail (p<0.001). Ninety percent of women reported not wanting to get pregnant. Consistent use of birth control (p=0.001) and alcohol problems (p=0.027) were associated with utilization of highly effective birth control prior to incarceration. Previous pregnancies (p=0.012) were the only factor associated with utilization of highly effective birth control after release from jail. Conclusions: Clinicians and public health practitioners can use findings from this study to develop clinical and intervention efforts aimed at improving unintended-pregnancy prevention among incarcerated women both during their confinement and during the tumultuous period after their release from jail. PMID:25555175

Highly Effective Birth Control Use Before and After Women's Incarceration.

PubMed

Ramaswamy, Megha; Chen, Hsiang-Feng; Cropsey, Karen L; Clarke, Jennifer G; Kelly, Patricia J

2015-06-01

We examined factors associated with women's use of highly effective birth control before and after incarceration, since women with ongoing criminal justice involvement bear a disproportionate burden of sexual and reproductive health problems, including high rates of unintended pregnancy and inconsistent contraceptive use. Using a longitudinal study design, we conducted surveys with 102 women in an urban midwestern jail and then followed up with 66 of them 6 months after incarceration. We used stepwise logistic regression to assess individual, interpersonal, resource-based, organizational, and environmental factors associated with utilizing highly effective birth control. Forty-two percent of women reported utilizing highly effective birth control (e.g., sterilization or other highly effective reversible methods) prior to incarceration, and 54% reported using these methods after release from jail (p<0.001). Ninety percent of women reported not wanting to get pregnant. Consistent use of birth control (p=0.001) and alcohol problems (p=0.027) were associated with utilization of highly effective birth control prior to incarceration. Previous pregnancies (p=0.012) were the only factor associated with utilization of highly effective birth control after release from jail. Clinicians and public health practitioners can use findings from this study to develop clinical and intervention efforts aimed at improving unintended-pregnancy prevention among incarcerated women both during their confinement and during the tumultuous period after their release from jail.

Release of Water Soluble Drugs from Dynamically Swelling POLY(2-HYDROXYETHYL Methacrylate - CO - Methacrylic Acid) Hydrogels.

NASA Astrophysics Data System (ADS)

Kou, Jim Hwai-Cher

In this study, ionizable copolymers of HEMA and methacrylic acid (MA) are investigated for their potential use in developing pH dependent oral delivery systems. Because of the MA units, these gels swell extensively at high pH. Since solute diffusion in the hydrophilic polymers depends highly on the water content of the matrix, it is anticipated that the release rate will be modulated by this pH induced swelling. From a practical point of view, the advantage of the present system is that one can minimize drug loss in the stomach and achieve a programmed release in intestine. This approach is expected to improve delivery of acid labile drugs or drugs that cause severe gastrointestinal side effects. This work mainly focuses on the basic understanding of the mechanism involved in drug release from the poly(HEMA -co- MA) gels, especially under dynamic swelling conditions. Equilibrium swelling is first characterized since water content is the major determinant of transport properties in these gels. Phenylpropanolamine (PPA) is chosen as the model drug for the release study and its diffusion characteristics in the gel matrix determined. The data obtained show that the PPA diffusivity follows the free volume theory of Yasuda, which explains the accelerating effect of swelling on drug release. A mathematical model based on a diffusion mechanism has been developed to describe PPA release from the swelling gels. Based on this model, several significant conclusions can be drawn. First, the release rate can be modulated by the aspect ratio of the cylindrical geometry, and this has a practical implication in dosage form design. Second, the release rate can be lowered quite considerably if the dimensional increase due to swelling is significant. Consequently, it is the balance between the drug diffusivity increase and the gel dimensional growth that determines the release rate from the swelling matrix. Third, quasi-steady release kinetics, which are characteristic of swelling release systems, can also be predicted by this model. PPA release from initially dry poly(HEMA -co- MA) gels has also been studied. The data show that the release rate is mainly controlled by the PPA loading level and quite insensitive to the methacrylic acid composition of the gels. These phenomena can be adequately explained by analyzing the transport resistances in the gels. The overall time scale of release from these gels were shown to be in the range which was suitable for oral controlled release applications. (Abstract shortened with permission of author.).

Plant litter decomposition and nutrient release in peatlands

NASA Astrophysics Data System (ADS)

Bragazza, Luca; Buttler, Alexandre; Siegenthaler, Andy; Mitchell, Edward A. D.

Decomposition of plant litter is a crucial process in controlling the carbon balance of peatlands. Indeed, as long as the rate of litter decomposition remains lower than the rate of above- and belowground litter production, a net accumulation of peat and, thus, carbon will take place. In addition, decomposition controls the release of important nutrients such as nitrogen, phosphorus, and potassium, the availability of which affects the structure and the functioning of plant communities. This chapter describes the role of the main drivers in affecting mass loss and nutrient release from recently deposited plant litter. In particular, the rate of mass loss of Sphagnum litter and vascular plant litter is reviewed in relation to regional climatic conditions, aerobic/anaerobic conditions, and litter chemistry. The rate of nutrient release is discussed in relation to the rate of mass loss and associated litter chemistry by means of a specific case study.

Cross-linked high amylose starch derivatives for drug release III. Diffusion properties.

PubMed

Mulhbacher, Jérôme; Mateescu, Mircea Alexandru

2005-06-13

Acetate (Ac-), aminoethyl (AE-) and carboxymethyl (CM-) derivatives of cross-linked high amylose starch (HASCL-6) were previously shown to control the release of drugs over 20 h from highly loaded (up to 60% drug) monolithic tablets. This report presents a diffusion analysis, aimed to facilitate a better understanding of the mechanisms involved in the control of the drug release from these hydrogels. The diffusion was found to depend on the molecular weight of the diffusant, whereas the partition coefficient depended on the affinities of the diffusant for the polymers and for the dissolution media via attractive or repulsive ionic interactions. The diffusion was also affected by the swelling of CM-HASCL-6, which, unexpectedly, increased with the decrease of the ionic strength. This diffusion analysis completes the swelling studies of HASCL-6 and of its derivatives, allowing the prediction of release kinetics of various active agents.

Development and in vitro evaluation of carboxymethyl chitosan based drug delivery system for the controlled release of propranolol hydrochloride

NASA Astrophysics Data System (ADS)

Hernawan; Nur Hayati, Septi; Nisa, Khoirun; Wheni Indrianingsih, Anastasia; Darsih, Cici; Kismurtono, Muhammad

2017-12-01

Propranolol hydrochloride is a nonselective β-adrenergic drug and has been used as angina pectoris, antihypertensive, and that of many other cardiovascular disorders. It has a relatively short plasma half-life and duration of action are considered too short in certain circumstances. Thus, it’s fascinating to elongate the action. The tablet formula was based on extended-release by a propranolol hydrochloride based carboxymethyl chitosan matrix. Here we used direct compression technique with internal wet granulation to prepare the tablets. The tablets were evaluated for physical properties (hardness, weight variation test, friability) and in vitro release studies. There was no interaction observed between propranolol hydrochloride and excipients. Dissolution profiles of each formulation were followed zero order model. In conclusion, these results strongly suggest that in appropriate proportions carboxymethyl chitosan with internal granulation is suitable for formulating propranolol hydrochloride controlled release.

Opiate-induced dopamine release is modulated by severity of alcohol dependence: an [(18)F]fallypride positron emission tomography study.

PubMed

Spreckelmeyer, Katja N; Paulzen, Michael; Raptis, Mardjan; Baltus, Thomas; Schaffrath, Sabrina; Van Waesberghe, Julia; Zalewski, Magdalena M; Rösch, Frank; Vernaleken, Ingo; Schäfer, Wolfgang M; Gründer, Gerhard

2011-10-15

Preclinical data implicate the reinforcing effects of alcohol to be mediated by interaction between the opioid and dopamine systems of the brain. Specifically, alcohol-induced release of β-endorphins stimulates μ-opioid receptors (MORs), which is believed to cause dopamine release in the brain reward system. Individual differences in opioid or dopamine neurotransmission have been suggested to be responsible for enhanced liability to abuse alcohol. In the present study, a single dose of the MOR agonist remifentanil was administered in detoxified alcohol-dependent patients and healthy control subjects to mimic the β-endorphin-releasing properties of ethanol and to assess the effects of direct MOR stimulation on dopamine release in the mesolimbic reward system. Availability of D(2/3) receptors was assessed before and after single-dose administration of the MOR agonist remifentanil in 11 detoxified alcohol-dependent patients and 11 healthy control subjects with positron emission tomography with the radiotracer [(18)F]fallypride. Severity of dependence as assessed with the Alcohol Use Disorders Identification Test was compared with remifentanil-induced percentage change in [(18)F]fallypride binding (Δ%BP(ND)). The [(18)F]fallypride binding potentials (BP(ND)s) were significantly reduced in the ventral striatum, dorsal putamen, and amygdala after remifentanil application in both patients and control subjects. In the patient group, ventral striatum Δ%BP(ND) was correlated with the Alcohol Use Disorders Identification Test score. The data provide evidence for a MOR-mediated interaction between the opioid and the dopamine system, supporting the assumption that one way by which alcohol unfolds its rewarding effects is via a MOR-(γ-aminobutyric acid)-dopamine pathway. No difference in dopamine release was found between patients and control subjects, but evidence for a patient-specific association between sensitivity to MOR stimulation and severity of alcohol dependence was found. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Long-Term Effectiveness and Safety of Dexmethylphenidate Extended-Release Capsules in Adult ADHD

ERIC Educational Resources Information Center

Adler, Lenard A.; Spencer, Thomas; McGough, James J.; Jiang, Hai; Muniz, Rafael

2009-01-01

Objective: This study evaluates dexmethylphenidate extended release (d-MPH-ER) in adults with ADHD. Method: Following a 5-week, randomized, controlled, fixed-dose study of d-MPH-ER 20 to 40 mg/d, 170 adults entered a 6-month open-label extension (OLE) to assess long-term safety, with flexible dosing of 20 to 40 mg/d. Exploratory effectiveness…

Quick release latch for reactor scram

DOEpatents

Johnson, Melvin L.; Shawver, Bruce M.

1976-01-01

A simple, reliable, and fast-acting means for releasing a control element and allowing it to be inserted rapidly into the core region of a nuclear reactor for scram purposes. A latch mechanism grips a coupling head on a nuclear control element to connect the control element to the control drive assembly. The latch mechanism is closed by tensioning a cable or rod with an actuator. The control element is released by de-energizing the actuator, providing fail-safe, rapid release of the control element to effect reactor shutdown. A sensing rod provides indication that the control element is properly positioned in the latch. Two embodiments are illustrated, one involving a collet-type latch mechanism, the other a pliers-type latch mechanism with the actuator located inside the reactor vessel.

Quick release latch for reactor scram

DOEpatents

Johnson, M.L.; Shawver, B.M.

1975-09-16

A simple, reliable, and fast-acting means for releasing a control element and allowing it to be inserted rapidly into the core region of a nuclear reactor for scram purposes is described. A latch mechanism grips a coupling head on a nuclear control element to connect the control element to the control drive assembly. The latch mechanism is closed by tensioning a cable or rod with an actuator. The control element is released by de-energizing the actuator, providing fail-safe, rapid release of the control element to effect reactor shutdown. A sensing rod provides indication that the control element is properly positioned in the latch. Two embodiments are illustrated, one involving a collet- type latch mechanism, the other a pliers-type latch mechanism with the actuator located inside the reactor vessel. (auth)

Controlling chitosan-based encapsulation for protein and vaccine delivery

PubMed Central

Koppolu, Bhanu prasanth; Smith, Sean G.; Ravindranathan, Sruthi; Jayanthi, Srinivas; Kumar, Thallapuranam K.S.; Zaharoff, David A.

2014-01-01

Chitosan-based nano/microencapsulation is under increasing investigation for the delivery of drugs, biologics and vaccines. Despite widespread interest, the literature lacks a defined methodology to control chitosan particle size and drug/protein release kinetics. In this study, the effects of precipitation-coacervation formulation parameters on chitosan particle size, protein encapsulation efficiency and protein release were investigated. Chitosan particle sizes, which ranged from 300 nm to 3 μm, were influenced by chitosan concentration, chitosan molecular weight and addition rate of precipitant salt. The composition of precipitant salt played a significant role in particle formation with upper Hofmeister series salts containing strongly hydrated anions yielding particles with a low polydispersity index (PDI) while weaker anions resulted in aggregated particles with high PDIs. Sonication power had minimal effect on mean particle size, however, it significantly reduced polydispersity. Protein loading efficiencies in chitosan nano/microparticles, which ranged from 14.3% to 99.2%, was inversely related to the hydration strength of precipitant salts, protein molecular weight and directly related to the concentration and molecular weight of chitosan. Protein release rates increased with particle size and were generally inversely related to protein molecular weight. This study demonstrates that chitosan nano/microparticles with high protein loading efficiencies can be engineered with well-defined sizes and controllable release kinetics through manipulation of specific formulation parameters. PMID:24560459

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

PubMed

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).

Aerosol emission monitoring in the production of silicon carbide nanoparticles by induction plasma synthesis

NASA Astrophysics Data System (ADS)

Thompson, Drew; Leparoux, Marc; Jaeggi, Christian; Buha, Jelena; Pui, David Y. H.; Wang, Jing

2013-12-01

In this study, the synthesis of silicon carbide (SiC) nanoparticles in a prototype inductively coupled thermal plasma reactor and other supporting processes, such as the handling of precursor material, the collection of nanoparticles, and the cleaning of equipment, were monitored for particle emissions and potential worker exposure. The purpose of this study was to evaluate the effectiveness of engineering controls and best practice guidelines developed for the production and handling of nanoparticles, identify processes which result in a nanoparticle release, characterize these releases, and suggest possible administrative or engineering controls which may eliminate or control the exposure source. No particle release was detected during the synthesis and collection of SiC nanoparticles and the cleaning of the reactor. This was attributed to most of these processes occurring in closed systems operated at slight underpressure. Other tasks occurring in more open spaces, such as the disconnection of a filter assembly from the reactor system and the use of compressed air for the cleaning of filters where synthesized SiC nanoparticles were collected, resulted in releases of submicrometer particles with a mode size of 170-180 nm. Observation of filter samples under scanning electron microscope confirmed that the particles were agglomerates of SiC nanoparticles.

Preparation and in vitro evaluation of guar gum based triple-layer matrix tablet of diclofenac sodium

PubMed Central

Chavda, H.V.; Patel, M.S.; Patel, C.N.

2012-01-01

The objective of the present study was to design an oral controlled drug delivery system for sparingly soluble diclofenac sodium (DCL) using guar gum as triple-layer matrix tablets. Matrix tablet granules containing 30% (D1), 40% (D2) or 50% (D3) of guar gum were prepared by the conventional wet granulation technique. Matrix tablets of diclofenac sodium were prepared by compressing three layers one by one. Centre layer of sandwich like structure was incorporated with matrix granules containing DCL which was covered on either side by guar gum granule layers containing either 70, 80 or 87% of guar gum as release retardant layers. The tablets were evaluated for hardness, thickness, drug content, and drug release studies. To ascertain the kinetics of drug release, the dissolution profiles were fitted to various mathematical models. The in vitro drug release from proposed system was best explained by the Hopfenberg model indicating that the release of drug from tablets displayed heterogeneous erosion. D3G3, containing 87% of guar gum in guar gum layers and 50% of guar gum in DCL matrix granule layer was found to provide the release rate for prolonged period of time. The results clearly indicate that guar gum could be a potential hydrophilic carrier in the development of oral controlled drug delivery systems. PMID:23181081

Microencapsulation: A promising technique for controlled drug delivery.

PubMed

Singh, M N; Hemant, K S Y; Ram, M; Shivakumar, H G

2010-07-01

MICROPARTICLES OFFER VARIOUS SIGNIFICANT ADVANTAGES AS DRUG DELIVERY SYSTEMS, INCLUDING: (i) an effective protection of the encapsulated active agent against (e.g. enzymatic) degradation, (ii) the possibility to accurately control the release rate of the incorporated drug over periods of hours to months, (iii) an easy administration (compared to alternative parenteral controlled release dosage forms, such as macro-sized implants), and (iv) Desired, pre-programmed drug release profiles can be provided which match the therapeutic needs of the patient. This article gives an overview on the general aspects and recent advances in drug-loaded microparticles to improve the efficiency of various medical treatments. An appropriately designed controlled release drug delivery system can be a foot ahead towards solving problems concerning to the targeting of drug to a specific organ or tissue, and controlling the rate of drug delivery to the target site. The development of oral controlled release systems has been a challenge to formulation scientist due to their inability to restrain and localize the system at targeted areas of gastrointestinal tract. Microparticulate drug delivery systems are an interesting and promising option when developing an oral controlled release system. The objective of this paper is to take a closer look at microparticles as drug delivery devices for increasing efficiency of drug delivery, improving the release profile and drug targeting. In order to appreciate the application possibilities of microcapsules in drug delivery, some fundamental aspects are briefly reviewed.

Microencapsulation: A promising technique for controlled drug delivery

PubMed Central

Singh, M.N.; Hemant, K.S.Y.; Ram, M.; Shivakumar, H.G.

2010-01-01

Microparticles offer various significant advantages as drug delivery systems, including: (i) an effective protection of the encapsulated active agent against (e.g. enzymatic) degradation, (ii) the possibility to accurately control the release rate of the incorporated drug over periods of hours to months, (iii) an easy administration (compared to alternative parenteral controlled release dosage forms, such as macro-sized implants), and (iv) Desired, pre-programmed drug release profiles can be provided which match the therapeutic needs of the patient. This article gives an overview on the general aspects and recent advances in drug-loaded microparticles to improve the efficiency of various medical treatments. An appropriately designed controlled release drug delivery system can be a foot ahead towards solving problems concerning to the targeting of drug to a specific organ or tissue, and controlling the rate of drug delivery to the target site. The development of oral controlled release systems has been a challenge to formulation scientist due to their inability to restrain and localize the system at targeted areas of gastrointestinal tract. Microparticulate drug delivery systems are an interesting and promising option when developing an oral controlled release system. The objective of this paper is to take a closer look at microparticles as drug delivery devices for increasing efficiency of drug delivery, improving the release profile and drug targeting. In order to appreciate the application possibilities of microcapsules in drug delivery, some fundamental aspects are briefly reviewed. PMID:21589795

Propolis--based chitosan varnish: drug delivery, controlled release and antimicrobial activity against oral pathogen bacteria.

PubMed

Franca, Juçara R; De Luca, Mariana P; Ribeiro, Tatiana G; Castilho, Rachel O; Moreira, Allyson N; Santos, Vagner R; Faraco, André A G

2014-12-12

Dental caries is the most prevalent oral disease in several Asian and Latin American countries. It is an infectious disease and different types of bacteria are involved in the process. Synthetic antimicrobials are used against this disease; however, many of these substances cause unwarranted undesirable effects like vomiting, diarrhea and tooth staining. Propolis, a resinous substance collected by honeybees, has been used to control the oral microbiota. So, the objective of this study was to develop and characterize sustained-release propolis-based chitosan varnish useful on dental cariogenic biofilm prevention, besides the in vitro antimicrobial activity. Three formulations of propolis - based chitosan varnish (PCV) containing different concentrations (5%, 10% and 15%) were produced by dissolution of propolis with chitosan on hydro-alcoholic vehicle. Bovine teeth were used for testing adhesion of coatings and to observe the controlled release of propolis associated with varnish. It was characterized by infrared spectroscopy, scanning electron microscopy, casting time, diffusion test in vitro antimicrobial activity and controlled release. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were tested for the main microorganisms involved in the cariogenic biofilm through the microdilution test in 96-well plates. The formulations presented a tooth surface adherence and were able to form films very fast on bovine tooth surface. Also, propolis-based chitosan varnishes have shown antimicrobial activity similar to or better than chlorhexidine varnish against all oral pathogen bacteria. All microorganisms were sensitive to propolis varnish and chitosan. MIC and MBC for microorganisms of cariogenic biofilme showed better results than chlorhexidine. Propolis active components were released for more than one week. All developed formulations turn them, 5%, 10% and 15% propolis content varnish, into products suitable for clinical application on dental caries prevention field, deserving clinical studies to confirm its in vivo activity.

[Research on controlling iron release of desalted water transmitted in existing water distribution system].

PubMed

Tian, Yi-Mei; Liu, Yang; Zhao, Peng; Shan, Jin-Lin; Yang, Suo-Yin; Liu, Wei

2012-04-01

Desalted water, with strong corrosion characteristics, would possibly lead to serious "red water" when transmitted and distributed in existing municipal water distribution network. The main reason for red water phenomenon is iron release in water pipes. In order to study the methods of controlling iron release in existing drinking water distribution pipe, tubercle analysis of steel pipe and cast iron pipe, which have served the distribution system for 30-40 years, was carried out, the main construction materials were Fe3O4 and FeOOH; and immersion experiments were carried in more corrosive pipes. Through changing mixing volume of tap water and desalted water, pH, alkalinity, chloride and sulfate, the influence of different water quality indexes on iron release were mainly analyzed. Meanwhile, based on controlling iron content, water quality conditions were established to meet with the safety distribution of desalted water: volume ratio of potable water and desalted water should be higher than or equal to 2, pH was higher than 7.6, alkalinity was higher than 200 mg x L(-1).

Novel system for reducing leaching of the herbicide metribuzin using clay-gel-based formulations.

PubMed

Maqueda, Celia; Villaverde, Jaime; Sopeña, Fátima; Undabeytia, Tomás; Morillo, Esmeralda

2008-12-24

Metribuzin is an herbicide widely used for weed control that has been identified as a groundwater pollutant. It contaminates the environment even when it is used according to the manufacturer's instructions. To reduce herbicide leaching and increase weed control, new controlled release formulations were developed by entrapping metribuzin within a sepiolite-gel-based matrix using two clay/herbicide proportions (0.5/0.2 and 1/0.2) (loaded at 28.6 and 16.7% a.i.) as a gel (G28, G16) or as a powder after freeze-drying (LF28, LF16). The release of metribuzin from the control released formulations into water was retarded, when compared with commercial formulation (CF) except in the case of G28. The mobility of metribuzin from control released formulations into soil columns of sandy soil was greatly diminished in comparison with CF. Most of the metribuzin applied as control released formulations (G16, LF28 and LF16) was found at a depth of 0-8 cm depth. In contrast, residues from CF and G28 along the column were almost negligible. Bioassays from these control released formulations showed high efficacy at 0-12 cm depth. The use of these novel formulations could minimize the risk of groundwater contamination while maintaining weed control for a longer period.

Evaluation of an Extended-Release, Abuse-Deterrent, Microsphere-in-Capsule Analgesic for the Management of Patients with Chronic Pain With Dysphagia (CPD).

PubMed

Fleming, Alison B; Carlson, Douglas R; Varanasi, Ravi K; Grima, Michael; Mayock, Stephen P; Saim, Said; Kopecky, Ernest A

2016-03-01

Patients who have chronic pain with dysphagia (difficulty swallowing) (CPD) often have difficulty taking oral medication and, as such, alter their medications by crushing or chewing in an attempt to make it easier to swallow. Such manipulation of currently marketed, extended-release (ER) opioid analgesics can significantly alter the pharmacokinetic (PK) properties of the formulations, resulting in poor treatment outcome or serious adverse events. There is an unmet medical need for oral ER opioid formulations suitable for patients with CPD. The primary objectives of this study were to conduct in vitro studies to evaluate alternate means of administration of a new, extended-release (ER), abuse-deterrent, microsphere-in-capsule formulation of oxycodone for patients with CPD. Specifically, these studies investigated the in vitro equivalence of drug release rates from Oxycodone DETERx® ER intact capsules (control condition) and administration via alternate modes-opening the capsule and sprinkling the microspheres onto soft foods or administration through enteral tubes. Secondary objectives were to compare alternate modes of administration of Oxycodone DETERx® to a commercially available ER-morphine product. Soft food study: Oxycodone DETERx® microspheres were sprinkled onto and mixed with several soft foods (ie, applesauce, vanilla pudding, strawberry jam, yogurt, and vanilla ice cream); the effect of drug contact time (0, 30, and 60 minutes) on drug release was studied. Enteral tube study: Oxycodone DETERx® microspheres were administered through varying sizes of nasogastric (10 and 12 Fr.) tubes and a 16 Fr. gastrostomy tube using 5 different delivery vehicles (ie, water, liquid nutritional feeds [Jevity®, Ensure®], and milk [whole milk and 2% milk]). Drug release rate was characterized using a standard in vitro dissolution methodology; dissolution of intact Oxycodone DETERx® capsules served as the control for both the soft food and enteral tube studies. Oxycodone concentration was measured using a standardized high-performance liquid chromatography (HPLC) assay. Similarity factor (f2) analysis was used to compare similarity of the dissolution profiles of test and control conditions. The mean dissolution profile of Oxycodone DETERx® microspheres sprinkled onto and mixed with each of the soft foods were similar (f2 > 50) to that of the control. Study drug-food contact time did not impact dissolution profiles. The dissolution data obtained from Oxycodone DETERx® microspheres passed through enteral feeding tubes of varying sizes were similar (f2 > 50) to that of the control. Unlike a marketed morphine sulfate ER pellet formulation, Oxycodone DETERx® did not clog any of the studied enteral tubes. A new ER, abuse-deterrent, microsphere-in-capsule formulation of oxycodone can be administered by sprinkling onto soft food without affecting the drug release profile of the formulation. The formulation can also be administered directly via enteral tubes without affecting drug release and without clogging enteral tubes. Oxycodone DETERx® may offer physicians and patients with CPD an alternate treatment option, especially in those patients who have dysphagia or an aversion to swallowing monolithic tablet/capsule formulations and for whom analgesic patches or other opioid formulations are not a viable therapeutic option. © 2015 World Institute of Pain.

Aminopropyl groups of the functionalized Mobil Crystalline Material 41 as a carrier for controlled diclofenac sodium and piroxicam delivery

PubMed Central

Khodaverdi, Elham; Ahmadi, Mina; Kamali, Hossein; Hadizadeh, Farzin

2017-01-01

Objective: Synthetic Mobil Crystalline Material 41 (MCM-41) as a mesoporous material and functionalized MCM-41 using aminopropyl groups were studied in order to investigate their ability to encapsulate and to control the release of diclofenac sodium and piroxicam. Materials and Methods: MCM-41 was synthesized through sol–gel procedure and functionalized with aminopropyl groups. The physicochemical properties of MCM-41 were studied through particle size analysis, infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, and carbon–hydrogen–nitrogen analysis. Diclofenac sodium and piroxicam were loaded into the MCM-41 matrix using the filtration and solvent evaporation methods. The drug-loading capacity was determined by ultraviolet, Fourier transform infrared, X-ray diffraction, and Brunauer–Emmett–Teller analysis. Results: According to the results for pure drug release, >57% was released in the 1st h, but when these drugs were loaded into pure Mobil Crystalline Material 41 (MCM-41) and functionalized MCM-41, the release into the simulated gastrointestinal medium was less, continuous, and slower. The release of piroxicam from functionalized MCM-41 was slower than that from MCM-41 in the simulated intestinal medium because of the formation of electrostatic bonds between piroxicam and the aminopropyl groups of the functionalized MCM-41. However, in the case of diclofenac sodium, there was no significant difference between pure MCM-41 and functionalized MCM-41. The difference between piroxicam and diclofenac sodium was due to the high solubility of diclofenac sodium in the intestinal medium (pH 6.8), which caused more rapid release from the matrixes than for piroxicam. Conclusion: Our findings indicate that, after functionalization of MCM-41, it could offer a good means of delivering controlled diclofenac sodium and piroxicam. PMID:29692976

Aminopropyl groups of the functionalized Mobil Crystalline Material 41 as a carrier for controlled diclofenac sodium and piroxicam delivery.

PubMed

Khodaverdi, Elham; Ahmadi, Mina; Kamali, Hossein; Hadizadeh, Farzin

2017-01-01

Synthetic Mobil Crystalline Material 41 (MCM-41) as a mesoporous material and functionalized MCM-41 using aminopropyl groups were studied in order to investigate their ability to encapsulate and to control the release of diclofenac sodium and piroxicam. MCM-41 was synthesized through sol-gel procedure and functionalized with aminopropyl groups. The physicochemical properties of MCM-41 were studied through particle size analysis, infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, and carbon-hydrogen-nitrogen analysis. Diclofenac sodium and piroxicam were loaded into the MCM-41 matrix using the filtration and solvent evaporation methods. The drug-loading capacity was determined by ultraviolet, Fourier transform infrared, X-ray diffraction, and Brunauer-Emmett-Teller analysis. According to the results for pure drug release, >57% was released in the 1 st h, but when these drugs were loaded into pure Mobil Crystalline Material 41 (MCM-41) and functionalized MCM-41, the release into the simulated gastrointestinal medium was less, continuous, and slower. The release of piroxicam from functionalized MCM-41 was slower than that from MCM-41 in the simulated intestinal medium because of the formation of electrostatic bonds between piroxicam and the aminopropyl groups of the functionalized MCM-41. However, in the case of diclofenac sodium, there was no significant difference between pure MCM-41 and functionalized MCM-41. The difference between piroxicam and diclofenac sodium was due to the high solubility of diclofenac sodium in the intestinal medium (pH 6.8), which caused more rapid release from the matrixes than for piroxicam. Our findings indicate that, after functionalization of MCM-41, it could offer a good means of delivering controlled diclofenac sodium and piroxicam.

Optimization of synthesis process of thermally-responsive poly-n-isopropylacrylamide nanoparticles for controlled release of antimicrobial hydrophobic compounds

NASA Astrophysics Data System (ADS)

Hill, Laura E.; Gomes, Carmen L.

2014-12-01

The goal of this study was to develop an effective method to synthesize poly-n-isopropylacrylamide (PNIPAAM) nanoparticles with entrapped cinnamon bark extract (CBE) to improve its delivery to foodborne pathogens and control its release with temperature stimuli. CBE was used as a model for hydrophobic natural antimicrobials. A top-down procedure using crosslinked PNIPAAM was compared to a bottom-up procedure using NIPAAM monomer. Both processes relied on self-assembly of the molecules into micelles around the CBE at 40 °C. Processing conditions were compared including homogenization time of the polymer, hydration time prior to homogenization, lyophilization, and the effect of particle ultrafiltration. The top-down versus bottom-up synthesis methods yielded particles with significantly different characteristics, especially their release profiles and antimicrobial activities. The synthesis methods affected particle size, with the bottom-up procedure resulting in smaller (P < 0.05) diameters than the top-down procedure. The controlled release profile of CBE from nanoparticles was dependent on the release media temperature. A faster, burst release was observed at 40 °C and a slower, more sustained release was observed at lower temperatures. PNIPAAM particles containing CBE were analyzed for their antimicrobial activity against Salmonella enterica serovar Typhimurium LT2 and Listeria monocytogenes Scott A. The PNIPAAM particles synthesized via the top-down procedure had a much faster release, which led to a greater (P < 0.05) antimicrobial activity. Both of the top-down nanoparticles performed similarly, therefore the 7 min homogenization time nanoparticles would be the best for this application, as the process time is shorter and little improvement was seen by using a slightly longer homogenization.

Effect of local drug delivery in chronic periodontitis patients: A meta-analysis

PubMed Central

Kalsi, Rupali; Vandana, K. L.; Prakash, Shobha

2011-01-01

Periodontal diseases are multi-factorial in etiology, and bacteria are one among these etiologic agents. Thus, an essential component of therapy is to eliminate or control these pathogens. This has been traditionally accomplished through mechanical means (scaling and root planing (SRP)), which is time-consuming, difficult, and, sometimes, ineffective. From about the past 30 years, locally delivered, anti-infective pharmacological agents, most recently employing sustained-release vehicles, have been introduced to achieve this goal. This systematic review is an effort to determine the efficacy of the currently available anti-infective agents, with and without concurrent SRP, in controlling chronic periodontitis. Four studies were included, which were all randomized controlled trials, incorporating a total patient population of 80, with 97 control sites and 111 test sites. A meta-analysis completed on these four studies including SRP and local sustained-release agents compared with SRP alone indicated significant adjunctive probing depth (PD) reduction for 10% Doxycycline hycylate (ATRIDOX), minocycline hydrochloride (ARESTIN), tetracycline hydrochloride (PERIODONTAL PLUS AB), and chlorhexidine gluconate (PERIOCHIP). Essentially, all studies reported substantial reductions in gingival inflammation, plaque scores, and bleeding indices, which were similar in both the control and the experimental groups. Use of antimicrobial sustained-release systems as an adjunct to SRP does not result in significant patient-centered adverse events. Local drug delivery combined with SRP appears to provide additional benefits in PD reduction compared with SRP alone. PMID:22368351

10 CFR 50.34a - Design objectives for equipment to control releases of radioactive material in effluents-nuclear...

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Design objectives for equipment to control releases of..., Certifications, and Regulatory Approvals; Form; Contents; Ineligibility of Certain Applicants § 50.34a Design objectives for equipment to control releases of radioactive material in effluents—nuclear power reactors. (a...

10 CFR 50.34a - Design objectives for equipment to control releases of radioactive material in effluents-nuclear...

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Design objectives for equipment to control releases of..., Certifications, and Regulatory Approvals; Form; Contents; Ineligibility of Certain Applicants § 50.34a Design objectives for equipment to control releases of radioactive material in effluents—nuclear power reactors. (a...

10 CFR 50.34a - Design objectives for equipment to control releases of radioactive material in effluents-nuclear...

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Design objectives for equipment to control releases of..., Certifications, and Regulatory Approvals; Form; Contents; Ineligibility of Certain Applicants § 50.34a Design objectives for equipment to control releases of radioactive material in effluents—nuclear power reactors. (a...

10 CFR 50.34a - Design objectives for equipment to control releases of radioactive material in effluents-nuclear...

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Design objectives for equipment to control releases of..., Certifications, and Regulatory Approvals; Form; Contents; Ineligibility of Certain Applicants § 50.34a Design objectives for equipment to control releases of radioactive material in effluents—nuclear power reactors. (a...

10 CFR 50.34a - Design objectives for equipment to control releases of radioactive material in effluents-nuclear...

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Design objectives for equipment to control releases of..., Certifications, and Regulatory Approvals; Form; Contents; Ineligibility of Certain Applicants § 50.34a Design objectives for equipment to control releases of radioactive material in effluents—nuclear power reactors. (a...

Performance and operational improvements made to the Waukesha AT27-GL engine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reinbold, E.O.

1996-12-31

This paper presents the results of combustion and engine performance studies performed on the AT27GL lean burn engine. One study was to evaluate the effect of the pre-combustion chamber cup geometry on engine performance under several operating conditions including: Air-Fuel Ratio (AFR), ignition timing, and engine load. The study examined several combustion parameters; including IMEP, coefficient of variation of IMEP, heat release rates, and maximum combustion pressures. The study also examined engine thermal efficiency, and brake specific emissions of Oxides of Nitrogen, Carbon Monoxide, and Total Hydrocarbons (gaseous). Studies were also performed on different spark plug designs, comparing firing voltages,more » and electrode temperatures while operating under conditions of varying AFR, and ignition timing. In addition an Air-Fuel-Ratio controller was recently tested and released on the engine. The controller was tested under conditions of varying fuel quality, along with a detonation control system.« less

The use of sequential mark-release-recapture experiments to estimate population size, survival and dispersal of male mosquitoes of the  Anopheles gambiae complex in Bana, a west African humid savannah village.

PubMed

Epopa, Patric Stephane; Millogo, Abdoul Azize; Collins, Catherine Matilda; North, Ace; Tripet, Frederic; Benedict, Mark Quentin; Diabate, Abdoulaye

2017-08-07

Vector control is a major component of the malaria control strategy. The increasing spread of insecticide resistance has encouraged the development of new tools such as genetic control which use releases of modified male mosquitoes. The use of male mosquitoes as part of a control strategy requires an improved understanding of male mosquito biology, including the factors influencing their survival and dispersal, as well as the ability to accurately estimate the size of a target mosquito population. This study was designed to determine the seasonal variation in population size via repeated mark-release-recapture experiments and to estimate the survival and dispersal of male mosquitoes of the Anopheles gambiae complex in a small west African village. Mark-release-recapture experiments were carried out in Bana Village over two consecutive years, during the wet and the dry seasons. For each experiment, around 5000 (3407-5273) adult male Anopheles coluzzii mosquitoes were marked using three different colour dye powders (red, blue and green) and released in three different locations in the village (centre, edge and outside). Mosquitoes were recaptured at sites spread over the village for seven consecutive days following the releases. Three different capture methods were used: clay pots, pyrethroid spray catches and swarm sampling. Swarm sampling was the most productive method for recapturing male mosquitoes in the field. Population size and survival were estimated by Bayesian analyses of the Fisher-Ford model, revealing an about 10-fold increase in population size estimates between the end of dry season (10,000-50,000) to the wet season (100,000-500,000). There were no detectable seasonal effects on mosquito survival, suggesting that factors other than weather may play an important role. Mosquito dispersal ranged from 40 to 549 m over the seven days of each study and was not influenced by the season, but mainly by the release location, which explained more than 44% of the variance in net dispersal distance. This study clearly shows that male-based MRR experiments can be used to estimate some parameters of wild male populations such as population size, survival, and dispersal and to estimate the spatial patterns of movement in a given locality.

Controlled release properties of zein-fatty acid blend films for multiple bioactive compounds.

PubMed

Arcan, Iskender; Yemenicioğlu, Ahmet

2014-08-13

To develop edible films having controlled release properties for multiple bioactive compounds, hydrophobicity and morphology of zein films were modified by blending zein with oleic (C18:1)Δ⁹, linoleic (C18:2)Δ(9,12), or lauric (C₁₂) acids in the presence of lecithin. The blend zein films showed 2-8.5- and 1.6-2.9-fold lower initial release rates for the model active compounds, lysozyme (LYS) and (+)-catechin (CAT), than the zein control films, respectively. The change of fatty acid chain length affected both CAT and LYS release rates while the change of fatty acid double bond number affected only the CAT release rate. The film morphologies suggested that the blend films owe their controlled release properties mainly to the microspheres formed within their matrix and encapsulation of active compounds. The blend films showed antilisterial activity and antioxidant activity up to 81 μmol Trolox/cm². The controlled release of multiple bioactive compounds from a single film showed the possibility of combining application of active and bioactive packaging technologies and improving not only safety and quality but also health benefits of packed food.

Development of novel cationic chitosan-and anionic alginate–coated poly(d,l-lactide-co-glycolide) nanoparticles for controlled release and light protection of resveratrol

PubMed Central

Sanna, Vanna; Roggio, Anna Maria; Siliani, Silvia; Piccinini, Massimo; Marceddu, Salvatore; Mariani, Alberto; Sechi, Mario

2012-01-01

Background Resveratrol, like other natural polyphenols, is an extremely photosensitive compound with low chemical stability, which limits the therapeutic application of its beneficial effects. The development of innovative formulation strategies, able to overcome physicochemical and pharmacokinetic limitations of this compound, may be achieved via suitable carriers able to associate controlled release and protection. In this context, nanotechnology is proving to be a powerful strategy. In this study, we developed novel cationic chitosan (CS)- and anionic alginate (Alg)-coated poly(d,l-lactide-co-glycolide) nanoparticles (NPs) loaded with the bioactive polyphenolic trans-(E)-resveratrol (RSV) for biomedical applications. Methods NPs were prepared by the nanoprecipitation method and characterized in terms of morphology, size and zeta potential, encapsulation efficiency, Raman spectroscopy, swelling properties, differential scanning calorimetry, and in vitro release studies. The protective effect of the nanosystems under the light-stressed RSV and long-term stability were investigated. Results NPs turned out to be spherical in shape, with size ranging from 135 to about 580 nm, depending on the composition and the amount of polyelectrolytes, while the encapsulation efficiencies increased from 8% of uncoated poly(d,l-lactide-co-glycolide) (PLGA) to 23% and 32% of Alg- and CS-coated PLGA NPs, respectively. All nanocarriers are characterized by a biphasic release pattern, and more effective controlled release rates are obtained for NPs formulated with higher polyelectrolyte concentrations. Stability studies revealed that encapsulation provides significant protection against light-exposure degradation, by reducing the trans–cis photoisomerization reaction. Moreover, the nanosystems are able to prevent the degradation of trans isoform and the leakage of RSV from the carrier for a period of 6 months. Conclusion Our findings indicated that the newly developed CS- and Alg-coated PLGA NPs are suitable to be used for the delivery of bioactive RSV. The encapsulation of RSV into optimized polymeric NPs provides improved drug loading, effective controlled release, and protection against light-exposure degradation, thus opening new perspectives for the delivery of bioactive related phytochemicals to be used for (nano)chemoprevention/chemotherapy. PMID:23093904

Improving Birth Control Service Utilization By Offering Services Prerelease Vs Postincarceration

PubMed Central

Clarke, Jennifer G.; Rosengard, Cynthia; Rose, Jennifer S.; Hebert, Megan R.; Peipert, Jeffrey; Stein, Michael D.

2006-01-01

Objectives. We examined whether incarcerated women would substantially increase birth control initiation if contraceptive services were available within the prison compared with after their release back into the community. Methods. During phase 1 of the study, a nurse educator met with women at the Rhode Island Adult Correctional Institute and offered them referrals for contraceptive services at a community health clinic after their release. During phase 2, contraceptive services were offered to women during their incarceration. Results. The majority of the participants (77.5%) reported a desire to initiate use of birth control methods. Within 4 weeks of their release, 4.4% of phase 1 participants initiated use of a contraceptive method, compared with 39.1% of phase 2 participants (odds ratio [OR]=14.6; 95% confidence interval [CI]=5.5, 38.8). Conclusions. Provision of contraceptive services to women during their incarceration is feasible and greatly increases birth control initiation compared to providing services only in the community. PMID:16571698

Cross-linked β-cyclodextrin and carboxymethyl cellulose hydrogels for controlled drug delivery of acyclovir

PubMed Central

Malik, Nadia Shamshad; Ahmad, Mahmood; Minhas, Muhammad Usman

2017-01-01

To explore the potential role of polymers in the development of drug-delivery systems, this study investigated the use of β-cyclodextrin (β-CD), carboxymethyl cellulose (CMC), acrylic acid (AA) and N’ N’-methylenebis-acrylamide (MBA) in the synthesis of hydrogels for controlled drug delivery of acyclovir (ACV). Different proportions of β-CD, CMC, AA and MBA were blended with each other to fabricate hydrogels via free radical polymerization technique. Fourier transform infrared spectroscopy (FTIR) revealed successful grafting of components into the polymeric network. Thermal and morphological characterization confirmed the formation of thermodynamically stable hydrogels having porous structure. The pH-responsive behaviour of hydrogels has been documented by swelling dynamics and drug release behaviour in simulated gastrointestinal fluids. Drug release kinetics revealed controlled release behaviour of the antiviral drug acyclovir in developed polymeric network. Cross-linked β-cyclodextrin and carboxymethyl cellulose hydrogels can be used as promising candidates for the design and development of controlled drug-delivery systems. PMID:28245257

Benefits of a self-myofascial release program on health-related quality of life in people with fibromyalgia: a randomized controlled trial.

PubMed

Ceca, Diego; Elvira, Laura; Guzmán, José F; Pablos, Ana

2017-01-01

Fibromyalgia (FM) is a disease with symptoms that significantly limit the life of affected patients. Earlier studies have shown that the application of self-myofascial release provides benefits in variables such as fatigue, range of motion (ROM) or perceived muscle pain in a healthy population. Despite this, the self-myofascial release technique has not yet been used in people with FM. This study aimed to find out the benefits of applying a self-myofascial release program on health-related quality of life in people with FM. Sixty-six participants with FM were randomized into two groups, intervention (N.=33) and control (N.=33). The intervention group (IG) participated in the self-myofascial release program for twenty weeks. The study assessed the impact of a self-myofascial release program on cervical spine, shoulder and hip ROM and self-reported disease impact. Two measurements were performed, one at baseline (preintervention) and one postintervention. Two-way mixed-effect (between-within) ANOVA was used for the statistical analysis. Significant changes (P<0.05) were achieved between the two measurements and between groups for final Fibromyalgia Impact Questionnaire (FIQ-S) Score and for five of its seven subscales, including: days per week feeling good, pain intensity, fatigue, stiffness and depression/sadness, as well as all the ROM variables evaluated (neck flexion, neck extension, lateral neck flexion and rotation (bilateral), shoulder flexion and abduction and hip abduction) excluding hip flexion. The application of a self-myofascial release program can improve the health-related quality of life of people with FM, provided that regular, structured practice is carried out.

Release of (14)C-labelled carbon nanotubes from polycarbonate composites.

PubMed

Rhiem, Stefan; Barthel, Anne-Kathrin; Meyer-Plath, Asmus; Hennig, Michael P; Wachtendorf, Volker; Sturm, Heinz; Schäffer, Andreas; Maes, Hanna M

2016-08-01

Waste disposal of carbon nanotube (CNT) containing products is expected to be the most important pathway for release of CNTs into the environment. In the present work, the use of radiolabelled CNTs ((14)C-CNT) for polycarbonate polymer nanocomposites with 1 wt% (14)C-CNT content allowed for the first time to quantify and differentiate the CNT release according to the type of impact along the materials' ageing history. After an initial exposure of the nanocomposite by solar-like irradiation, further environmental impacts were applied to composite material. They aimed at mimicking disposal site conditions that may induce further ageing effects and CNT release. This study included shaking in water, rapid temperature changes, soaking in humic acid solution as well as waste water effluent, and, finally, gentle mechanical abrasion. All ageing impacts were applied sequentially, both on pristine (control) and on solar-irradiated nanocomposites. All experiments were accompanied by absolute quantification of radioactive release as well as chemical and morphological analyses of the nanocomposite surfaces using infra-red (IR) spectroscopy, X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). The morphological analysis showed that spectral irradiation can uncover CNT networks on the outer nanocomposite surface layers by polymer degradation. After having subjected the solar-irradiated nanocomposite to all studied disposal site effect, the total radioactive release was quantified to amount to 64 mg CNT/m(2), whereas only 0.8 mg CNT/m(2) were found for the un-irradiated control sample. Solar degradation of polymers was thus found to significantly increase the propensity of the studied polymer nanocomposites to release CNTs during ageing effects at the product's end-of-life typical for disposal sites. Copyright © 2016. Published by Elsevier Ltd.

In Vivo Analytical Performance of Nitric Oxide-Releasing Glucose Biosensors

PubMed Central

2015-01-01

The in vivo analytical performance of percutaneously implanted nitric oxide (NO)-releasing amperometric glucose biosensors was evaluated in swine for 10 d. Needle-type glucose biosensors were functionalized with NO-releasing polyurethane coatings designed to release similar total amounts of NO (3.1 μmol cm–2) for rapid (16.0 ± 4.4 h) or slower (>74.6 ± 16.6 h) durations and remain functional as outer glucose sensor membranes. Relative to controls, NO-releasing sensors were characterized with improved numerical accuracy on days 1 and 3. Furthermore, the clinical accuracy and sensitivity of rapid NO-releasing sensors were superior to control and slower NO-releasing sensors at both 1 and 3 d implantation. In contrast, the slower, extended, NO-releasing sensors were characterized by shorter sensor lag times (<4.2 min) in response to intravenous glucose tolerance tests versus burst NO-releasing and control sensors (>5.8 min) at 3, 7, and 10 d. Collectively, these results highlight the potential for NO release to enhance the analytical utility of in vivo glucose biosensors. Initial results also suggest that this analytical performance benefit is dependent on the NO-release duration. PMID:24984031

In vivo analytical performance of nitric oxide-releasing glucose biosensors.

PubMed

Soto, Robert J; Privett, Benjamin J; Schoenfisch, Mark H

2014-07-15

The in vivo analytical performance of percutaneously implanted nitric oxide (NO)-releasing amperometric glucose biosensors was evaluated in swine for 10 d. Needle-type glucose biosensors were functionalized with NO-releasing polyurethane coatings designed to release similar total amounts of NO (3.1 μmol cm(-2)) for rapid (16.0 ± 4.4 h) or slower (>74.6 ± 16.6 h) durations and remain functional as outer glucose sensor membranes. Relative to controls, NO-releasing sensors were characterized with improved numerical accuracy on days 1 and 3. Furthermore, the clinical accuracy and sensitivity of rapid NO-releasing sensors were superior to control and slower NO-releasing sensors at both 1 and 3 d implantation. In contrast, the slower, extended, NO-releasing sensors were characterized by shorter sensor lag times (<4.2 min) in response to intravenous glucose tolerance tests versus burst NO-releasing and control sensors (>5.8 min) at 3, 7, and 10 d. Collectively, these results highlight the potential for NO release to enhance the analytical utility of in vivo glucose biosensors. Initial results also suggest that this analytical performance benefit is dependent on the NO-release duration.

Polymer-based delivery systems for support and delivery of bacteriophages

NASA Astrophysics Data System (ADS)

Brown, Alyssa Marie

One of the most urgent problems in the fields of medicine and agriculture is the decreasing effectiveness of antibiotics. Once a miracle drug, antibiotics have recently become associated with the creation of antibiotic-resistant bacteria. The main limitations of these treatments include lack of both adaptability and specificity. To overcome these shortcomings of current antibiotic treatments, there has been a renewed interest in bacteriophage research. Bacteriophages are naturally-occurring viruses that lyse bacteria. They are highly specific, with each bacteriophage type lysing a narrow range of bacteria strains. Bacteriophages are also ubiquitous biological entities, populating environments where bacterial growth is supported. Just as humans are exposed to bacteria in their daily lives, we are exposed to bacteriophages as well. To use bacteriophages in practical applications, they must be delivered to the site of an infection in a controlled-release system. Two systems were studied to observe their support of bacteriophage lytic activity, as well as investigate the possibility of controlling bacteriophage release rates. First, hydrogels were studied, using crosslinking and blending techniques to achieve a range of release profiles. Second, polyanhydride microparticles were studied, evaluating release rates as a function of monomer chemistries.

Magnetic pH-responsive poly(methacrylic acid-co-acrylic acid)-co-polyvinylpyrrolidone magnetic nano-carrier for controlled delivery of fluvastatin.

PubMed

Amoli-Diva, Mitra; Pourghazi, Kamyar; Mashhadizadeh, Mohammad Hossein

2015-02-01

A novel pH-responsive polymer, poly(methacrylic acid-co-acrylic acid)-co-polyvinyl-pyrrolidone (polymeric nano-carrier) was synthesized and used for encapsulation of 3-aminopropyl triethoxysilane modified Fe3O4 nanoparticles to prepare a new magnetic nano-carrier. The loading and release characteristics of both polymeric and magnetic nano-carriers were investigated using fluvastatin as the model drug. The loading behavior of the carriers was studied by varying concentration of fluvastatin in aqueous medium at 25°C and their release was followed spectrophotometrically (at 304 nm) at 37°C in three different solutions (buffered at pH1.2, 5.5 and 7.2) to simulate gastric and intestine medium. The effect of different parameters on the release of fluvastatin such as the amount of methacrylic acid monomer, cross-linker amount, initiator amount, and magnetic nanoparticles content was also studied. Considering the release kinetics and mechanism of the magnetic nanocarrier besides swelling behavior study of the polymeric nano-carrier reveal Fickian pattern and diffusion controlled mechanism for delivery of fluvastatin. Copyright © 2014 Elsevier B.V. All rights reserved.

Controlled release of alendronate from nitrogen-doped mesoporous carbon

DOE PAGES

Saha, Dipendu; Spurri, Amanda; Chen, Jihua; ...

2016-04-13

With this study, we have synthesized a nitrogen doped mesoporous carbon with the BET surface area of 1066 m 2/g, total pore volume 0.6 cm 3/g and nitrogen content of 0.5%. Total alendronate adsorption in this carbon was ~5%. The release experiments were designed in four different media with sequential pH values of 1.2, 4.5, 6.8 and 7.4 for 3, 1, 3 and 5 h, respectively and at 37 °C to imitate the physiological conditions of stomach, duodenum, small intestine and colon, respectively. Release of the drug demonstrated a controlled fashion; only 20% of the drug was released in themore » media with pH = 1.2, whereas 64% of the drug was released in pH = 7.4. This is in contrary to pure alendronate that was completely dissolved within 30 min in the first release media (pH = 1.2) only. The relatively larger uptake of alendronate in this carbon and its sustained fashion of release can be attributed to the hydrogen bonding between the drug and the nitrogen functionalities on carbon surface. Based on this result, it can be inferred that this formulation may lower the side effects of oral delivery of alendronate.« less

Applying Learning Analytics to Investigate Timed Release in Online Learning

ERIC Educational Resources Information Center

Martin, Florence; Whitmer, John C.

2016-01-01

Adaptive learning gives learners control of context, pace, and scope of their learning experience. This strategy can be implemented in online learning by using the "Adaptive Release" feature in learning management systems. The purpose of this study was to use learning analytics research methods to explore the extent to which the adaptive…

Risk assessment and stakeholder perceptions in novel biological control agent release: YST as a case study

USDA-ARS?s Scientific Manuscript database

The objectives of risk assessment are to learn about whether a candidate agent would be safe to use in the environment where release is planned, and to present such information in a clear, understandable format to regulators, stakeholders, and the public. Plant pathogens evaluated for biological co...

Release and monitoring of Laricobius nigrinus (Coleoptera: Derodontidae) for classical biological control of the hemlock woolly adelgid in the Eastern U.S.

Treesearch

David L. Mausel; Scott M. Salom; Loke T. Kok

2007-01-01

Studies are being conducted to determine optimal release procedures for establishment and sampling methodology of Laricobius nigrinus Fender (Coleoptera: Derodontidae), a predator of the hemlock woolly adelgid, Adelges tsugae Annand (Hemiptera: Adelgidae) on eastern hemlock, Tsuga canadensis (L.) Carriere, trees...

Efficacy and Safety of Dexmethylphenidate Extended-Release Capsules in Children with Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Greenhill, Laurence L.; Muniz, Rafael; Ball, Roberta R.; Levine, Alan; Pestreich, Linda; Jiang, Hai

2006-01-01

Objective: The efficacy and safety of dexmethylphenidate extended release (d-MPH-ER) was compared to placebo in pediatric patients with attention-deficit/hyperactivity disorder (ADHD). Method: This multicenter, randomized, double-blind, placebo-controlled, parallel-group, two-phase study included 97 patients (ages 6-17 years) with…

Simulated Driving Changes in Young Adults with ADHD Receiving Mixed Amphetamine Salts Extended Release and Atomoxetine

ERIC Educational Resources Information Center

Kay, Gary G.; Michaels, M. Alex; Pakull, Barton

2009-01-01

Background: Psychostimulant treatment may improve simulated driving performance in young adults with attention-deficit/hyperactivity disorder (ADHD). Method: This was a randomized, double-blind, placebo-controlled, crossover study of simulated driving performance with mixed amphetamine salts--extended release (MAS XR) 50 mg/day (Cohort 1) and…

Polyvinyl alcohol hydrogels for iontohporesis

NASA Astrophysics Data System (ADS)

Bera, Prasanta; Alam, Asif Ali; Arora, Neha; Tibarewala, Dewaki Nandan; Basak, Piyali

2013-06-01

Transdermal therapeutic systems propound controlled release of active ingredients through the skin into the systemic circulation in a predictive manner. Drugs administered through these systems escape first-pass metabolism and maintain a steady state scenario similar to a continuous intravenous infusion for up to several days. The iontophoresis deal with the systemic delivery of the bioactive agents (drug) by applying an electric current. It is basically an injection without the needle. The iontophoretic system requires a gel-based matrix to accommodate the bioactive agent. Hydrogels have been used by many investigators in controlled-release drug delivery systems because of their good tissue compatibility and easy manipulation of swelling level and, thereby, solute permeability. In this work we have prepared polyvinyl alcohol (PVA) hydrogel. We have cross linked polyvinyl alcohol chemically with Glutaraldehyde with different wt%. FTIR study reveals the chemical changes during cross linking. Swelling in water, is done to have an idea about drug loading and drug release from the membrane. After drug loading to the hydrogels, we have studied the drug release property of the hydrogels using salicylic acid as a model drug.

Preparation of mesoporous silica microparticles by sol-gel/emulsion route for protein release.

PubMed

Vlasenkova, Mariya I; Dolinina, Ekaterina S; Parfenyuk, Elena V

2018-04-06

Encapsulation of therapeutic proteins into particles from appropriate material can improve both stability and delivery of the drugs, and the obtained particles can serve as a platform for development of their new oral formulations. The main goal of this work was development of sol-gel/emulsion method for preparation of silica microcapsules capable of controlled release of encapsulated protein without loss of its native structure. For this purpose, the reported in literature direct sol-gel/W/O/W emulsion method of protein encapsulation was used with some modifications, because the original method did not allow to prepare silica microcapsules capable for protein release. The particles were synthesized using sodium silicate and tetraethoxysilane as silica precursors and different compositions of oil phase. In vitro kinetics of bovine serum albumin (BSA) release in buffer (pH 7.4) was studied by Fourier transform infrared (FTIR) and fluorescence spectrometry, respectively. Structural state of encapsulated BSA and after release was evaluated. It was found that the synthesis conditions influenced substantially the porous structure of the unloaded silica particles, release properties of the BSA-loaded silica particles and structural state of the encapsulated and released protein. The modified synthesis conditions made it possible to obtain the silica particles capable of controlled release of the protein during a week without loss of the protein native structure.

The effect of glutathione as chain transfer agent in PNIPAAm-based thermo-responsive hydrogels for controlled release of proteins.

PubMed

Drapala, Pawel W; Jiang, Bin; Chiu, Yu-Chieh; Mieler, William F; Brey, Eric M; Kang-Mieler, Jennifer J; Pérez-Luna, Victor H

2014-03-01

To control degradation and protein release using thermo-responsive hydrogels for localized delivery of anti-angiogenic proteins. Thermo-responsive hydrogels derived from N-isopropylacrylamide (NIPAAm) and crosslinked with poly(ethylene glycol)-co-(L-lactic acid) diacrylate (Acry-PLLA-b-PEG-b-PLLA-Acry) were synthesized via free radical polymerization in the presence of glutathione, a chain transfer agent (CTA) added to modulate their degradation and release properties. Immunoglobulin G (IgG) and the recombinant proteins Avastin® and Lucentis® were encapsulated in these hydrogels and their release was studied. The encapsulation efficiency of IgG was high (75-87%) and decreased with CTA concentration. The transition temperature of these hydrogels was below physiological temperature, which is important for minimally invasive therapies involving these materials. The toxicity from unreacted monomers and free radical initiators was eliminated with a minimum of three buffer extractions. Addition of CTA accelerated degradation and resulted in complete protein release. Glutathione caused the degradation products to become solubilized even at 37°C. Hydrogels prepared without glutathione did not disintegrate nor released protein completely after 3 weeks at 37°C. PEGylation of IgG postponed the burst release effect. Avastin® and Lucentis® released from degraded hydrogels retained their biological activity. These systems offer a promising platform for the localized delivery of proteins.

A shallow subsurface controlled release facility in Bozeman, Montana, USA, for testing near surface CO2 detection techniques and transport models

USGS Publications Warehouse

Spangler, L.H.; Dobeck, L.M.; Repasky, K.S.; Nehrir, A.R.; Humphries, S.D.; Keith, C.J.; Shaw, J.A.; Rouse, J.H.; Cunningham, A.B.; Benson, S.M.; Oldenburg, C.M.; Lewicki, J.L.; Wells, A.W.; Diehl, J.R.; Strazisar, B.R.; Fessenden, J.E.; Rahn, T.A.; Amonette, J.E.; Barr, J.L.; Pickles, W.L.; Jacobson, J.D.; Silver, E.A.; Male, E.J.; Rauch, H.W.; Gullickson, K.S.; Trautz, R.; Kharaka, Y.; Birkholzer, J.; Wielopolski, L.

2010-01-01

A controlled field pilot has been developed in Bozeman, Montana, USA, to study near surface CO2 transport and detection technologies. A slotted horizontal well divided into six zones was installed in the shallow subsurface. The scale and CO2 release rates were chosen to be relevant to developing monitoring strategies for geological carbon storage. The field site was characterized before injection, and CO2 transport and concentrations in saturated soil and the vadose zone were modeled. Controlled releases of CO2 from the horizontal well were performed in the summers of 2007 and 2008, and collaborators from six national labs, three universities, and the U.S. Geological Survey investigated movement of CO2 through the soil, water, plants, and air with a wide range of near surface detection techniques. An overview of these results will be presented. ?? 2009 The Author(s).

The hypothalamic paraventricular nucleus has a pivotal role in regulation of prolactin release in lactating rats.

PubMed

Kiss, J Z; Kanyicska, B; Nagy, G Y

1986-08-01

The affect of paraventricular nucleus (PVN) lesions on PRL secretory response to suckling was studied in adult female rats. Basal levels of PRL were similar in the control and lesioned groups. Substantial decreases in PRL levels occurred after separation of pups from their mothers in the control as well as lesioned animals. When mothers and pups were reunited, the circulating PRL concentrations of the control groups rose immediately from basal values of 50-100 micrograms/liter to reach peaks of 450-550 micrograms/liter. PVN lesions significantly decreased the suckling-induced rise of PRL levels. Furthermore, PVN lesions abolished the high amplitude, episodic pattern of PRL release in continuously lactating rats. These findings are consistent with the view that PVN neurons produce PRL releasing factor(s), which is (are) required for normal secretory patterns of PRL in lactating rats.

Programmable display of DNA-protein chimeras for controlling cell-hydrogel interactions via reversible intermolecular hybridization.

PubMed

Zhang, Zhaoyang; Li, Shihui; Chen, Niancao; Yang, Cheng; Wang, Yong

2013-04-08

Extensive studies have been recently carried out to achieve dynamic control of cell-material interactions primarily through physicochemical stimulation. The purpose of this study was to apply reversible intermolecular hybridization to program cell-hydrogel interactions in physiological conditions based on DNA-antibody chimeras and complementary oligonucleotides. The results showed that DNA oligonucleotides could be captured to and released from the immobilizing DNA-functionalized hydrogels with high specificity via DNA hybridization. Accordingly, DNA-antibody chimeras were captured to the hydrogels, successfully inducing specific cell attachment. The cell attachment to the hydrogels reached the plateau at approximately half an hour after the functionalized hydrogels and the cells were incubated together. The attached cells were rapidly released from the bound hydrogels when triggering complementary oligonucleotides were introduced to the system. However, the capability of the triggering complementary oligonucleotides in releasing cells was affected by the length of intermolecular hybridization. The length needed to be at least more than 20 base pairs in the current experimental setting. Notably, because the procedure of intermolecular hybridization did not involve any harsh condition, the released cells maintained the same viability as that of the cultured cells. The functionalized hydrogels also exhibited the potential to catch and release cells repeatedly. Therefore, this study demonstrates that it is promising to regulate cell-material interactions dynamically through the DNA-programmed display of DNA-protein chimeras.

Continuous twin screw granulation of controlled release formulations with various HPMC grades.

PubMed

Vanhoorne, V; Janssens, L; Vercruysse, J; De Beer, T; Remon, J P; Vervaet, C

2016-09-25

HPMC is a popular matrix former to formulate tablets with extended drug release. Tablets with HPMC are preferentially produced by direct compression. However, granulation is often required prior to tableting to overcome poor flowability of the formulation. While continuous twin screw granulation has been extensively evaluated for granulation of immediate release formulations, twin screw granulation of controlled release formulations including the dissolution behavior of the formulations received little attention. Therefore, the influence of the HPMC grade (viscosity and substitution degree) and the particle size of theophylline on critical quality attributes of granules (continuously produced via twin screw granulation) and tablets was investigated in the current study. Formulations with 20 or 40% HPMC, 20% theophylline and lactose were granulated with water at fixed process parameters via twin screw granulation. The torque was influenced by the viscosity and substitution degree of HPMC, but was not a limiting factor for the granulation process. An optimal L/S ratio was selected for each formulation based on the granule size distribution. The granule size distributions were influenced by the substitution degree and concentration of HPMC and the particle size of theophylline. Raman and UV spectroscopic analysis on 8 sieve fractions of granules indicated an inhomogeneous distribution of theophylline over the size fractions. However, this phenomenon was not correlated with the hydration rate or viscosity of HPMC. Controlled release of theophylline could be obtained over 24h with release profiles close to zero-order. The release of theophylline could be tailored via selection of the substitution degree and viscosity of HPMC. Copyright © 2016 Elsevier B.V. All rights reserved.

Effective genetic modification and differentiation of hMSCs upon controlled release of rAAV vectors using alginate/poloxamer composite systems.

PubMed

Díaz-Rodríguez, P; Rey-Rico, A; Madry, H; Landin, M; Cucchiarini, M

2015-12-30

Viral vectors are common tools in gene therapy to deliver foreign therapeutic sequences in a specific target population via their natural cellular entry mechanisms. Incorporating such vectors in implantable systems may provide strong alternatives to conventional gene transfer procedures. The goal of the present study was to generate different hydrogel structures based on alginate (AlgPH155) and poloxamer PF127 as new systems to encapsulate and release recombinant adeno-associated viral (rAAV) vectors. Inclusion of rAAV in such polymeric capsules revealed an influence of the hydrogel composition and crosslinking temperature upon the vector release profiles, with alginate (AlgPH155) structures showing the fastest release profiles early on while over time vector release was more effective from AlgPH155+PF127 [H] capsules crosslinked at a high temperature (50°C). Systems prepared at room temperature (AlgPH155+PF127 [C]) allowed instead to achieve a more controlled release profile. When tested for their ability to target human mesenchymal stem cells, the different systems led to high transduction efficiencies over time and to gene expression levels in the range of those achieved upon direct vector application, especially when using AlgPH155+PF127 [H]. No detrimental effects were reported on either cell viability or on the potential for chondrogenic differentiation. Inclusion of PF127 in the capsules was also capable of delaying undesirable hypertrophic cell differentiation. These findings are of promising value for the further development of viral vector controlled release strategies. Copyright © 2015 Elsevier B.V. All rights reserved.

Procain and diethylaminoethanol influence on the release of free oxygen radicals by polymorphonuclear leukocytes, in rabbits and humans.

PubMed

Dolganiuc, A; Radu, D; Olinescu, A; Vrăbiescu, A

1998-01-01

The investigations were conducted on 3 groups of New Zealand rabbits: 1) controls; 2) injected with procain, i.m. 15 mg/kg body weight, daily, for 30 days; 3) injected with diethylaminoethanol (DEAE), 15 mg/kg body weight, daily, for 35 days. The study was made also on human leukocytes, isolated from the peripheral blood of 10 clinically healthy subjects (adults), procain and DEAE action being investigated in vitro. The free oxygen radicals (FOR) released by PMN leukocytes were evaluated by chemiluminescence, in vitro. Addition of procain or DEAE had no effect on the release of FOR by PMN leukocytes of control rabbits. In the experiment made on rabbits treated with procain or DEAE, the release of FOR by PMN leukocytes was much more reduced, as compared to controls. In the rabbits treated with procain, the intensity of the emitted light was 2.27 mV, in those treated with DEAE, 3.46 mV, while in the controls, the mean value was 6.74 mV. In the in vitro experiments performed on human PMN cells stimulated with opsonized zymosan (OZ), addition of procain or DEAE had an inhibiting effect on the FOR release. As compared to control, the means of the FOR values decreased from 59 to 41.2 mV in case of procain addition and from 67.7 to 50 mV in case of DEAE addition. The fact that the inflammation is associated with accumulation of free radicals, suggests the opportunity to test these substances, especially DEAE, as antioxidant agents.

Floating tablets for controlled release of ofloxacin via compression coating of hydroxypropyl cellulose combined with effervescent agent.

PubMed

Qi, Xiaole; Chen, Haiyan; Rui, Yao; Yang, Fengjiao; Ma, Ning; Wu, Zhenghong

2015-07-15

To prolong the residence time of dosage forms within gastrointestinal trace until all drug released at desired rate was one of the real challenges for oral controlled-release drug delivery system. Herein, we developed a fine floating tablet via compression coating of hydrophilic polymer (hydroxypropyl cellulose) combined with effervescent agent (sodium bicarbonate) to achieve simultaneous control of release rate and location of ofloxacin. Sodium alginate was also added in the coating layer to regulate the drug release rate. The effects of the weight ratio of drug and the viscosity of HPC on the release profile were investigated. The optimized formulations were found to immediately float within 30s and remain lastingly buoyant over a period of 12 h in simulated gastric fluid (SGF, pH 1.2) without pepsin, indicating a satisfactory floating and zero-order drug release profile. In addition, the oral bioavailability experiment in New Zealand rabbits showed that, the relative bioavailability of the ofloxacin after administrated of floating tablets was 172.19%, compared to marketed common release tablets TaiLiBiTuo(®). These results demonstrated that those controlled-released floating tables would be a promising gastro-retentive delivery system for drugs acting in stomach. Copyright © 2015 Elsevier B.V. All rights reserved.

Quantification of intracellular payload release from polymersome nanoparticles

NASA Astrophysics Data System (ADS)

Scarpa, Edoardo; Bailey, Joanne L.; Janeczek, Agnieszka A.; Stumpf, Patrick S.; Johnston, Alexander H.; Oreffo, Richard O. C.; Woo, Yin L.; Cheong, Ying C.; Evans, Nicholas D.; Newman, Tracey A.

2016-07-01

Polymersome nanoparticles (PMs) are attractive candidates for spatio-temporal controlled delivery of therapeutic agents. Although many studies have addressed cellular uptake of solid nanoparticles, there is very little data available on intracellular release of molecules encapsulated in membranous carriers, such as polymersomes. Here, we addressed this by developing a quantitative assay based on the hydrophilic dye, fluorescein. Fluorescein was encapsulated stably in PMs of mean diameter 85 nm, with minimal leakage after sustained dialysis. No fluorescence was detectable from fluorescein PMs, indicating quenching. Following incubation of L929 cells with fluorescein PMs, there was a gradual increase in intracellular fluorescence, indicating PM disruption and cytosolic release of fluorescein. By combining absorbance measurements with flow cytometry, we quantified the real-time intracellular release of a fluorescein at a single-cell resolution. We found that 173 ± 38 polymersomes released their payload per cell, with significant heterogeneity in uptake, despite controlled synchronisation of cell cycle. This novel method for quantification of the release of compounds from nanoparticles provides fundamental information on cellular uptake of nanoparticle-encapsulated compounds. It also illustrates the stochastic nature of population distribution in homogeneous cell populations, a factor that must be taken into account in clinical use of this technology.

Cognitive Improvement of Attention and Inhibition in the Late Afternoon in Children With Attention-Deficit Hyperactivity Disorder (ADHD) Treated With Osmotic-Release Oral System Methylphenidate.

PubMed

Slama, Hichem; Fery, Patrick; Verheulpen, Denis; Vanzeveren, Nathalie; Van Bogaert, Patrick

2015-07-01

Long-acting medications have been developed and approved for use in the treatment of attention-deficit hyperactivity disorder (ADHD). These compounds are intended to optimize and maintain symptoms control throughout the day. We tested prolonged effects of osmotic-release oral system methylphenidate on both attention and inhibition, in the late afternoon. A double-blind, randomized, placebo-controlled study was conducted in 36 boys (7-12 years) with ADHD and 40 typically developing children. The ADHD children received an individualized dose of placebo or osmotic-release oral system methylphenidate. They were tested about 8 hours after taking with 2 continuous performance tests (continuous performance test-X [CPT-X] and continuous performance test-AX [CPT-AX]) and a counting Stroop. A positive effect of osmotic-release oral system methylphenidate was present in CPT-AX with faster and less variable reaction times under osmotic-release oral system methylphenidate than under placebo, and no difference with typically developing children. In the counting Stroop, we found a decreased interference with osmotic-release oral system methylphenidate but no difference between children with ADHD under placebo and typically developing children. © The Author(s) 2014.

Antibiotic release from biodegradable PHBV microparticles.

PubMed

Sendil, D; Gürsel, I; Wise, D L; Hasirci, V

1999-05-20

For the treatment of periodontal diseases, design of a controlled release system seemed very appropriate for an effective, long term result. In this study a novel, biodegradable microbial polyester, poly(3-hydroxybutyrate-co-3-hydroxyvalerate), PHBV of various valerate contents containing a well established antibiotic, tetracycline, known to be effective against many of the periodontal disease related microorganisms, was used in the construction of a controlled release system. Tetracycline was loaded in the PHBV microspheres and microcapsules both in its acidic (TC) and in neutral form (TCN). Microcapsules of PHBV were prepared under different conditions using w/o/w double emulsion and their properties such as encapsulation efficiency, loading, release characteristics, and morphological properties were investigated. It was found that concentration of emulsifiers polyvinyl alcohol (PVA) and gelatin (varied between 0-4%) influenced the encapsulation efficiency appreciably. In order to increase encapsulation efficiency (from the obtained range of 18.1-30.1%) and slow down the release of the highly soluble tetracycline.HCl, it was neutralized with NaOH. Encapsulation efficiency of neutralized tetracycline was much higher (51.9-65.3%) due to the insoluble form of the drug used during encapsulation. The release behaviour of neither of the drugs was found to be of zero order. Rather the trends fitted reasonably well to Higuchi's approach for release from spherical micropheres. Biodegradability was not an appreciable parameter in the release from microcapsules because release was complete before any signs of degradation were observed.

ATP during early bladder stretch is important for urgency in detrusor overactivity patients.

PubMed

Cheng, Y; Mansfield, K J; Allen, W; Chess-Williams, R; Burcher, E; Moore, K H

2014-01-01

ATP is an important mediator of urgency in women with detrusor overactivity (DO). In order to understand how different degrees of bladder stretch elicited ATP release in DO patients compared with controls, sequential aliquots were collected during cystometry and ATP release was measured at each degree of bladder filling, in female patients with DO and controls. In both DO and control groups, ATP release was induced during bladder filling, suggesting that stretch stimulated further ATP release. However, the luminal ATP concentrations were already high at early filling stage (200 mL), which was even greater than those at the later filling stages (400 mL and maximum cystometric capacity, MCC), indicating that a substantial ATP release has been induced during early filling (200 mL) in both DO and controls. In DO, ATP release at 200 mL was significantly higher in those with low first desire to void (FDV) (≤ 200 mL) than in those with higher FDV (> 200 mL); this may suggest that ATP release at early stretch may play an important role in urgency (early sensation) in DO. ATP concentrations remained unchanged after voiding, suggesting that voiding did not further induce ATP release into intraluminal fluid.

Intercalation and controlled release of 2,4-dichlorophenoxyacetic acid using rhombohedral [LiAl2(OH)6]Cl·xH2O

NASA Astrophysics Data System (ADS)

Ragavan, Anusha; Khan, Aamir I.; O'Hare, Dermot

2006-05-01

2,4-Dichlorophenoxyacetic acid (2,4-D) has been fully intercalated into the rhombohedral polymorph of [LiAl2(OH)6]Cl·xH2O ([rhom-Li Al] LDH) by an ion exchange method. The controlled release of 2,4-D from the interlamellar spaces of [rhom-Li Al] LDH has been studied in a phosphate buffer, natural rainwater and deionised water. In buffer solution and rainwater, the intercalated herbicide is exchanged for anions in solution. In contrast, in deionised water the herbicide is released as part of the Li+/herbicide ion pair, leading to the formation of Al(OH)3 and the solvated ions.

Effect of food on early drug exposure from extended-release stimulants: results from the Concerta, Adderall XR Food Evaluation (CAFE) Study.

PubMed

Auiler, J F; Liu, K; Lynch, J M; Gelotte, C K

2002-01-01

Stimulant therapy is the mainstay of treatment for children, adolescents and adults with attention-deficit/hyperactivity disorder (ADHD). Once-daily, extended-release oral formulations offer long acting control of symptoms by modifying drug delivery and absorption. In particular, consistency in early drug exposure is important for symptom control during school or work hours. Because these once-daily formulations are usually taken in the morning, the timing of the doses with breakfast is important. This study compared the effect of a high-fat breakfast on early drug exposure from a morning dose of two extended-release stimulant formulations: the osmotic-controlled OROS tablet of methylphenidate HCI (CONCERTA) and the capsule containing extended-release beads of mixed amphetamine salts (ADDERALL XR). The study had a single-dose, open-label, randomised, four-treatment, crossover design in which healthy subjects received either 36 mg CONCERTA or 20 mg ADDERALL XR in the morning after an overnight fast or a high-fat breakfast. Serial blood samples were collected over 28h to determine plasma concentrations of methylphenidate and amphetamine. The food effect on early drug exposure and the pharmacokinetic profiles up to 8 h after dosing of the two extended-release stimulants were directly compared using partial area (AUC(p4h), AUC(p6h) and AUC(p8h)) fed/fasted ratios. Amphetamine concentrations were markedly lower when the subjects had eaten breakfast, resulting in lower early drug exposures (p < 0.0001). By contrast, methylphenidate concentrations over the same 8 h were unaffected by breakfast, providing consistent levels of early drug exposure. Therefore, as a child's or adult's eating pattern varies, methylphenidate exposure over the first 8 h would be expected to have less day-to-day variation compared with amphetamine exposure. The osmotic-controlled OROS tablet provides a reliable and consistent delivery of methylphenidate HCI, independent of food, for patients with ADHD.

Modeling transport kinetics in clinoptilolite-phosphate rock systems

NASA Technical Reports Server (NTRS)

Allen, E. R.; Ming, D. W.; Hossner, L. R.; Henninger, D. L.

1995-01-01

Nutrient release in clinoptilolite-phosphate rock (Cp-PR) systems occurs through dissolution and cation-exchange reactions. Investigating the kinetics of these reactions expands our understanding of nutrient release processes. Research was conducted to model transport kinetics of nutrient release in Cp-PR systems. The objectives were to identify empirical models that best describe NH4, K, and P release and define diffusion-controlling processes. Materials included a Texas clinoptilolite (Cp) and North Carolina phosphate rock (PR). A continuous-flow thin-disk technique was used. Models evaluated included zero order, first order, second order, parabolic diffusion, simplified Elovich, Elovich, and power function. The power-function, Elovich, and parabolic-diffusion models adequately described NH4, K, and P release. The power-function model was preferred because of its simplicity. Models indicated nutrient release was diffusion controlled. Primary transport processes controlling nutrient release for the time span observed were probably the result of a combination of several interacting transport mechanisms.

Clinical risk factors for death after release from prison in Washington State: A nested case control study

PubMed Central

Binswanger, Ingrid A.; Stern, Marc F.; Yamashita, Traci E.; Mueller, Shane R.; Baggett, Travis P.; Blatchford, Patrick J.

2015-01-01

Background and aims While mortality rates after prison release are high, little is known about clinical risk factors for death. We sought to identify risk and protective factors for all-cause and accidental poisoning (overdose) death. Design Nested case control study of people released from prison. Setting Washington State Department of Corrections, Washington, USA. Participants Cases (699 all-cause deaths, of which 88 were among women, and 206 additional overdose deaths, of which 76 were among women) between 1999 and 2009 matched 1:1 to controls on sex, age and year of release using risk set sampling. Measurements Prison medical charts were abstracted for clinical information. Independent associations between clinical characteristics and all-cause and overdose mortality were assessed using conditional logistic regression. Findings Key independent risk factors for all-cause mortality included homelessness (Odds Ratio [OR] 1.53, 95% Confidence Interval [CI] 1.06, 2.23), injection drug use (OR 1.54, 95% CI 1.15, 2.05), tobacco use (OR 1.50, 95% CI 1.06, 2.12), cirrhosis (OR 4.42, 95% CI 1.63, 11.98), and psychiatric medications before release (OR 2.37, 95% CI 1.71, 3.29). Independent risk factors for overdose mortality included substance dependence (OR 2.33, 95% CI 1.32, 4.11), injection drug use (OR 2.43, 95% CI 1.53, 3.86), panic disorder (OR 3.87, 95% CI 1.62, 9.21), psychiatric prescriptions before release (OR 2.44, 95% CI 1.55, 3.85), and problems with opiates/sedatives (OR 2.81, 95% CI 1.40, 5.63). Substance use disorder treatment during the index incarceration was protective for all-cause (OR 0.67, 95% CI 0.49, 0.91) and overdose (OR 0.57, 95% CI 0.35, 0.90) mortality. Conclusions Injection drug use and substance use disorders are risk factors for death after release from prison. In-prison substance use treatment services may reduce the risk. PMID:26476210

Effect of Alkaline Peroxides on the Surface of Cobalt Chrome Alloy: An In Vitro Study.

PubMed

Vasconcelos, Glenda Lara Lopes; Curylofo, Patricia Almeida; Raile, Priscilla Neves; Macedo, Ana Paula; Paranhos, Helena Freitas Oliveira; Pagnano, Valeria Oliveira

2018-03-24

Removable denture hygiene care is very important for the longevity of the rehabilitation treatment; however, it is necessary to analyze the effects that denture cleansers can cause on the surfaces of prostheses. Thus, this study evaluated the effect of alkaline peroxide-effervescent tablets on the surface of cobalt-chromium alloys (Co-Cr) used in removable partial dentures. Circular metallic specimens (12 × 3 mm) were fabricated and were immersed (n = 16) in: control, Polident 3 Minute (P3M), Steradent (S), Efferdent (E), Polident for Partials (PFP), and Corega Tabs (CT). The surface roughness (μm) (n = 10) was measured before and after periods of cleanser immersion corresponding to 0.5, 1, 2, 3, 4, and 5 years. Ion release was analyzed (n = 5) for Co, Cr, and molybdenum (Mo). Scanning electron microscopy (SEM) analysis and an Energy-dispersive X-ray spectroscopy (EDS) were conducted in one specimen. The surface roughness data were statistically analyzed (α = 0.05) with the Kruskal-Wallis test to compare the solutions, and the Friedman test compared the immersion durations. Ion release analysis was performed using 2-way ANOVA and Tukey's test. There was no significant surface roughness difference when comparing the solutions (p > 0.05) and the immersion durations (p = 0.137). Regarding ion release (μg/L), CT, E, and control produced a greater release of Co ions than S (p < 0.05). CT produced a greater release of Cr ions than control, S, and P3M (p < 0.05). Finally, E caused the greatest release of Mo ions (p < 0.05). SEM confirmed that the solutions did not damage the surfaces and EDS confirmed that there were no signs of oxidation. The various solutions tested did not have any deleterious effects on the Co-Cr alloy surface. Steradent, however, presented the smallest ionic release. © 2018 by the American College of Prosthodontists.

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

PubMed

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.

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

PubMed

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

2017-03-30

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

Scalable privacy-preserving data sharing methodology for genome-wide association studies.

PubMed

Yu, Fei; Fienberg, Stephen E; Slavković, Aleksandra B; Uhler, Caroline

2014-08-01

The protection of privacy of individual-level information in genome-wide association study (GWAS) databases has been a major concern of researchers following the publication of "an attack" on GWAS data by Homer et al. (2008). Traditional statistical methods for confidentiality and privacy protection of statistical databases do not scale well to deal with GWAS data, especially in terms of guarantees regarding protection from linkage to external information. The more recent concept of differential privacy, introduced by the cryptographic community, is an approach that provides a rigorous definition of privacy with meaningful privacy guarantees in the presence of arbitrary external information, although the guarantees may come at a serious price in terms of data utility. Building on such notions, Uhler et al. (2013) proposed new methods to release aggregate GWAS data without compromising an individual's privacy. We extend the methods developed in Uhler et al. (2013) for releasing differentially-private χ(2)-statistics by allowing for arbitrary number of cases and controls, and for releasing differentially-private allelic test statistics. We also provide a new interpretation by assuming the controls' data are known, which is a realistic assumption because some GWAS use publicly available data as controls. We assess the performance of the proposed methods through a risk-utility analysis on a real data set consisting of DNA samples collected by the Wellcome Trust Case Control Consortium and compare the methods with the differentially-private release mechanism proposed by Johnson and Shmatikov (2013). Copyright © 2014 Elsevier Inc. All rights reserved.

Surface Modifications of Titanium Implants by Multilayer Bioactive Coatings with Drug Delivery Potential: Antimicrobial, Biological, and Drug Release Studies

NASA Astrophysics Data System (ADS)

Ordikhani, Farideh; Zustiak, Silviya Petrova; Simchi, Abdolreza

2016-04-01

Recent strategies to locally deliver antimicrobial agents to combat implant-associated infections—one of the most common complications in orthopedic surgery—are gaining interest. However, achieving a controlled release profile over a desired time frame remains a challenge. In this study, we present an innovative multifactorial approach to combat infections which comprises a multilayer chitosan/bioactive glass/vancomycin nanocomposite coating with an osteoblastic potential and a drug delivery capacity. The bioactive drug-eluting coating was prepared on the surface of titanium foils by a multistep electrophoretic deposition technique. The adopted deposition strategy allowed for a high antibiotic loading of 1038.4 ± 40.2 µg/cm2. The nanocomposite coating exhibited a suppressed burst release with a prolonged sustained vancomycin release for up to 6 weeks. Importantly, the drug release profile was linear with respect to time, indicating a zero-order release kinetics. An in vitro bactericidal assay against Staphylococcus aureus confirmed that releasing the drug reduced the risk of bacterial infection. Excellent biocompatibility of the developed coating was also demonstrated by in vitro cell studies with a model MG-63 osteoblast cell line.

An effective treatment approach of DPP-IV inhibitor encapsulated polymeric nanoparticles conjugated with anti-CD-4 mAb for type 1 diabetes.

PubMed

Thondawada, Mahesh; Wadhwani, Ashish Devidas; S Palanisamy, Dhanabal; Rathore, Hanumant Singh; Gupta, Ramesh C; Chintamaneni, Pavan Kumar; Samanta, Malay K; Dubala, Anil; Varma, Sameer; Krishnamurthy, Praveen T; Gowthamarajan, Kuppusamy

2018-07-01

Nanotechnology based biomedical approaches and surface modification techniques made it easier for targeting specific site and improving the treatment efficacy. The present study reports on targeted polymeric nanoparticles conjugated with antibody as a site-specific carrier system for effective treatment of type 1 diabetes. Sitagliptin (SP)-loaded Poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NP) were prepared by nanoprecipitation cum solvent evaporation method and were characterized in terms of morphology, size, surface charge, and entrapment efficiency. Optimized batch demonstrated a particle size of 105.24 nm, with significant entrapment efficacy. In vitro release studies exhibited a controlled release pattern of 67.76 ± 1.30% in 24 h, and a maximum of 96.59 ± 1.26% at the end of 48 h. Thiol groups were introduced on the surface of SP-NPs whose concentration on SP-NPs was 27 ± 2.6 mmol/mol PLGA-NPs, anti-CD4 antibody clone Q4120 was conjugated to the thiolated SP-NPs via a sulfo-MBS cross-linker, ∼70% conjugation was observed. The in vitro cytotoxicity studies performed on RIN-5 F cells for mAb-SP-NPs presented an IC 50 of 76 µg/mL, and the insulin release assay had revealed an increased release at 5.15 ± 0.16 IU/mL. The results indicate that mAb-SP-NPs allowed a controlled release of SP and thereby produced insulin levels comparable with control. Therefore, mAb-SP-NPs system appears to be effective in the treatment of auto immune diabetes, subject to further analysis.

Biocompatibility and antifibrotic effect of UV-cross-linked hyaluronate as a release-system for tranilast after trabeculectomy in a rabbit model--a pilot study.

PubMed

Spitzer, Martin S; Sat, Macarena; Schramm, Charlotte; Schnichels, Sven; Schultheiss, Maximilian; Yoeruek, Efdal; Dzhelebov, Dimitar; Szurman, Peter

2012-06-01

To analyze the release kinetics and the clinical and histological effects of UV-cross-linked hyaluronic acid as a release-system for the transforming growth factor β-2 antagonist tranilast with anti-phlogistic properties on intraocular pressure after trabeculectomy in an aggressive scarring animal model. Hyaluronate acid was UV-cross linked and loaded with tranilast. The release of tranilast into a buffered salt solution was assessed spectrophotometrically. Glaucoma filtration surgery, similar to that performed in clinical practice, was performed on chinchilla rabbits. The rabbits were divided in 3 groups. (Group A: trabeculectomy alone, group B: trabeculectomy with a cross-linked hyaluronic acid gel preparation and group C: trabeculectomy with cross-linked hyaluronic gel preparation mixed with tranilast). Antifibrotic efficacy was established by clinical response and histologic examination. The cross-linked gels released tranilast for up to 26 h. The release plotted as a function of the square root of time was consistent with a largely diffusion-controlled release system. Both the gel preparation alone and the gel preparation mixed with tranilast were well tolerated in vivo. No adverse effects such as inflammation, corneal toxicity or blurring of the optical media were observed. The intraocular pressure reached preoperative levels within 9 days after surgery in control animals and group B, but remained significantly reduced (p = 0.00016) in the group with tranilast until day 22. The data of this pilot study suggest that the intraoperative application of UV-crossed linked hyaluronic acid used as a slow release system for tranilast may improve the surgical outcome of glaucoma filtration surgery.

Effect of food characteristics, storage conditions, and electron beam irradiation on active agent release from polyamide-coated LDPE films.

PubMed

Han, J; Castell-Perez, M E; Moreira, R G

2008-03-01

We investigated the effect of electron beam irradiation, storage conditions, and model food pH on the release characteristics of trans-cinnamaldehyde incorporated into polyamide-coated low-density polyethylene (LDPE) films. Active agent release rate on irradiated films (up to 20.0 kGy) decreased by 69% compared with the nonirradiated controls, from 0.252 to 0.086 microg/mL/h. Storage temperature (4, 21, and 35 degrees C) and pH (4, 7, and 10) of the food simulant solutions (10% aqueous ethanol) affected the release rate of trans-cinnamaldehyde. As expected, antimicrobial release rate decreased to 0.013 microg/mL/h at the refrigerated temperature (4 degrees C) compared to the higher temperatures (0.029 and 0.035 microg/mL/h at 21 and 35 degrees C). The fastest release rate occurred when exposed to the acidic food simulant solution (pH 4). In aqueous solution, trans-cinnamaldehyde was highly unstable to ionizing radiation, with loss in concentration from 24.50 to 1.36 microg/mL after exposure to 2.0 kGy. Fourier transform infrared (FTIR) analysis revealed that exposure to ionizing radiation up to 10.0 kGy did not affect the structural conformation of LDPE/polyamide films and the trans-cinnamaldehyde in the films, though it induced changes in the functional group of trans-cinnamaldehyde when dose increased up to 20.0 kGy. Studies with a radiation-stable compound (naphthalene) showed that ionizing radiation induced the crosslinking in polymer networks of LDPE/polyamide film and caused slow and gradual release of the compound. This study demonstrated that irradiation serves as a controlling factor for release of active compounds, with potential applications in the development of antimicrobial packaging systems.

Influence of the Formulation Parameters on the Particle Size and Encapsulation Efficiency of Resveratrol in PLA and PLA-PEG Blend Nanoparticles: A Factorial Design.

PubMed

Lindner, Gabriela da Rocha; Dalmolin, Luciana Facco; Khalil, Najeh Maissar; Mainardes, Rubiana Mara

2015-12-01

Polymeric nanoparticles are colloidal systems that promote protection and modification of physicochemical characteristics of a drug and that also ensure controlled and extended drug release. This paper reports a 2(3) factorial design study to optimize poly(lactide) (PLA) and poly(lactide)-polyethylene glycol (PLA-PEG) blend nanoparticles containing resveratrol (RVT) for prolonged release. The independent variables analyzed were solvent composition, surfactant concentration and ratio of aqueous to organic phase (two levels each factor). Mean particle size and RVT encapsulation efficiency were set as the dependent variables. The selected optimized parameters were set as organic phase comprised of a mixture of dichloromethane and ethyl acetate, 1% of surfactant polyvinyl alcohol and a 3:1 ratio of aqueous to organic phase, for both PLA and PLA-PEG blend nanoparticles. This formulation originated nanoparticles with size of 228 ± 10 nm and 185 ± 70 nm and RVT encapsulation efficiency of 82 ± 10% and 76 ± 7% for PLA and PLA-PEG blend nanoparticles, respectively. The in vitro release study showed a biphasic pattern with prolonged RVT release and PEG did not influence the RVT release. The in vitro release data were in favor of Higuchi-diffusion kinetics for both nanoformulations and the Kossmeyer-Peppas coefficient indicated that anomalous transport was the main release mechanism of RVT. PLA and PLA-PEG blend nanoparticles produced with single emulsion-solvent evaporation technology were found to be a promising approach for the incorporation of RVT and promoted its controlled release. The factorial design is a tool of great value in choosing formulations with optimized parameters.

Control of drug release through the in situ assembly of stimuli-responsive ordered mesoporous silica with magnetic particles.

PubMed

Zhu, Shenmin; Zhou, Zhengyang; Zhang, Di

2007-12-03

A site-selective controlled delivery system for controlled drug release is fabricated through the in situ assembly of stimuli-responsive ordered SBA-15 and magnetic particles. This approach is based on the formation of ordered mesoporous silica with magnetic particles formed from Fe(CO)5 via the surfactant-template sol-gel method and control of transport through polymerization of N-isopropyl acrylamide inside the pores. Hydrophobic Fe(CO)5 acts as a swelling agent as well as being the source of the magnetic particles. The obtained system demonstrates a high pore diameter (7.1 nm) and pore volume (0.41 cm(3) g(-1)), which improves drug storage for relatively large molecules. Controlled drug release through the porous network is demonstrated by measuring the uptake and release of ibuprofen (IBU). The delivery system displays a high IBU storage capacity of 71.5 wt %, which is almost twice as large as the highest value based on SBA-15 ever reported. In vitro testing of IBU loading and release exhibits a pronounced transition at around 32 degrees C, indicating a typical thermosensitive controlled release.

Implantable microencapsulated dopamine (DA): prolonged functional release of DA in denervated striatal tissue.

PubMed

McRae, A; Hjorth, S; Mason, D; Dillon, L; Tice, T

1990-01-01

Biodegradable controlled-release microcapsule systems made with the biocompatible biodegradable polyester excipient poly [DL-lactide-co-gly-colide] constitute an exciting new technology for drug delivery to the central nervous system (CNS). The present study describes functional observations indicating that implantation of dopamine (DA) microcapsules encapsulated within two different polymer excipients into denervated striatal tissue assures a prolonged release of the transmitter in vivo. This technology has a considerable potential for basic and possibly clinical research.

Coatings from blends of Eudragit® RL and L55: a novel approach in pH-controlled drug release.

PubMed

Wulff, R; Leopold, C S

2014-12-10

The aim of the present study was to investigate the drug release from theophylline pellets coated with blends of quaternary polymethacrylate and methacrylic acid-ethyl acrylate copolymers. Pellets were coated with blends of Eudragit(®) RL PO (RL) and Eudragit(®) L 100-55 (L55) in either organic solution or aqueous dispersion at various copolymer ratios. Generally, the coatings were less permeable for theophylline in phosphate buffer pH 6.8 than they were in hydrochloric acid pH 1.2. Further dissolution experiments revealed that the differences in drug release are caused by the different pH values. A design of experiments for historical data was performed on drug release data of pellets with different coating levels and blend ratios of RL and L55. Drug release in hydrochloric acid was predominantly affected by the coating level, whereas for drug release in phosphate buffer pH 6.8 the blend ratio was the determining factor. As expected, dissolution experiments at different pH values showed that drug release depends on the ratio of dissociated L55 to RL because ionization is a requirement for the functional groups to interact. With the dissolution test for delayed-release solid dosage forms (Ph. Eur.) it was demonstrated that the unique release behavior in neutral media is preserved after the exposition to hydrochloric acid. These findings indicate that the combination of RL and L55 in coatings prepared from solutions is a promising approach for controlled drug release. Copyright © 2014 Elsevier B.V. All rights reserved.

Floating matrix tablets based on low density foam powder: effects of formulation and processing parameters on drug release.

PubMed

Streubel, A; Siepmann, J; Bodmeier, R

2003-01-01

The aim of this study was to develop and physicochemically characterize single unit, floating controlled drug delivery systems consisting of (i). polypropylene foam powder, (ii). matrix-forming polymer(s), (iii). drug, and (iv). filler (optional). The highly porous foam powder provided low density and, thus, excellent in vitro floating behavior of the tablets. All foam powder-containing tablets remained floating for at least 8 h in 0.1 N HCl at 37 degrees C. Different types of matrix-forming polymers were studied: hydroxypropyl methylcellulose (HPMC), polyacrylates, sodium alginate, corn starch, carrageenan, gum guar and gum arabic. The tablets eroded upon contact with the release medium, and the relative importance of drug diffusion, polymer swelling and tablet erosion for the resulting release patterns varied significantly with the type of matrix former. The release rate could effectively be modified by varying the "matrix-forming polymer/foam powder" ratio, the initial drug loading, the tablet geometry (radius and height), the type of matrix-forming polymer, the use of polymer blends and the addition of water-soluble or water-insoluble fillers (such as lactose or microcrystalline cellulose). The floating behavior of the low density drug delivery systems could successfully be combined with accurate control of the drug release patterns.

Active food packaging based on molecularly imprinted polymers: study of the release kinetics of ferulic acid.

PubMed

Otero-Pazos, Pablo; Rodríguez-Bernaldo de Quirós, Ana; Sendón, Raquel; Benito-Peña, Elena; González-Vallejo, Victoria; Moreno-Bondi, M Cruz; Angulo, Immaculada; Paseiro-Losada, Perfecto

2014-11-19

A novel active packaging based on molecularly imprinted polymer (MIP) was developed for the controlled release of ferulic acid. The release kinetics of ferulic acid from the active system to food simulants (10, 20, and 50% ethanol (v/v), 3% acetic acid (w/v), and vegetable oil), substitutes (95% ethanol (v/v) and isooctane), and real food samples at different temperatures were studied. The key parameters of the diffusion process were calculated by using a mathematical modeling based on Fick's second law. The ferulic acid release was affected by the temperature as well as the percentage of ethanol of the simulant. The fastest release occurred in 95% ethanol (v/v) at 20 °C. The diffusion coefficients (D) obtained ranged between 1.8 × 10(-11) and 4.2 × 10(-9) cm(2)/s. A very good correlation between experimental and estimated data was obtained, and consequently the model could be used to predict the release of ferulic acid into food simulants and real food samples.

Impact of microparticle formulation approaches on drug burst release: a level A IVIVC.

PubMed

Ishak, Rania A H; Mortada, Nahed D; Zaki, Noha M; El-Shamy, Abd El-Hamid A; Awad, Gehanne A S

2014-01-01

To study the effect of poly(d,l-lactic-co-glycolic acid) (PLGA) microparticles (MPs) preparation techniques on particle physical characterization with special emphasis on burst drug release. A basic drug clozapine was used in combination with acid-terminated PLGA. Two approaches for MP preparation were compared; the in situ forming microparticle (ISM) and the emulsion-solvent evaporation (ESE) methods using an experimental design. The MPs obtained were compared according to their physical characterization, burst release and T80%. An in vivo pharmacokinetic study with in vitro-in vivo correlation (IVIVC) was also performed for the selected formula. Both methods were able to sustain drug release for three weeks. ISM produced more porous particles and was not effective as ESE for controlling burst release. A good IVIVC (R(2) = 0.9755) was attained when injecting the selected formula into rats. MPs prepared with ESE showed a minimum burst release and a level A IVIVC was obtained when administered to rats.

Analysis of the release process of phenylpropanolamine hydrochloride from ethylcellulose matrix granules IV.(1)) Evaluation of the controlled release properties for in vivo and in vitro release systems.

PubMed

Fukui, Atsuko; Fujii, Ryuta; Yonezawa, Yorinobu; Sunada, Hisakazu

2007-11-01

In the pharmaceutical preparation of a controlled release drug, it is very important and necessary to understand the release properties. The dissolution test is a very important and useful method for understanding and predicting drug-release properties. It was readily confirmed in the previous paper that the release process could be assessed quantitatively by a combination of the square-root time law and cube-root law equations for ethylcellulose (EC) matrix granules of phenylpropanolamine hydrochloride (PPA). In this paper EC layered granules were used in addition to EC matrix. The relationship between release property and the concentration of PPA in plasma after administration using beagle dogs were examined. Then it was confirmed that the correlativity for EC layered granules and EC matrix were similar each other. Therefore, it was considered that the dissolution test is useful for prediction of changes in concentration of PPA in the blood with time. And it was suggested that EC layered granules were suitable as a controlled release system as well as EC matrix.

Multiple emulsions as effective platforms for controlled anti-cancer drug delivery.

PubMed

Dluska, Ewa; Markowska-Radomska, Agnieszka; Metera, Agata; Tudek, Barbara; Kosicki, Konrad

2017-09-01

Developing pH-responsive multiple emulsion platforms for effective glioblastoma multiforme therapy with reduced toxicity, a drug release study and modeling. Cancer cell line: U87 MG, multiple emulsions with pH-responsive biopolymer and encapsulated doxorubicin (DOX); preparation of multiple emulsions in a Couette-Taylor flow biocontactor, in vitro release study of DOX (fluorescence intensity analysis), in vitro cytotoxicity study (alamarBlue cell viability assay) and numerical simulation of DOX release rates. The multiple emulsions offered a high DOX encapsulation efficiency (97.4 ± 1%) and pH modulated release rates of a drug. Multiple emulsions with a low concentration of DOX (0.02 μM) exhibited broadly advanced cell (U87 MG) cytotoxicity than free DOX solution used at the same concentration. Emulsion platforms could be explored for potential delivery of chemotherapeutics in glioblastoma multiforme therapy.

Effect of sepsis on calcium uptake and content in skeletal muscle and regulation in vitro by calcium of total and myofibrillar protein breakdown in control and septic muscle: Results from a preliminary study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Benson, D.W.; Hasselgren, P.O.; Hiyama, D.T.

Because high calcium concentration in vitro stimulates muscle proteolysis, calcium has been implicated in the pathogenesis of increased muscle breakdown in different catabolic conditions. Protein breakdown in skeletal muscle is increased during sepsis, but the effect of sepsis on muscle calcium uptake and content is not known. In this study the influence of sepsis, induced in rats by cecal ligation and puncture, on muscle calcium uptake and content was studied. Sixteen hours after cecal ligation and puncture or sham operation, calcium content of the extensor digitorum longus (EDL) and soleus (SOL) muscles was determined with an atomic absorption spectrometer. Calciummore » uptake was measured in intact SOL muscles incubated in the presence of calcium 45 (45Ca) for between 1 and 120 minutes. Total and myofibrillar protein breakdown was determined in SOL muscles, incubated in the presence of different calcium concentrations (0; 2.5; 5.0 mmol/L), and measured as release into the incubation medium of tyrosine and 3-methylhistidine (3-MH), respectively. Calcium content was increased by 51% (p less than 0.001) during sepsis in SOL and by 10% (p less than 0.05) in EDL muscle. There was no difference in 45Ca uptake between control and septic muscles during the early phase (1 to 5 minutes) of incubation. During more extended incubation (30 to 120 minutes), muscles from septic rats took up significantly more 45Ca than control muscles (p less than 0.05). Tyrosine release by incubated SOL muscles from control and septic rats was increased when calcium was added to the incubation medium, and at a calcium concentration of 2.5 mmol/L, the increase in tyrosine release was greater in septic than in control muscle. Addition of calcium to the incubation medium did not affect 3-MH release in control or septic muscle.« less