Vaginal rings for delivery of HIV microbicides

PubMed Central

Malcolm, R Karl; Fetherston, Susan M; McCoy, Clare F; Boyd, Peter; Major, Ian

2012-01-01

Following the successful development of long-acting steroid-releasing vaginal ring devices for the treatment of menopausal symptoms and contraception, there is now considerable interest in applying similar devices to the controlled release of microbicides against HIV. In this review article, the vaginal ring concept is first considered within the wider context of the early advances in controlled-release technology, before describing the various types of ring device available today. The remainder of the article highlights the key developments in HIV microbicide-releasing vaginal rings, with a particular focus on the dapivirine ring that is presently in late-stage clinical testing. PMID:23204872

Vaginal rings for delivery of HIV microbicides.

PubMed

Malcolm, R Karl; Fetherston, Susan M; McCoy, Clare F; Boyd, Peter; Major, Ian

2012-01-01

Following the successful development of long-acting steroid-releasing vaginal ring devices for the treatment of menopausal symptoms and contraception, there is now considerable interest in applying similar devices to the controlled release of microbicides against HIV. In this review article, the vaginal ring concept is first considered within the wider context of the early advances in controlled-release technology, before describing the various types of ring device available today. The remainder of the article highlights the key developments in HIV microbicide-releasing vaginal rings, with a particular focus on the dapivirine ring that is presently in late-stage clinical testing.

Controlling protein release using biodegradable microparticles

NASA Astrophysics Data System (ADS)

Kline, Benjamin Patrick

Research in the field of protein therapeutics has exploded over the past decade and continues to grow in both academia and in industry. Protein drugs have advantages of being highly specific and highly active making them coveted targets for high profile disease states like cancer and multiple sclerosis. Unfortunately, their many advantages are complemented by their obstacles. Because proteins are highly active and highly specific, the window between efficacy and toxicity is very narrow and drug development can be long and arduous. In addition, protein activity is dependent on its specific folding conformation that is easily disrupted by a variety of development processes. This research aimed to identify microparticle formulations to control protein release and also to determine which formulation parameters affected burst release, encapsulation, and steady-state release the most. It was found that polymer type and composition were two of the most important factors. Long-term controlled release of bovine serum albumin (BSA) was achieved as well as a wide variety of release profiles. A method was identified for micronizing protein at low cost to retain activity and coacervation was evaluated as a method for preparing protein loaded microspheres. This research provides a basis from which researchers can create better controlled release formulations for future protein therapeutics.

A simple and rapid approach to evaluate the in vitro in vivo role of release controlling agent ethyl cellulose ether derivative polymer.

PubMed

Akhlaq, Muhammad; Khan, Gul Majid; Jan, Syed Umer; Wahab, Abdul; Hussain, Abid; Nawaz, Asif; Abdelkader, Hamdy

2014-11-01

Diclofenac sodium (DCL-Na) conventional oral tablets exhibit serious side effects when given for a longer period leading to noncompliance. Controlled release matrix tablets of diclofenac sodium were formulated using simple blending (F-1), solvent evaporation (F-2) and co-precipitation techniques (F-3). Ethocel® Standard 7 FP Premium Polymer (15%) was used as a release controlling agent. Drug release study was conducted in 7.4 pH phosphate buffer solutions as dissolution medium in vitro. Pharmacokinetic parameters were evaluated using albino rabbits. Solvent evaporation technique was found to be the best release controlling technique thereby prolonging the release rate up to 24 hours. Accelerated stability studies of the optimized test formulation (F-2) did not show any significant change (p<0.05) in the physicochemical characteristics and release rate when stored for six months. A simple and rapid method was developed for DCL-Na active moiety using HPLC-UV at 276nm. The optimized test tablets (F-2) significantly (p<0.05) exhibited peaks plasma concentration (cmax=237.66±1.98) and extended the peak time (tmax=4.63±0.24). Good in-vitro in vivo correlation was found (R(2)=0.9883) against drug absorption and drug release. The study showed that once-daily controlled release matrix tablets of DCL-Na were successfully developed using Ethocel® Standard 7 FP Premium.

Prosthetic Engineering

MedlinePlus

... torque adapter in the pylons of transtibial amputees. Energy Storage & Release Many ambulatory lower limb amputees exhibit ... Future Directions Current Project Summaries Development of Controlled Energy Storage and Release Prosthetic Foot Development of Inverting- ...

Fabrication of Plasmonic Nanorod-Embedded Dipeptide Microspheres via the Freeze-Quenching Method for Near-Infrared Laser-Triggered Drug-Delivery Applications.

PubMed

Erdogan, Hakan; Yilmaz, Mehmet; Babur, Esra; Duman, Memed; Aydin, Halil M; Demirel, Gokhan

2016-05-09

Control of drug release by an external stimulus may provide remote controllability, low toxicity, and reduced side effects. In this context, varying physical external stimuli, including magnetic and electric fields, ultrasound, light, and pharmacological stimuli, have been employed to control the release rate of drug molecules in a diseased region. However, the design and development of alternative on-demand drug-delivery systems that permit control of the dosage of drug released via an external stimulus are still required. Here, we developed near-infrared laser-activatable microspheres based on Fmoc-diphenylalanine (Phe-Phe) dipeptides and plasmonic gold nanorods (AuNRs) via a simple freeze-quenching approach. These plasmonic nanoparticle-embedded microspheres were then employed as a smart drug-delivery platform for native, continuous, and pulsatile doxorubicin (DOX) release. Remarkable sustained, burst, and on-demand DOX release from the fabricated microspheres were achieved by manipulating the laser exposure time. Our results demonstrate that AuNR-embedded dipeptide microspheres have great potential for controlled drug-delivery systems.

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.

Accelerated in-vitro release testing methods for extended-release parenteral dosage forms.

PubMed

Shen, Jie; Burgess, Diane J

2012-07-01

This review highlights current methods and strategies for accelerated in-vitro drug release testing of extended-release parenteral dosage forms such as polymeric microparticulate systems, lipid microparticulate systems, in-situ depot-forming systems and implants. Extended-release parenteral dosage forms are typically designed to maintain the effective drug concentration over periods of weeks, months or even years. Consequently, 'real-time' in-vitro release tests for these dosage forms are often run over a long time period. Accelerated in-vitro release methods can provide rapid evaluation and therefore are desirable for quality control purposes. To this end, different accelerated in-vitro release methods using United States Pharmacopeia (USP) apparatus have been developed. Different mechanisms of accelerating drug release from extended-release parenteral dosage forms, along with the accelerated in-vitro release testing methods currently employed are discussed. Accelerated in-vitro release testing methods with good discriminatory ability are critical for quality control of extended-release parenteral products. Methods that can be used in the development of in-vitro-in-vivo correlation (IVIVC) are desirable; however, for complex parenteral products this may not always be achievable. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

Accelerated in vitro release testing methods for extended release parenteral dosage forms

PubMed Central

Shen, Jie; Burgess, Diane J.

2012-01-01

Objectives This review highlights current methods and strategies for accelerated in vitro drug release testing of extended release parenteral dosage forms such as polymeric microparticulate systems, lipid microparticulate systems, in situ depot-forming systems, and implants. Key findings Extended release parenteral dosage forms are typically designed to maintain the effective drug concentration over periods of weeks, months or even years. Consequently, “real-time” in vitro release tests for these dosage forms are often run over a long time period. Accelerated in vitro release methods can provide rapid evaluation and therefore are desirable for quality control purposes. To this end, different accelerated in vitro release methods using United States Pharmacopoeia (USP) apparatus have been developed. Different mechanisms of accelerating drug release from extended release parenteral dosage forms, along with the accelerated in vitro release testing methods currently employed are discussed. Conclusions Accelerated in vitro release testing methods with good discriminatory ability are critical for quality control of extended release parenteral products. Methods that can be used in the development of in vitro-in vivo correlation (IVIVC) are desirable, however for complex parenteral products this may not always be achievable. PMID:22686344

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

PubMed Central

King, William J.; Krebsbach, Paul H.

2013-01-01

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

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

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.

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.

Enclosure fire hazard analysis using relative energy release criteria. [burning rate and combustion control

NASA Technical Reports Server (NTRS)

Coulbert, C. D.

1978-01-01

A method for predicting the probable course of fire development in an enclosure is presented. This fire modeling approach uses a graphic plot of five fire development constraints, the relative energy release criteria (RERC), to bound the heat release rates in an enclosure as a function of time. The five RERC are flame spread rate, fuel surface area, ventilation, enclosure volume, and total fuel load. They may be calculated versus time based on the specified or empirical conditions describing the specific enclosure, the fuel type and load, and the ventilation. The calculation of these five criteria, using the common basis of energy release rates versus time, provides a unifying framework for the utilization of available experimental data from all phases of fire development. The plot of these criteria reveals the probable fire development envelope and indicates which fire constraint will be controlling during a criteria time period. Examples of RERC application to fire characterization and control and to hazard analysis are presented along with recommendations for the further development of the concept.

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

PubMed

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

2018-02-10

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

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.

Slow Release Of Reagent Chemicals From Gel Matrices

NASA Technical Reports Server (NTRS)

Debnam, William J.; Barber, Patrick G.; Coleman, James

1988-01-01

Procedure developed for slow release of reagent chemicals into solutions. Simple and inexpensive and not subject to failure of equipment. Use of toothpaste-type tube or pump dispenser conceivably provides more controlled technique for storage and dispensation of gel matrix. Possible uses include controlled, slow release of reagents in chemical reactions, crystal growth, space-flight experiments, and preformed gel medications from packets.

Leachate Concentrations of Ammonium, Nitrate, and Phosphorus as Affected by Nutrient Release from Four Different Types of Controlled-Release Fertilizers and Crop Development of Containerized Waxleaf Privet.

USDA-ARS?s Scientific Manuscript database

Concentrations of ammonium, nitrate, and phosphorus in irrigation leachate were measured weekly over a 47-week period from a high-fertility, neutral-pH substrate into which four types of 12-month controlled-release fertilizers (Osmocote, Nutricote, Polyon, or Multicote) were incorporated. Containers...

Leachate Concentrations of Ammonium, Nitrate, and Phosphorus as Affected by Nutrient Release From Four Different Types of Controlled-Release Fertilizers and Crop Development of Containerized Azaleas

USDA-ARS?s Scientific Manuscript database

Concentrations of ammonium, nitrate, and phosphorus in irrigation leachate were measured weekly over a 47-week period from a low-fertility, acid-based substrate into which four types of 12-month controlled-release fertilizers (Osmocote, Nutricote, Polyon, or Multicote) were incorporated. Containers ...

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.

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.

Bioresponsive controlled release from mesoporous silica nanocontainers with glucometer readout.

PubMed

Hou, Li; Zhu, Chunling; Wu, Xiaoping; Chen, Guonan; Tang, Dianping

2014-02-11

A novel sensing platform for monitoring small molecules without the need for sample separation and washing is developed by using a commercialized personal glucose meter based on bioresponsive controlled release of glucose from aptamer-gated mesoporous silica nanocontainers.

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

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.

Release and control of hydrogen sulfide during sludge thermal drying.

PubMed

Weng, Huanxin; Dai, Zhixi; Ji, Zhongqiang; Gao, Caixia; Liu, Chongxuan

2015-10-15

The release of hydrogen sulfide (H2S) during sludge drying is a major environmental problem because of its toxicity to human health. A series of experiments were performed to investigate the mechanisms and factors controlling the H2S release. Results of this study show that: (1) the biomass and activity of sulfate-reducing bacteria (SRB) in sludge were the major factors controlling the amount of H2S release, (2) the sludge drying temperature had an important effect on both the extent and the timing of H2S release from the sludge, and (3) decreasing sludge pH increased the H2S release. Based on the findings from this study, a new system that integrates sludge drying and H2S gas treatment was developed, by which 97.5% of H2S and 99.7% of smoke released from sludge treatments was eliminated. Copyright © 2015 Elsevier B.V. All rights reserved.

Release and control of hydrogen sulfide during sludge thermal drying

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

Weng, Huanxin; Dai, Zhixin; Ji, Zhongqiang

2015-04-15

The release of hydrogen sulfide (H2S) during sludge drying is a major environmental problem because of its toxicity to human health. A series of experiments were performed to investigate the mechanisms and factors controlling the H2S release. Results of this study show that: 1) the biomass and activity of sulfate-reducing bacteria (SRB) in sludge were the major factors controlling the amount of H2S release, 2) the sludge drying temperature had an important effect on both the extent and the timing of H2S release from the sludge, and 3) decreasing sludge pH increased the H2S release. Based on the findings frommore » this study, a new system that integrates sludge drying and H2S gas treatment was developed to reduce the amount of H2S released from sludge treatments.« less

Transition in Gas Turbine Engine Control System Architecture: Modular, Distributed, Embedded

DTIC Science & Technology

2009-08-01

Design + Development + Certification + Procurement + Life Cycle Cost = Net Savings for our Customers Approved for Public Release 16 Economic ...Supporting Small Quantity Electronics Need Broadly Applicable High Temperature Electronics Supply Base Approved for Public Release 17 Economic ...rc ec ures Approved for Public Release 18 Economic Drivers for New FADEC Designs FADEC Implementation Time Pacing Engine Development Issues • FADEC

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.

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

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.

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

PubMed

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

2017-03-01

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

Characterization of new functionalized calcium carbonate-polycaprolactone composite material for application in geometry-constrained drug release formulation development.

PubMed

Wagner-Hattler, Leonie; Schoelkopf, Joachim; Huwyler, Jörg; Puchkov, Maxim

2017-10-01

A new mineral-polymer composite (FCC-PCL) performance was assessed to produce complex geometries to aid in development of controlled release tablet formulations. The mechanical characteristics of a developed material such as compactibility, compressibility and elastoplastic deformation were measured. The results and comparative analysis versus other common excipients suggest efficient formation of a complex, stable and impermeable geometries for constrained drug release modifications under compression. The performance of the proposed composite material has been tested by compacting it into a geometrically altered tablet (Tablet-In-Cup, TIC) and the drug release was compared to commercially available product. The TIC device exhibited a uniform surface, showed high physical stability, and showed absence of friability. FCC-PCL composite had good binding properties and good compactibility. It was possible to reveal an enhanced plasticity characteristic of a new material which was not present in the individual components. The presented FCC-PCL composite mixture has the potential to become a successful tool to formulate controlled-release dosage solid forms.

Development of a Method to Measure Organotin Release Rates

DTIC Science & Technology

1989-12-01

tributyltin per liter Pm Micrometers mm Millimeters NOSC Naval Ocean Systems Center RCW Relative confidence width TBT Tributyltin TBTCl Tributyltin ...organotin paint research is to develop a coating which controls fouling effec- tively with a minimum release of tributyltin ( TBT ). In addition to...DTNSRDC) are conducting a series of experiments in order to determine the tributyltin ( TBT ) release rates of various organotin antifouling paints. The

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.

Blood, sweat, tears and success of technology transfer long-term controlled-release of herbicides

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

Van Voris, P.; Cataldo, D.A.; Burton, F.G.

The problems encountered, the technical difficulties that had to be overcome, and the successful transfer of technology related to controlled-release of pesticides is reviewed. Research on control-release of pesticides to date has resulted in products designed to extend bioactivity for periods of several days, months, or at most, several years. However, research supported by the U.S. Department of Energy directed toward solving problems associated with plant-root penetration through caps and liners engineered to minimize leaching or movement of buried nuclear and chemical wastes has resulted in development of a long-term controlled-release herbicide delivery system designed to stop root growth formore » periods of up to 100 years. Through the unique combination of polymers with a herbicidally active dinitroaniline, a cylindrical pellet was developed that continuously releases a herbicide for a period of up to 100 years. Equilibrium concentration of the herbicide in soil adjacent to the pellet and the bioactive lifetime of the device can be adjusted by changing the size of the pellet; the type of polymer; the type, quality, and quantity of carrier; and/or the concentration and type of dinitroaniline was used.« 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.

Regenerated cellulose capsules for controlled drug delivery: Part III. Developing a fabrication method and evaluating extemporaneous utility for controlled-release.

PubMed

Bhatt, Bhavik; Kumar, Vijay

2016-08-25

In this article, we describe a method to utilize cellulose dissolved in dimethyl sulfoxide and paraformaldehyde solvent system to fabricate two-piece regenerated cellulose hard shell capsules for their potential use as an oral controlled drug delivery a priori vehicle. A systematic evaluation of solution rheology as well as resulting capsule mechanical, visual and thermal analysis was performed to develop a suitable method to repeatedly fabricate RC hard shell capsule halves. Because of the viscoelastic nature of the cellulose solution, a combination of dip-coating and casting method, herein referred to as dip-casting method, was developed. The dip-casting method was formalized by utilizing two-stage 2(2) full factorial design approach in order to determine a suitable approach to fabricate capsules with minimal variability. Thermal annealing is responsible for imparting shape rigidity of the capsules. Proof-of-concept analysis for the utility of these capsules in controlled drug delivery was performed by evaluating the release of KCl from them as well as from commercially available USP equivalent formulations. Release of KCl from cellulose capsules was comparable to extended release capsule formulation. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

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

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.

X-ray Radiation-Controlled NO-Release for On-Demand Depth-Independent Hypoxic Radiosensitization.

PubMed

Fan, Wenpei; Bu, Wenbo; Zhang, Zhen; Shen, Bo; Zhang, Hui; He, Qianjun; Ni, Dalong; Cui, Zhaowen; Zhao, Kuaile; Bu, Jiwen; Du, Jiulin; Liu, Jianan; Shi, Jianlin

2015-11-16

Multifunctional stimuli-responsive nanotheranostic systems are highly desirable for realizing simultaneous biomedical imaging and on-demand therapy with minimized adverse effects. Herein, we present the construction of an intelligent X-ray-controlled NO-releasing upconversion nanotheranostic system (termed as PEG-USMSs-SNO) by engineering UCNPs with S-nitrosothiol (R-SNO)-grafted mesoporous silica. The PEG-USMSs-SNO is designed to respond sensitively to X-ray radiation for breaking down the S-N bond of SNO to release NO, which leads to X-ray dose-controlled NO release for on-demand hypoxic radiosensitization besides upconversion luminescent imaging through UCNPs in vitro and in vivo. Thanks to the high live-body permeability of X-ray, our developed PEG-USMSs-SNO may provide a new technique for achieving depth-independent controlled NO release and positioned radiotherapy enhancement against deep-seated solid tumors. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

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.

Semi-Passive Oxidation-Based Approaches for Control of Large, Dilute Groundwater Plumes of Chlorinated Ethylenes

DTIC Science & Technology

2014-04-01

Permanganate gel (PG) for groundwater remediation: Compatibility, gelation, and release characteristics...26 4.4. Development and characterization of slow-release permanganate gel (SRP-G) for groundwater remediation...34 4.6. Geopolymers as slow-release materials for potassium permanganate

Development of a chitosan based double layer-coated tablet as a platform for colon-specific drug delivery

PubMed Central

Kim, Min Soo; Yeom, Dong Woo; Kim, Sung Rae; Yoon, Ho Yub; Kim, Chang Hyun; Son, Ho Yong; Kim, Jin Han; Lee, Sangkil; Choi, Young Wook

2017-01-01

A double layer-coated colon-specific drug delivery system (DL-CDDS) was developed, which consisted of chitosan (CTN) based polymeric subcoating of the core tablet containing citric acid for microclimate acidification, followed by an enteric coating. The polymeric composition ratio of Eudragit E100 and ethyl cellulose and amount of subcoating were optimized using a two-level factorial design method. Drug-release characteristics in terms of dissolution efficiency and controlled-release duration were evaluated in various dissolution media, such as simulated colonic fluid in the presence or absence of CTNase. Microflora activation and a stepwise mechanism for drug release were postulated. Consequently, the optimized DL-CDDS showed drug release in a controlled manner by inhibiting drug release in the stomach and intestine, but releasing the drug gradually in the colon (approximately 40% at 10 hours and 92% at 24 hours in CTNase-supplemented simulated colonic fluid), indicating its feasibility as a novel platform for CDD. PMID:28053506

Packing of Fruit Fly Parasitoids for Augmentative Releases

PubMed Central

Montoya, Pablo; Cancino, Jorge; Ruiz, Lía

2012-01-01

The successful application of Augmentative Biological Control (ABC) to control pest fruit flies (Diptera: Tephritidae) confronts two fundamental requirements: (1) the establishment of efficient mass rearing procedures for the species to be released, and (2) the development of methodologies for the packing and release of parasitoids that permit a uniform distribution and their optimal field performance under an area-wide approach. Parasitoid distributions have been performed by ground and by air with moderate results; both options face challenges that remain to be addressed. Different devices and strategies have been used for these purposes, including paper bags and the chilled adult technique, both of which are commonly used when releasing sterile flies. However, insect parasitoids have morphological and behavioral characteristics that render the application of such methodologies suboptimal. In this paper, we discuss an alternate strategy for the augmentative release of parasitoids and describe packing conditions that favor the rearing and emergence of adult parasitoids for increased field performance. We conclude that the use of ABC, including the packaging of parasitoids, requires ongoing development to ensure that this technology remains a viable and effective control technique for pest fruit flies. PMID:26466634

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

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.

Drug Loading and Release Behavior Depending on the Induced Porosity of Chitosan/Cellulose Multilayer Nanofilms.

PubMed

Park, Sohyeon; Choi, Daheui; Jeong, Hyejoong; Heo, Jiwoong; Hong, Jinkee

2017-10-02

The ability to control drug loading and release is the most important feature in the development of medical devices. In this research, we prepared a functional nanocoating technology to incorporate a drug-release layer onto a desired substrate. The multilayer films were prepared using chitosan (CHI) and carboxymethyl cellulose (CMC) polysaccharides by the layer-by-layer (LbL) method. By using chemical cross-linking to change the inner structure of the assembled multilayer, we could control the extent of drug loading and release. The cross-linked multilayer film had a porous structure and enhanced water wettability. Interestingly, more of the small-molecule drug was loaded into and released from the non-cross-linked multilayer film, whereas more of the macromolecular drug was loaded into and released from the cross-linked multilayer film. These results indicate that drug loading and release can be easily controlled according to the molecular weight of the desired drug by changing the structure of the film.

Release and establishment of Megamelus scutellaris (Hemiptera: Delphacidae) in Florida

USDA-ARS?s Scientific Manuscript database

Megamelus scutellaris (Berg) (Hemiptera: Delphacidae) was recently developed as a classical biological control agent for waterhyacinth, Eichhornia crassipes Mart. Solms, and released in Florida. Releases were conducted at 10 sites around the state every 4-6 weeks until late fall then halted until t...

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.

Development of orally disintegrating tablets comprising controlled-release multiparticulate beads

PubMed Central

2012-01-01

Melperone is an atypical antipsychotic agent that has shown a wide spectrum of neuroleptic properties, particularly effective in the treatment of senile dementia and Parkinson’s-associated psychosis, and is marketed in Europe as an immediate-release (IR) tablet and syrup. An orally disintegrating tablet (ODT) dosage form would be advantageous for patients who experience difficulty in swallowing large tablets or capsules or those who experience dysphagia. Controlled-release (CR) capsule and ODT formulations containing melperone HCl were developed with target in vitro release profiles suitable for a once-daily dosing regimen. Both dosage forms allow for the convenient production of dose-proportional multiple strengths. Two ODT formulations exhibiting fast and medium release profiles and one medium release profile capsule formulation (each 50 mg) were tested in vivo using IR syrup as the reference. The two medium release formulations were shown to be bioequivalent to each other and are suitable for once-daily dosing. Based on the analytical and organoleptic test results, as well as the blend uniformity and in-process compression data at various compression forces using coated beads produced at one-tenth (1/10) commercial scale, both formulations in the form of CR capsules and CR ODTs have shown suitability for progression into further clinical development. PMID:22356215

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.

Development of mesoporous silica-based nanoparticles with controlled release capability for cancer therapy☆

PubMed Central

Mekaru, Harutaka; Lu, Jie; Tamanoi, Fuyuhiko

2015-01-01

Nanoparticles that respond to internal and external stimuli to carry out controlled release of anticancer drugs have been developed. In this review, we focus on the development of mesoporous silica based nanoparticles, as this type of materials provides a relatively stable material that is amenable to various chemical modifications. We first provide an overview of various designs employed to construct MSN-based controlled release systems. These systems respond to internal stimuli such as pH, redox state and the presence of biomolecules as well as to external stimuli such as light and magnetic field. They are at a different stage of development; depending on the system, their operation has been demonstrated in aqueous solution, in cancer cells or in animal models. Efforts to develop MSNs with multi-functionality will be discussed. Safety and biodegradation of MSNs, issues that need to be overcome for clinical development of MSNs, will be discussed. Advances in the synthesis of mechanized theranostic nanoparticles open up the possibility to start envisioning future needs for medical equipment. PMID:26434537

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.

EMERGENCY RESPONSE EQUIPMENT TO CLEAN UP HAZARDOUS CHEMICAL RELEASES AT SPILLS AND UNCONTROLLED WASTE SITES

EPA Science Inventory

This paper reviews some of the research activities of the U.S. Environmental Protection Agency (EPA) regarding the development of emergency response equipment to control hazardous chemical releases. Several devices and systems have been developed by EPA for environmental emergenc...

Controlled-release of tea polyphenol from gelatin films incorporated with different ratios of free/nanoencapsulated tea polyphenols into fatty food simulants

USDA-ARS?s Scientific Manuscript database

Gelatin films having controlled-release properties were developed by incorporation of different free/encapsulated tea polyphenol (TP) ratios through modifying the encapsulation efficiency (EE) of TP-loaded chitosan nanoparticles. Different EEs were obtained by adjusting the chitosan hydrochloride (C...

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.

Development of Process Analytical Technology (PAT) methods for controlled release pellet coating.

PubMed

Avalle, P; Pollitt, M J; Bradley, K; Cooper, B; Pearce, G; Djemai, A; Fitzpatrick, S

2014-07-01

This work focused on the control of the manufacturing process for a controlled release (CR) pellet product, within a Quality by Design (QbD) framework. The manufacturing process was Wurster coating: firstly layering active pharmaceutical ingredient (API) onto sugar pellet cores and secondly a controlled release (CR) coating. For each of these two steps, development of a Process Analytical Technology (PAT) method is discussed and also a novel application of automated microscopy as the reference method. Ultimately, PAT methods should link to product performance and the two key Critical Quality Attributes (CQAs) for this CR product are assay and release rate, linked to the API and CR coating steps respectively. In this work, the link between near infra-red (NIR) spectra and those attributes was explored by chemometrics over the course of the coating process in a pilot scale industrial environment. Correlations were built between the NIR spectra and coating weight (for API amount), CR coating thickness and dissolution performance. These correlations allow the coating process to be monitored at-line and so better control of the product performance in line with QbD requirements. Copyright © 2014 Elsevier B.V. All rights reserved.

Munc13 controls the location and efficiency of dense-core vesicle release in neurons.

PubMed

van de Bospoort, Rhea; Farina, Margherita; Schmitz, Sabine K; de Jong, Arthur; de Wit, Heidi; Verhage, Matthijs; Toonen, Ruud F

2012-12-10

Neuronal dense-core vesicles (DCVs) contain diverse cargo crucial for brain development and function, but the mechanisms that control their release are largely unknown. We quantified activity-dependent DCV release in hippocampal neurons at single vesicle resolution. DCVs fused preferentially at synaptic terminals. DCVs also fused at extrasynaptic sites but only after prolonged stimulation. In munc13-1/2-null mutant neurons, synaptic DCV release was reduced but not abolished, and synaptic preference was lost. The remaining fusion required prolonged stimulation, similar to extrasynaptic fusion in wild-type neurons. Conversely, Munc13-1 overexpression (M13OE) promoted extrasynaptic DCV release, also without prolonged stimulation. Thus, Munc13-1/2 facilitate DCV fusion but, unlike for synaptic vesicles, are not essential for DCV release, and M13OE is sufficient to produce efficient DCV release extrasynaptically.

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.

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.

Controlled poorly soluble drug release from solid self-microemulsifying formulations with high viscosity hydroxypropylmethylcellulose.

PubMed

Yi, Tao; Wan, Jiangling; Xu, Huibi; Yang, Xiangliang

2008-08-07

The objective of this work was the development of a controlled release system based on self-microemulsifying mixture aimed for oral delivery of poorly water-soluble drugs. HPMC-based particle formulations were prepared by spray drying containing a model drug (nimodipine) of low water solubility and hydroxypropylmethylcellulose (HPMC) of high viscosity. One type of formulations contained nimodipine mixed with HPMC and the other type of formulations contained HPMC and nimodipine dissolved in a self-microemulsifying system (SMES) consisting of ethyl oleate, Cremophor RH 40 and Labrasol. Based on investigation by transmission electron microscopy (TEM), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray powder diffraction, differences were found in the particle structure between both types of formulations. In vitro release was performed and characterized by the power law. Nimodipine release from both types of formulations showed a controlled release profile and the two power law parameters, n and K, correlated to the viscosity of HPMC. The parameters were also influenced by the presence of SMES. For the controlled release solid SMES, oil droplets containing dissolved nimodipine diffused out of HPMC matrices following exposure to aqueous media. Thus, it is possible to control the in vitro release of poorly soluble drugs from solid oral dosage forms containing SMES.

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

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.

Modulation of drug release kinetics of shellac-based matrix tablets by in-situ polymerization through annealing process.

PubMed

Limmatvapirat, Sontaya; Limmatvapirat, Chutima; Puttipipatkhachorn, Satit; Nunthanid, Jurairat; Luangtana-anan, Manee; Sriamornsak, Pornsak

2008-08-01

A new oral-controlled release matrix tablet based on shellac polymer was designed and developed, using metronidazole (MZ) as a model drug. The shellac-based matrix tablets were prepared by wet granulation using different amounts of shellac and lactose. The effect of annealing temperature and pH of medium on drug release from matrix tablets was investigated. The increased amount of shellac and increased annealing temperature significantly affected the physical properties (i.e., tablet hardness and tablet disintegration) and MZ release from the matrix tablets. The in-situ polymerization played a major role on the changes in shellac properties during annealing process. Though the shellac did not dissolve in acid medium, the MZ release in 0.1N HCl was faster than in pH 7.3 buffer, resulting from a higher solubility of MZ in acid medium. The modulation of MZ release kinetics from shellac-based matrix tablets could be accomplished by varying the amount of shellac or annealing temperature. The release kinetics was shifted from relaxation-controlled release to diffusion-controlled release when the amount of shellac or the annealing temperature was increased.

Construction of a controlled-release delivery system for pesticides using biodegradable PLA-based microcapsules.

PubMed

Liu, Baoxia; Wang, Yan; Yang, Fei; Wang, Xing; Shen, Hong; Cui, Haixin; Wu, Decheng

2016-08-01

Conventional pesticides usually need to be used in more than recommended dosages due to their loss and degradation, which results in a large waste of resources and serious environmental pollution. Encapsulation of pesticides in biodegradable carriers is a feasible approach to develop environment-friendly and efficient controlled-release delivery system. In this work, we fabricated three kinds of polylactic acid (PLA) carriers including microspheres, microcapsules, and porous microcapsules for controlled delivery of Lambda-Cyhalothrin (LC) via premix membrane emulsification (PME). The microcapsule delivery system had better water dispersion than the other two systems. Various microcapsules with a high LC contents as much as 40% and tunable sizes from 0.68 to 4.6μm were constructed by manipulating the process parameters. Compared with LC technical and commercial microcapsule formulation, the microcapsule systems showed a significantly sustained release of LC for a longer period. The LC release triggered by LC diffusion and matrix degradation could be optimally regulated by tuning LC contents and particle sizes of the microcapsules. This multi-regulated release capability is of great significance to achieve the precisely controlled release of pesticides. A preliminary bioassay against plutella xylostella revealed that 0.68μm LC-loaded microcapsules with good UV and thermal stability exhibited an activity similar to a commercial microcapsule formulation. These results demonstrated such an aqueous microcapsule delivery system had a great potential to be further explored for developing an effective and environmentally friendly pesticide-release formulation. Copyright © 2016 Elsevier B.V. All rights reserved.

Assessment of research and development (R and D) needs in LPG safety and environmental control

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

DeSteese, J.G.

1982-05-01

The report characterizes the LPG industry covering all operations from production to end use, reviews current knowledge of LPG release phenomenology, summarizes the status of current LPG release prevention and control methodology, and identifies any remaining safety and environmental problems and recommends R and D strategies that may mitigate these problems. (ACR)

Field validation of a three chemical controlled release dispenser to attract codling moth (Cydia pomonella) (Lepidoptera: Tortricidae)

USDA-ARS?s Scientific Manuscript database

Male and female codling moths, Cydia pomonella, were shown to be attracted to three chemical kairoonomal lure comprised of pear ester, acetic acid, and n-butyl sulfide. A novel controlled-release device based on sachets was developed in the laboratory and field tested to optimize the attractivness ...

Can Nanofluidic Chemical Release Enable Fast, High Resolution Neurotransmitter-Based Neurostimulation?

PubMed

Jones, Peter D; Stelzle, Martin

2016-01-01

Artificial chemical stimulation could provide improvements over electrical neurostimulation. Physiological neurotransmission between neurons relies on the nanoscale release and propagation of specific chemical signals to spatially-localized receptors. Current knowledge of nanoscale fluid dynamics and nanofluidic technology allows us to envision artificial mechanisms to achieve fast, high resolution neurotransmitter release. Substantial technological development is required to reach this goal. Nanofluidic technology-rather than microfluidic-will be necessary; this should come as no surprise given the nanofluidic nature of neurotransmission. This perspective reviews the state of the art of high resolution electrical neuroprostheses and their anticipated limitations. Chemical release rates from nanopores are compared to rates achieved at synapses and with iontophoresis. A review of microfluidic technology justifies the analysis that microfluidic control of chemical release would be insufficient. Novel nanofluidic mechanisms are discussed, and we propose that hydrophobic gating may allow control of chemical release suitable for mimicking neurotransmission. The limited understanding of hydrophobic gating in artificial nanopores and the challenges of fabrication and large-scale integration of nanofluidic components are emphasized. Development of suitable nanofluidic technology will require dedicated, long-term efforts over many years.

Environmental Release Prevention and Control Plan (ERP and CP) annual review and update for 1993

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

Jannik, G.T.; Mamatey, A.; Arnett, M.

1993-10-05

In the Environmental Release Prevention and Control Plan (ERP and CP), WSRC made a commitment to conduct the following follow-up activities and actions: (1) Complete the action items developed in response to the findings and recommendation of the Environmental Release Prevention Taskteam (WSRC-RP-92-356). (2) Complete all batch and continuous release procedure revisions to incorporate the attributes that WSRC senior management required of each procedure. (3) DOE-SR Assistance Managers and WSRC counterparts to reach consensus and closure on the identified engineered solutions documented in the ERP and CP, develop and drive implementation of facility changes per the agreements. (4) Continue tomore » analyze releases and monitor performance in accordance with the ERP and CP, and utilize the ALARA Release Guides Committee to drive improvements. (5) Conduct annual re-evaluations of the cost benefit analyses of the identified engineered solutions, and identify new options and alternatives for each outfall in response to site mission and facility changes. This report documents the efforts that have been completed over the past year in response to these commitments.« less

Controlled release of chlorhexidine digluconate using β-cyclodextrin and microfibrillated cellulose.

PubMed

Lavoine, Nathalie; Tabary, Nicolas; Desloges, Isabelle; Martel, Bernard; Bras, Julien

2014-09-01

This study aims to develop a high-performance delivery system using microfibrillated cellulose (MFC)-coated papers as a controlled release system combined with the well-known drug delivery agent, β-cyclodextrin (βCD). Chlorhexidine digluconate (CHX), an antibacterial molecule, was mixed with a suspension of MFC or a βCD solution or mixed with both the substances, before coating onto a cellulosic substrate. The intermittent diffusion of CHX (i.e., diffusion interrupted by the renewal of the release medium periodically) was conducted in an aqueous medium, and the release mechanism of CHX was elucidated by field emission gun-scanning electron microscopy, SEM, NMR, and Fourier transform infrared analyses. According to the literature, both βCD and MFC are efficient controlled delivery systems. This study indicated that βCD releases CHX more gradually and over a longer period of time compared to MFC, which is mainly due to the ability of βCD to form an inclusion complex with CHX. Furthermore from the release study, a complementary action when the two compounds were combined was deduced. MFC mainly affected the burst effect, while βCD primarily controlled the amount of CHX released over time. In this paper, two different types of controlled release systems are proposed and compared. Depending on the final application, the use of βCD alone would release low amounts of active molecules over time (slow delivery), whereas the combination of β-cyclodextrin and MFC would be more suitable for the release of higher amounts of active molecules over time (rapid delivery). Copyright © 2014 Elsevier B.V. All rights reserved.

Adaptive release of natural enemies in a pest-natural enemy system with pesticide resistance.

PubMed

Liang, Juhua; Tang, Sanyi; Cheke, Robert A; Wu, Jianhong

2013-11-01

Integrated pest management options such as combining chemical and biological control are optimal for combating pesticide resistance, but pose questions if a pest is to be controlled to extinction. These questions include (i) what is the relationship between the evolution of pesticide resistance and the number of natural enemies released? (ii) How does the cumulative number of natural enemies dying affect the number of natural enemies to be released? To address these questions, we developed two novel pest-natural enemy interaction models incorporating the evolution of pesticide resistance. We investigated the number of natural enemies to be released when threshold conditions for the extinction of the pest population in two different control tactics are reached. Our results show that the number of natural enemies to be released to ensure pest eradication in the presence of increasing pesticide resistance can be determined analytically and depends on the cumulative number of dead natural enemies before the next scheduled release time.

Enhancement of Antiviral Agents Through the Use of Controlled-Release Technology.

DTIC Science & Technology

DL-lactide-co-glycolide) to be used as the polymeric excipients in the microencapsulation work. In addition, we have actively pursued development and testing of poly(I.C) and Je vaccine microcapsule formulations....of this research program are a) To develop a programmed-release delivery system ( microcapsule system) designed to enhance the immunogenic potential of...release microcapsule delivery systems that will enhance the effects of the following immune modulators and antiviral agents: muramyl tripeptide (MTP

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.

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

PubMed

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

2012-02-01

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

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.

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.

The ATP hydrolysis and phosphate release steps control the time course of force development in rabbit skeletal muscle.

PubMed

Sleep, John; Irving, Malcolm; Burton, Kevin

2005-03-15

The time course of isometric force development following photolytic release of ATP in the presence of Ca(2+) was characterized in single skinned fibres from rabbit psoas muscle. Pre-photolysis force was minimized using apyrase to remove contaminating ATP and ADP. After the initial force rise induced by ATP release, a rapid shortening ramp terminated by a step stretch to the original length was imposed, and the time course of the subsequent force redevelopment was again characterized. Force development after ATP release was accurately described by a lag phase followed by one or two exponential components. At 20 degrees C, the lag was 5.6 +/- 0.4 ms (s.e.m., n = 11), and the force rise was well fitted by a single exponential with rate constant 71 +/- 4 s(-1). Force redevelopment after shortening-restretch began from about half the plateau force level, and its single-exponential rate constant was 68 +/- 3 s(-1), very similar to that following ATP release. When fibres were activated by the addition of Ca(2+) in ATP-containing solution, force developed more slowly, and the rate constant for force redevelopment following shortening-restretch reached a maximum value of 38 +/- 4 s(-1) (n = 6) after about 6 s of activation. This lower value may be associated with progressive sarcomere disorder at elevated temperature. Force development following ATP release was much slower at 5 degrees C than at 20 degrees C. The rate constant of a single-exponential fit to the force rise was 4.3 +/- 0.4 s(-1) (n = 22), and this was again similar to that after shortening-restretch in the same activation at this temperature, 3.8 +/- 0.2 s(-1). We conclude that force development after ATP release and shortening-restretch are controlled by the same steps in the actin-myosin ATPase cycle. The present results and much previous work on mechanical-chemical coupling in muscle can be explained by a kinetic scheme in which force is generated by a rapid conformational change bracketed by two biochemical steps with similar rate constants -- ATP hydrolysis and the release of inorganic phosphate -- both of which combine to control the rate of force development.

Sugar and pH dual-responsive mesoporous silica nanocontainers based on competitive binding mechanisms

NASA Astrophysics Data System (ADS)

Yilmaz, M. Deniz; Xue, Min; Ambrogio, Michael W.; Buyukcakir, Onur; Wu, Yilei; Frasconi, Marco; Chen, Xinqi; Nassar, Majed S.; Stoddart, J. Fraser; Zink, Jeffrey I.

2014-12-01

A sugar and pH dual-responsive controlled release system, which is highly specific towards molecular stimuli, has been developed based on the binding between catechol and boronic acid on a platform of mesoporous silica nanoparticles (MSNs). By grafting phenylboronic acid stalks onto the silica surface, catechol-containing β-cyclodextrins can be attached to the orifices of the MSNs' nanopores through formation of boronate esters which block access to the nanopores. These esters are stable enough to prevent cargo molecules from escaping. The boronate esters disassociate in the presence of sugars, enabling the molecule-specific controlled-release feature of this hybrid system. The rate of release has been found to be tunable by varying both the structures and the concentrations of sugars, as a result of the competitive binding nature associated with the mechanism of its operation. Acidification also induces the release of cargo molecules. Further investigations show that the presence of both a low pH and sugar molecules provides cooperative effects which together control the rate of release.A sugar and pH dual-responsive controlled release system, which is highly specific towards molecular stimuli, has been developed based on the binding between catechol and boronic acid on a platform of mesoporous silica nanoparticles (MSNs). By grafting phenylboronic acid stalks onto the silica surface, catechol-containing β-cyclodextrins can be attached to the orifices of the MSNs' nanopores through formation of boronate esters which block access to the nanopores. These esters are stable enough to prevent cargo molecules from escaping. The boronate esters disassociate in the presence of sugars, enabling the molecule-specific controlled-release feature of this hybrid system. The rate of release has been found to be tunable by varying both the structures and the concentrations of sugars, as a result of the competitive binding nature associated with the mechanism of its operation. Acidification also induces the release of cargo molecules. Further investigations show that the presence of both a low pH and sugar molecules provides cooperative effects which together control the rate of release. Electronic supplementary information (ESI) available: Synthetic schemes, electron microscopy images and nitrogen adsorption/desorption isotherms of the nanoparticles, FT-IR spectra, isothermal titration calorimetry, X-ray photoelectron spectra and time-of-flight secondary ion mass spectra. DLS results for nanoparticle stability. See DOI: 10.1039/c4nr04796f

Nanostructured Diclofenac Sodium Releasing Material

NASA Astrophysics Data System (ADS)

Nikkola, L.; Vapalahti, K.; Harlin, A.; Seppälä, J.; Ashammakhi, N.

2008-02-01

Various techniques have been developed to produce second generation biomaterials for tissue repair. These include extrusion, molding, salt leaching, spinning etc, but success in regenerating tissues has been limited. It is important to develop porous material, yet with a fibrous structure for it to be biomimetic. To mimic biological tissues, the extra-cellular matrix usually contains fibers in nano scale. To produce nanostructures, self-assembly or electrospinning can be used. Adding a drug release function to such a material may advance applications further for use in controlled tissue repair. This turns the resulting device into a multifunctional porous, fibrous structure to support cells and drug releasing properties in order to control tissue reactions. A bioabsorbable poly(ɛ-caprolactone-co-D,L lactide) 95/5 (PCL) was made into diluted solution using a solvent, to which was added 2w-% of diclofenac sodium (DS). Nano-fibers were made by electrospinning onto substrate. Microstructure of the resulting nanomat was studied using SEM and drug release profiles with UV/VIS spectroscopy. Thickness of the electrospun nanomat was about 2 mm. SEM analysis showed that polymeric nano-fibers containing drug particles form a highly interconnected porous nano structure. Average diameter of the nano-fibers was 130 nm. There was a high burst peak in drug release, which decreased to low levels after one day. The used polymer has slow a degradation rate and though the nanomat was highly porous with a large surface area, drug release rate is slow. It is feasible to develop a nano-fibrous porous structure of bioabsorbable polymer, which is loaded with test drug. Drug release is targeted at improving the properties of biomaterial for use in controlled tissue repair and regeneration.

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

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.

Recent Advance on Mesoporous Silica Nanoparticles-Based Controlled Release System: Intelligent Switches Open up New Horizon

PubMed Central

Sun, Ruijuan; Wang, Wenqian; Wen, Yongqiang; Zhang, Xueji

2015-01-01

Mesoporous silica nanoparticle (MSN)-based intelligent transport systems have attracted many researchers’ attention due to the characteristics of uniform pore and particle size distribution, good biocompatibility, high surface area, and versatile functionalization, which have led to their widespread application in diverse areas. In the past two decades, many kinds of smart controlled release systems were prepared with the development of brilliant nano-switches. This article reviews and discusses the advantages of MSN-based controlled release systems. Meanwhile, the switching mechanisms based on different types of stimulus response are systematically analyzed and summarized. Additionally, the application fields of these devices are further discussed. Obviously, the recent evolution of smart nano-switches promoted the upgrading of the controlled release system from the simple “separated” switch to the reversible, multifunctional, complicated logical switches and selective switches. Especially the free-blockage switches, which are based on hydrophobic/hydrophilic conversion, have been proposed and designed in the last two years. The prospects and directions of this research field are also briefly addressed, which could be better used to promote the further development of this field to meet the needs of mankind. PMID:28347110

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.

The potential of magneto-electric nanocarriers for drug delivery

PubMed Central

Kaushik, Ajeet; Jayant, Rahul Dev; Sagar, Vidya; Nair, Madhavan

2015-01-01

Introduction The development and design of personalized nanomedicine for better health quality is receiving great attention. In order to deliver and release a therapeutic concentration at the target site, novel nanocarriers (NCs) were designed, for example, magneto-electric (ME) which possess ideal properties of high drug loading, site-specificity and precise on-demand controlled drug delivery. Areas covered This review explores the potential of ME-NCs for on-demand and site-specific drug delivery and release for personalized therapeutics. The main features including effect of magnetism, improvement in drug loading, drug transport across blood-brain barriers and on-demand controlled release are also discussed. The future directions and possible impacts on upcoming nanomedicine are highlighted. Expert opinion Numerous reports suggest that there is an urgent need to explore novel NC formulations for safe and targeted drug delivery and release at specific disease sites. The challenges of formulation lie in the development of NCs that improve biocompatibility and surface modifications for optimum drug loading/preservation/transmigration and tailoring of electrical–magnetic properties for on-demand drug release. Thus, the development of novel NCs is anticipated to overcome the problems of targeted delivery of therapeutic agents with desired precision that may lead to better patient compliance. PMID:24986772

The potential of magneto-electric nanocarriers for drug delivery.

PubMed

Kaushik, Ajeet; Jayant, Rahul Dev; Sagar, Vidya; Nair, Madhavan

2014-10-01

The development and design of personalized nanomedicine for better health quality is receiving great attention. In order to deliver and release a therapeutic concentration at the target site, novel nanocarriers (NCs) were designed, for example, magneto-electric (ME) which possess ideal properties of high drug loading, site-specificity and precise on-demand controlled drug delivery. This review explores the potential of ME-NCs for on-demand and site-specific drug delivery and release for personalized therapeutics. The main features including effect of magnetism, improvement in drug loading, drug transport across blood-brain barriers and on-demand controlled release are also discussed. The future directions and possible impacts on upcoming nanomedicine are highlighted. Numerous reports suggest that there is an urgent need to explore novel NC formulations for safe and targeted drug delivery and release at specific disease sites. The challenges of formulation lie in the development of NCs that improve biocompatibility and surface modifications for optimum drug loading/preservation/transmigration and tailoring of electrical-magnetic properties for on-demand drug release. Thus, the development of novel NCs is anticipated to overcome the problems of targeted delivery of therapeutic agents with desired precision that may lead to better patient compliance.

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.

Classification of stimuli-responsive polymers as anticancer drug delivery systems.

PubMed

Taghizadeh, Bita; Taranejoo, Shahrouz; Monemian, Seyed Ali; Salehi Moghaddam, Zoha; Daliri, Karim; Derakhshankhah, Hossein; Derakhshani, Zaynab

2015-02-01

Although several anticancer drugs have been introduced as chemotherapeutic agents, the effective treatment of cancer remains a challenge. Major limitations in the application of anticancer drugs include their nonspecificity, wide biodistribution, short half-life, low concentration in tumor tissue and systemic toxicity. Drug delivery to the tumor site has become feasible in recent years, and recent advances in the development of new drug delivery systems for controlled drug release in tumor tissues with reduced side effects show great promise. In this field, the use of biodegradable polymers as drug carriers has attracted the most attention. However, drug release is still difficult to control even when a polymeric drug carrier is used. The design of pharmaceutical polymers that respond to external stimuli (known as stimuli-responsive polymers) such as temperature, pH, electric or magnetic field, enzymes, ultrasound waves, etc. appears to be a successful approach. In these systems, drug release is triggered by different stimuli. The purpose of this review is to summarize different types of polymeric drug carriers and stimuli, in addition to the combination use of stimuli in order to achieve a better controlled drug release, and it discusses their potential strengths and applications. A survey of the recent literature on various stimuli-responsive drug delivery systems is also provided and perspectives on possible future developments in controlled drug release at tumor site have been discussed.

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.

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.

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.

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).

Investigation into the Effect of Ethylcellulose Viscosity Variation on the Drug Release of Metoprolol Tartrate and Acetaminophen Extended Release Multiparticulates-Part I.

PubMed

Mehta, R; Teckoe, J; Schoener, C; Workentine, S; Ferrizzi, D; Rajabi-Siahboomi, A

2016-12-01

Ethylcellulose is one of the most commonly used polymers to develop reservoir type extended release multiparticulate dosage forms. For multiparticulate extended release dosage forms, the drug release is typically governed by the properties of the barrier membrane coating. The ICH Pharmaceutical Development Guideline (ICH Q8) requires an understanding of the influence of critical material attributes and critical process parameters on the drug release of a pharmaceutical product. Using this understanding, it is possible to develop robust formulations with consistent drug release characteristics. Critical material attributes for ethylcellulose were evaluated, and polymer molecular weight variation (viscosity) was considered to be the most critical attribute that can impact drug release. To investigate the effect of viscosity variation within the manufacturer's specifications of ethylcellulose, extended release multiparticulate formulations of two model drugs, metoprolol tartrate and acetaminophen, were developed using ETHOCEL™ as the rate controlling polymer. Quality by Design (QbD) samples of ETHOCEL Std. 10, 20, and 100 Premium grades representing the low, medium, and high molecular weight (viscosity) material were organically coated onto drug layered multiparticulates to a 15% weight gain (WG). The drug release was found to be similar (f 2  > 50) for both metoprolol tartrate and acetaminophen multiparticulates at different coating weight gains of ethylcellulose, highlighting consistent and robust drug release performance. The use of ETHOCEL QbD samples also serves as a means to develop multiparticulate dosage formulations according to regulatory guidelines.

Inlay osmotic pump tablets containing metformin and glipizide.

PubMed

Patel, R B; Patel, G N; Patel, H R; Patel, M M

2011-10-01

The goal of diabetes therapy today is to achieve and maintain as near normal glycemia as possible to prevent the long-term microvascular and macrovascular complications of an elevated blood glucose. A newly developed inlay osmotic pump tablet (IOPT) can deliver glipizide (GLZ) and metformin HCl (MET) gradually in controlled manner. The aim of present investigation was to prepare the IOPT that can deliver >75% of GLZ in 2 h, whereas MET released after 2 h and sustained up to 12 h. In the present work, HP-β-CD was used to modify the solubility of GLZ before incorporating in the osmotic system and MET was spray-dried with HPMC A15C to modify its release profile, flow property, and compressibility. Various parameters mainly G(75%) (75% GLZ release), t(LMET) (lag time of MET release from device), Q(10 h) (percent of MET released within 10 h), and RSQ(ZERO) (R(2) of release data fitted to zero-order equation) were used to compare different formulations. The effects of different formulation variables, that is, osmagents, concentration of hydrophilic polymer, diameter of drug releasing orifice, and coating composition on the drug release profile were investigated. The release rate of GLZ could be effectively modified by the addition of sodium carbonate and sodium chloride, whereas the release rate of MET was adjusted by dual-coating system and by addition of hydrophilic polymer. The developed inlay osmotic system could be effective in the multidrug therapy of diabetes by delivering both drugs in a controlled manner.

γ-PARCEL: Control of Molecular Release Using γ-Rays.

PubMed

Murayama, Shuhei; Jo, Jun-ichiro; Arai, Kazutaka; Nishikido, Fumihiko; Bakalova, Rumiana; Yamaya, Taiga; Saga, Tsuneo; Kato, Masaru; Aoki, Ichio

2015-12-01

We previously have developed the photoresponsive tetra-gel and nanoparticles for controlling the function of the encapsulated substance by UV irradiation. However, the penetration ability of the UV is not high enough. Here, we developed a radiation-responsive tetra-gel and nanoparticle based on γ-ray-responsive X-shaped polyethylene glycol (PEG) linker with a disulfide bond. The nanoparticle could retain small molecules and biomacromolecules. γ-Rays were used as a trigger signal because of their higher penetrating ability. This allowed a spatiotemporal release and control of the encapsulated substances from the nanoparticle in the deeper region, which is impossible by using light exposure (ultraviolet, visible, and near-infrared).

Multiple functionalization of fluorescent nanoparticles for specific biolabeling and drug delivery of dopamine

NASA Astrophysics Data System (ADS)

Malvindi, Maria Ada; di Corato, Riccardo; Curcio, Annalisa; Melisi, Daniela; Rimoli, Maria Grazia; Tortiglione, Claudia; Tino, Angela; George, Chandramohan; Brunetti, Virgilio; Cingolani, Roberto; Pellegrino, Teresa; Ragusa, Andrea

2011-12-01

The development of fluorescent biolabels for specific targeting and controlled drug release is of paramount importance in biological applications due to their potential in the generation of novel tools for simultaneous diagnosis and treatment of diseases. Dopamine is a neurotransmitter involved in several neurological diseases, such as Parkinson's disease and attention deficit hyperactivity disorder (ADHD), and the controlled delivery of its agonists already proved to have beneficial effects both in vitro and in vivo. Here, we report the synthesis and multiple functionalization of highly fluorescent CdSe/CdS quantum rods for specific biolabeling and controlled drug release. After being transferred into aqueous media, the nanocrystals were made highly biocompatible through PEG conjugation and covered by a carbohydrate shell, which allowed specific GLUT-1 recognition. Controlled attachment of dopamine through an ester bond also allowed hydrolysis by esterases, yielding a smart nanotool for specific biolabeling and controlled drug release.The development of fluorescent biolabels for specific targeting and controlled drug release is of paramount importance in biological applications due to their potential in the generation of novel tools for simultaneous diagnosis and treatment of diseases. Dopamine is a neurotransmitter involved in several neurological diseases, such as Parkinson's disease and attention deficit hyperactivity disorder (ADHD), and the controlled delivery of its agonists already proved to have beneficial effects both in vitro and in vivo. Here, we report the synthesis and multiple functionalization of highly fluorescent CdSe/CdS quantum rods for specific biolabeling and controlled drug release. After being transferred into aqueous media, the nanocrystals were made highly biocompatible through PEG conjugation and covered by a carbohydrate shell, which allowed specific GLUT-1 recognition. Controlled attachment of dopamine through an ester bond also allowed hydrolysis by esterases, yielding a smart nanotool for specific biolabeling and controlled drug release. Electronic supplementary information (ESI) available: TEM images, absorption and emission spectra, ζ-potential and DLS graphics, gel electrophoresis images, cyclic voltammograms, western blot and RT-PCR data. See DOI: 10.1039/c1nr10797f

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

Gen IV Materials Handbook Beta Release for Structural and Functional Evaluation

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

Ren, Weiju; Luttrell, Claire

2006-09-12

Development of the Gen IV Materials Handbook is briefly summarized up to date. Current status of the Handbook website construction is described. The developed Handbook components and access control of the beta version are discussed for the present evaluation release. Detailed instructions and examples are given to provide guidance for evaluators to browse the constructed parts and use all the currently developed functionalities of the Handbook in evaluation.

Development of a CO2 releasing co-formulation 1 based on starch, Saccharomyces cerevisiae and Beauveria bassiana attractive towards western corn rootworm larvae

USDA-ARS?s Scientific Manuscript database

CO2 is known as an attractant for many soil-dwelling pests. To implement an attract-and-kill strategy for soil pest control, CO2 emitting formulations need to be developed. This work aimed at the development of a slow release bead system in order to bridge the gap between application and hatching of...

Controlled delivery of metoclopramide using an injectable semi-solid poly(ortho ester) for veterinary application.

PubMed

Schwach-Abdellaoui, Khadija; Moreau, Marinette; Schneider, Marc; Boisramć, Bernard; Gurny, Robert

2002-11-06

In animal health care, current therapeutic regimens for gastrointestinal disorders require repeated oral or parenteral dosage forms of anti-emetic agents. However, fluctuations of plasma concentrations produce severe side effects. The aim of this work is to develop a subcutaneous and biodegradable controlled release system containing metoclopramide (MTC). Semi-solid poly(ortho ester)s (POE) prepared by a transesterification reaction between trimethyl orthoacetate and 1,2,6,-hexanetriol were investigated as injectable bioerodible polymers for the controlled release of MTC. MTC is present in the polymeric matrix as a solubilised form and it is released rapidly from the POE by erosion and diffusion because of its acidic character and its high hydrosolubility. If a manual injection is desired, only low molecular weight can be used. However, low molecular weight POEs release the drug rapidly. In order to extend polymer lifetime and decrease drug release rate, a sparingly water-soluble base Mg(OH)(2) was incorporated to the formulation. It was possible to produce low molecular weight POE that can be manually injected and releasing MTC over a period of several days.

Chitosan cross-linked with poly(ethylene glycol)dialdehyde via reductive amination as effective controlled release carriers for oral protein drug delivery.

PubMed

Jing, Zi-Wei; Ma, Zhi-Wei; Li, Chen; Jia, Yi-Yang; Luo, Min; Ma, Xi-Xi; Zhou, Si-Yuan; Zhang, Bang-Le

2017-02-15

The covalently cross-linked chitosan-poly(ethylene glycol) 1540 derivatives have been developed as a controlled release system with potential for the delivery of protein drug. The swelling characteristics of the hydrogels based on these derivatives as the function of different PEG content and the release profiles of a model protein (bovine serum albumin, BSA) from the hydrogels were evaluated in simulated gastric fluid with or without enzyme in order to simulate the gastrointestinal tract conditions. The derivatives cross-linked with difunctional PEG 1540 -dialdehyde via reductive amination can swell in alkaline pH and remain insoluble in acidic medium. The cumulative release amount of BSA was relatively low in the initial 2h and increased significantly at pH 7.4 with intestinal lysozyme for additional 12h. The results proved that the release-and-hold behavior of the cross-linked CS-PEG 1540 H-CS hydrogel provided a swell and intestinal enzyme controlled release carrier system, which is suitable for oral protein drug delivery. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Effect of Single, Binary and Ternary Anions of Chloride, Carbonate and Phosphate on the Release of 2,4-Dichlorophenoxyacetate Intercalated into the Zn-Al-layered Double Hydroxide Nanohybrid

NASA Astrophysics Data System (ADS)

Hussein, Mohd Zobir; Jaafar, Adila Mohamad; Yahaya, Asmah Hj.; Zainal, Zulkarnain

2009-11-01

Intercalation of beneficial anion into inorganic host has lead to an opportunity to synthesize various combinations of new organic-inorganic nanohybrids with various potential applications; especially, for the controlled release formulation and storage purposes. Investigation on the release behavior of 2,4-dichlorophenoxyacetate (2,4-D) intercalated into the interlayer of Zn-Al-layered double hydroxide (ZAN) have been carried out using single, binary and ternary aqueous systems of chloride, carbonate and phosphate. The release behavior of the active agent 2,4-D from its double-layered hydroxide nanohybrid ZANDI was found to be of controlled manner governed by pseudo-second order kinetics. It was found that carbonate medium yielded the highest accumulated release of 2,4-D, while phosphate in combination with carbonate and/or nitrate speeds up the release rate of 2,4-D. These results indicate that it is possible to design and develop new delivery system of latex stimulant compound with controlled release property based on 2,4-D that is known as a substance to increase latex production of rubber tree, Hevea brasiliensis.

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.

A self-referential HOWTO on release engineering

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

Galassi, Mark C.

Release engineering is a fundamental part of the software development cycle: it is the point at which quality control is exercised and bug fixes are integrated. The way in which software is released also gives the end user her first experience of a software package, while in scientific computing release engineering can guarantee reproducibility. For these reasons and others, the release process is a good indicator of the maturity and organization of a development team. Software teams often do not put in place a release process at the beginning. This is unfortunate because the team does not have early andmore » continuous execution of test suites, and it does not exercise the software in the same conditions as the end users. I describe an approach to release engineering based on the software tools developed and used by the GNU project, together with several specific proposals related to packaging and distribution. I do this in a step-by-step manner, demonstrating how this very paper is written and built using proper release engineering methods. Because many aspects of release engineering are not exercised in the building of the paper, the accompanying software repository also contains examples of software libraries.« less

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.

Polymer Nanosheet Containing Star-Like Copolymers: A Novel Scalable Controlled Release System.

PubMed

Cao, Peng-Fei; de Leon, Al; Rong, Lihan; Yin, Ke-Zhen; Abenojar, Eric C; Su, Zhe; Tiu, Brylee David B; Exner, Agata A; Baer, Eric; Advincula, Rigoberto C

2018-04-26

Poly(ε-caprolactone) (PCL)-based nanomaterials, such as nanoparticles and liposomes, have exhibited great potential as controlled release systems, but the difficulties in large-scale fabrication limit their practical applications. Among the various methods being developed to fabricate polymer nanosheets (PNSs) for different applications, such as Langmuir-Blodgett technique and layer-by-layer assembly, are very effort consuming, and only a few PNSs can be obtained. In this paper, poly(ε-caprolactone)-based PNSs with adjustable thickness are obtained in large quantity by simple water exposure of multilayer polymer films, which are fabricated via a layer multiplying coextrusion method. The PNS is also demonstrated as a novel controlled guest release system, in which release kinetics are adjustable by the nanosheet thickness, pH values of the media, and the presence of protecting layers. Theoretical simulations, including Korsmeyer-Peppas model and Finite-element analysis, are also employed to discern the observed guest-release mechanisms. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Controlled release of therapeutics using interpenetrating polymeric networks.

PubMed

Aminabhavi, Tejraj M; Nadagouda, Mallikarjuna N; More, Uttam A; Joshi, Shrinivas D; Kulkarni, Venkatrao H; Noolvi, Malleshappa N; Kulkarni, Padmakar V

2015-04-01

The ever-increasing developments in pharmaceutical formulations have led to the widespread use of biodegradable polymers in various forms and configurations. In particular, interpenetrating network (IPN) and semi-IPN polymer structures that are capable of releasing drugs in a controlled manner have gained much wider importance in recent years. Recently, IPNs and semi-IPNs have emerged as innovative materials of choice in controlled release (CR) of drugs as the release from these systems depends on pH of the media and temperature in addition to the nature of the system. These networks can be prepared as smart hydrogels following chemical or physical crosslinking methods to show remarkable drug release patterns compared to single polymer systems. A large number of IPNs and semi-IPNs have been reported in the literature. The present review is focused on the preparation methods and their CR properties with reference to anticancer, anti-asthmatic, antibiotic, anti-inflammatory, anti-tuberculosis and antihypertensive drugs, as majority of these drugs have been reported to be the ideal choices for using IPNs and semi-IPNs.

Controlled drug-release system based on pH-sensitive chloride-triggerable liposomes.

PubMed

Wehunt, Mark P; Winschel, Christine A; Khan, Ali K; Guo, Tai L; Abdrakhmanova, Galya R; Sidorov, Vladimir

2013-03-01

New pH-sensitive lipids were synthesized and utilized in formulations of liposomes suitable for controlled drug release. These liposomes contain various amounts of NaCl in the internal aqueous compartments. The release of the drug model is triggered by an application of HCl cotransporter and exogenous physiologically relevant NaCl solution. HCl cotransporter allows an uptake of HCl by liposomes to the extent of their being proportional to the transmembrane Cl(-) gradient. Therefore, each set of liposomes undergoes internal acidification, which, ultimately, leads to the hydrolysis of the pH-sensitive lipids and content release at the desired time. The developed system releases the drug model in a stepwise fashion, with the release stages separated by periods of low activity. These liposomes were found to be insensitive to physiological concentrations of human serum albumin and to be nontoxic to cells at concentrations exceeding pharmacological relevance. These results render this new drug-release model potentially suitable for in vivo applications.

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.

Heritable strategies for controlling insect vectors of disease.

PubMed

Burt, Austin

2014-01-01

Mosquito-borne diseases are causing a substantial burden of mortality, morbidity and economic loss in many parts of the world, despite current control efforts, and new complementary approaches to controlling these diseases are needed. One promising class of new interventions under development involves the heritable modification of the mosquito by insertion of novel genes into the nucleus or of Wolbachia endosymbionts into the cytoplasm. Once released into a target population, these modifications can act to reduce one or more components of the mosquito population's vectorial capacity (e.g. the number of female mosquitoes, their longevity or their ability to support development and transmission of the pathogen). Some of the modifications under development are designed to be self-limiting, in that they will tend to disappear over time in the absence of recurrent releases (and hence are similar to the sterile insect technique, SIT), whereas other modifications are designed to be self-sustaining, spreading through populations even after releases stop (and hence are similar to traditional biological control). Several successful field trials have now been performed with Aedes mosquitoes, and such trials are helping to define the appropriate developmental pathway for this new class of intervention.

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.

Optimum timing for integrated pest management: modelling rates of pesticide application and natural enemy releases.

PubMed

Tang, Sanyi; Tang, Guangyao; Cheke, Robert A

2010-05-21

Many factors including pest natural enemy ratios, starting densities, timings of natural enemy releases, dosages and timings of insecticide applications and instantaneous killing rates of pesticides on both pests and natural enemies can affect the success of IPM control programmes. To address how such factors influence successful pest control, hybrid impulsive pest-natural enemy models with different frequencies of pesticide sprays and natural enemy releases were proposed and analyzed. With releasing both more or less frequent than the sprays, a stability threshold condition for a pest eradication periodic solution is provided. Moreover, the effects of times of spraying pesticides (or releasing natural enemies) and control tactics on the threshold condition were investigated with regard to the extent of depression or resurgence resulting from pulses of pesticide applications. Multiple attractors from which the pest population oscillates with different amplitudes can coexist for a wide range of parameters and the switch-like transitions among these attractors showed that varying dosages and frequencies of insecticide applications and the numbers of natural enemies released are crucial. To see how the pesticide applications could be reduced, we developed a model involving periodic releases of natural enemies with chemical control applied only when the densities of the pest reached the given Economic Threshold. The results indicate that the pest outbreak period or frequency largely depends on the initial densities and the control tactics. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

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.

Regulating the path from legacy recognition, through recovery to release from regulatory control.

PubMed

Sneve, Malgorzata Karpow; Smith, Graham

2015-04-01

Past development of processes and technologies using radioactive material led to construction of many facilities worldwide. Some of these facilities were built and operated before the regulatory infrastructure was in place to ensure adequate control of radioactive material during operation and decommissioning. In other cases, controls were in place but did not meet modern standards, leading to what is now considered to have been inadequate control. Accidents and other events have occurred resulting in loss of control of radioactive material and unplanned releases to the environment. The legacy from these circumstances is that many countries have areas or facilities at which abnormal radiation conditions exist at levels that give rise to concerns about environmental and human health of potential interest to regulatory authorities. Regulation of these legacy situations is complex. This paper examines the regulatory challenges associated with such legacy management and brings forward suggestions for finding the path from: legacy recognition; implementation, as necessary, of urgent mitigation measures; development of a longer-term management strategy, through to release from regulatory control. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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.

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

PubMed

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

2013-06-01

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

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.

Dual controlled release, in situ gelling periodontal sol of metronidazole benzoate and serratiopeptidase: statistical optimization and mechanistic evaluation.

PubMed

Kumari, Neeraj; Pathak, Kamla

2012-01-01

In situ gelling syringeable periodontal sol capable of dual controlled delivery of metronidazole benzoate and serratiopeptidase was designed based on 2(3) factorial design with drug, poloxamer 407 and aerosil as independent variables and sol gel transition characteristics, %CDR(48h) and palatability as responses. The sols had agreeable taste, were mucoadhesive, syringeable and inverted into gels at periodontal cavity temperature. F8 with optimal drug release was identified as the best formulation. The dispersion characteristics of poloxamer significantly affected the pharmacotechnical properties of the in situ gelling systems. Extra design checkpoint generated using Design Expert software 8.02 (Stat-Ease, USA) validated the experimental design. Thus a thermoreversible, in situ gelling and syringeable periodontal sol with acceptable taste characteristics that offered controlled release of metronidazole benzoate and serratiopeptidase was developed for application into the periodontal pocket. The developed optimized sol was satisfactory in terms of taste, syringeability, palatability and incorporation of serratiopeptidase as anti-inflammatory agent, has the potential of developing a therapeutically efficacious system for treatment of periodontal inflammatory anaerobic infections.

Controlled Release of Chitosan and Sericin from the Microspheres-Embedded Wound Dressing for the Prolonged Anti-microbial and Wound Healing Efficacy.

PubMed

Aramwit, Pornanong; Yamdech, Rungnapha; Ampawong, Sumate

2016-05-01

One approach in wound dressing development is to incorporate active molecules or drugs in the dressing. In order to reduce the frequency of dressing changes as well as to prolong wound healing efficacy, wound dressings that can sustain the release of the active molecules should be developed. In our previous work, we developed chitosan/sericin (CH/SS) microspheres that released sericin in a controlled rate. However, the difficulty of applying the microspheres that easily diffuse and quickly degrade onto the wound was its limitations. In this study, we aimed to develop wound dressing materials which are easier to apply and to provide extended release of sericin. Different amounts of CH/SS microspheres were embedded into various compositions of polyvinyl alcohol/gelatin (PVA/G) scaffolds and fabricated using freeze-drying and glutaraldehyde crosslinking techniques. The obtained CH/SS microspheres-embedded scaffolds with appropriate design and formulation were introduced as a wound dressing material. Sericin was released from the microspheres and the scaffolds in a sustained manner. Furthermore, an optimized formation of the microspheres-embedded scaffolds (2PVA2G+2CHSS) was shown to possess an effective antimicrobial activity against both gram-positive and gram-negative bacteria. These microspheres-embedded scaffolds were not toxic to L929 mouse fibroblast cells, and they did not irritate the tissue when applied to the wound. Finally, probably by the sustained release of sericin, these microspheres-embedded scaffolds could promote wound healing as well as or slightly better than a clinically used wound dressing (Allevyn®) in a mouse model. The antimicrobial CH/SS microspheres-embedded PVA/G scaffolds with sustained release of sericin would appear to be a promising candidate for wound dressing application.

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.

[Testing of medicinal products produced from pooled plasma].

PubMed

Unkelbach, U; Hunfeld, A; Breitner-Ruddock, S

2014-10-01

Medicinal products produced from human plasma fall under the administrative batch release procedure of the competent authority. In Germany, this has been carried out since 1995 by the Paul Ehrlich Institute (PEI), the responsible state control agency for blood products. Medicinal products released for the European and national market are tested for quality, efficacy and safety. Experimental testing of the final product and the starting materials, the plasma pools, as well as control of the production documentation guarantee a constantly high product safety. In the 28,000 batches tested since the beginning of the state controlled batch release testing of these blood products at the PEI, there has been no transmission of infectious viruses (HIV, HBV and HCV) to any patient. The batch release has made a contribution to the improvement of product quality. This procedure is still an important tool to ensure safety of blood products. The PEI is integrated in the batch release network of the European Directorate for the Quality of Medicines & Health Care (EDQM) in Strasbourg. Regulations and guidelines for official control authority batch release (OCABR) ensure harmonized procedures for mutual recognition of batch release on the European level. The EU certificates and German national certificates are requested and accepted in over 70 countries worldwide. Experimental testing in the EU and the requisite certificates have developed into a seal of quality for the world market.

Gelatin device for the delivery of growth factors involved in endochondral ossification.

PubMed

Ahrens, Lucas A J; Vonwil, Daniel; Christensen, Jon; Shastri, V Prasad

2017-01-01

Controlled release drug delivery systems are well established as oral and implantable dosage forms. However, the controlled release paradigm can also be used to present complex soluble signals responsible for cellular organization during development. Endochondral ossification (EO), the developmental process of bone formation from a cartilage matrix is controlled by several soluble signals with distinct functions that vary in structure, molecular weight and stability. This makes delivering them from a single vehicle rather challenging. Herein, a gelatin-based delivery system suitable for the delivery of small molecules as well as recombinant human (rh) proteins (rhWNT3A, rhFGF2, rhVEGF, rhBMP4) is reported. The release behavior and biological activity of the released molecules was validated using analytical and biological assays, including cell reporter systems. The simplicity of fabrication of the gelatin device should foster its adaptation by the diverse scientific community interested in interrogating developmental processes, in vivo.

Controlled release of volatiles under mild reaction conditions: from nature to everyday products.

PubMed

Herrmann, Andreas

2007-01-01

Volatile organic compounds serve in nature as semiochemicals for communication between species, and are often used as flavors and fragrances in our everyday life. The quite limited longevity of olfactive perception has led to the development of pro-perfumes or pro-fragrances--ideally nonvolatile and odorless fragrance precursors which release the active volatiles by bond cleavage. Only a limited amount of reaction conditions, such as hydrolysis, temperature changes, as well as the action of light, oxygen, enzymes, or microorganisms, can be used to liberate the many different chemical functionalities. This Review describes the controlled chemical release of fragrances and discusses additional challenges such as precursor stability during product storage as well as some aspects concerning toxicity and biodegradability. As the same systems can be applied in different areas of research, the scope of this Review covers fragrance delivery as well as the controlled release of volatiles in general.

Gelatin device for the delivery of growth factors involved in endochondral ossification

PubMed Central

Ahrens, Lucas A. J.; Vonwil, Daniel; Christensen, Jon

2017-01-01

Controlled release drug delivery systems are well established as oral and implantable dosage forms. However, the controlled release paradigm can also be used to present complex soluble signals responsible for cellular organization during development. Endochondral ossification (EO), the developmental process of bone formation from a cartilage matrix is controlled by several soluble signals with distinct functions that vary in structure, molecular weight and stability. This makes delivering them from a single vehicle rather challenging. Herein, a gelatin-based delivery system suitable for the delivery of small molecules as well as recombinant human (rh) proteins (rhWNT3A, rhFGF2, rhVEGF, rhBMP4) is reported. The release behavior and biological activity of the released molecules was validated using analytical and biological assays, including cell reporter systems. The simplicity of fabrication of the gelatin device should foster its adaptation by the diverse scientific community interested in interrogating developmental processes, in vivo. PMID:28380024

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

Smart Drug Delivery Systems in Cancer Therapy.

PubMed

Unsoy, Gozde; Gunduz, Ufuk

2018-02-08

Smart nanocarriers have been designed for tissue-specific targeted drug delivery, sustained or triggered drug release and co-delivery of synergistic drug combinations to develop safer and more efficient therapeutics. Advances in drug delivery systems provide reduced side effects, longer circulation half-life and improved pharmacokinetics. Smart drug delivery systems have been achieved successfully in the case of cancer. These nanocarriers can serve as an intelligent system by considering the differences of tumor microenvironment from healthy tissue, such as low pH, low oxygen level, or high enzymatic activity of matrix metalloproteinases. The performance of anti-cancer agents used in cancer diagnosis and therapy is improved by enhanced cellular internalization of smart nanocarriers and controlled drug release. Here, we review targeting, cellular internalization; controlled drug release and toxicity of smart drug delivery systems. We are also emphasizing the stimulus responsive controlled drug release from smart nanocarriers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Carbon monoxide – physiology, detection and controlled release

PubMed Central

Heinemann, Stefan H.; Hoshi, Toshinori; Westerhausen, Matthias

2014-01-01

Carbon monoxide (CO) is increasingly recognized as a cell-signalling molecule akin to nitric oxide (NO). CO has attracted particular attention as a potential therapeutic agent because of its reported anti-hypertensive, anti-inflammatory and cell-protective effects. We discuss recent progress in identifying new effector systems and elucidating the mechanisms of action of CO on, e.g., ion channels, as well as the design of novel methods to monitor CO in cellular environments. We also report on recent developments in the area of CO-releasing molecules (CORMs) and materials for controlled CO application. Novel triggers for CO release, metal carbonyls and degradation mechanisms of CORMs, are highlighted. In addition, potential formulations of CORMs for targeted CO release are discussed. PMID:24556640

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.

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.

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.

Generating news media interest in tobacco control; challenges in an advanced policy environment.

PubMed

MacKenzie, Ross; Chapman, Simon

2012-08-01

To determine the efficacy of using media releases for tobacco control advocacy in Australia's advanced policy environment. Between February and August 2010, news releases that summarised either newly published but unpublicized research findings, or local developments in tobacco control, were sent to NSW media outlets. Reports arising from the releases were tracked using commercial services Media Monitors and Factiva, as well as Google and Google News. Other tobacco control related news items during the same period were also tracked and recorded. Twenty-one news releases generated 93 news items across all news media, with a quarter of these related to a story of porcine haemoglobin in cigarette filters. By comparison, 'live' policy issues (especially plain packaging and a significant tobacco tax increase) covered in this period attracted 1,033 news stories in the Australian media. Press releases describing recently published, but underpublicized research were issued in weeks where no major competing tobacco control news occurred. Results of this project indicate that in environments with advanced tobacco policy, media opportunities related to tobacco control advocacy are limited, as many objectives have been achieved. The media can still play a key advocacy role in such environments, and advocates need to be particularly vigilant for opportunities that do arise. The paper also highlights the increasingly important role of internet-based media, including opportunities presented by social media for tobacco control.

Motor Function and Dopamine Release Measurements in Transgenic Huntington’s Disease Model Rats

PubMed Central

Ortiz, Andrea N.; Osterhaus, Gregory L.; Lauderdale, Kelli; Mahoney, Luke; Fowler, Stephen C.; von Hörsten, Stephan; Riess, Olaf; Johnson, Michael A.

2013-01-01

Huntington’s disease (HD) is a fatal, genetic, neurodegenerative disorder characterized by deficits in motor and cognitive function. Here, we have quantitatively characterized motor deficiencies and dopamine release dynamics in transgenic HD model rats. Behavioral analyses were conducted using a newly-developed force-sensing runway and a previously-developed force-plate actometer. Gait disturbances were readily observed in transgenic HD rats at 12 to 15 months of age. Additionally, dopamine system challenge by ip injection of amphetamine also revealed that these rats were resistant to the expression of focused stereotypy compared to wild-type controls. Moreover, dopamine release, evoked by the application of single and multiple electrical stimulus pulses applied at different frequencies, and measured using fast-scan cyclic voltammetry at carbon-fiber microelectrodes, was diminished in transgenic HD rats compared to age-matched wild-type control rats. Collectively, these results underscore the potential contribution of dopamine release alterations to the expression of motor impairments in transgenic HD rats. PMID:22418060

Polysaccharides-based multiparticulated interpolyelectrolyte complexes for controlled benznidazole release.

PubMed

García, Mónica C; Manzo, Rubén H; Jimenez-Kairuz, Alvaro

2018-07-10

Polysaccharides-based delivery systems and interpolyelectrolyte complexes (IPECs) are interesting alternatives to control the release of drugs, thereby improving therapies. Benznidazole (BZ) is the selected drug for Chagas disease pharmacotherapy. However, its side effects limit its efficacy and safety. We developed novel multiparticulated BZ-loaded IPECs based on chitosan and alginic acid, and investigated their physicochemical and pharmacotechnical properties. IPECs were obtained using the casting solvent method, followed by wet granulation. They presented ionic interaction between the biopolymers, revealed that free BZ was uniformly distributed and showed adequate flow properties for hard gelatin-capsule formulation. The multiparticles exhibited mucoadhesion properties and revealed modulation of BZ release, depending on the release media, in accordance with the fluid uptake. The IPECs developed possess interesting properties that are promising for the design of novel alternatives to improve Chagas disease pharmacotherapy, which would diminish BZ's adverse effects and/or allow a reduction in the frequency of BZ administration. Copyright © 2018 Elsevier B.V. All rights reserved.

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

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.

Light induced cytosolic drug delivery from liposomes with gold nanoparticles.

PubMed

Lajunen, Tatu; Viitala, Lauri; Kontturi, Leena-Stiina; Laaksonen, Timo; Liang, Huamin; Vuorimaa-Laukkanen, Elina; Viitala, Tapani; Le Guével, Xavier; Yliperttula, Marjo; Murtomäki, Lasse; Urtti, Arto

2015-04-10

Externally triggered drug release at defined targets allows site- and time-controlled drug treatment regimens. We have developed liposomal drug carriers with encapsulated gold nanoparticles for triggered drug release. Light energy is converted to heat in the gold nanoparticles and released to the lipid bilayers. Localized temperature increase renders liposomal bilayers to be leaky and triggers drug release. The aim of this study was to develop a drug releasing system capable of releasing its cargo to cell cytosol upon triggering with visible and near infrared light signals. The liposomes were formulated using either heat-sensitive or heat- and pH-sensitive lipid compositions with star or rod shaped gold nanoparticles. Encapsulated fluorescent probe, calcein, was released from the liposomes after exposure to the light. In addition, the pH-sensitive formulations showed a faster drug release in acidic conditions than in neutral conditions. The liposomes were internalized into human retinal pigment epithelial cells (ARPE-19) and human umbilical vein endothelial cells (HUVECs) and did not show any cellular toxicity. The light induced cytosolic delivery of calcein from the gold nanoparticle containing liposomes was shown, whereas no cytosolic release was seen without light induction or without gold nanoparticles in the liposomes. The light activated liposome formulations showed a controlled content release to the cellular cytosol at a specific location and time. Triggering with visual and near infrared light allows good tissue penetration and safety, and the pH-sensitive liposomes may enable selective drug release in the intracellular acidic compartments (endosomes, lysosomes). Thus, light activated liposomes with gold nanoparticles are an attractive option for time- and site-specific drug delivery into the target cells. Copyright © 2015 Elsevier B.V. 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.

Acoustically-Responsive Scaffolds: Control of Growth Factor Release for Tissue Regeneration Using Ultrasound

NASA Astrophysics Data System (ADS)

Moncion, Alexander

Administration of exogenous growth factors (GFs) is a proposed method of stimulating tissue regeneration. Conventional administration routes, such as at-site or systemic injections, have yielded problems with efficacy and/or safety, thus hindering the translation of GF-based regenerative techniques. Hydrogel scaffolds are commonly used as biocompatible delivery vehicles for GFs. Yet hydrogels do not afford spatial or temporal control of GF release - two critical parameters for tissue regeneration. Controlled delivery of GFs is critical for angiogenesis, which is a crucial process in tissue engineering that provides oxygen and nutrients to cells within an implanted hydrogel scaffold. Angiogenesis requires multiple GFs that are presented with distinct spatial and temporal profiles. Thus, controlled release of GFs with spatiotemporal modulation would significantly improve tissue regeneration by recapitulating endogenous GF presentation. In order to achieve this goal, we have developed acoustically-responsive scaffolds (ARSs), which are fibrin hydrogels doped with sonosensitive perfluorocarbon (PFC) emulsions capable of encapsulating various payloads. Focused, mega-Hertz range, ultrasound (US) can modulate the release of a payload non-invasively and in an on-demand manner from ARSs via physical mechanisms termed acoustic droplet vaporization (ADV) and inertial cavitation (IC). This work presents the relationship between the ADV/IC thresholds and various US and hydrogel parameters. These physical mechanisms were used for the controlled release of fluorescent dextran in vitro and in vivo to determine the ARS and US parameters that yielded optimal payload release. The optimal ARS and US parameters were used to demonstrate the controlled release of basic fibroblast growth factor from an in vivo subcutaneous implant model - leading to enhanced angiogenesis and perfusion. Additionally, different acoustic parameters and PFCs were tested and optimized to demonstrate the controlled release of two encapsulated payloads within an ARS. Overall, ARSs are a promising platform for GF delivery in tissue regeneration applications.

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.

Calcium Binding-Mediated Sustained Release of Minocycline from Hydrophilic Multilayer Coatings Targeting Infection and Inflammation

PubMed Central

Zhang, Zhiling; Nix, Camilla A.; Ercan, Utku K.; Gerstenhaber, Jonathan A.; Joshi, Suresh G.; Zhong, Yinghui

2014-01-01

Infection and inflammation are common complications that seriously affect the functionality and longevity of implanted medical implants. Systemic administration of antibiotics and anti-inflammatory drugs often cannot achieve sufficient local concentration to be effective, and elicits serious side effects. Local delivery of therapeutics from drug-eluting coatings presents a promising solution. However, hydrophobic and thick coatings are commonly used to ensure sufficient drug loading and sustained release, which may limit tissue integration and tissue device communications. A calcium-mediated drug delivery mechanism was developed and characterized in this study. This novel mechanism allows controlled, sustained release of minocycline, an effective antibiotic and anti-inflammatory drug, from nanoscale thin hydrophilic polyelectrolyte multilayers for over 35 days at physiologically relevant concentrations. pH-responsive minocycline release was observed as the chelation between minocycline and Ca2+ is less stable at acidic pH, enabling ‘smart’ drug delivery in response to infection and/or inflammation-induced tissue acidosis. The release kinetics of minocycline can be controlled by varying initial loading, Ca2+ concentration, and Ca2+ incorporation into different layers, enabling facile development of implant coatings with versatile release kinetics. This drug delivery platform can potentially be used for releasing any drug that has high Ca2+ binding affinity, enabling its use in a variety of biomedical applications. PMID:24409292

Active Flow Control for High-Speed Weapon Release from a Bay

DTIC Science & Technology

2004-06-01

and supersonic microjets . Each of these control devices offers unique attributes for high-speed weapon release and was the subject of considerable...final HIFEX actuator is the supersonic microjet , a device developed at Florida A&M/Florida State University and described by [3]. Small (0.016-inch...effectiveness of the microjets is that they destroy the spanwise coherence of the instabilities generated in an open weapons bay. Figure 4 illustrates the

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.

Dual turn-on fluorescence signal-based controlled release system for real-time monitoring of drug release dynamics in living cells and tumor tissues.

PubMed

Kong, Xiuqi; Dong, Baoli; Song, Xuezhen; Wang, Chao; Zhang, Nan; Lin, Weiying

2018-01-01

Controlled release systems with capabilities for direct and real-time monitoring of the release and dynamics of drugs in living systems are of great value for cancer chemotherapy. Herein, we describe a novel dual turn-on fluorescence signal-based controlled release system ( CDox ), in which the chemotherapy drug doxorubicin ( Dox ) and the fluorescent dye ( CH ) are conjugated by a hydrazone moiety, a pH-responsive cleavable linker. CDox itself shows nearly no fluorescence as the fluorescence of CH and Dox is essentially quenched by the C=N isomerization and N-N free rotation. However, when activated under acidic conditions, CDox could be hydrolyzed to afford Dox and CH , resulting in dual turn-on signals with emission peaks at 595 nm and 488 nm, respectively. Notably, CDox exhibits a desirable controlled release feature as the hydrolysis rate is limited by the steric hindrance effect from both the Dox and CH moieties. Cytotoxicity assays indicate that CDox shows much lower cytotoxicity relative to Dox , and displays higher cell inhibition rate to cancer than normal cells. With the aid of the dual turn-on fluorescence at different wavelengths, the drug release dynamics of CDox in living HepG2 and 4T-1 cells was monitored in double channels in a real-time fashion. Importantly, two-photon fluorescence imaging of CDox in living tumor tissues was also successfully performed by high-definition 3D imaging. We expect that the unique controlled release system illustrated herein could provide a powerful means to investigate modes of action of drugs, which is critical for development of much more robust and effective chemotherapy drugs.

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.

Mission Accomplished? We Need a Guide to the 'Post Release' World of Wolbachia for Aedes-borne Disease Control.

PubMed

Ritchie, Scott A; van den Hurk, Andrew F; Smout, Michael J; Staunton, Kyran M; Hoffmann, Ary A

2018-03-01

Historically, sustained control of Aedes aegypti, the vector of dengue, chikungunya, yellow fever, and Zika viruses, has been largely ineffective. Subsequently, two novel 'rear and release' control strategies utilizing mosquitoes infected with Wolbachia are currently being developed and deployed widely. In the incompatible insect technique, male Aedes mosquitoes, infected with Wolbachia, suppress populations through unproductive mating. In the transinfection strategy, both male and female Wolbachia-infected Ae. aegypti mosquitoes rapidly infect the wild population with Wolbachia, blocking virus transmission. It is critical to monitor the long-term stability of Wolbachia in host populations, and also the ability of this bacterium to continually inhibit virus transmission. Ongoing release and monitoring programs must be future-proofed should political support weaken when these vectors are successfully controlled. Copyright © 2017 Elsevier Ltd. All rights reserved.

Optical control of insulin release using a photoswitchable sulfonylurea.

PubMed

Broichhagen, Johannes; Schönberger, Matthias; Cork, Simon C; Frank, James A; Marchetti, Piero; Bugliani, Marco; Shapiro, A M James; Trapp, Stefan; Rutter, Guy A; Hodson, David J; Trauner, Dirk

2014-10-14

Sulfonylureas are widely prescribed for the treatment of type 2 diabetes mellitus (T2DM). Through their actions on ATP-sensitive potassium (KATP) channels, sulfonylureas boost insulin release from the pancreatic beta cell mass to restore glucose homeostasis. A limitation of these compounds is the elevated risk of developing hypoglycemia and cardiovascular disease, both potentially fatal complications. Here, we describe the design and development of a photoswitchable sulfonylurea, JB253, which reversibly and repeatedly blocks KATP channel activity following exposure to violet-blue light. Using in situ imaging and hormone assays, we further show that JB253 bestows light sensitivity upon rodent and human pancreatic beta cell function. Thus, JB253 enables the optical control of insulin release and may offer a valuable research tool for the interrogation of KATP channel function in health and T2DM.

Spatiotemporal Programing for the On-Demand Release of Bupivacaine Based on an Injectable Composite Hydrogel.

PubMed

Dinh, Van Vuong; Suh, Yun-Suhk; Yang, Han-Kwang; Lim, Yong Taik

2016-12-01

We report a programed drug delivery system that can tailor the release of anesthetic bupivacaine in a spatiotemporally controlled manner. The drug delivery system was developed through the combination of a collagen-based injectable hydrogel and 2 types of poly(lactic-co-glycolic acid) (PLGA) particles. As a rapid-release platform (90% release after 24 h), bupivacaine hydrochloride was incorporated into collagen/poly(γ-glutamic acid) hydrogel, which exhibited gel formation at body temperature. PLGA microparticles (diameter 1-3 μm) containing bupivacaine base showed a very slow release of bupivacaine (95% after 240 h), whereas PLGA nanoparticles (124 ± 30 nm) containing bupivacaine base demonstrated an intermediate release rate (95% after 160 h). By changing the relative composition ratio between the 3 components in these injectable composite hydrogels, the release of bupivacaine could be easily controlled from very rapid (within 1 day) to very delayed (up to 9 days). The experimental results on the release data (cumulative release, time point release, average release rate) were coincident with the release profile generated by computer simulation. These injectable composite hydrogels with systematically tunable mixing ratios are expected to serve as a promising technology for the on-demand release of bupivacaine in pain management. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Development of Ocular Delivery System for Glaucoma Therapy Using Natural Hydrogel as Film Forming Agent and Release Modifier.

PubMed

Kulkarni, Giriraj T; Sethi, Nitin; Awasthi, Rajendra; Pawar, Vivek Kumar; Pahuja, Vineet

2016-01-01

Glaucoma is characterized by increased intraocular pressure, which results in damage to the optic nerve. The existing therapy with conventional eye drops is inefficient due to nasolachrymal drainage, resulting in a reduced corneal residence of the drug. The objective was to develop controlled-release ocular films of timolol maleate using natural hydrogel from Tamarindus indica seeds as a sustaining and film-forming agent, to overcome the problems associated with eye drops. The hydrogel was isolated using hot aqueous extraction followed by precipitation with ethanol. Six batches of ocular films were prepared and evaluated for drug content, weight variation, thickness, diameter and in vitro release profile. The ideal batch of the films was subjected to stability, pharmacodynamic and ocular safety studies. The yield of the hydrogel was 58.29%. The thickness of the ocular films was in the range of 0.17 to 0.25 mm and the weight of the films was found to increase with the increase in polymer content. The drug release from the films was found to be controlled over a period of 8 h. The films were found to be stable and were able to reduce the intraocular pressure for 24 h in a more efficient manner than the eye drops. The films were found to be practically non-irritating to the eye. It can be concluded that the hydrogel from tamarind seeds can be used as a film-forming and release-controlling agent for the development of an ocular drug delivery system for the effective therapy of glaucoma.

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.

Injectable controlled release depots for large molecules

PubMed Central

Schwendeman, Steven P.; Shah, Ronak B.; Bailey, Brittany A.; Schwendeman, Anna S.

2014-01-01

Biodegradable, injectable depot formulations for long-term controlled drug release have improved therapy for a number of drug molecules and led to over a dozen highly successful pharmaceutical products. Until now, success has been limited to several small molecules and peptides, although remarkable improvements have been accomplished in some of these cases. For example, twice-a-year depot injections with leuprolide are available compared to the once-a-day injection of the solution dosage form. Injectable depots are typically prepared by encapsulation of the drug in poly(lactic-co-glycolic acid) (PLGA), a polymer that is used in children every day as a resorbable suture material, and therefore, highly biocompatible. PLGAs remain today as one of the few “real world” biodegradable synthetic biomaterials used in US FDA-approved parenteral long-acting-release (LAR) products. Despite their success, there remain critical barriers to the more widespread use of PLGA LAR products, particularly for delivery of more peptides and other large molecular drugs, namely proteins. In this review, we describe key concepts in the development of injectable PLGA controlled-release depots for peptides and proteins, and then use this information to identify key issues impeding greater widespread use of PLGA depots for this class of drugs. Finally, we examine important approaches, particularly those developed in our research laboratory, toward overcoming these barriers to advance commercial LAR development. PMID:24929039

A minocycline-releasing PMMA system as a space maintainer for staged bone reconstructions-in vitro antibacterial, cytocompatibility and anti-inflammatory characterization.

PubMed

Silva, Tiago; Grenho, Liliana; Barros, Joana; Silva, José Carlos; Pinto, Rosana V; Matos, Ana; Colaço, Bruno; Fernandes, Maria Helena; Bettencourt, Ana; Gomes, Pedro S

2017-06-06

In the present work, we study the development and biological characterization of a polymethyl methacrylate (PMMA)-based minocycline delivery system, to be used as a space maintainer within craniofacial staged regenerative interventions. The developed delivery systems were characterized regarding solid state characteristics and assayed in vitro for antibacterial and anti-inflammatory activity, and cytocompatibility with human bone cells. A drug release profile allowed for an initial burst release and a more sustained and controlled release over time, with minimum inhibitory concentrations for the assayed and relevant pathogenic bacteria (i.e., Staphylococcus aureus, slime-producer Staphylococcus epidermidis and Escherichia coli) being easily attained in the early time points, and sustained up to 72 h. Furthermore, an improved osteoblastic cell response-with enhancement of cell adhesion and cell proliferation-and increased anti-inflammatory activity were verified in developed systems, compared to a control (non minocycline-loaded PMMA cement). The obtained results converge to support the possible efficacy of the developed PMMA-based minocycline delivery systems for the clinical management of complex craniofacial trauma. Here, biomaterials with space maintenance properties are necessary for the management of staged reconstructive approaches, thus minimizing the risk of peri-operative infections and enhancing the local tissue healing and early stages of regeneration.

Photoactivatable Lipid-based Nanoparticles as a Vehicle for Dual Agent Delivery | NCI Technology Transfer Center | TTC

Cancer.gov

Researchers at the National Cancer Institute (NCI) RNA Biology Laboratory have developed nanoparticles that can deliver an agent (i.e., therapeutic or imaging) and release the agent upon targeted photoactivation allowing for controlled temporal and localized release of the agent.

Releasing Playfulness in the Adult through Creative Drama.

ERIC Educational Resources Information Center

Monaghan, Therese A.

This dissertation explores the possibilities for releasing playfulness in adults through creative drama. A playful attitude, the capacity to enjoy action for its own sake, is difficult to maintain in a technological society which demands rational control, achievement, and conformity. Creative drama can provide a way to develop playfulness in our…

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.

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.

Sol-gel encapsulation for controlled drug release and biosensing

NASA Astrophysics Data System (ADS)

Fang, Jonathan

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

Eco-friendly PEG-based controlled release nano-formulations of Mancozeb: Synthesis and bioefficacy evaluation against phytopathogenic fungi Alternaria solani and Sclerotium rolfsii.

PubMed

Majumder, Sujan; Shakil, Najam A; Kumar, Jitendra; Banerjee, Tirthankar; Sinha, Parimal; Singh, Braj B; Garg, Parul

2016-12-01

Controlled release (CR) nano-formulations of Mancozeb (manganese-zinc double salt of N,N-bisdithiocarbamic acid), a protective fungicide, have been prepared using laboratory-synthesized poly(ethylene glycols) (PEGs)-based functionalized amphiphilic copolymers without using any surfactants or external additives. The release kinetics of the developed Mancozeb CR formulations were studied and compared with that of commercially available 42% suspension concentrate and 75% wettable powder. Maximum amount of Mancozeb was released on 42nd day for PEG-600 and octyl chain, PEG-1000 and octyl chain, and PEG-600 and hexadecyl chain, on 35th day for PEG-1000 and hexadecyl chain, on 28th day for PEG-1500 and octyl chain, PEG-2000 and octyl chain, PEG-1500 and hexadecyl chain, and PEG-2000 and hexadecyl chain in comparison to both commercial formulations (15th day). The diffusion exponent (n value) of Mancozeb in water ranged from 0.42 to 0.62 in tested formulations. The half-release (t 1/2 ) values ranged from 17.35 to 35.14 days, and the period of optimum availability of Mancozeb ranged from 18.54 to 35.42 days. Further, the in vitro bioefficacy evaluation of developed formulations was done against plant pathogenic fungi Alternaria solani and Sclerotium rolfsii by poison food technique. Effective dose for 50% inhibition in mgL -1 (ED 50 ) values of developed formulations varied from 1.31 to 2.79 mg L -1 for A. solani, and 1.60 to 3.14 mg L -1 for S. rolfsii. The present methodology is simple, economical, and eco-friendly for the development of environment-friendly CR formulations of Mancozeb. These formulations can be used to optimize the release of Mancozeb to achieve disease control for the desired period depending upon the matrix of the polymer used. Importantly, the maximum amount of active ingredient remains available for a reasonable period after application. In addition, the developed CR formulations were found to be suitable for fungicidal applications, allowing use of Mancozeb in lower doses.

Resistance to genetic insect control: Modelling the effects of space.

PubMed

Watkinson-Powell, Benjamin; Alphey, Nina

2017-01-21

Genetic insect control, such as self-limiting RIDL 2 (Release of Insects Carrying a Dominant Lethal) technology, is a development of the sterile insect technique which is proposed to suppress wild populations of a number of major agricultural and public health insect pests. This is achieved by mass rearing and releasing male insects that are homozygous for a repressible dominant lethal genetic construct, which causes death in progeny when inherited. The released genetically engineered ('GE') insects compete for mates with wild individuals, resulting in population suppression. A previous study modelled the evolution of a hypothetical resistance to the lethal construct using a frequency-dependent population genetic and population dynamic approach. This found that proliferation of resistance is possible but can be diluted by the introgression of susceptible alleles from the released homozygous-susceptible GE males. We develop this approach within a spatial context by modelling the spread of a lethal construct and resistance trait, and the effect on population control, in a two deme metapopulation, with GE release in one deme. Results show that spatial effects can drive an increased or decreased evolution of resistance in both the target and non-target demes, depending on the effectiveness and associated costs of the resistant trait, and on the rate of dispersal. A recurrent theme is the potential for the non-target deme to act as a source of resistant or susceptible alleles for the target deme through dispersal. This can in turn have a major impact on the effectiveness of insect population control. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

A novel approach for the preparation of highly loaded polymeric controlled release dosage forms of diltiazem HCl and diclofenac sodium.

PubMed

Kakish, Hanan F; Tashtoush, Bassam; Ibrahim, Hussein G; Najib, Naji M

2002-07-01

In this investigation, modified-release dosage forms of diltiazem HCl (DT) and diclofenac sodium (DS) were prepared. The development work comprised two main parts: (a) loading the drug into ethylene vinyl acetate (EVA) polymer, and (b) generation of a non-uniform concentration distribution of the drug within the polymer matrix. Phase separation technique was successfully used to load DT and DS into the polymer at significantly high levels, up to 81 and 76%, respectively. Size diameter of the resultant microspheres was between 1.6 and 2.0mm. Controlled-extraction of loaded microspheres and high vacuum freeze-drying were used to generate the non-uniform concentration distribution and to immobilize the new drug distribution within the matrix. Parameters controlling the different processes were investigated, and hence optimal processing conditions were used to prepare the dosage forms. Rates of drug release from the two dosage forms in water and in media having different pH were found to be constant for an appreciable length of time (>8h) followed by a slow decline; a characteristic of a non-Fickian diffusion process. Scanning electron microscopy studies suggested that the resultant release behavior was the outcome of the combined effects of the non-uniform distribution of the drug in the matrix and the apparent changes in the pores and surface characteristics of the microspheres. Comparison of release rate-time plots of dissolution data of marketed products with the newly developed dosage forms indicated the ability of the latter to sustain more zero order release.

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.

NASA develops new digital flight control system

NASA Technical Reports Server (NTRS)

Mewhinney, Michael

1994-01-01

This news release reports on the development and testing of a new integrated flight and propulsion automated control system that aerospace engineers at NASA's Ames Research Center have been working on. The system is being tested in the V/STOL (Vertical/Short Takeoff and Landing) Systems Research Aircraft (VSRA).

Bioactive Nano-Fibrous Scaffolds for Bone and Cartilage Tissue Engineering

NASA Astrophysics Data System (ADS)

Feng, Kai

Scaffolds that can mimic the structural features of natural extracellular matrix and can deliver biomolecules in a controlled fashion may provide cells with a favorable microenvironment to facilitate tissue regeneration. Biodegradable nanofibrous scaffolds with interconnected pore network have previously been developed in our laboratory to mimic collagen matrix and advantageously support both bone and cartilage regeneration. This dissertation project aims to expand both the structural complexity and the biomolecule delivery capacity of such biomimetic scaffolds for tissue engineering. We first developed a nanofibrous scaffold that can release an antibiotic (doxycycline) with a tunable release rate and a tunable dosage, which was demonstrated to be able to inhibit bacterial growth over a prolonged time period. We then developed a nanofibrous tissue-engineciing scaffold that can release basic fibroblast growth factor (bFGF) in a spatially and temporally controlled fashion. In a mouse subcutaneous implantation model, the bFGF-releasing scaffold was shown to enhance cell penetration, tissue ingrowth and angiogenesis. It was also found that both the dose and the release rate of bFGF play roles in the biologic function of the scaffold. After that, we developed a nanofibrous PLLA scaffold that can release both bone morphogenetic protein 7 (BMP-7) and platelet-derived growth factor (PDGF) with distinct dosages and release kinetics. It was demonstrated that BMP-7 and PDGF could synergistically enhance bone regeneration using a mouse ectopic bone formation model and a rat periodontal fenestration defect regeneration model. The regeneration outcome was dependent on the dosage, the ratio and the release kinetics of the two growth factors. Last, we developed an anisotropic composite scaffold with an upper layer mimicking the superficial zone of cartilage and a lower layer mimicking the middle zone of cartilage. The thin superficial layer was fabricated using an electrospinning technique to support a more parallel ECM orientation to the cartilage surface. The lower layer was fabricated using a phase-separation technique to support a more isotropic ECM distribution. Human bone marrow-derived mesenchymal stem cells (hMSCs) were seeded on this complex scaffold and cultured under chondrogenic conditions. The results showed that the composite scaffold was indeed able to support anisotropic cartilage tissue structure formation.

Enzyme-Responsive Nanomaterials for Controlled Drug Delivery

PubMed Central

Hu, Quanyin; Katti, Prateek S.; Gu, Zhen

2015-01-01

Enzymes underpin physiological function and exhibit dysregulation in many disease-associated microenvironments and aberrant cell processes. Exploiting altered enzyme activity and expression for diagnostics, drug targeting, and drug release is tremendously promising. When combined with booming research in nanobiotechnology, enzyme-responsive nanomaterials for controlled drug release have achieved significant development and been studied as an important class of drug delivery devices in nanomedicine. In this review, we describe enzymes such as proteases, phospholipase and oxidoreductases that serve as delivery triggers. Subsequently, we explore recently developed enzyme-responsive nanomaterials with versatile applications for extracellular and intracellular drug delivery. We conclude by discussing future opportunities and challenges in this area. PMID:25251024

Enzyme-responsive nanomaterials for controlled drug delivery

NASA Astrophysics Data System (ADS)

Hu, Quanyin; Katti, Prateek S.; Gu, Zhen

2014-10-01

Enzymes underpin physiological function and exhibit dysregulation in many disease-associated microenvironments and aberrant cell processes. Exploiting altered enzyme activity and expression for diagnostics, drug targeting, and drug release is tremendously promising. When combined with booming research in nanobiotechnology, enzyme-responsive nanomaterials used for controlled drug release have achieved significant development and have been studied as an important class of drug delivery strategies in nanomedicine. In this review, we describe enzymes such as proteases, phospholipases and oxidoreductases that serve as delivery triggers. Subsequently, we explore recently developed enzyme-responsive nanomaterials with versatile applications for extracellular and intracellular drug delivery. We conclude by discussing future opportunities and challenges in this area.

AND logic-like pH- and light-dual controlled drug delivery by surface modified mesoporous silica nanoparticles.

PubMed

Zhao, Junwei; He, Zhaoshuai; Li, Biao; Cheng, Tanyu; Liu, Guohua

2017-04-01

Recently, the controlled drug delivery system has become a potential platform for biomedical application. Herein, we developed a pH and light-dual controlled cargo release system exhibiting AND logic based on MCM-41 mesoporous silica nanoparticles, which was surface modified using β-cyclodextrin (β-CD) with imine bond and azobenzene derivative. The complex of β-CD and azobenzene derivative effectively blocked the cargo delivery in pH=7.0 phosphate buffered saline (PBS) solution without 365nm UV light irradiation. The cargo was fully released when both factors of acidic environment (pH=5.0 PBS) and 365nm UV light irradiation were satisfied, meanwhile only very little cargo was delivered if one factor was satisfied. The result also demonstrates that the opening/closing of the gate and the release of the cargo in small portions can be controlled. Copyright © 2016 Elsevier B.V. All rights reserved.

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

Controlled drug delivery through a novel PEG hydrogel encapsulated silica aerogel system.

PubMed

Giray, Seda; Bal, Tuğba; Kartal, Ayse M; Kızılel, Seda; Erkey, Can

2012-05-01

A novel composite material consisting of a silica aerogel core coated by a poly(ethylene) glycol (PEG) hydrogel was developed. The potential of this novel composite as a drug delivery system was tested with ketoprofen as a model drug due to its solubility in supercritical carbon dioxide. The results indicated that both drug loading capacity and drug release profiles could be tuned by changing hydrophobicity of aerogels, and that drug loading capacity increased with decreased hydrophobicity, while slower release rates were achieved with increased hydrophobicity. Furthermore, higher concentration of PEG diacrylate in the prepolymer solution of the hydrogel coating delayed the release of the drug which can be attributed to the lower permeability at higher PEG diacrylate concentrations. The novel composite developed in this study can be easily implemented to achieve the controlled delivery of various drugs and/or proteins for specific applications. Copyright © 2012 Wiley Periodicals, Inc.

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.

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.

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.

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.

Development of a multi-layered vaginal tablet containing dapivirine, levonorgestrel and acyclovir for use as a multipurpose prevention technology.

PubMed

McConville, Christopher; Major, Ian; Devlin, Brid; Brimer, Andrew

2016-07-01

Multipurpose prevention technologies (MPTs) are preferably single dosage forms designed to simultaneously address multiple sexual and reproductive health needs, such as unintended pregnancy, HIV infection and other sexually transmitted infections (STIs). This manuscript describes the development of a range of multi-layered vaginal tablets, with both immediate and sustained release layers capable of delivering the antiretroviral drug dapivirine, the contraceptive hormone levonorgestrel, and the anti-herpes simplex virus drug acyclovir at independent release rates from a single dosage form. Depending on the design of the tablet in relation to the type (immediate or sustained release) or number of layers, the dose of each drug could be individually controlled. For example one tablet design was able to provide immediate release of all three drugs, while another tablet design was able to provide immediate release of both acyclovir and levonorgestrel, while providing sustained release of Dapivirine for up to 8h. A third tablet design was able to provide immediate release of both acyclovir and levonorgestrel, a large initial burst of Dapivirine, followed by sustained release of Dapivirine for up to 8h. All of the tablets passed the test for friability with a percent friability of less than 1%. The hardness of all tablet designs was between 115 and 153N, while their drug content met the European Pharmacopeia 2.9.40 Uniformity of Dosage units acceptance value at levels 1 and 2. Finally, the accelerated stability of all three actives was significantly enhanced in comparison with a mixed drug control. Copyright © 2016 Elsevier B.V. All rights reserved.

Development of immature tiger-fly Coenosia attenuata (Stein) reared on larvae of the fungus gnat Bradysia impatiens (Johannsen) in coir substrate

USDA-ARS?s Scientific Manuscript database

The ability to rear a beneficial predatory insect is often required for its use in inoculative releases for classical biological control applications. However, affordable mass production is required before a beneficial predatory insect will be commercialized for large scale repetitive releases. The...

Polyurethane intravaginal ring for controlled delivery of dapivirine, a nonnucleoside reverse transcriptase inhibitor of HIV-1.

PubMed

Gupta, Kavita M; Pearce, Serena M; Poursaid, Azadeh E; Aliyar, Hyder A; Tresco, Patrick A; Mitchnik, Mark A; Kiser, Patrick F

2008-10-01

Women-controlled methods for prevention of male-to-female sexual transmission of HIV-1 are urgently needed. Providing inhibitory concentrations of HIV-1 reverse transcriptase inhibitors to impede the replication of the virus in the female genital tissue offers a mechanism for prophylaxis of HIV-1. To this end, an intravaginal ring device that can provide long duration delivery of dapivirine, a nonnucleoside reverse transcriptase inhibitor of HIV-1, was developed utilizing a medical-grade polyether urethane. Monolithic intravaginal rings were fabricated and sustained release with cumulative flux linear with time was demonstrated under sink conditions for a period of 30 days. The release rate was directly proportional to the amount of drug loaded. Another release study conducted for a week utilizing liposome dispersions as sink conditions, to mimic the partitioning of dapivirine into vaginal tissue, also demonstrated release rates constant with time. These results qualify polyether urethanes for development of intravaginal rings for sustained delivery of microbicidal agents. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association

Development of CNC prototype for the characterization of the nanoparticle release during physical manipulation of nanocomposites.

PubMed

Gendre, Laura; Marchante, Veronica; Abhyankar, Hrushikesh A; Blackburn, Kim; Temple, Clive; Brighton, James L

2016-01-01

This work focuses on the release of nanoparticles from commercially used nanocomposites during machining operations. A reliable and repeatable method was developed to assess the intentionally exposure to nanoparticles, in particular during drilling. This article presents the description and validation of results obtained from a new prototype used for the measurement and monitoring of nanoparticles in a controlled environment. This methodology was compared with the methodologies applied in other studies. Also, some preliminary experiments on drilling nanocomposites are included. Size, shape and chemical composition of the released nanoparticles were investigated in order to understand their hazard potential. No significant differences were found in the amount of nanoparticles released between samples with and without nanoadditives. Also, no chemical alteration was observed between the dust generated and the bulk material. Finally, further developments of the prototype are proposed.

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.

An in situ-forming phospholipid-based phase transition gel prolongs the duration of local anesthesia for ropivacaine with minimal toxicity.

PubMed

Li, Hanmei; Liu, Tao; Zhu, Yuxuan; Fu, Qiang; Wu, Wanxia; Deng, Jie; Lan, Li; Shi, Sanjun

2017-08-01

An injectable, phospholipid-based phase transition gel (PPTG) has been developed for prolonging the release of ropivacaine (RO) for local anesthesia. PPTG was prepared by mixing phospholipids, medium-chain triglyceride and ethanol. Prior to injection, the PPTG is in a sol state with low viscosity. After subcutaneous injection, the PPTG rapidly forms a gel in situ, which acts as a drug release depot as verified by in vitro release profiles and in vivo pharmacokinetics. Administering RO-PPTG to rats led to a significantly smaller initial burst release than administering RO solution or RO base suspension. Nerve blockade in guinea pigs lasted 3-fold longer after injection of RO-PPTG than after injection of RO solution. RO-PPTG showed good biocompatibility and excellent degradability in vivo. These results suggest that this PPTG-based depot system may be useful for sustained release of local anesthetics to prolong analgesia without causing systemic toxicity. The sustained release of local anesthetics at the surgical site after a single injection is the optimal method to control post-surgical pain. In situ forming implant is an attractive alternative for the sustained release of local anesthetics. However, its practical use is highly limited by certain drawbacks including high viscosity, involved toxic organic solvents and fast drug release. To date, phospholipids-based phase transition gel (PPTG) is emerging for clinical development because of the non-toxicity, biocompatibility and ready availability of phospholipids in body. Thus, we present a novel strategy for sustained release of local anesthetics to control post-surgical pain based on PPTG, which showed a prolonged duration of nerve blockade and excellent biocompatibility. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

NIR-driven Smart Theranostic Nanomedicine for On-demand Drug Release and Synergistic Antitumour Therapy.

PubMed

Zhao, Pengfei; Zheng, Mingbin; Luo, Zhenyu; Gong, Ping; Gao, Guanhui; Sheng, Zonghai; Zheng, Cuifang; Ma, Yifan; Cai, Lintao

2015-09-24

Smart nanoparticles (NPs) that respond to external and internal stimulations have been developing to achieve optimal drug release in tumour. However, applying these smart NPs to attain high antitumour performance is hampered by limited drug carriers and inefficient spatiotemporal control. Here we report a noninvasive NIR-driven, temperature-sensitive DI-TSL (DOX/ICG-loaded temperature sensitive liposomes) co-encapsulating doxorubicin (DOX) and indocyanine green (ICG). This theranostic system applies thermo-responsive lipid to controllably release drug, utilizes the fluorescence (FL) of DOX/ICG to real-time trace the distribution of NPs, and employs DOX/ICG to treat cancer by chemo/photothermal therapy. DI-TSL exhibits uniform size distribution, excellent FL/size stability, enhanced response to NIR-laser, and 3 times increased drug release through laser irradiation. After endocytosis by MCF-7 breast adenocarcinoma cells, DI-TSL in cellular endosomes can cause hyperthermia through laser irradiation, then endosomes are disrupted and DI-TSL 'opens' to release DOX simultaneously for increased cytotoxicity. Furthermore, DI-TSL shows laser-controlled release of DOX in tumour, enhanced ICG and DOX retention by 7 times and 4 times compared with free drugs. Thermo-sensitive DI-TSL manifests high efficiency to promote cell apoptosis, and completely eradicate tumour without side-effect. DI-TSL may provide a smart strategy to release drugs on demand for combinatorial cancer therapy.

NIR-driven Smart Theranostic Nanomedicine for On-demand Drug Release and Synergistic Antitumour Therapy

NASA Astrophysics Data System (ADS)

Zhao, Pengfei; Zheng, Mingbin; Luo, Zhenyu; Gong, Ping; Gao, Guanhui; Sheng, Zonghai; Zheng, Cuifang; Ma, Yifan; Cai, Lintao

2015-09-01

Smart nanoparticles (NPs) that respond to external and internal stimulations have been developing to achieve optimal drug release in tumour. However, applying these smart NPs to attain high antitumour performance is hampered by limited drug carriers and inefficient spatiotemporal control. Here we report a noninvasive NIR-driven, temperature-sensitive DI-TSL (DOX/ICG-loaded temperature sensitive liposomes) co-encapsulating doxorubicin (DOX) and indocyanine green (ICG). This theranostic system applies thermo-responsive lipid to controllably release drug, utilizes the fluorescence (FL) of DOX/ICG to real-time trace the distribution of NPs, and employs DOX/ICG to treat cancer by chemo/photothermal therapy. DI-TSL exhibits uniform size distribution, excellent FL/size stability, enhanced response to NIR-laser, and 3 times increased drug release through laser irradiation. After endocytosis by MCF-7 breast adenocarcinoma cells, DI-TSL in cellular endosomes can cause hyperthermia through laser irradiation, then endosomes are disrupted and DI-TSL ‘opens’ to release DOX simultaneously for increased cytotoxicity. Furthermore, DI-TSL shows laser-controlled release of DOX in tumour, enhanced ICG and DOX retention by 7 times and 4 times compared with free drugs. Thermo-sensitive DI-TSL manifests high efficiency to promote cell apoptosis, and completely eradicate tumour without side-effect. DI-TSL may provide a smart strategy to release drugs on demand for combinatorial cancer therapy.

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.

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

PubMed

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

2017-04-01

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

Novel strategy for prevention of esophageal stricture after endoscopic surgery.

PubMed

Mizutani, Taro; Tadauchi, Akimitsu; Arinobe, Manabu; Narita, Yuji; Kato, Ryuji; Niwa, Yasumasa; Ohmiya, Naoki; Itoh, Akihiro; Hirooka, Yoshiki; Honda, Hiroyuki; Ueda, Minoru; Goto, Hidemi

2010-01-01

Recently, novel endoscopic surgery, including endoscopic submucosal dissection (ESD), was developed to resect a large superficial gastrointestinal cancer. However, circumferential endoscopic surgery in the esophagus can lead to esophageal stricture that affects the patient's quality of life. This major complication is caused by scar formation, and develops during the two weeks after endoscopic surgery. We hypothesized that local administration of a controlled release anti-scarring agent can prevent esophageal stricture after endoscopic surgery. The aims of this study were to develop an endoscopically injectable anti-scarring drug delivery system, and to verify the efficacy of our strategy to prevent esophageal stricture. We focused on 5-Fluorouracil (5-FU) as an anti-scarring agent, which has already been shown to be effective not only for treatment of cancers, but also for treatment of hypertrophic skin scars. 5-FU was encapsulated by liposome, and then mixed with injectable 2% atelocollagen (5FLC: 5FU-liposome-collagen) to achieve sustained release. An in vitro 5-FU releasing test from 5FLC was performed using high-performance liquid chromatography (HPLC). Inhibition of cell proliferation was investigated using normal human dermal fibroblast cells (NHDF) with 5FLC. In addition, a canine esophageal mucosal resection was carried out, and 5FLC was endoscopically injected into the ulcer immediately after the operation, and compared with a similar specimen injected with saline as a control. 5-FU was gradually released from 5FLC for more than 2 weeks in vitro. The solution of 5-FU released from 5FLC inhibited NHDF proliferation more effectively than 5-FU alone. In the canine model, no findings of stricture were observed in the 5FLC-treated dog at 4 weeks after the operation and no vomiting occurred. In contrast, marked esophageal strictures were observed with repeated vomiting in the control group. Submucosal fibrosis was markedly reduced histologically in the 5FLC-treated dog compared with the control. 5FLC showed sustained release of 5-FU and decreased cell proliferation in vitro. The clinically relevant canine model demonstrated that local endoscopic injection of 5FLC can prevent post-operative esophageal stricture. These results suggest that our strategy may be useful for preventing post-operative esophageal stricture.

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.

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.

Microporous silk fibroin scaffolds embedding PLGA microparticles for controlled growth factor delivery in tissue engineering.

PubMed

Wenk, Esther; Meinel, Anne J; Wildy, Sarah; Merkle, Hans P; Meinel, Lorenz

2009-05-01

The development of prototype scaffolds for either direct implantation or tissue engineering purposes and featuring spatiotemporal control of growth factor release is highly desirable. Silk fibroin (SF) scaffolds with interconnective pores, carrying embedded microparticles that were loaded with insulin-like growth factor I (IGF-I), were prepared by a porogen leaching protocol. Treatments with methanol or water vapor induced water insolubility of SF based on an increase in beta-sheet content as analyzed by FTIR. Pore interconnectivity was demonstrated by SEM. Porosities were in the range of 70-90%, depending on the treatment applied, and were better preserved when methanol or water vapor treatments were prior to porogen leaching. IGF-I was encapsulated into two different types of poly(lactide-co-glycolide) microparticles (PLGA MP) using uncapped PLGA (50:50) with molecular weights of either 14 or 35 kDa to control IGF-I release kinetics from the SF scaffold. Embedded PLGA MP were located in the walls or intersections of the SF scaffold. Embedment of the PLGA MP into the scaffolds led to more sustained release rates as compared to the free PLGA MP, whereas the hydrolytic degradation of the two PLGA MP types was not affected. The PLGA types used had distinct effects on IGF-I release kinetics. Particularly the supernatants of the lower molecular weight PLGA formulations turned out to release bioactive IGF-I. Our studies justify future investigations of the developed constructs for tissue engineering applications.

Chitosan nanoparticle based delivery systems for sustainable agriculture.

PubMed

Kashyap, Prem Lal; Xiang, Xu; Heiden, Patricia

2015-01-01

Development of technologies that improve food productivity without any adverse impact on the ecosystem is the need of hour. In this context, development of controlled delivery systems for slow and sustained release of agrochemicals or genetic materials is crucial. Chitosan has emerged as a valuable carrier for controlled delivery of agrochemicals and genetic materials because of its proven biocompatibility, biodegradability, non-toxicity, and adsorption abilities. The major advantages of encapsulating agrochemicals and genetic material in a chitosan matrix include its ability to function as a protective reservoir for the active ingredients, protecting the ingredients from the surrounding environment while they are in the chitosan domain, and then controlling their release, allowing them to serve as efficient gene delivery systems for plant transformation or controlled release of pesticides. Despite the great progress in the use of chitosan in the area of medical and pharmaceutical sciences, there is still a wide knowledge gap regarding the potential application of chitosan for encapsulation of active ingredients in agriculture. Hence, the present article describes the current status of chitosan nanoparticle-based delivery systems in agriculture, and to highlight challenges that need to be overcome. Copyright © 2015 Elsevier B.V. All rights reserved.

A new amoxicillin/clavulanate therapeutic system: preparation, in vitro and pharmacokinetic evaluation.

PubMed

Kerc, Janez; Opara, Jerneja

2007-04-20

A new peroral amoxicillin/clavulanate therapeutic system composed of immediate release tablet and controlled release floating capsule was developed and evaluated by in vivo bioavailability study. Pharmacokinetic (PK) parameters for amoxicillin and clavulanic acid of the new therapeutic systems: AUCt, AUCi, (AUCt/AUCi), Cmax, Tmax, kel, T(1/2) and additionally for amoxicillin T(4) and T(2) were calculated from the plasma levels. The study confirmed enhanced pharmacokinetic parameters of a newly developed therapeutic system containing 1500 mg of amoxicillin and 125 mg of clavulanic acid. Prolonged time over MIC of amoxicillin in relation to a regular immediate release amoxicillin/clavulanate formulation was confirmed.

Multi-Drug-Loaded Microcapsules with Controlled Release for Management of Parkinson's Disease.

PubMed

Baek, Jong-Suep; Choo, Chee Chong; Qian, Cheng; Tan, Nguan Soon; Shen, Zexiang; Loo, Say Chye Joachim

2016-07-01

Parkinson's disease (PD) is a progressive disease of the nervous system, and is currently managed through commercial tablets that do not sufficiently enable controlled, sustained release capabilities. It is hypothesized that a drug delivery system that provides controlled and sustained release of PD drugs would afford better management of PD. Hollow microcapsules composed of poly-l-lactide (PLLA) and poly (caprolactone) (PCL) are prepared through a modified double-emulsion technique. They are loaded with three PD drugs, i.e., levodopa (LD), carbidopa (CD), and entacapone (ENT), at a ratio of 4:1:8, similar to commercial PD tablets. LD and CD are localized in both the hollow cavity and PLLA/PCL shell, while ENT is localized in the PLLA/PCL shell. Release kinetics of hydrophobic ENT is observed to be relatively slow as compared to the other hydrophilic drugs. It is further hypothesized that encapsulating ENT into PCL as a surface coating onto these microcapsules can aid in accelerating its release. Now, these spray-coated hollow microcapsules exhibit similar release kinetics, according to Higuchi's rate, for all three drugs. The results suggest that multiple drug encapsulation of LD, CD, and ENT in gastric floating microcapsules could be further developed for in vivo evaluation for the management of PD. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Selection of PLA polymers for the development of injectable prilocaine controlled release microparticles: usefulness of thermal analysis.

PubMed

Bragagni, Marco; Beneitez, Cristina; Martín, Cristina; Hernán Pérez de la Ossa, Dolores; Mura, Paola Angela; Gil-Alegre, María Esther

2013-01-30

The use of injectable local anaesthetics for the treatment of severe postoperative pain is limited by the short duration of the painkilling effect. Pre-formulation studies were carried out for the development of an injectable microparticle formulation for controlled release of prilocaine, an amino-amide type local anaesthetic suitable for intravenous, subcutaneous and intramuscular administration. To the best of our knowledge, the encapsulation of prilocaine into microparticles has not been investigated yet. Three different poly-lactic-acid (PLA) polymers were separately employed for the preparation of the microparticles. Thermal analyses by differential scanning calorimetry (DSC) were carried out for the characterization of the raw materials, to assess the drug-polymer compatibility and miscibility, to investigate the effects of the production process on the components. Empty and prilocaine loaded microparticles were prepared by double emulsion method. All formulations were fully characterized in terms of drug content, morphology, size and in vitro drug release. The preliminary value of PRL solubility in the polymer material determined by DSC was evaluated and discussed as a predictive value for encapsulation efficiency and controlled release. DSC analysis turned out to be a usefulness tool for a fast polymer selection. Microparticles prepared with PLA R202 and R203S showed desirable characteristics for subcutaneous administration and could represent two promising formulations for the development of innovative pharmacological tools in the treatment of postoperative pain. Copyright © 2012 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.

Development of novel small molecules for imaging and drug release

NASA Astrophysics Data System (ADS)

Cao, Yanting

Small organic molecules, including small molecule based fluorescent probes, small molecule based drugs or prodrugs, and smart multifunctional fluorescent drug delivery systems play important roles in biological research, drug discovery, and clinical practices. Despite the significant progress made in these fields, the development of novel and diverse small molecules is needed to meet various demands for research and clinical applications. My Ph.D study focuses on the development of novel functional molecules for recognition, imaging and drug release. In the first part, a turn-on fluorescent probe is developed for the detection of intracellular adenosine-5'-triphosphate (ATP) levels based on multiplexing recognitions. Considering the unique and complicated structure of ATP molecules, a fluorescent probe has been implemented with improved sensitivity and selectivity due to two synergistic binding recognitions by incorporating of 2, 2'-dipicolylamine (Dpa)-Zn(II) for targeting of phospho anions and phenylboronic acid group for cis-diol moiety. The novel probe is able to detect intracellular ATP levels in SH-SY5Y cells. Meanwhile, the advantages of multiplexing recognition design concept have been demonstrated using two control molecules. In the second part, a prodrug system is developed to deliver multiple drugs within one small molecule entity. The prodrug is designed by using 1-(2-nitrophenyl)ethyl (NPE) as phototrigger, and biphenol biquaternary ammonium as the prodrug. With controlled photo activation, both DNA cross-linking agents mechlorethamine and o-quinone methide are delivered and released at the preferred site, leading to efficient DNA cross-links formation and cell death. The prodrug shows negligible cytotoxicity towards normal skin cells (Hekn cells) with and without UV activation, but displays potent activity towards cancer cells (HeLa cells) upon UV activation. The multiple drug release system may hold a great potential for practical application. In the last part, a new photo-initiated fluorescent anticancer prodrug for DNA alkylating agent mechlorethamine releasing and monitoring has been developed. The theranostic prodrug consists a photolabile NPE group, an inactive form of mechlorethamine and a nonfluorescent coumarin in one small molecule. It is demonstrated that the prodrug shows negligible cytotoxicity towards normal skin cells (Hekn cells) with and without UV activation, while the original parent drug mechlorethamine can be photocontrol-released and induces effective DNA cross-linking activity. Importantly, the drug release progress can be conveniently monitored by the 'off-on' fluorescence enhancement in cells. Moreover, the selective prodrug is not only cell permeable but also nuclear permeable. Therefore, the prodrug serves as a promising drug delivery system for spatiotemporal control release and monitoring of an anticancer drug to obtain the optimal treatment efficacy.

Recent Advances in Drug Eluting Stents

PubMed Central

Puranik, Amey S.; Dawson, Eileen R.; Peppas, Nicholas A.

2013-01-01

One of the most common medical interventions to reopen an occluded vessel is the implantation of a coronary stent. While this method of treatment is effective initially, restenosis, or the re-narrowing of the artery frequently occurs largely due to neointimal hyperplasia of smooth muscle cells. Drug eluting stents were developed in order to provide local, site-specific, controlled release of drugs that can inhibit neointima formation. By implementing a controlled release delivery system it may be possible to control the time release of the pharmacological factors and thus be able to bypass some of the critical events associated with stent hyperplasia and prevent the need for subsequent intervention. However, since the advent of first-generation drug eluting stents, long-term adverse effects have raised concerns regarding their safety. These limitations in safety and efficacy have triggered considerable research in developing biodegradable stents and more potent drug delivery systems. In this review, we shed light on the current state-of-the-art in drug eluting stents, problems related to them and highlight some of the ongoing research in this area. PMID:23117022

Preparation and Characterization of Ternary Antimicrobial Films of β-Cyclodextrin/Allyl Isothiocyanate/Polylactic Acid for the Enhancement of Long-Term Controlled Release

PubMed Central

Wang, Jinpeng; Qiu, Chao; Narsimhan, Ganesan; Jin, Zhengyu

2017-01-01

Allyl isothiocyanate (AITC) are natural essential oil components that have outstanding antimicrobial activities. However, low water solubility, high volatility, and easy degradation by heat, restricting their application in food packing industry. Development of the inclusion complex of β-cyclodextrin/AITC (β-CD/AITC) is a promising solution. Furthermore, the incorporation of β-CD/AITC complex into polylactic acid (PLA) films would be an attractive method to develop food antimicrobial materials. The aim of this study was to evaluate the enhancement in physicochemical properties, antimicrobial activities, and controlled release of β-CD/AITC from such films. The addition of β-CD/AITC significantly increased the flexibility and thermal stability of films. The Fourier transform infrared (FTIR) results revealed that the interactions between β-CD/AITC and PLA films occurred. The controlled release of AITC encapsulated in β-CD was significantly affected by relative humidity and temperature. The PLA films containing β-CD/AITC can be applied as an effective antimicrobial packing material for food and non-food applications. PMID:29053573

Modulation of cultured neural networks using neurotrophin release from hydrogel-coated microelectrode arrays

NASA Astrophysics Data System (ADS)

Jun, Sang Beom; Hynd, Matthew R.; Dowell-Mesfin, Natalie M.; Al-Kofahi, Yousef; Roysam, Badrinath; Shain, William; Kim, Sung June

2008-06-01

Polyacrylamide and poly(ethylene glycol) diacrylate hydrogels were synthesized and characterized for use as drug release and substrates for neuron cell culture. Protein release kinetics was determined by incorporating bovine serum albumin (BSA) into hydrogels during polymerization. To determine if hydrogel incorporation and release affect bioactivity, alkaline phosphatase was incorporated into hydrogels and a released enzyme activity determined using the fluorescence-based ELF-97 assay. Hydrogels were then used to deliver a brain-derived neurotrophic factor (BDNF) from hydrogels polymerized over planar microelectrode arrays (MEAs). Primary hippocampal neurons were cultured on both control and neurotrophin-containing hydrogel-coated MEAs. The effect of released BDNF on neurite length and process arborization was investigated using automated image analysis. An increased spontaneous activity as a response to the released BDNF was recorded from the neurons cultured on the top of hydrogel layers. These results demonstrate that proteins of biological interest can be incorporated into hydrogels to modulate development and function of cultured neural networks. These results also set the stage for development of hydrogel-coated neural prosthetic devices for local delivery of various biologically active molecules.

Timolol maleate release from hyaluronic acid-containing model silicone hydrogel contact lens materials.

PubMed

Korogiannaki, Myrto; Guidi, Giuliano; Jones, Lyndon; Sheardown, Heather

2015-09-01

This study was designed to assess the impact of a releasable wetting agent, such as hyaluronic acid (HA), on the release profile of timolol maleate (TM) from model silicone hydrogel contact lens materials. Polyvinylpyrrolidone (PVP) was used as an alternative wetting agent for comparison. The model lenses consisted of a hydrophilic monomer, either 2-hydroxyethyl methacrylate or N,N-dimethylacrylamide and a hydrophobic silicone monomer of methacryloxypropyltris (trimethylsiloxy) silane. The loading of the wetting and the therapeutic agent occurred during the synthesis of the silicone hydrogels through the method of direct entrapment. The developed materials were characterized by minimal changes in the water uptake, while lower molecular weight of HA improved their surface wettability. The transparency of the examined silicone hydrogels was found to be affected by the miscibility of the wetting agent in the prepolymer mixture as well as the composition of the developed silicone hydrogels. Sustained release of TM from 4 to 14 days was observed, with the drug transport occurring presumably through the hydrophilic domains of the silicone hydrogels. The release profile was strongly dependent on the hydrophilic monomer composition, the distribution of hydrophobic (silane) domains, and the affinity of the therapeutic agent for the silicone hydrogel matrix. Noncovalent entrapment of the wetting agent did not change the in vitro release duration and kinetics of TM, however the drug release profile was found to be controlled by the simultaneous release of TM and HA or PVP. In the case of HA, depending on the HA:drug ratio, the release rate was decreased and controlled by the release of HA, likely due to electrostatic interactions between protonated TM and anionic HA. Overall, partitioning of the drug within the hydrophilic domains of the silicone hydrogels as well as interactions with the wetting agent determined the drug release profile. © The Author(s) 2015.

Development of a CO2 -releasing coformulation based on starch, Saccharomyces cerevisiae and Beauveria bassiana attractive towards western corn rootworm larvae.

PubMed

Vemmer, Marina; Schumann, Mario; Beitzen-Heineke, Wilhelm; French, Bryan W; Vidal, Stefan; Patel, Anant V

2016-11-01

CO 2 is known as an attractant for many soil-dwelling pests. To implement an attract-and-kill strategy for soil pest control, CO 2 -emitting formulations need to be developed. The aim of the present work was to develop a slow-release bead system in order to bridge the gap between application and hatching of western corn rootworm larvae. We compared different Ca-alginate beads containing Saccharomyces cerevisiae for their potential to release CO 2 over a period of several weeks. The addition of starch improved CO 2 release, resulting in significantly higher CO 2 concentrations in soil for at least 4 weeks. The missing amylase activity was compensated for either by microorganisms present in the soil or by coencapsulation of Beauveria bassiana. Formulations containing S. cerevisiae, starch and B. bassiana were attractive for western corn rootworm larvae within the first 4 h following exposure; however, when considering the whole testing period, the maize root systems remained more attractive for the larvae. Coencapsulation of S. cerevisiae, starch and B. bassiana is a promising approach for the development of attractive formulations for soil applications. For biological control strategies, the attractiveness needs to be increased by phagostimuli to extend contact between larvae and the entomopathogenic fungus growing out of these formulations. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

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.

Microencapsulation of aspartame by double emulsion followed by complex coacervation to provide protection and prolong sweetness.

PubMed

Rocha-Selmi, Glaucia A; Bozza, Fernanda T; Thomazini, Marcelo; Bolini, Helena M A; Fávaro-Trindade, Carmen S

2013-08-15

The objective of this work was to microencapsulate aspartame by double emulsion followed by complex coacervation, aiming to protect it and control its release. Six treatments were prepared using sunflower oil to prepare the primary emulsion and gelatin and gum Arabic as the wall materials. The microcapsules were evaluated structurally with respect to their sorption isotherms and release into water (36°C and 80°C). The microcapsules were multinucleated, not very water-soluble or hygroscopic and showed reduced rates of equilibrium moisture content and release at both temperatures. FTIR confirmed complexation between the wall materials and the intact nature of aspartame. The results indicated it was possible to encapsulate aspartame with the techniques employed and that these protected the sweetener even at 80°C. The reduced solubility and low release rates indicated the enormous potential of the vehicle developed in controlling the release of the aspartame into the food, thus prolonging its sweetness. Copyright © 2013 Elsevier Ltd. All rights reserved.

The effect of the molecular orientation on the release of antimicrobial substances from uniaxially drawn polymer matrixes.

PubMed

Iconomopoulou, S M; Voyiatzis, G A

2005-03-21

A new method of controlled release of low molecular weight biocides incorporated in polymer matrixes is described. The molecular orientation of uniaxially drawn biocide doped polymer films is suggested as a significant parameter for controlled release monitoring. Triclosan, a well-established widespread antibacterial agent, has been incorporated into high density polyethylene (HDPE) films that have been subsequently uniaxially drawn at different draw ratios. The molecular orientation developed was estimated utilizing polarized mu-Raman spectra. Biocide incorporated polymer films, drawn at different draw ratios, have been immersed in ethanol-water solutions (EtOH) and in physiological saline. The release of Triclosan out of the polymer matrix was probed with UV-Vis absorption spectroscopy for a period of time up to 15 months. In all cases, although the film surface of the drawn samples exposed to the liquid solution was higher than the undrawn one, the relevant release rate from the drawn specimens was lower than the non-stretched samples depending on the molecular orientation developed during the drawing process. A note is made of the fact that no significant molecular orientation relaxation of the polyethylene films has been observed even after such a long time of immersion of the drawn films in the liquid solutions.

Methylphenidate and dexmethylphenidate formulations for children with attention-deficit/hyperactivity disorder.

PubMed

Sugrue, David; Bogner, Robin; Ehret, Megan J

2014-07-15

Current literature on the safety and efficacy of various intermediate- and long-acting preparations of methylphenidate and dexmethylphenidate for pediatric attention-deficit/hyperactivity disorder (ADHD) is reviewed. The efficacy of methylphenidate in controlling ADHD symptoms is firmly established. Given the drug's relatively short half-life in pediatric patients (about 2.5 hours), a number of intermediate- and long-acting products have been developed; these extended-release methylphenidate products provide the same efficacy as immediate-release (IR) formulations, with the convenience of less frequent dosing. Intermediate-acting methylphenidate preparations have effects lasting as long as 8 hours, but peak concentrations are not attained for up to 5 hours, and many patients may require twice-daily dosing. Long-acting methylphenidate products developed to address these challenges include a controlled-release tablet and bimodal-delivery capsules containing mixtures of IR and extended-release beads (durations of effect, 8-12 hours). Options for patients with difficulty swallowing tablets or capsules include a once-daily transdermal delivery system and a once-daily liquid formulation. Dexmethylphenidate (the more pharmacologically active d-isomer of racemic methylphenidate) can provide efficacy comparable to that of IR methylphenidate at half the dose; an extended-release form of dexmethylphenidate can provide less fluctuation in peak and trough concentrations than the IR form. Methylphenidate and dexmethylphenidate products in capsule form can be opened and sprinkled on applesauce. The various formulations of IR and intermediate- and extended-release methylphenidate and dexmethylphenidate can be useful options in satisfying patients' individual needs in the management of ADHD. All are equally efficacious in controlling ADHD symptoms. Copyright © 2014 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Synthesis and characterization of mesoporous magnetic nanocomposites wrapped with chitosan gatekeepers for pH-sensitive controlled release of doxorubicin.

PubMed

Wu, Juan; Jiang, Wei; Shen, Yewen; Jiang, Wei; Tian, Renbing

2017-01-01

Multifunctional nanocarriers based on the Fe 3 O 4 nanoparticles core and mesoporous silica shell (mSiO 2 ) were synthesized for controlled drug release through magnetic targeting and pH-sensitive performances. The developed Fe 3 O 4 @mSiO 2 nanocarriers exhibited a suitable size (63nm) and good magnetic responsibility, doxorubicin (DOX) could be successfully loaded into the mesoporous of Fe 3 O 4 @mSiO 2 via electrostatic interaction, and the drug loading content and loading efficiency are 29.3% and 93.6%, respectively. The chitosan (CS) was employed to wrap the Fe 3 O 4 @mSiO 2 -DOX as the blocking agent to inhibit premature drug release, and the final CS/Fe 3 O 4 @mSiO 2 -DOX exhibited excellent pH-sensitivity, 86.1% DOX was released within 48h at pH4.0. Furthermore, all the release behaviors fit the Higuchi model very well and a purely diffusion-controlled process played a major role on DOX release from CS/Fe 3 O 4 @mSiO 2 -DOX. In addition, MTT assays in human liver hepatocellular carcinoma cells (HepG2) demonstrated that the CS/Fe 3 O 4 @mSiO 2 -DOX had high anti-tumor activity, while the Fe 3 O 4 @mSiO 2 nanocarriers were practically non-toxic. Thus, our results revealed that the CS/Fe 3 O 4 @mSiO 2 -DOX could play an important role in the development of intracellular delivery nanodevices for cancer therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed

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

2006-02-17

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

Influence of 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.

Controlled release systems containing solid dispersions: strategies and mechanisms.

PubMed

Tran, Phuong Ha-Lien; Tran, Thao Truong-Dinh; Park, Jun Bom; Lee, Beom-Jin

2011-10-01

In addition to a number of highly soluble drugs, most new chemical entities under development are poorly water-soluble drugs generally characterized by an insufficient dissolution rate and a small absorption window, leading to the low bioavailability. Controlled-release (CR) formulations have several potential advantages over conventional dosage forms, such as providing a uniform and prolonged therapeutic effect to improve patient compliance, reducing the frequency of dosing, minimizing the number of side effects, and reducing the strength of the required dose while increasing the effectiveness of the drug. Solid dispersions (SD) can be used to enhance the dissolution rate of poorly water-soluble drugs and to sustain the drug release by choosing an appropriate carrier. Thus, a CR-SD comprises both functions of SD and CR for poorly water-soluble drugs. Such CR dosage forms containing SD provide an immediately available dose for an immediate action followed by a gradual and continuous release of subsequent doses to maintain the plasma concentration of poorly water-soluble drugs over an extended period of time. This review aims to summarize all currently known aspects of controlled release systems containing solid dispersions, focusing on the preparation methods, mechanisms of action and characterization of physicochemical properties of the system.

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 Strategies for Bone, Cartilage, and Osteochondral Engineering—Part II: Challenges on the Evolution from Single to Multiple Bioactive Factor Delivery

PubMed Central

Santo, Vítor E.; Mano, João F.; Reis, Rui L.

2013-01-01

The development of controlled release systems for the regeneration of bone, cartilage, and osteochondral interface is one of the hot topics in the field of tissue engineering and regenerative medicine. However, the majority of the developed systems consider only the release of a single growth factor, which is a limiting step for the success of the therapy. More recent studies have been focused on the design and tailoring of appropriate combinations of bioactive factors to match the desired goals regarding tissue regeneration. In fact, considering the complexity of extracellular matrix and the diversity of growth factors and cytokines involved in each biological response, it is expected that an appropriate combination of bioactive factors could lead to more successful outcomes in tissue regeneration. In this review, the evolution on the development of dual and multiple bioactive factor release systems for bone, cartilage, and osteochondral interface is overviewed, specifically the relevance of parameters such as dosage and spatiotemporal distribution of bioactive factors. A comprehensive collection of studies focused on the delivery of bioactive factors is also presented while highlighting the increasing impact of platelet-rich plasma as an autologous source of multiple growth factors. PMID:23249320

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.

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.

A simple, cost-effective emitter for controlled release of fish pheromones: development, testing, and application to management of the invasive sea lamprey

USGS Publications Warehouse

Wagner, Michael C.; Hanson, James E.; Meckley, Trevor D.; Johnson, Nicholas; Bals, Jason D.

2018-01-01

Semiochemicals that elicit species-specific attraction or repulsion have proven useful in the management of terrestrial pests and hold considerable promise for control of nuisance aquatic species, particularly invasive fishes. Because aquatic ecosystems are typically large and open, use of a semiochemical to control a spatially dispersed invader will require the development of a cost-effective emitter that is easy to produce, environmentally benign, inexpensive, and controls the release of the semiochemical without altering its structure. We examined the release properties of five polymers, and chose polyethylene glycol (PEG) as the best alternative. In a series of laboratory and field experiments, we examined the response of the invasive sea lamprey to PEG, and to a partial sex pheromone emitted from PEG that has proven effective as a trap bait to capture migrating sea lamprey prior to spawning. Our findings confirm that the sea lamprey does not behaviorally respond to PEG, and that the attractant response to the pheromone component was conserved when emitted from PEG. Further, we deployed the pheromone-PEG emitters as trap bait during typical control operations in three Great Lakes tributaries, observing similar improvements in trap performance when compared to a previous study using mechanically pumped liquid pheromone. Finally, the polymer emitters tended to dissolve unevenly in high flow conditions. We demonstrate that housing the emitter stabilizes the dissolution rate at high water velocity. We conclude the performance characteristics of PEG emitters to achieve controlled-release of a semiochemical are sufficient to recommend its use in conservation and management activities related to native and invasive aquatic organisms.

A simple, cost-effective emitter for controlled release of fish pheromones: Development, testing, and application to management of the invasive sea lamprey

PubMed Central

Meckley, Trevor D.; Johnson, Nicholas S.; Bals, Jason D.

2018-01-01

Semiochemicals that elicit species-specific attraction or repulsion have proven useful in the management of terrestrial pests and hold considerable promise for control of nuisance aquatic species, particularly invasive fishes. Because aquatic ecosystems are typically large and open, use of a semiochemical to control a spatially dispersed invader will require the development of a cost-effective emitter that is easy to produce, environmentally benign, inexpensive, and controls the release of the semiochemical without altering its structure. We examined the release properties of five polymers, and chose polyethylene glycol (PEG) as the best alternative. In a series of laboratory and field experiments, we examined the response of the invasive sea lamprey to PEG, and to a partial sex pheromone emitted from PEG that has proven effective as a trap bait to capture migrating sea lamprey prior to spawning. Our findings confirm that the sea lamprey does not behaviorally respond to PEG, and that the attractant response to the pheromone component was conserved when emitted from PEG. Further, we deployed the pheromone-PEG emitters as trap bait during typical control operations in three Great Lakes tributaries, observing similar improvements in trap performance when compared to a previous study using mechanically pumped liquid pheromone. Finally, the polymer emitters tended to dissolve unevenly in high flow conditions. We demonstrate that housing the emitter stabilizes the dissolution rate at high water velocity. We conclude the performance characteristics of PEG emitters to achieve controlled-release of a semiochemical are sufficient to recommend its use in conservation and management activities related to native and invasive aquatic organisms. PMID:29897927

A simple, cost-effective emitter for controlled release of fish pheromones: Development, testing, and application to management of the invasive sea lamprey.

PubMed

Wagner, C Michael; Hanson, James E; Meckley, Trevor D; Johnson, Nicholas S; Bals, Jason D

2018-01-01

Semiochemicals that elicit species-specific attraction or repulsion have proven useful in the management of terrestrial pests and hold considerable promise for control of nuisance aquatic species, particularly invasive fishes. Because aquatic ecosystems are typically large and open, use of a semiochemical to control a spatially dispersed invader will require the development of a cost-effective emitter that is easy to produce, environmentally benign, inexpensive, and controls the release of the semiochemical without altering its structure. We examined the release properties of five polymers, and chose polyethylene glycol (PEG) as the best alternative. In a series of laboratory and field experiments, we examined the response of the invasive sea lamprey to PEG, and to a partial sex pheromone emitted from PEG that has proven effective as a trap bait to capture migrating sea lamprey prior to spawning. Our findings confirm that the sea lamprey does not behaviorally respond to PEG, and that the attractant response to the pheromone component was conserved when emitted from PEG. Further, we deployed the pheromone-PEG emitters as trap bait during typical control operations in three Great Lakes tributaries, observing similar improvements in trap performance when compared to a previous study using mechanically pumped liquid pheromone. Finally, the polymer emitters tended to dissolve unevenly in high flow conditions. We demonstrate that housing the emitter stabilizes the dissolution rate at high water velocity. We conclude the performance characteristics of PEG emitters to achieve controlled-release of a semiochemical are sufficient to recommend its use in conservation and management activities related to native and invasive aquatic organisms.

Development of drug-loaded polymer microcapsules for treatment of epilepsy.

PubMed

Chen, Yu; Gu, Qi; Yue, Zhilian; Crook, Jeremy M; Moulton, Simon E; Cook, Mark J; Wallace, Gordon G

2017-09-26

Despite significant progress in developing new drugs for seizure control, epilepsy still affects 1% of the global population and is drug-resistant in more than 30% of cases. To improve the therapeutic efficacy of epilepsy medication, a promising approach is to deliver anti-epilepsy drugs directly to affected brain areas using local drug delivery systems. The drug delivery systems must meet a number of criteria, including high drug loading efficiency, biodegradability, neuro-cytocompatibility and predictable drug release profiles. Here we report the development of fibre- and sphere-based microcapsules that exhibit controllable uniform morphologies and drug release profiles as predicted by mathematical modelling. Importantly, both forms of fabricated microcapsules are compatible with human brain derived neural stem cells and differentiated neurons and neuroglia, indicating clinical compliance for neural implantation and therapeutic drug delivery.

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

Tough Composite Hydrogels with High Loading and Local Release of Biological Drugs.

PubMed

Li, Jianyu; Weber, Eckhard; Guth-Gundel, Sabine; Schuleit, Michael; Kuttler, Andreas; Halleux, Christine; Accart, Nathalie; Doelemeyer, Arno; Basler, Anne; Tigani, Bruno; Wuersch, Kuno; Fornaro, Mara; Kneissel, Michaela; Stafford, Alexander; Freedman, Benjamin R; Mooney, David J

2018-05-01

Hydrogels are under active development for controlled drug delivery, but their clinical translation is limited by low drug loading capacity, deficiencies in mechanical toughness and storage stability, and poor control over the drug release that often results in burst release and short release duration. This work reports a design of composite clay hydrogels, which simultaneously achieve a spectrum of mechanical, storage, and drug loading/releasing properties to address the critical needs from translational perspectives. The clay nanoparticles provide large surface areas to adsorb biological drugs, and assemble into microparticles that are physically trapped within and toughen hydrogel networks. The composite hydrogels demonstrate feasibility of storage, and extended release of large quantities of an insulin-like growth factor-1 mimetic protein (8 mg mL -1 ) over four weeks. The release rate is primarily governed by ionic exchange and can be upregulated by low pH, which is typical for injured tissues. A rodent model of Achilles tendon injury is used to demonstrate that the composite hydrogels allow for highly extended and localized release of biological drugs in vivo, while demonstrating biodegradation and biocompatibility. These attributes make the composite hydrogel a promising system for drug delivery and regenerative medicine. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Methotrexate inhibits neutrophil function by stimulating adenosine release from connective tissue cells

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

Cronstein, B.N.; Eberle, M.A.; Levin, R.I.

1991-03-15

Although commonly used to control a variety of inflammatory diseases, the mechanism of action of a low dose of methotrexate remains a mystery. Methotrexate accumulates intracellularly where it may interfere with purine metabolism. Therefore, the authors determined whether a 48-hr pretreatment with methotrexate affected adenosine release from ({sup 14}C)adenine-labeled human fibroblasts and umbilical vein endothelial cells. Methotrexate significantly increased adenosine release by fibroblasts. The effect of methotrexate on adenosine release was not due to cytotoxicity since cells treated with maximal concentrations of methotrexate took up ({sup 14}C)adenine and released {sup 14}C-labeled purine (a measure of cell injury) in a mannermore » identical to control cells. Methotrexate treatment of fibroblasts dramatically inhibited adherence to fibroblasts by both unstimulated neutrophils and stimulated neutrophils. One hypothesis that explains the effect of methotrexate on adenosine release is that, by inhibition of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase, methotrexate induces the accumulation of AICAR, the nucleoside precursor of which has previously been shown to cause adenosine release from ischemic cardiac tissue. The observation that the antiinflammatory actions of methotrexate are due to the capacity of methotrexate to induce adenosine release may form the basis for the development of an additional class of antiinflammatory drugs.« less

pH Responsive Microcapsules for Corrosion Control

NASA Technical Reports Server (NTRS)

Calle, Luz Marina; Li, Wenyan; Muehlberg, Aaron; Boraas, Samuel; Webster, Dean; JohnstonGelling, Victoria; Croll, Stuart; Taylor, S Ray; Contu, Francesco

2008-01-01

The best coatings for corrosion protection provide not only barriers to the environment, but also a controlled release of a corrosion inhibitor, as demanded by the presence of corrosion or mechanical damage. NASA has developed pH sensitive microcapsules (patent pending) that can release their core contents when corrosion starts. The objectives of the research presented here were to encapsulate non-toxic corrosion inhibitors, to incorporate the encapsulated inhibitors into paint formulations, and to test the ability of the paints to control corrosion. Results showed that the encapsulated corrosion inhibitors, specifically Ce(NO3)3 , are effective to control corrosion over long periods of time when incorporated at relatively high pigment volume concentrations into a paint formulation.

New multivariable capabilities of the INCA program

NASA Technical Reports Server (NTRS)

Bauer, Frank H.; Downing, John P.; Thorpe, Christopher J.

1989-01-01

The INteractive Controls Analysis (INCA) program was developed at NASA's Goddard Space Flight Center to provide a user friendly, efficient environment for the design and analysis of control systems, specifically spacecraft control systems. Since its inception, INCA has found extensive use in the design, development, and analysis of control systems for spacecraft, instruments, robotics, and pointing systems. The (INCA) program was initially developed as a comprehensive classical design analysis tool for small and large order control systems. The latest version of INCA, expected to be released in February of 1990, was expanded to include the capability to perform multivariable controls analysis and design.

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.

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.

Controlled drug release by polymer dissolution. II: Enzyme-mediated delivery device.

PubMed

Heller, J; Trescony, P V

1979-07-01

A novel, closed-loop drug delivery system was developed where the presence or absence of an external compound controls drug delivery from a bioerodible polymer. In the described delivery system, hydrocortisone was incorporated into a n-hexyl half-ester of a methyl vinyl ehter-maleic anhydride copolymer, and the polymer-drug mixture was fabricated into disks. These disks were then coated with a hydrogel containing immobilized urease. In a medium of constant pH and in the absence of external urea, the hydrocortisone release was that normally expected for that polymer at the given pH. With external urea, ammonium bicarbonate and ammonium hydroxide were generated within the hydrogel, which accelerated polymer erosion and drug release. The drug delivery rate increase was proportional to the amount of external urea and was reversible; that is, when external urea was removed, the drug release rate gradually returned to its original value.

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.

Anti-biofilm effect of a butenolide/polymer coating and metatranscriptomic analyses.

PubMed

Ding, Wei; Ma, Chunfeng; Zhang, Weipeng; Chiang, Hoyin; Tam, Chunkit; Xu, Ying; Zhang, Guangzhao; Qian, Pei-Yuan

2018-01-01

Butenolide is an environmentally friendly antifouling natural product, but its efficiency and mechanism in preventing biofilm formation have not been examined. Furthermore, controlling the release of butenolide from paints into seawater is technically challenging. A coating was developed by mixing butenolide with a biodegradable polymer, poly (ε-caprolactone)-based polyurethane, and a one-month in situ anti-biofilm test was conducted in a subtidal area. The constant release of butenolide from the surface suggested that its release was well controlled. Direct observation and confocal microscope investigation indicated that the coating was effective against both biofilm formation and attachment of large fouling organisms. Metatranscriptomic analysis of biofilm samples implied that the coating selectively inhibited the adhesion of microbes from a variety of phyla and targeted particular functional pathways including energy metabolism, drug transport and toxin release. These integrated analyses demonstrated the potential application of this butenolide/polymer coating as an anti-biofilm material.

Building CHAOS: An Operating System for Livermore Linux Clusters

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

Garlick, J E; Dunlap, C M

2003-02-21

The Livermore Computing (LC) Linux Integration and Development Project (the Linux Project) produces and supports the Clustered High Availability Operating System (CHAOS), a cluster operating environment based on Red Hat Linux. Each CHAOS release begins with a set of requirements and ends with a formally tested, packaged, and documented release suitable for use on LC's production Linux clusters. One characteristic of CHAOS is that component software packages come from different sources under varying degrees of project control. Some are developed by the Linux Project, some are developed by other LC projects, some are external open source projects, and some aremore » commercial software packages. A challenge to the Linux Project is to adhere to release schedules and testing disciplines in a diverse, highly decentralized development environment. Communication channels are maintained for externally developed packages in order to obtain support, influence development decisions, and coordinate/understand release schedules. The Linux Project embraces open source by releasing locally developed packages under open source license, by collaborating with open source projects where mutually beneficial, and by preferring open source over proprietary software. Project members generally use open source development tools. The Linux Project requires system administrators and developers to work together to resolve problems that arise in production. This tight coupling of production and development is a key strategy for making a product that directly addresses LC's production requirements. It is another challenge to balance support and development activities in such a way that one does not overwhelm the other.« less

Development and in vitro evaluation of expandable gastroretentive dosage forms based on compressed collagen sponges.

PubMed

Gröning, R; Cloer, C; Müller, R S

2006-07-01

The objective of this study was to develop and evaluate new collagen gastroretentive dosage forms (GRDFs) which expand in the stomach after contact with gastric fluids. The GRDFs should remain in the stomach for a prolonged period of time due to their size. The dosage forms were prepared from collagen sponges. The sponges were manufactured by freeze-drying a riboflavin-containing collagen solution. A computer controlled material supply was constructed to transport precompressed collagen into a tablet machine. A second type of tablet was manufactured by combining compressed collagen sponges with hydrophilic matrix layers of hydroxypropylmethylcellulose. Matrix layers containing captopril or aciclovir were developed. In vitro experiments were performed with both types of dosage forms. The collagen tablets expand within a few minutes after contact with artificial gastric juice and form a drug delivery system with a size of 8 mm x 18 mm x 60 mm. Riboflavin is released over 16 h. If two layer tablets are used, the release of aciclovir or captopril can be controlled by the composition of the sustained release layer.

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

PubMed

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

2015-09-01

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

Development and Characterization of Liquid Crystal-Gold Nanoparticle Hybrid Materials for Optical Applications

NASA Astrophysics Data System (ADS)

Quint, Makiko T.

Hybrid material, mixtures of two or more materials with new properties, represents an exciting class of new materials for a variety of potential applications such as displays, optoelectronics, and sensors due to their unique physical and optical properties. The scope of this dissertation is to produce two new plasmonic applications by combining liquid crystals with gold nanoparticles. The first application is gold nanoparticle coated liquid crystal thin film. Most liquid crystal (LC) thin films require external voltage to reorient LC molecules. Recent advances in optical controlling technology of LC molecule behavior, resulting in the reduction of energy consumption, have stimulated research and development of new LC thin films. In order to re-orient LC molecules by just using light, the common approach is to include either a photo-responsive LC host, one that require high power light and severely narrows the range of usable materials, or add photo-active dye or polymer layer, photodegradation over time. Our work designing an all-optical method for LC re-orientation that overcomes all the limitations mentioned above. We have successfully both in- and out-of-plane spatial orientation of nematic liquid crystal (LC) molecules by leveraging the highly localized electric fields produced in the near-field regime of a gold nanoparticle (AuNP) layer. This re-orientation of LC molecules in thin LC-AuNP film is all-optical, driven by a small resonance excitation power with the localized surface plasmon absorption of the AuNPs at room temperature. The second application is LC mediated nano-assembled gold microcapsules. This application has a potential in controlled-release cargo-style delivery system. Targeted delivery systems with controlled release mechanisms have been the subject of extensive research more than fifty years. One is to control the release process remotely by using optical excitation. Optical actuation of delivery capsules, which plasmonic nanoparticle such as gold, allows rapid release at specific locations and uses the photothermal effect to unload contents. Almost all gold-based delivery applications including Au coated nanocrystals or AuNPs with soft materials like gels and polymers are not suitable for control release applications in real life since these applications do not provide robust leakage-free containment lower than the American National Standards Institute (ANSI) maximum permissible light exposure limit. We have successfully managed the difficulties mentioned above and produced a new gold-based delivery application. The application is spherical capsules with a densely packed wall of AuNPs. The rigid capsule wall allows encapsulation of cargo that can be contained, virtually leakage-free, over several months. Further, by leveraging LSPR of AuNPs, we can rupture the microshells using optical excitation with ultralow power (< 2 mW), controllably and rapidly releasing the encapsulated contents in less than 5 seconds. Our results exhibiting the capture and optically regulated release of encapsulated substances are a novel platform that combines controlled-release cargo-style delivery and photothermal therapy in one versatile and multifunctional unit. Both our applications are overcoming current limitations and promising future research directions towards the next generation of LC-AuNPs hybrid material research and developments.

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.

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.

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.

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.

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.

Triggered-release polymeric conjugate micelles for on-demand intracellular drug delivery

NASA Astrophysics Data System (ADS)

Cao, Yanwu; Gao, Min; Chen, Chao; Fan, Aiping; Zhang, Ju; Kong, Deling; Wang, Zheng; Peer, Dan; Zhao, Yanjun

2015-03-01

Nanoscale drug delivery platforms have been developed over the past four decades that have shown promising clinical results in several types of cancer and inflammatory disorders. These nanocarriers carrying therapeutic payloads are maximizing the therapeutic outcomes while minimizing adverse effects. Yet one of the major challenges facing drug developers is the dilemma of premature versus on-demand drug release, which influences the therapeutic regiment, efficacy and potential toxicity. Herein, we report on redox-sensitive polymer-drug conjugate micelles for on-demand intracellular delivery of a model active agent, curcumin. Biodegradable methoxy poly(ethylene glycol)-poly(lactic acid) copolymer (mPEG-PLA) was conjugated with curcumin via a disulfide bond or ester bond (control), respectively. The self-assembled redox-sensitive micelles exhibited a hydrodynamic size of 115.6 ± 5.9 (nm) with a zeta potential of -10.6 ± 0.7 (mV). The critical micelle concentration was determined at 6.7 ± 0.4 (μg mL-1). Under sink conditions with a mimicked redox environment (10 mM dithiothreitol), the extent of curcumin release at 48 h from disulfide bond-linked micelles was nearly three times higher compared to the control micelles. Such rapid release led to a lower half maximal inhibitory concentration (IC50) in HeLa cells at 18.5 ± 1.4 (μg mL-1), whereas the IC50 of control micelles was 41.0 ± 2.4 (μg mL-1). The cellular uptake study also revealed higher fluorescence intensity for redox-sensitive micelles. In conclusion, the redox-sensitive polymeric conjugate micelles could enhance curcumin delivery while avoiding premature release, and achieving on-demand release under the high glutathione concentration in the cell cytoplasm. This strategy opens new avenues for on-demand drug release of nanoscale intracellular delivery platforms that ultimately might be translated into pre-clinical and future clinical practice.

Triggered-release polymeric conjugate micelles for on-demand intracellular drug delivery.

PubMed

Cao, Yanwu; Gao, Min; Chen, Chao; Fan, Aiping; Zhang, Ju; Kong, Deling; Wang, Zheng; Peer, Dan; Zhao, Yanjun

2015-03-20

Nanoscale drug delivery platforms have been developed over the past four decades that have shown promising clinical results in several types of cancer and inflammatory disorders. These nanocarriers carrying therapeutic payloads are maximizing the therapeutic outcomes while minimizing adverse effects. Yet one of the major challenges facing drug developers is the dilemma of premature versus on-demand drug release, which influences the therapeutic regiment, efficacy and potential toxicity. Herein, we report on redox-sensitive polymer-drug conjugate micelles for on-demand intracellular delivery of a model active agent, curcumin. Biodegradable methoxy poly(ethylene glycol)-poly(lactic acid) copolymer (mPEG-PLA) was conjugated with curcumin via a disulfide bond or ester bond (control), respectively. The self-assembled redox-sensitive micelles exhibited a hydrodynamic size of 115.6 ± 5.9 (nm) with a zeta potential of -10.6 ± 0.7 (mV). The critical micelle concentration was determined at 6.7 ± 0.4 (μg mL(-1)). Under sink conditions with a mimicked redox environment (10 mM dithiothreitol), the extent of curcumin release at 48 h from disulfide bond-linked micelles was nearly three times higher compared to the control micelles. Such rapid release led to a lower half maximal inhibitory concentration (IC50) in HeLa cells at 18.5 ± 1.4 (μg mL(-1)), whereas the IC50 of control micelles was 41.0 ± 2.4 (μg mL(-1)). The cellular uptake study also revealed higher fluorescence intensity for redox-sensitive micelles. In conclusion, the redox-sensitive polymeric conjugate micelles could enhance curcumin delivery while avoiding premature release, and achieving on-demand release under the high glutathione concentration in the cell cytoplasm. This strategy opens new avenues for on-demand drug release of nanoscale intracellular delivery platforms that ultimately might be translated into pre-clinical and future clinical practice.

78 FR 77557 - Releasing Information; General Provisions; Accounting and Reporting Requirements; Reports of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-24

..., including controls for maintaining the confidentiality of borrower information. The system of internal... develop and implement an effective system of internal controls over the central data repository to ensure..., and maintain an effective system of internal controls over the data included in the report of accounts...

3D inkjet printing of tablets exploiting bespoke complex geometries for controlled and tuneable drug release.

PubMed

Kyobula, Mary; Adedeji, Aremu; Alexander, Morgan R; Saleh, Ehab; Wildman, Ricky; Ashcroft, Ian; Gellert, Paul R; Roberts, Clive J

2017-09-10

A hot melt 3D inkjet printing method with the potential to manufacture formulations in complex and adaptable geometries for the controlled loading and release of medicines is presented. This first use of a precisely controlled solvent free inkjet printing to produce drug loaded solid dosage forms is demonstrated using a naturally derived FDA approved material (beeswax) as the drug carrier and fenofibrate as the drug. Tablets with bespoke geometries (honeycomb architecture) were fabricated. The honeycomb architecture was modified by control of the honeycomb cell size, and hence surface area to enable control of drug release profiles without the need to alter the formulation. Analysis of the formed tablets showed the drug to be evenly distributed within the beeswax at the bulk scale with evidence of some localization at the micron scale. An analytical model utilizing a Fickian description of diffusion was developed to allow the prediction of drug release. A comparison of experimental and predicted drug release data revealed that in addition to surface area, other factors such as the cell diameter in the case of the honeycomb geometry and material wettability must be considered in practical dosage form design. This information when combined with the range of achievable geometries could allow the bespoke production of optimized personalised medicines for a variety of delivery vehicles in addition to tablets, such as medical devices for example. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Nanostructured gellan and xanthan hydrogel depot integrated within a baghdadite scaffold augments bone regeneration.

PubMed

Sehgal, Rekha R; Roohani-Esfahani, S I; Zreiqat, Hala; Banerjee, Rinti

2017-04-01

Controlled delivery of biological cues through synthetic scaffolds to enhance the healing capacity of bone defects is yet to be realized clinically. The purpose of this study was development of a bioactive tissue-engineered scaffold providing the sustained delivery of an osteoinductive drug, dexamethasone disodium phosphate (DXP), encapsulated within chitosan nanoparticles (CN). Porous baghdadite (BD; Ca 3 ZrSi 2 O 9 ) scaffolds, a zirconia-modified calcium silicate ceramic, was coated with DXP-encapsulated CN nanoparticles (DXP-CN) using nanostructured gellan and xanthan hydrogel (GX). Crosslinker and GX polymer concentrations were optimized to achieve a homogeneous distribution of hydrogel coating within BD scaffolds. Dynamic laser scattering indicated an average size of 521 ± 21 nm for the DXP-CN nanoparticles. In vitro drug-release studies demonstrated that the developed DXP-CN-GX hydrogel-coated BD scaffolds (DXP-CN-GX-BD) resulted in a sustained delivery of DXP over the 5 days (78 ± 6% of drug release) compared with burst release over 1 h, seen from free DXP loaded in uncoated BD scaffolds (92 ± 8% release in 1 h). To estimate the influence of controlled delivery of DXP from the developed scaffolds, the effect on MG 63 cells was evaluated using various bone differentiation assays. Cell culture within DXP-CN-GX-BD scaffolds demonstrated a significant increase in the expression of early and late osteogenic markers of alkaline phosphatase activity, collagen type 1 and osteocalcin, compared to the uncoated BD scaffold. The results suggest that the DXP-releasing nanostructured hydrogel integrated within the BD scaffold caused sustained release of DXP, improving the potential for osteogenic differentiation. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

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.

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.

Novel HPLC Analysis of Hydrocortisone in Conventional and Controlled-Release Pharmaceutical Preparations.

PubMed

Adi-Dako, Ofosua; Oppong Bekoe, Samuel; Ofori-Kwakye, Kwabena; Appiah, Enoch; Peprah, Paul

2017-01-01

An isocratic sensitive and precise reverse phase high-performance liquid chromatography (RP-HPLC) method was developed and validated for the determination and quantification of hydrocortisone in controlled-release and conventional (tablets and injections) pharmaceutical preparations. Chromatographic separation was achieved on an ODS (C18), 5  μ m, 4.6 × 150 mm, with an isocratic elution using a freshly prepared mobile phase of composition methanol : water : acetic acid (60 : 30 : 10, v/v/v) at a flow rate of 1.0 ml/min. The detection of the drug was successfully achieved at a wavelength of 254 nm. The retention time obtained for the drug was 2.26 min. The proposed method produced linear detectable responses in the concentration range of 0.02 to 0.4 mg/ml of hydrocortisone. High recoveries of 98-101% were attained at concentration levels of 80%, 100%, and 120%. The intraday and interday precision (RSD) were 0.19-0.55% and 0.33-0.71%, respectively. A comparison of hydrocortisone analyses data from the developed method and the official USP method showed no significant difference ( p > 0.05) at a 95% confidence interval. The method was successfully applied to the determination and quantification of hydrocortisone in six controlled-release and fifteen conventional release pharmaceutical preparations.

Novel HPLC Analysis of Hydrocortisone in Conventional and Controlled-Release Pharmaceutical Preparations

PubMed Central

Oppong Bekoe, Samuel; Appiah, Enoch; Peprah, Paul

2017-01-01

An isocratic sensitive and precise reverse phase high-performance liquid chromatography (RP-HPLC) method was developed and validated for the determination and quantification of hydrocortisone in controlled-release and conventional (tablets and injections) pharmaceutical preparations. Chromatographic separation was achieved on an ODS (C18), 5 μm, 4.6 × 150 mm, with an isocratic elution using a freshly prepared mobile phase of composition methanol : water : acetic acid (60 : 30 : 10, v/v/v) at a flow rate of 1.0 ml/min. The detection of the drug was successfully achieved at a wavelength of 254 nm. The retention time obtained for the drug was 2.26 min. The proposed method produced linear detectable responses in the concentration range of 0.02 to 0.4 mg/ml of hydrocortisone. High recoveries of 98–101% were attained at concentration levels of 80%, 100%, and 120%. The intraday and interday precision (RSD) were 0.19–0.55% and 0.33–0.71%, respectively. A comparison of hydrocortisone analyses data from the developed method and the official USP method showed no significant difference (p > 0.05) at a 95% confidence interval. The method was successfully applied to the determination and quantification of hydrocortisone in six controlled-release and fifteen conventional release pharmaceutical preparations. PMID:28660092

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

Towards Comprehensive Cardiac Repair and Regeneration after Myocardial Infarction: Aspects to Consider and Proteins to Deliver

PubMed Central

Awada, Hassan K.; Hwang, Mintai P.; Wang, Yadong

2016-01-01

Ischemic heart disease is a leading cause of death worldwide. After the onset of myocardial infarction, many pathological changes take place and progress the disease towards heart failure. Pathologies such as ischemia, inflammation, cardiomyocyte death, ventricular remodeling and dilation, and interstitial fibrosis, develop and involve the signaling of many proteins. Proteins can play important roles in limiting or countering pathological changes after infarction. However, they typically have short half-lives in vivo in their free form and can benefit from the advantages offered by controlled release systems to overcome their challenges. The controlled delivery of an optimal combination of proteins per their physiologic spatiotemporal cues to the infarcted myocardium holds great potential to repair and regenerate the heart. The effectiveness of therapeutic interventions depends on the elucidation of the molecular mechanisms of the cargo proteins and the spatiotemporal control of their release. It is likely that multiple proteins will provide a more comprehensive and functional recovery of the heart in a controlled release strategy. PMID:26757257

A novel controlled release ethanol emitter: preparation and effect on some postharvest quality parameters of Chinese bayberry during storage.

PubMed

Mu, Honglei; Gao, Haiyan; Chen, Hangjun; Fang, Xiangjun; Han, Qiang

2017-11-01

Reducing spoilage and prolonging the shelf-life of food materials are both critically important in the food industry. Among the many available preservatives, ethanol has been widely used for the storage of fruits and vegetables. Although a few ethanol emitters are available in the form of antimicrobial packaging, these ethanol emitters demonstrate high volatility, uncontrolled release and other disadvantages, and so the practical applications are limited. A novel ethanol gel with a controlled release rate was prepared by a gelatification reaction between ethanol and sodium stearate to overcome the disadvantage of conventional ethanol emitters. The hardness, adhesiveness and cohesiveness of developed ethanol gels increased, whereas the springiness decreased along with an increase in the sodium stearate concentration. The release rate of ethanol in the gels was controlled by the concentration of sodium stearate, in which a first-order release kinetic was observed. The release rate constant (k) of the gels with 12.5, 37.5, 62.5 g kg -1 of sodium stearate was 0.58 ± 0.029, 0.49 ± 0.035 and 0.41 ± 0.021 h -1 , respectively, at 25 °C. The application of the controlled release ethanol emitter with respect to the storage of Chinese bayberry fruit demonstrated its ability to reduce the decay rate, maintain firmness and inhibit increased malondialdehyde content at 4 °C. In terms of practical applications, an appropriate sodium stearate content can be selected in accordance with the storage period, aiming to achieve precise storage goals. Therefore, the ethanol emitter has potential application prospects as an active packaging for Chinese bayberry fruit, as well as for other perishable products. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

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.

OPTIMIZATION OF INTEGRATED URBAN WET-WEATHER CONTROL STRATEGIES

EPA Science Inventory

An optimization method for urban wet weather control (WWC) strategies is presented. The developed optimization model can be used to determine the most cost-effective strategies for the combination of centralized storage-release systems and distributed on-site WWC alternatives. T...

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...

Recent Developments on Autonomous Corrosion Protection Through Encapsulation

NASA Technical Reports Server (NTRS)

Li, W.; Buhrow, J. W.; Calle, L. M.; Gillis, M.; Blanton, M.; Hanna, J.; Rawlins, J.

2015-01-01

This paper concerns recent progress in the development of a multifunctional smart coating, based on microencapsulation, for the autonomous detection and control of corrosion. Microencapsulation has been validated and optimized to incorporate desired corrosion control functionalities, such as early corrosion detection and inhibition, through corrosion-initiated release of corrosion indicators and inhibitors, as well as self-healing agent release triggered by mechanical damage. While proof-of-concept results have been previously reported, more recent research and development efforts have concentrated on improving coating compatibility and synthesis procedure scalability, with a targeted goal of obtaining easily dispersible pigment-grade type microencapsulated materials. The recent progress has resulted in the development of pH-sensitive microparticles as a corrosion-triggered delivery system for corrosion indicators and inhibitors. The synthesis and early corrosion indication results obtained with coating formulations that incorporate these microparticles are reported. The early corrosion indicating results were obtained with color changing and with fluorescent indicators.

3D Printed Programmable Release Capsules.

PubMed

Gupta, Maneesh K; Meng, Fanben; Johnson, Blake N; Kong, Yong Lin; Tian, Limei; Yeh, Yao-Wen; Masters, Nina; Singamaneni, Srikanth; McAlpine, Michael C

2015-08-12

The development of methods for achieving precise spatiotemporal control over chemical and biomolecular gradients could enable significant advances in areas such as synthetic tissue engineering, biotic-abiotic interfaces, and bionanotechnology. Living organisms guide tissue development through highly orchestrated gradients of biomolecules that direct cell growth, migration, and differentiation. While numerous methods have been developed to manipulate and implement biomolecular gradients, integrating gradients into multiplexed, three-dimensional (3D) matrices remains a critical challenge. Here we present a method to 3D print stimuli-responsive core/shell capsules for programmable release of multiplexed gradients within hydrogel matrices. These capsules are composed of an aqueous core, which can be formulated to maintain the activity of payload biomolecules, and a poly(lactic-co-glycolic) acid (PLGA, an FDA approved polymer) shell. Importantly, the shell can be loaded with plasmonic gold nanorods (AuNRs), which permits selective rupturing of the capsule when irradiated with a laser wavelength specifically determined by the lengths of the nanorods. This precise control over space, time, and selectivity allows for the ability to pattern 2D and 3D multiplexed arrays of enzyme-loaded capsules along with tunable laser-triggered rupture and release of active enzymes into a hydrogel ambient. The advantages of this 3D printing-based method include (1) highly monodisperse capsules, (2) efficient encapsulation of biomolecular payloads, (3) precise spatial patterning of capsule arrays, (4) "on the fly" programmable reconfiguration of gradients, and (5) versatility for incorporation in hierarchical architectures. Indeed, 3D printing of programmable release capsules may represent a powerful new tool to enable spatiotemporal control over biomolecular gradients.

Controlling the Release of Indomethacin from Glass Solutions Layered with a Rate Controlling Membrane Using Fluid-Bed Processing. Part 2: The Influence of Formulation Parameters on Drug Release.

PubMed

Dereymaker, Aswin; Pelgrims, Jirka; Engelen, Frederik; Adriaensens, Peter; Van den Mooter, Guy

2017-04-03

This study aimed to investigate the pharmaceutical performance of an indomethacin-polyvinylpyrrolidone (PVP) glass solution applied using fluid bed processing as a layer on inert sucrose spheres and subsequently top-coated with a release rate controlling membrane consisting of either ethyl cellulose or Eudragit RL. The implications of the addition of a pore former (PVP) and the coating medium (ethanol or water) on the diffusion and release behavior were also considered. In addition, the role of a charge interaction between drug and controlled release polymer on the release was investigated. Diffusion experiments pointed to the influence of pore former concentration, rate controlling polymer type, and coating solvent on the permeability of the controlled release membranes. This can be translated to drug release tests, which show the potential of diffusion tests as a preliminary screening test and that diffusion is the main factor influencing release. Drug release tests also showed the effect of coating layer thickness. A charge interaction between INDO and ERL was demonstrated, but this had no negative effect on drug release. The higher diffusion and release observed in ERL-based rate controlling membranes was explained by a higher hydrophilicity, compared to EC.

Evaluation of superabsorbent linseed-polysaccharides as a novel stimuli-responsive oral sustained release drug delivery system.

PubMed

Haseeb, Muhammad Tahir; Hussain, Muhammad Ajaz; Bashir, Sajid; Ashraf, Muhammad Umer; Ahmad, Naveed

2017-03-01

Advancement in technology has transformed the conventional dosage forms to intelligent drug delivery systems. Such systems are helpful for targeted and efficient drug delivery with minimum side effects. Drug release from these systems is governed and controlled by external stimuli (pH, enzymes, ions, glucose, etc.). Polymeric biomaterial having stimuli-responsive properties has opened a new area in drug delivery approach. Potential of a polysaccharide (rhamnogalacturonan)-based hydrogel from Linseeds (Linum usitatissimum L.) was investigated as an intelligent drug delivery material. Different concentrations of Linseed hydrogel (LSH) were used to prepare caffeine and diacerein tablets and further investigated for pH and salt solution-responsive swelling, pH-dependent drug release, and release kinetics. Morphology of tablets was observed using SEM. LSH tablets exhibited dynamic swelling-deswelling behavior with tendency to swell at pH 7.4 and in deionized water while deswell at pH 1.2, in normal saline and ethanol. Consequently, pH controlled release of the drugs was observed from tablets with lower release (<10%) at pH 1.2 and higher release at pH 6.8 and 7.4. SEM showed elongated channels in swollen then freeze-dried tablets. The drug release was greatly influenced by the amount of LSH in the tablets. Drug release from LSH tablets was governed by the non-Fickian diffusion. These finding indicates that LSH holds potential to be developed as sustained release material for tablet.

An Improved Inventory Control Model for the Brazilian Navy Supply System

DTIC Science & Technology

2001-12-01

Portuguese Centro de Controle de Inventario da Marinha, the Brazilian Navy Inventory Control Point (ICP) developed an empirical model called SPAADA...NAVAL POSTGRADUATE SCHOOL Monterey, California THESIS Approved for public release; distribution is unlimited AN IMPROVED INVENTORY CONTROL ...AN IMPROVED INVENTORY CONTROL MODEL FOR THE BRAZILIAN NAVY SUPPLY SYSTEM Contract Number Grant Number Program Element Number Author(s) Moreira

Encapsulation of methotrexate loaded magnetic microcapsules for magnetic drug targeting and controlled drug release

NASA Astrophysics Data System (ADS)

Chakkarapani, Prabu; Subbiah, Latha; Palanisamy, Selvamani; Bibiana, Arputha; Ahrentorp, Fredrik; Jonasson, Christian; Johansson, Christer

2015-04-01

We report on the development and evaluation of methotrexate magnetic microcapsules (MMC) for targeted rheumatoid arthritis therapy. Methotrexate was loaded into CaCO3-PSS (poly (sodium 4-styrenesulfonate)) doped microparticles that were coated successively with poly (allylamine hydrochloride) and poly (sodium 4-styrenesulfonate) by layer-by-layer technique. Ferrofluid was incorporated between the polyelectrolyte layers. CaCO3-PSS core was etched by incubation with EDTA yielding spherical MMC. The MMC were evaluated for various physicochemical, pharmaceutical parameters and magnetic properties. Surface morphology, crystallinity, particle size, zeta potential, encapsulation efficiency, loading capacity, drug release pattern, release kinetics and AC susceptibility studies revealed spherical particles of ~3 μm size were obtained with a net zeta potential of +24.5 mV, 56% encapsulation and 18.6% drug loading capacity, 96% of cumulative drug release obeyed Hixson-Crowell model release kinetics. Drug excipient interaction, surface area, thermal and storage stability studies for the prepared MMC was also evaluated. The developed MMC offer a promising mode of targeted and sustained release drug delivery for rheumatoid arthritis therapy.

Release of endogenous amino acids from the hippocampus and brain stem from developing and adult mice in ischemia.

PubMed

Oja, Simo S; Saransaari, Pirjo

2009-09-01

The release of neurotransmitters and modulators has been studied mostly using labeled preloaded compounds. For several reasons, however, the estimated release may not reliably reflect the release of endogenous compounds. The basal and K(+)-evoked release of the neuroactive endogenous amino acids GABA, glycine, taurine, L-glutamate and L-aspartate was now studied in slices from the hippocampus and brain stem from 7-day-old and 3-month-old mice under control and ischemic conditions. The release of synaptically not active L-glutamine, L-alanine, L-threonine and L-serine was assessed for comparison. The estimates for the hippocampus and brainstem were markedly different and also different in developing and adult mice. GABA release was much greater in 3-month-old than in 7-day-old mice, whereas with taurine the situation was the opposite, in the hippocampus in particular. K(+) stimulation enhanced glycine release more in the mature than immature brain stem while in the hippocampus the converse was observed. Ischemia enhanced the release of all neuroactive amino acids in both brain regions, the effects being relatively most pronounced in the case of GABA, aspartate and glutamate in the hippocampus in 3-month-old mice, and taurine in 7-day-old and glycine in 3-month-old mice in the brain stem. These results are qualitatively similar to those obtained on earlier experiments with labeled preloaded amino acids. However, the magnitudes of the release cannot be quite correctly estimated using radioactive labels. In developing mice only taurine release may counteract the harmful effects of excitatory amino acids in ischemia in both hippocampus and brain stem.

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.

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.

Advancing Knowledge on Fugitive Natural Gas from Energy Resource Development at a Controlled Release Field Observatory

NASA Astrophysics Data System (ADS)

Cahill, A. G.; Chao, J.; Forde, O.; Prystupa, E.; Mayer, K. U.; Black, T. A.; Tannant, D. D.; Crowe, S.; Hallam, S.; Mayer, B.; Lauer, R. M.; van Geloven, C.; Welch, L. A.; Salas, C.; Levson, V.; Risk, D. A.; Beckie, R. D.

2017-12-01

Fugitive gas, comprised primarily of methane, can be unintentionally released from upstream oil and gas development either at surface from leaky infrastructure or in the subsurface through failure of energy well bore integrity. For the latter, defective cement seals around energy well casings may permit buoyant flow of natural gas from the deeper subsurface towards shallow aquifers, the ground surface and potentially into the atmosphere. Concerns associated with fugitive gas release at surface and in the subsurface include contributions to greenhouse gas emissions, subsurface migration leading to accumulation in nearby infrastructure and impacts to groundwater quality. Current knowledge of the extent of fugitive gas leakage including how to best detect and monitor over time, and particularly its migration and fate in the subsurface, is incomplete. We have established an experimental field observatory for evaluating fugitive gas leakage in an area of historic and ongoing hydrocarbon resource development within the Montney Resource Play of the Western Canadian Sedimentary Basin, British Columbia, Canada. Natural gas will be intentionally released at surface and up to 25 m below surface at various rates and durations. Resulting migration patterns and impacts will be evaluated through examination of the geology, hydrogeology, hydro-geochemistry, isotope geochemistry, hydro-geophysics, vadose zone and soil gas processes, microbiology, and atmospheric conditions. The use of unmanned aerial vehicles and remote sensors for monitoring and detection of methane will also be assessed for suitability as environmental monitoring tools. Here we outline the experimental design and describe initial research conducted to develop a detailed site conceptual model of the field observatory. Subsequently, results attained from pilot surface and sub-surface controlled natural gas releases conducted in late summer 2017 will be presented as well as results of numerical modelling conducted to plan methane release experiments in 2018 and onwards. This research will create knowledge which informs strategies to detect and monitor fugitive gas fluxes at the surface and in groundwater; as well as guide associated regulatory and technical policies.

Control of excessive neural circuit excitability and prevention of epileptic seizures by endocannabinoid signaling.

PubMed

Sugaya, Yuki; Kano, Masanobu

2018-05-08

Progress in research on endocannabinoid signaling has greatly advanced our understanding of how it controls neural circuit excitability in health and disease. In general, endocannabinoid signaling at excitatory synapses suppresses seizures by inhibiting glutamate release. In contrast, endocannabinoid signaling promotes seizures by inhibiting GABA release at inhibitory synapses. The physiological distribution of endocannabinoid signaling molecules becomes disrupted with the development of epileptic focus in patients with mesial temporal lobe epilepsy and in animal models of experimentally induced epilepsy. Augmentation of endocannabinoid signaling can promote the development of epileptic focus at initial stages. However, at later stages, increased endocannabinoid signaling delays it and suppresses spontaneous seizures. Thus, the regulation of endocannabinoid signaling at specific synapses that cause hyperexcitability during particular stages of disease development may be effective for treating epilepsy and epileptogenesis.

Physicochemical properties affect the synthesis, controlled delivery, degradation and pharmacokinetics of inorganic nanoporous materials.

PubMed

Yazdi, Iman K; Ziemys, Arturas; Evangelopoulos, Michael; Martinez, Jonathan O; Kojic, Milos; Tasciotti, Ennio

2015-10-01

Controlling size, shape and uniformity of porous constructs remains a major focus of the development of porous materials. Over the past two decades, we have seen significant developments in the fabrication of new, porous-ordered structures using a wide range of materials, resulting in properties well beyond their traditional use. Porous materials have been considered appealing, due to attractive properties such as pore size length, morphology and surface chemistry. Furthermore, their utilization within the life sciences and medicine has resulted in significant developments in pharmaceutics and medical diagnosis. This article focuses on various classes of porous materials, providing an overview of principle concepts with regard to design and fabrication, surface chemistry and loading and release kinetics. Furthermore, predictions from a multiscale mathematical model revealed the role pore length and diameter could have on payload release kinetics.

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

Recent development, applications, and perspectives of mesoporous silica particles in medicine and biotechnology.

PubMed

Pasqua, Luigi; Cundari, Sante; Ceresa, Cecilia; Cavaletti, Guido

2009-01-01

Mesoporous silica particles (MSP) are a new development in nanotechnology. Covalent modification of the surface of the silica is possible both on the internal pore and on the external particle surface. It allows the design of functional nanostructured materials with properties of organic, biological and inorganic components. Research and development are ongoing on the MSP, which have applications in catalysis, drug delivery and imaging. The most recent and interesting advancements in size, morphology control and surface functionalization of MSP have enhanced the biocompatibility of these materials with high surface areas and pore volumes. In the last 5 years several reports have demonstrated that MSP can be efficiently internalized using in vitro and animal models. The functionalization of MSP with organic moieties or other nanostructures brings controlled release and molecular recognition capabilities to these mesoporous materials for drug/gene delivery and sensing applications, respectively. Herein, we review recent research progress on the design of functional MSP materials with various mechanisms of targeting and controlled release.

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.

Controlled Release of Antimicrobial ClO2 Gas from a Two-Layer Polymeric Film System.

PubMed

Bai, Zhifeng; Cristancho, Diego E; Rachford, Aaron A; Reder, Amy L; Williamson, Alexander; Grzesiak, Adam L

2016-11-16

We report a two-component label system comprising a chlorite-containing polymer film and an acid-containing polymer film that can release antimicrobial ClO 2 gas upon adhering the two films together to enable a reaction of the chlorite and acid under moisture exposure. The chlorite-containing film comprises a commercial acrylate-based pressure-sensitive adhesive polymer impregnated with sodium chlorite. The acid-containing film comprises a commercial poly(vinyl alcohol) polymer loaded with tartaric acid. Both of the films were prepared on low ClO 2 -absorbing substrate films from stable aqueous systems of the polymers with high reagent loading. Rapid and sustained releases of significant amounts of ClO 2 gas from the label system were observed in an in situ quantification system using UV-vis spectroscopy. It was found that the ClO 2 release is slower at a lower temperature and can be accelerated by moisture in the atmosphere and the films. Controlled release of ClO 2 gas from the label system was demonstrated by tailoring film composition and thickness. A model was developed to extract release kinetics and revealed good conversions of the label system. This two-component system can potentially be applied as a two-part label without premature release for applications in food packaging.

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.

Solid dispersions in the development of a nimodipine floating tablet formulation and optimization by artificial neural networks and genetic programming.

PubMed

Barmpalexis, Panagiotis; Kachrimanis, Kyriakos; Georgarakis, Emanouil

2011-01-01

The present study investigates the use of nimodipine-polyethylene glycol solid dispersions for the development of effervescent controlled release floating tablet formulations. The physical state of the dispersed nimodipine in the polymer matrix was characterized by differential scanning calorimetry, powder X-ray diffraction, FT-IR spectroscopy and polarized light microscopy, and the mixture proportions of polyethylene glycol (PEG), polyvinyl-pyrrolidone (PVP), hydroxypropylmethylcellulose (HPMC), effervescent agents (EFF) and nimodipine were optimized in relation to drug release (% release at 60 min, and time at which the 90% of the drug was dissolved) and floating properties (tablet's floating strength and duration), employing a 25-run D-optimal mixture design combined with artificial neural networks (ANNs) and genetic programming (GP). It was found that nimodipine exists as mod I microcrystals in the solid dispersions and is stable for at least a three-month period. The tablets showed good floating properties and controlled release profiles, with drug release proceeding via the concomitant operation of swelling and erosion of the polymer matrix. ANNs and GP both proved to be efficient tools in the optimization of the tablet formulation, and the global optimum formulation suggested by the GP equations consisted of PEG=9%, PVP=30%, HPMC=36%, EFF=11%, nimodipine=14%. Copyright © 2010 Elsevier B.V. All rights reserved.

Development and characterization of polymer-oil nanostructured carrier (PONC) for controlled delivery of all-trans retinoic acid (ATRA)

NASA Astrophysics Data System (ADS)

Narvekar, Mayuri M.

The commonly used PLGA-based delivery systems are often limited by their inadequate drug loading and release properties. This study reports the integration of oil into PLGA to form the prototype of a hybrid drug carrier PONC. Our primary goal is to confer the key strength of lipid-based drug carriers, i.e. efficient encapsulation of lipophilic compounds, to a PLGA system without taking away its various useful qualities. The PONC were formulated by emulsification solvent evaporation technique, which were then characterized for particle size, encapsulation efficiency, drug release and anticancer efficacy. The ATRA loaded PONC showed excellent encapsulation efficiency and release kinetics. Even after surface functionalization with PEG , controlled drug release kinetics was maintained, with 88.5% of the encapsulated ATRA released from the PEG-PONC in a uniform manner over 120 hours. It also showed favorable physicochemical properties and serum stability. PEG-PONC has demonstrated substantially superior activity over the free ATRA in ovarian cancer cells that are non-responsive to the standard chemotherapy. The newly developed PEG-PONC significantly reduced the IC50 values (p<0.05) in the chemoresistant cells in both MTT and colony formation assays. Hence, this new ATRA-nanoformulation may offer promising means for the delivery of lipophilic compounds like all-trans retinoic acid to treat highly resistant ovarian cancer.

FY17Q4 Ristra project: Release Version 1.0 of a production toolkit

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

Hungerford, Aimee L.; Daniel, David John

2017-09-21

The Next Generation Code project will release Version 1.0 of a production toolkit for multi-physics application development on advanced architectures. Features of this toolkit will include remap and link utilities, control and state manager, setup, visualization and I/O, as well as support for a variety of mesh and particle data representations. Numerical physics packages that operate atop this foundational toolkit will be employed in a multi-physics demonstration problem and released to the community along with results from the demonstration.

Development and agronomical validation of new fertilizer compositions of high bioavailability and reduced potential nutrient losses.

PubMed

Erro, Javier; Urrutia, Oscar; San Francisco, Sara; Garcia-Mina, Jose M

2007-09-19

To optimize the economical cost of each unit of fertilizer applied and to reduce the environmental contamination caused by nutrient losses, the development of highly efficient granulated fertilizers is of great importance. This study proposes a strategy that consists of developing specific fertilizers having nutrient release patterns that are dependent on plant activity in the rhizosphere. This type of fertilizer is named "rhizosphere-controlled fertilizer" (RCF fertilizer). This fertilizer is based on the introduction of an organomineral matrix composed of metal [Mg (Ca is also possible), Zn (Fe and other metals are also possible)]-humic phosphates. The presence of this matrix modifies the nutrient release pattern of the fertilizer. In this way there are two main nutrient fractions: (i) a water-soluble fraction or "starter" fraction and (ii) a "rhizosphere-controlled" fraction insoluble in water but soluble by the action of the rhizospheric acids released by plants and microorganisms. This study shows the chemical and structural characterization of the organomineral matrix, as well as its efficiency in slowing the nutrient release rate of the RCF fertilizer, principally with respect to P and N. It is demonstrated how these properties of the matrix were also reflected in the significant reduction in both ammonia volatilization and N leaching in a pot system consisting of wheat plants cultivated in a calcareous soil and fertilized with a RCF fertilizer.

The Trojan female technique: a novel, effective and humane approach for pest population control.

PubMed

Gemmell, Neil J; Jalilzadeh, Aidin; Didham, Raphael K; Soboleva, Tanya; Tompkins, Daniel M

2013-12-22

Humankind's ongoing battle with pest species spans millennia. Pests cause or carry disease, damage or consume food crops and other resources, and drive global environmental change. Conventional approaches to pest management usually involve lethal control, but such approaches are costly, of varying efficiency and often have ethical issues. Thus, pest management via control of reproductive output is increasingly considered an optimal solution. One of the most successful such 'fertility control' strategies developed to date is the sterile male technique (SMT), in which large numbers of sterile males are released into a population each generation. However, this approach is time-consuming, labour-intensive and costly. We use mathematical models to test a new twist on the SMT, using maternally inherited mitochondrial (mtDNA) mutations that affect male, but not female reproductive fitness. 'Trojan females' carrying such mutations, and their female descendants, produce 'sterile-male'-equivalents under natural conditions over multiple generations. We find that the Trojan female technique (TFT) has the potential to be a novel humane approach for pest control. Single large releases and relatively few small repeat releases of Trojan females both provided effective and persistent control within relatively few generations. Although greatest efficacy was predicted for high-turnover species, the additive nature of multiple releases made the TFT applicable to the full range of life histories modelled. The extensive conservation of mtDNA among eukaryotes suggests this approach could have broad utility for pest control.

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

PubMed

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

2012-05-30

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

An optimization formulation for characterization of pulsatile cortisol secretion.

PubMed

Faghih, Rose T; Dahleh, Munther A; Brown, Emery N

2015-01-01

Cortisol is released to relay information to cells to regulate metabolism and reaction to stress and inflammation. In particular, cortisol is released in the form of pulsatile signals. This low-energy method of signaling seems to be more efficient than continuous signaling. We hypothesize that there is a controller in the anterior pituitary that leads to pulsatile release of cortisol, and propose a mathematical formulation for such controller, which leads to impulse control as opposed to continuous control. We postulate that this controller is minimizing the number of secretory events that result in cortisol secretion, which is a way of minimizing the energy required for cortisol secretion; this controller maintains the blood cortisol levels within a specific circadian range while complying with the first order dynamics underlying cortisol secretion. We use an ℓ0-norm cost function for this controller, and solve a reweighed ℓ1-norm minimization algorithm for obtaining the solution to this optimization problem. We use four examples to illustrate the performance of this approach: (i) a toy problem that achieves impulse control, (ii) two examples that achieve physiologically plausible pulsatile cortisol release, (iii) an example where the number of pulses is not within the physiologically plausible range for healthy subjects while the cortisol levels are within the desired range. This novel approach results in impulse control where the impulses and the obtained blood cortisol levels have a circadian rhythm and an ultradian rhythm that are in agreement with the known physiology of cortisol secretion. The proposed formulation is a first step in developing intermittent controllers for curing cortisol deficiency. This type of bio-inspired pulse controllers can be employed for designing non-continuous controllers in brain-machine interface design for neuroscience applications.

MO-AB-BRA-02: Modeling Nanoparticle-Eluting Spacer Degradation During Brachytherapy Application with in Situ Dose-Painting

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

Boateng, F; Ngwa, W; Harvard Medical School, Boston, MA

Purpose: Brachytherapy application with in situ dose-painting using gold nanoparticles (GNP) released from GNP-loaded brachytherapy spacers has been proposed as an innovative approach to increase therapeutic efficacy during brachytherapy. This work investigates the dosimetric impact of slow versus burst release of GNP from next generation biodegradable spacers. Methods: Mathematical models were developed based on experimental data to study the release of GNP from a spacer designed with FDA approved poly(lactic-co-glycolic acid) (PLGA) polymer. The diffusion controlled released process and PLGA polymer degradation kinetics was incorporated in the calculations for the first time. An in vivo determined diffusion coefficient was usedmore » for determining the concentration profiles and corresponding dose enhancement based on initial GNP-loading concentrations of 7 mg/g. Results: The results showed that there is significant delay before the concentration profile of GNP diffusion in the tumor is similar to that when burst release is assumed as in previous studies. For example, in the case of burst release after spacer administration, it took up to 25 days for all the GNP to be released from the spacer using diffusion controlled release process only. However, it took up to 45 days when a combined model for both diffusion and polymer degradation processes was used. Based on the tumor concentration profiles, a significant dose enhancement factor (DEF >20%), could be attained at a tumor distances of 5 mm from a spacer loaded with 10 nm GNP sizes. Conclusion: The results highlight the need to take the slow release of GNP from spacers and factors such as biodegradation of polymers into account in research development of GNP-eluting spacers for brachytherapy applications with in-situ dose-painting using gold nanoparticles. The findings suggest that I-125 may be the more appropriate for such applications given the relatively longer half-live compared to other radioisotopes like Pd-103 and Cs-131.« less

Preparation of Spray-Dried Soy Isoflavone-Loaded Gelatin Microspheres for Enhancement of Dissolution: Formulation, Characterization and in Vitro Evaluation

PubMed Central

Panizzon, Gean Pier; Bueno, Fernanda Giacomini; Ueda-Nakamura, Tânia; Nakamura, Celso Vataru; Dias Filho, Benedito Prado

2014-01-01

The most bioactive soy isoflavones (SI), daidzein (DAI) and genistein (GEN) have poor water solubility, which reduces their bioavailability and health benefits and limits their use in industry. The goal of this study was to develop and characterize a new gelatin matrix to microencapsulate DAI and GEN from soy extract (SE) by spray drying, in order to obtain solid dispersions to overcome solubility problems and to allow controlled release. The influences of 1:2 (MP2) and 1:3 (MP3) SE/polymer ratios on the solid state, yield, morphology, encapsulation efficiency, particle size distribution, release kinetics and cumulative release were evaluated. Analyses showed integral microparticles and high drug content. MP3 and MP2 yield were 43.6% and 55.9%, respectively, with similar mean size (p > 0.05), respectively. X-ray diffraction revealed the amorphous solid state of SE. In vitro release tests showed that dissolution was drastically increased. The results indicated that SE microencapsulation might offer a good system to control SI release, as an alternative to improve bioavailability and industrial applications. PMID:25494200

Controlled-release tablet formulation of isoniazid.

PubMed

Jain, N K; Kulkarni, K; Talwar, N

1992-04-01

Guar (GG) and Karaya gums (KG) alone and in combination with hydroxy-propylmethylcellulose (HPMC) were evaluated as release retarding materials to formulate a controlled-release tablet dosage form of isoniazid (1). In vitro release of 1 from tablets followed non-Fickian release profile with rapid initial release. Urinary excretion studies in normal subjects showed steady-state levels of 1 for 13 h. In vitro and in vivo data correlated (r = 0.9794). The studies suggested the potentiality of GG and KG as release retarding materials in formulating controlled-release tablet dosage forms of 1.

Stabilization and target delivery of Nattokinase using compression coating.

PubMed

Law, D; Zhang, Z

2007-05-01

The aim of the work is to develop a new formulation in order to stabilize a nutraceutical enzyme Nattokinase (NKCP) in powders and to control its release rate when it passes through the gastrointestinal tract of human. NKCP powders were first compacted into a tablet, which was then coated with a mixture of an enteric material Eudragit L100-55 (EL100-55) and Hydroxypropylcellulose (HPC) by direct compression. The activity of the enzyme was determined using amidolytic assay and its release rates in artificial gastric juice and an intestinal fluid were quantified using bicinchoninic acid assay. Results have shown that the activity of NKCP was pressure independent and the coated tablets protected NKCP from being denatured in the gastric juice, and realized its controlled release to the intestine based on in vitro experiments.

pyam: Python Implementation of YaM

NASA Technical Reports Server (NTRS)

Myint, Steven; Jain, Abhinandan

2012-01-01

pyam is a software development framework with tools for facilitating the rapid development of software in a concurrent software development environment. pyam provides solutions for development challenges associated with software reuse, managing multiple software configurations, developing software product lines, and multiple platform development and build management. pyam uses release-early, release-often development cycles to allow developers to integrate their changes incrementally into the system on a continual basis. It facilitates the creation and merging of branches to support the isolated development of immature software to avoid impacting the stability of the development effort. It uses modules and packages to organize and share software across multiple software products, and uses the concepts of link and work modules to reduce sandbox setup times even when the code-base is large. One sidebenefit is the enforcement of a strong module-level encapsulation of a module s functionality and interface. This increases design transparency, system stability, and software reuse. pyam is written in Python and is organized as a set of utilities on top of the open source SVN software version control package. All development software is organized into a collection of modules. pyam packages are defined as sub-collections of the available modules. Developers can set up private sandboxes for module/package development. All module/package development takes place on private SVN branches. High-level pyam commands support the setup, update, and release of modules and packages. Released and pre-built versions of modules are available to developers. Developers can tailor the source/link module mix for their sandboxes so that new sandboxes (even large ones) can be built up easily and quickly by pointing to pre-existing module releases. All inter-module interfaces are publicly exported via links. A minimal, but uniform, convention is used for building modules.

Dam pre-release as an important operation strategy in reducing flood impact in Malaysia

NASA Astrophysics Data System (ADS)

Hidayah Ishak, Nurul; Mustafa Hashim, Ahmad

2018-03-01

The 2014 flood was reported to be one of the worst natural disaster has ever affected several states in the northern part of Peninsular Malaysia. Overwhelming rainfall was noted as one of the main factors causing such impact, which was claimed to be unprecedented to some extent. The state of Perak, which is blessed with four cascading dams had also experienced flood damage at a scale that was considered the worst in history. The rainfall received had caused the dam to reach danger level that necessitated additional discharge to be released. Safety of the dams was of great importance and such unavoidable additional discharge was allowed to avoid catastrophic failure of the dam structures. This paper discusses the dam pre-release as a significant dam management strategy in reducing flood impact. An important balance between required dam storage to be maintained and the risk element that can be afforded is the crucial factor in such enhanced operation strategy. While further possibility in developing a carefully engineered dam pre-release strategy can be explored for dam operation in Malaysia, this has already been introduced in some developed countries. Australia and South Africa are examples where pre-release has been practiced and proven to reduce flood risk. The concept involves controlling the dam lake level throughout the year, in reference to the rainfall data and the hydrological properties for the catchment area of the dams. Plentiful data analysis need to be done in contemplation of producing the optimal pre-release model. The amount of heavy rainfalls received is beyond human control but the distribution of the discharge from the dams can be further managed with the appropriate pre-release strategy.

Rational design on controlled release ion-exchange polymeric microspheres and polymer-lipid hybrid nanoparticles for the delivery of water-soluble drugs through a multidisciplinary approach

NASA Astrophysics Data System (ADS)

Li, Yongqiang

Sulfopropyl dextran sulfate (SP-DS) microspheres and polymer-lipid hybrid nanoparticles (PLN) for the delivery of water-soluble anticancer drugs and P-glycoprotein inhibitors were developed by our group recently and demonstrated effectiveness in local chemotherapy. To optimize the delivery performance of these particulate systems, particularly PLN, an integrated multidisciplinary approach was developed, based on an in-depth understanding of drug-excipient interactions, internal structure, drug loading and release mechanisms, and application of advanced modeling/optimization techniques. An artificial neural networks (ANN) simulator capable of formulation optimization and drug release prediction was developed. In vitro drug release kinetics of SP-DS microspheres, with various drug loading and in different release media, were predicted by ANN. The effects of independent variables on drug release were evaluated. Good modeling performance suggested that ANN is a useful tool to predict drug release from ion-exchange microspheres. To further improve the performance of PLN, drug-polymer-lipid interactions were characterized theoretically and experimentally using verapamil hydrochloride (VRP) as a model drug and dextran sulfate sodium (DS) as a counter-ion polymer. VRP-DS complexation followed a stoichiometric rule and solid-state transformation of VRP were observed. Dodecanoic acid (DA) was identified as the lead lipid carrier material. Based upon the optimized drug-polymer-lipid interactions, PLN with high drug loading capacity (36%, w/w) and sustained release without initial burst release were achieved. VRP remained amorphous and was molecularly dispersed within PLN. H-bonding contributed to the miscibility between the VRP-DS complex and DA. Drug release from PLN was mainly controlled by diffusion and ion-exchange processes. Drug loading capacity and particle size of PLN depend on the formulation factors of the weight ratio of drug to lipid and concentrations of surfactants applied. A three-factor spherical composite experimental design was used to map the cause-and-effect relationship. PLN with high drug loading efficiency (92%) and small particle size (100 nm) were predicted by ANN and confirmed by experiment. The roles of various factors on the properties of PLN were also investigated. In summary, this thesis demonstrates that an integrated multidisciplinary strategy ranging from preformulation to formulation to optimization is suitable for the rational design of SP-DS microspheres and PLN with desired properties.

Smart Coating for Corrosion Indication and Prevention: Recent Progress

NASA Technical Reports Server (NTRS)

Li, Wenyan; Hintze, Paul; Calle, Luz M.; Buhrow, Jerry; Curran, Jerry; Muehlberg, A. J.; Gelling, V. J.; Webster, D. C.; Croll, S. G.; Contu, F.;

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.

An implantable smart magnetic nanofiber device for endoscopic hyperthermia treatment and tumor-triggered controlled drug release.

PubMed

Sasikala, Arathyram Ramachandra Kurup; Unnithan, Afeesh Rajan; Yun, Yeo-Heung; Park, Chan Hee; Kim, Cheol Sang

2016-02-01

The study describes the design and synthesis of an implantable smart magnetic nanofiber device for endoscopic hyperthermia treatment and tumor-triggered controlled drug release. This device is achieved using a two-component smart nanofiber matrix from monodisperse iron oxide nanoparticles (IONPs) as well as bortezomib (BTZ), a chemotherapeutic drug. The IONP-incorporated nanofiber matrix was developed by electrospinning a biocompatible and bioresorbable polymer, poly (d,l-lactide-co-glycolide) (PLGA), and tumor-triggered anticancer drug delivery is realized by exploiting mussel-inspired surface functionalization using 2-(3,4-dihydroxyphenyl)ethylamine (dopamine) to conjugate the borate-containing BTZ anticancer drug through a catechol metal binding in a pH-sensitive manner. Thus, an implantable smart magnetic nanofiber device can be exploited to both apply hyperthermia with an alternating magnetic field (AMF) and to achieve cancer cell-specific drug release to enable synergistic cancer therapy. These results confirm that the BTZ-loaded mussel-inspired magnetic nanofiber matrix (BTZ-MMNF) is highly beneficial not only due to the higher therapeutic efficacy and low toxicity towards normal cells but also, as a result of the availability of magnetic nanoparticles for repeated hyperthermia application and tumor-triggered controlled drug release. The current work report on the design and development of a smart nanoplatform responsive to a magnetic field to administer both hyperthermia and pH-dependent anticancer drug release for the synergistic anticancer treatment. The iron oxide nanoparticles (IONPs) incorporated nanofiber matrix was developed by electrospinning a biocompatible polymer, poly (d,l-lactide-co-glycolide) (PLGA), and tumor-triggered anticancer drug delivery is realized by surface functionalization using 2-(3,4-dihydroxyphenyl)ethylamine (dopamine) to conjugate the boratecontaining anticancer drug bortezomib through a catechol metal binding in a pH-sensitive manner. This implantable magnetic nanofiber device can be exploited to apply hyperthermia with an alternating magnetic field and to achieve cancer cell-specific drug release to enable synergistic cancer therapy, which results in an improvement in both quality of life and patient compliance. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Precision Departure Release Capability (PDRC) Final Report

NASA Technical Reports Server (NTRS)

Engelland, Shawn A.; Capps, Richard; Day, Kevin Brian; Kistler, Matthew Stephen; Gaither, Frank; Juro, Greg

2013-01-01

After takeoff, aircraft must merge into en route (Center) airspace traffic flows that may be subject to constraints that create localized demand/capacity imbalances. When demand exceeds capacity, Traffic Management Coordinators (TMCs) and Frontline Managers (FLMs) often use tactical departure scheduling to manage the flow of departures into the constrained Center traffic flow. Tactical departure scheduling usually involves a Call for Release (CFR) procedure wherein the Tower must call the Center to coordinate a release time prior to allowing the flight to depart. In present-day operations release times are computed by the Center Traffic Management Advisor (TMA) decision support tool, based upon manual estimates of aircraft ready time verbally communicated from the Tower to the Center. The TMA-computed release time is verbally communicated from the Center back to the Tower where it is relayed to the Local controller as a release window that is typically three minutes wide. The Local controller will manage the departure to meet the coordinated release time window. Manual ready time prediction and verbal release time coordination are labor intensive and prone to inaccuracy. Also, use of release time windows adds uncertainty to the tactical departure process. Analysis of more than one million flights from January 2011 indicates that a significant number of tactically scheduled aircraft missed their en route slot due to ready time prediction uncertainty. Uncertainty in ready time estimates may result in missed opportunities to merge into constrained en route flows and lead to lost throughput. Next Generation Air Transportation System plans call for development of Tower automation systems capable of computing surface trajectory-based ready time estimates. NASA has developed the Precision Departure Release Capability (PDRC) concept that improves tactical departure scheduling by automatically communicating surface trajectory-based ready time predictions and departure runway assignments to the Center scheduling tool. The PDRC concept also incorporates earlier NASA and FAA research into automation-assisted CFR coordination. The PDRC concept reduces uncertainty by automatically communicating coordinated release times with seconds-level precision enabling TMCs and FLMs to work with target times rather than windows. NASA has developed a PDRC prototype system that integrates the Center's TMA system with a research prototype Tower decision support tool. A two-phase field evaluation was conducted at NASA's North Texas Research Station in Dallas/Fort Worth. The field evaluation validated the PDRC concept and demonstrated reduced release time uncertainty while being used for tactical departure scheduling of more than 230 operational flights over 29 weeks of operations. This paper presents research results from the PDRC research activity. Companion papers present the Concept of Operations and a Technology Description.

Precision Departure Release Capability (PDRC) Technology Description

NASA Technical Reports Server (NTRS)

Engelland, Shawn A.; Capps, Richard; Day, Kevin; Robinson, Corissia; Null, Jody R.

2013-01-01

After takeoff, aircraft must merge into en route (Center) airspace traffic flows which may be subject to constraints that create localized demand-capacity imbalances. When demand exceeds capacity, Traffic Management Coordinators (TMCs) often use tactical departure scheduling to manage the flow of departures into the constrained Center traffic flow. Tactical departure scheduling usually involves use of a Call for Release (CFR) procedure wherein the Tower must call the Center TMC to coordinate a release time prior to allowing the flight to depart. In present-day operations release times are computed by the Center Traffic Management Advisor (TMA) decision support tool based upon manual estimates of aircraft ready time verbally communicated from the Tower to the Center. The TMA-computed release is verbally communicated from the Center back to the Tower where it is relayed to the Local controller as a release window that is typically three minutes wide. The Local controller will manage the departure to meet the coordinated release time window. Manual ready time prediction and verbal release time coordination are labor intensive and prone to inaccuracy. Also, use of release time windows adds uncertainty to the tactical departure process. Analysis of more than one million flights from January 2011 indicates that a significant number of tactically scheduled aircraft missed their en route slot due to ready time prediction uncertainty. Uncertainty in ready time estimates may result in missed opportunities to merge into constrained en route flows and lead to lost throughput. Next Generation Air Transportation System (NextGen) plans call for development of Tower automation systems capable of computing surface trajectory-based ready time estimates. NASA has developed the Precision Departure Release Capability (PDRC) concept that uses this technology to improve tactical departure scheduling by automatically communicating surface trajectory-based ready time predictions to the Center scheduling tool. The PDRC concept also incorporates earlier NASA and FAA research into automation-assisted CFR coordination. The PDRC concept helps reduce uncertainty by automatically communicating coordinated release times with seconds-level precision enabling TMCs to work with target times rather than windows. NASA has developed a PDRC prototype system that integrates the Center's TMA system with a research prototype Tower decision support tool. A two-phase field evaluation was conducted at NASA's North Texas Research Station (NTX) in Dallas-Fort Worth. The field evaluation validated the PDRC concept and demonstrated reduced release time uncertainty while being used for tactical departure scheduling of more than 230 operational flights over 29 weeks of operations. This paper presents the Technology Description. Companion papers include the Final Report and a Concept of Operations.

Precision Departure Release Capability (PDRC): NASA to FAA Research Transition

NASA Technical Reports Server (NTRS)

Engelland, Shawn; Davis, Thomas J.

2013-01-01

After takeoff, aircraft must merge into en route (Center) airspace traffic flows which may be subject to constraints that create localized demand-capacity imbalances. When demand exceeds capacity, Traffic Management Coordinators (TMCs) and Frontline Managers (FLMs) often use tactical departure scheduling to manage the flow of departures into the constrained Center traffic flow. Tactical departure scheduling usually involves use of a Call for Release (CFR) procedure wherein the Tower must call the Center to coordinate a release time prior to allowing the flight to depart. In present-day operations release times are computed by the Center Traffic Management Advisor (TMA) decision support tool based upon manual estimates of aircraft ready time verbally communicated from the Tower to the Center. The TMA-computed release time is verbally communicated from the Center back to the Tower where it is relayed to the Local controller as a release window that is typically three minutes wide. The Local controller will manage the departure to meet the coordinated release time window. Manual ready time prediction and verbal release time coordination are labor intensive and prone to inaccuracy. Also, use of release time windows adds uncertainty to the tactical departure process. Analysis of more than one million flights from January 2011 indicates that a significant number of tactically scheduled aircraft missed their en route slot due to ready time prediction uncertainty. Uncertainty in ready time estimates may result in missed opportunities to merge into constrained en route flows and lead to lost throughput. Next Generation Air Transportation System plans call for development of Tower automation systems capable of computing surface trajectory-based ready time estimates. NASA has developed the Precision Departure Release Capability (PDRC) concept that improves tactical departure scheduling by automatically communicating surface trajectory-based ready time predictions and departure runway assignments to the Center scheduling tool. The PDRC concept also incorporates earlier NASA and FAA research into automation-assisted CFR coordination. The PDRC concept reduces uncertainty by automatically communicating coordinated release times with seconds-level precision enabling TMCs and FLMs to work with target times rather than windows. NASA has developed a PDRC prototype system that integrates the Center's TMA system with a research prototype Tower decision support tool. A two-phase field evaluation was conducted at NASA's North Texas Research Station in Dallas-Fort Worth. The field evaluation validated the PDRC concept and demonstrated reduced release time uncertainty while being used for tactical departure scheduling of more than 230 operational flights over 29 weeks of operations.

Precision Departure Release Capability (PDRC) Concept of Operations

NASA Technical Reports Server (NTRS)

Engelland, Shawn; Capps, Richard A.; Day, Kevin Brian

2013-01-01

After takeoff, aircraft must merge into en route (Center) airspace traffic flows which may be subject to constraints that create localized demandcapacity imbalances. When demand exceeds capacity Traffic Management Coordinators (TMCs) often use tactical departure scheduling to manage the flow of departures into the constrained Center traffic flow. Tactical departure scheduling usually involves use of a Call for Release (CFR) procedure wherein the Tower must call the Center TMC to coordinate a release time prior to allowing the flight to depart. In present-day operations release times are computed by the Center Traffic Management Advisor (TMA) decision support tool based upon manual estimates of aircraft ready time verbally communicated from the Tower to the Center. The TMA-computed release is verbally communicated from the Center back to the Tower where it is relayed to the Local controller as a release window that is typically three minutes wide. The Local controller will manage the departure to meet the coordinated release time window. Manual ready time prediction and verbal release time coordination are labor intensive and prone to inaccuracy. Also, use of release time windows adds uncertainty to the tactical departure process. Analysis of more than one million flights from January 2011 indicates that a significant number of tactically scheduled aircraft missed their en route slot due to ready time prediction uncertainty. Uncertainty in ready time estimates may result in missed opportunities to merge into constrained en route flows and lead to lost throughput. Next Generation Air Transportation System (NextGen) plans call for development of Tower automation systems capable of computing surface trajectory-based ready time estimates. NASA has developed the Precision Departure Release Capability (PDRC) concept that uses this technology to improve tactical departure scheduling by automatically communicating surface trajectory-based ready time predictions to the Center scheduling tool. The PDRC concept also incorporates earlier NASA and FAA research into automation-assisted CFR coordination. The PDRC concept helps reduce uncertainty by automatically communicating coordinated release times with seconds-level precision enabling TMCs to work with target times rather than windows. NASA has developed a PDRC prototype system that integrates the Center's TMA system with a research prototype Tower decision support tool. A two-phase field evaluation was conducted at NASA's North Texas Research Station (NTX) in DallasFort Worth. The field evaluation validated the PDRC concept and demonstrated reduced release time uncertainty while being used for tactical departure scheduling of more than 230 operational flights over 29 weeks of operations. This paper presents the Concept of Operations. Companion papers include the Final Report and a Technology Description. ? SUBJECT:

Mechanics of wafer bonding: Effect of clamping

NASA Astrophysics Data System (ADS)

Turner, K. T.; Thouless, M. D.; Spearing, S. M.

2004-01-01

A mechanics-based model is developed to examine the effects of clamping during wafer bonding processes. The model provides closed-form expressions that relate the initial geometry and elastic properties of the wafers to the final shape of the bonded pair and the strain energy release rate at the interface for two different clamping configurations. The results demonstrate that the curvature of bonded pairs may be controlled through the use of specific clamping arrangements during the bonding process. Furthermore, it is demonstrated that the strain energy release rate depends on the clamping configuration and that using applied loads usually leads to an undesirable increase in the strain energy release rate. The results are discussed in detail and implications for process development and bonding tool design are highlighted.

Permeability of starch gel matrices and select films to solvent vapors

USDA-ARS?s Scientific Manuscript database

The controlled release of volatile, agrochemicals is critical in developing approaches to pest control that are economically viable and environmentally sound. Dispensing systems that are made of materials that degrade in agricultural environments when they are spent offer distinct advantages over no...

Development of Bilayer Tablets with Modified Release of Selected Incompatible Drugs.

PubMed

Dhiman, Neha; Awasthi, Rajendra; Jindal, Shammy; Khatri, Smriti; Dua, Kamal

2016-01-01

The oral route is considered to be the most convenient and commonly-employed route for drug delivery. When two incompatible drugs need to be administered at the same time and in a single formulation, bilayer tablets are the most appropriate dosage form to administer such incompatible drugs in a single dose. The aim of the present investigation was to develop bilayered tablets of two incompatible drugs; telmisartan and simvastatin. The bilayer tablets were prepared containing telmisartan in a conventional release layer using croscarmellose sodium as a super disintegrant and simvastatin in a slow-release layer using HPMC K15M, Carbopol 934P and PVP K 30 as matrix forming polymers. The tablets were evaluated for various physical properties, drug-excipient interactions using FTIR spectroscopy and in vitro drug release using 0.1M HCl (pH 1.2) for the first hour and phosphate buffer (pH 6.8) for the remaining period of time. The release kinetics of simvastatin from the slow release layer were evaluated using the zero order, first order, Higuchi equation and Peppas equation. All the physical parameters (such as hardness, thickness, disintegration, friability and layer separation tests) were found to be satisfactory. The FTIR studies indicated the absence of interactions between the components within the individual layers, suggesting drug-excipient compatibility in all the formulations. No drug release from the slow-release layer was observed during the first hour of the dissolution study in 0.1M HCl. The release-controlling polymers had a significant effect on the release of simvastatin from the slow-release layer. Thus, the formulated bilayer tablets avoided incompatibility issues and proved the conventional release of telmisartan (85% in 45 min) and slow release of simvastatin (80% in 8 h). Stable and compatible bilayer tablets containing telmisartan and simvastatin were developed with better patient compliance as an alternative to existing conventional dosage forms.

Biphasic magnetic nanoparticles-nanovesicle hybrids for chemotherapy and self-controlled hyperthermia.

PubMed

Gogoi, Manashjit; Sarma, Haladhar D; Bahadur, Dhirendra; Banerjee, Rinti

2014-05-01

The aim was to develop magnetic nanovesicles for chemotherapy and self-controlled hyperthermia that prevent overheating of tissues. Magnetic nanovesicles containing paclitaxel and a dextran-coated biphasic suspension of La0.75Sr0.25MnO3 and Fe3O4 nanoparticles (magnetic nanoparticles) were developed. Encapsulation efficiencies of magnetic nanoparticles and paclitaxel were 67 ± 5 and 83 ± 3%, respectively. Sequential release performed at 37°C for 1 h followed by 44°C for another 1 h (as expected for intratumoral injection), showed a cumulative release of 6.6% (109.6 µg), which was above the IC50 of the drug. In an alternating current magnetic field, the temperature remained controlled at 44°C and a synergistic cytotoxicity of paclitaxel and hyperthermia was observed in MCF-7 cells. Magnetic nanovesicles containing biphasic suspensions La0.75Sr0.25MnO3 and Fe3O4 nanoparticles encapsulating paclitaxel have potential for combined self-controlled hyperthermia and chemotherapy.

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.

Human transport protein carrier for controlled photoactivation of antitumor prodrug and real-time intracellular tumor imaging.

PubMed

Li, Xi; Mu, Jing; Liu, Fang; Tan, Eddy Wei Ping; Khezri, Bahareh; Webster, Richard D; Yeow, Edwin Kok Lee; Xing, Bengang

2015-05-20

Current anticancer chemotherapy often suffers from poor tumor selectivity and serious drug resistance. Proper vectors for targeted delivery and controlled drug release play crucial roles in improving the therapeutic selectivity to tumor areas and also overcoming the resistance of cancer cells. In this work, we developed a novel human serum albumin (HSA) protein-based nanocarrier system, which combines the photoactivatable Pt(IV) antitumor prodrug for realizing the controlled release and fluorescent light-up probe for evaluations of drug action and efficacy. The constructed Pt(IV)-probe@HSA platform can be locally activated by light irradiation to release the active Pt species, which results in enhanced cell death at both drug-sensitive A2780 and cisplatin-resistant A2780cis cell lines when compared to the free prodrug molecules. Simultaneously, the cytotoxicity caused by light controlled drug release would further lead to the cellular apoptosis and trigger the activation of caspases 3, one crucial protease enzyme in apoptotic process, which could cleave the recognition peptide moiety (DEVD) with a flanking fluorescent resonance energy transfer (FRET) pair containing near-infrared (NIR) fluorophore Cy5 and quencher Qsy21 on the HSA nanocarrier surface. The turn-on fluorescence in response to caspase-3 could be assessed by fluorescence microscopy and flow cytometry analysis. Our results supported the hypothesis that such a unique design may present a successful platform for multiple roles: (i) a biocompatible protein-based nanocarrier for drug delivery, (ii) the controlled drug release with strengthened therapeutic effects, (iii) real-time monitoring of antitumor drug efficacy at the earlier stage.

Marine structure derived calcium phosphate-polymer biocomposites for local antibiotic delivery.

PubMed

Macha, Innocent J; Cazalbou, Sophie; Ben-Nissan, Besim; Harvey, Kate L; Milthorpe, Bruce

2015-01-20

Hydrothermally converted coralline hydroxyapatite (HAp) particles loaded with medically active substances were used to develop polylactic acid (PLA) thin film composites for slow drug delivery systems. The effects of HAp particles within PLA matrix on the gentamicin (GM) release and release kinetics were studied. The gentamicin release kinetics seemed to follow Power law Korsmeyer Peppas model with mainly diffusional process with a number of different drug transport mechanisms. Statistical analysis shows very significant difference on the release of gentamicin between GM containing PLA (PLAGM) and GM containing HAp microspheres within PLA matrix (PLAHApGM) devices, which PLAHApGM displays lower release rates. The use of HAp particles improved drug stabilization and higher drug encapsulation efficiency of the carrier. HAp is also the source of Ca2+ for the regeneration and repair of diseased bone tissue. The release profiles, exhibited a steady state release rate with significant antimicrobial activity against Staphylococcus aureus (S. aureus) (SH1000) even at high concentration of bacteria. The devices also indicated significant ability to control the growth of bacterial even after four weeks of drug release. Clinical release profiles can be easily tuned from drug-HAp physicochemical interactions and degradation kinetics of polymer matrix. The developed systems could be applied to prevent microbial adhesion to medical implant surfaces and to treat infections mainly caused by S. aureus in surgery.

Marine Structure Derived Calcium Phosphate–Polymer Biocomposites for Local Antibiotic Delivery

PubMed Central

Macha, Innocent J.; Cazalbou, Sophie; Ben-Nissan, Besim; Harvey, Kate L.; Milthorpe, Bruce

2015-01-01

Hydrothermally converted coralline hydroxyapatite (HAp) particles loaded with medically active substances were used to develop polylactic acid (PLA) thin film composites for slow drug delivery systems. The effects of HAp particles within PLA matrix on the gentamicin (GM) release and release kinetics were studied. The gentamicin release kinetics seemed to follow Power law Korsmeyer Peppas model with mainly diffusional process with a number of different drug transport mechanisms. Statistical analysis shows very significant difference on the release of gentamicin between GM containing PLA (PLAGM) and GM containing HAp microspheres within PLA matrix (PLAHApGM) devices, which PLAHApGM displays lower release rates. The use of HAp particles improved drug stabilization and higher drug encapsulation efficiency of the carrier. HAp is also the source of Ca2+ for the regeneration and repair of diseased bone tissue. The release profiles, exhibited a steady state release rate with significant antimicrobial activity against Staphylococcus aureus (S. aureus) (SH1000) even at high concentration of bacteria. The devices also indicated significant ability to control the growth of bacterial even after four weeks of drug release. Clinical release profiles can be easily tuned from drug-HAp physicochemical interactions and degradation kinetics of polymer matrix. The developed systems could be applied to prevent microbial adhesion to medical implant surfaces and to treat infections mainly caused by S. aureus in surgery. PMID:25608725

Development and characterisation of electrospun timolol maleate-loaded polymeric contact lens coatings containing various permeation enhancers.

PubMed

Mehta, Prina; Al-Kinani, Ali A; Arshad, Muhammad Sohail; Chang, Ming-Wei; Alany, Raid G; Ahmad, Zeeshan

2017-10-30

Despite exponential growth in research relating to sustained and controlled ocular drug delivery, anatomical and chemical barriers of the eye still pose formulation challenges. Nanotechnology integration into the pharmaceutical industry has aided efforts in potential ocular drug device development. Here, the integration and in vitro effect of four different permeation enhancers (PEs) on the release of anti-glaucoma drug timolol maleate (TM) from polymeric nanofiber formulations is explored. Electrohydrodynamic (EHD) engineering, more specifically electrospinning, was used to engineer nanofibers (NFs) which coated the exterior of contact lenses. Parameters used for engineering included flow rates ranging from 8 to 15μL/min and a novel EHD deposition system was used; capable of hosting four lenses, masked template and a ground electrode to direct charged atomised structures. SEM analysis of the electrospun structures confirmed the presence of smooth nano-fibers; whilst thermal analysis confirmed the stability of all formulations. In vitro release studies demonstrated a triphasic release; initial burst release with two subsequent sustained release phases with most of the drug being released after 24h (86.7%) Biological evaluation studies confirmed the tolerability of all formulations tested with release kinetics modelling results showing drug release was via quasi-Fickian or Fickian diffusion. There were evident differences (p<0.05) in TM release dependant on permeation enhancer. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

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.

Molecularly Imprinted Polymers: Novel Discovery for Drug Delivery.

PubMed

Dhanashree, Surve; Priyanka, Mohite; Manisha, Karpe; Vilasrao, Kadam

2016-01-01

Molecularly imprinted polymers (MIP) are novel carriers synthesized by imprinting of a template over a polymer. This paper presents the recent application of MIP for diagnostic and therapeutic drug delivery. MIP owing to their 3D polymeric structures and due to bond formation with the template serves as a reservoir of active causing stimuli sensitive, enantioselective, targetted and/or controlled release. The review elaborates about key factors for optimization of MIP, controlled release by MIP for various administration routes various forms like patches, contact lenses, nanowires along with illustrations. To overcome the limitation of organic solvent usage causing increased cost, water compatible MIP and use of supercritical fluid technology for molecular imprinting were developed. Novel methods for developing water compatible MIP like pickering emulsion polymerization, co-precipitation method, cyclodextrin imprinting, surface grafting, controlled/living radical chain polymerization methods are described with illustration in this review. Various protein imprinting methods like bulk, epitope and surface imprinting are described along with illustrations. Further, application of MIP in microdevices as biomimetic sensing element for personalized therapy is elaborated. Although development and application of MIP in drug delivery is still at its infancy, constant efforts of researchers will lead to a novel intelligent drug delivery with commercial value. Efforts should be directed in developing solid oral dosage forms consisting of MIP for therapeutic protein and peptide delivery and targeted release of potent drugs addressing life threatening disease like cancer. Amalgamation of bio-engineering and pharmaceutical techniques can make these future prospects into reality.

Hindered disulfide bonds to regulate release rate of model drug from mesoporous silica.

PubMed

Nadrah, Peter; Maver, Uroš; Jemec, Anita; Tišler, Tatjana; Bele, Marjan; Dražić, Goran; Benčina, Mojca; Pintar, Albin; Planinšek, Odon; Gaberšček, Miran

2013-05-01

With the advancement of drug delivery systems based on mesoporous silica nanoparticles (MSNs), a simple and efficient method regulating the drug release kinetics is needed. We developed redox-responsive release systems with three levels of hindrance around the disulfide bond. A model drug (rhodamine B dye) was loaded into MSNs' mesoporous voids. The pore opening was capped with β-cyclodextrin in order to prevent leakage of drug. Indeed, in absence of a reducing agent the systems exhibited little leakage, while the addition of dithiothreitol cleaved the disulfide bonds and enabled the release of cargo. The release rate and the amount of released dye were tuned by the level of hindrance around disulfide bonds, with the increased hindrance causing a decrease in the release rate as well as in the amount of released drug. Thus, we demonstrated the ability of the present mesoporous systems to intrinsically control the release rate and the amount of the released cargo by only minor structural variations. Furthermore, an in vivo experiment on zebrafish confirmed that the present model delivery system is nonteratogenic.

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

NASA Astrophysics Data System (ADS)

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

2017-07-01

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

Fabrication and physical-chemical characterisation of polyelectrolyte microparticles: platform for controlled release of bioactives.

PubMed

Sun, Yuhui; Travas-Sejdic, Jadranka; Wen, Jingyuan; Alany, Raid G

2009-08-01

Porous CaCO(3) microparticles were fabricated by colloidal crystallization. Two oppositely charged polyelectrolytes, poly (styrene sulfonate, PSS) and poly (allylamine hydrochloride, PAH) were adsorbed layer-by-layer on the CaCO(3) templates. Polyelectrolyte microcapsules were then obtained by removing the CaCO(3) core. Scanning electron microscopy (SEM), energy-dispersion X-ray analysis (EDX), laser diffraction particle sizing and Raman spectroscopy were employed to characterize the physico-chemical properties of the constructed microcapsules. In vitro drug release studies were conducted using the model water-soluble drug Rhodamine B. Factors such as the number of polyelectrolyte layers and pH were investigated. SEM micrographs revealed uniform CaCO(3) microparticles, nearly spherical in shape with pronounced surface roughness, and highly developed interior porous structure. The surface of polyelectrolyte coated particles became rougher than the initial CaCO(3) microparticles. The acquired SEM micrographs of the (PSS/PAH)(n) microcapsules indicated that the number of layers affected the morphology of the microcapsules. The (PSS/PAH)(3) microcapsules revealed a very porous network with many holes resembling the initial morphology of CaCO(3) microparticles. Raman spectra showed peaks at 1125 cm(-1) (S=O bond) and 1600 cm(-1) (aromatic ring stretching) which represented the PSS molecule. The thickness of each layer was about 10 to 20 nm and it can be tailored to such nanometer level by controlling the number of adsorbed layers. The in vitro release of Rhodamine B was dependent on both the number of wall bilayers as well as the pH of the release media. These systems provide an opportunity for the development of controlled release dosage forms with greater effectiveness in the treatment of chronic conditions.

pH responsive alginate polymeric rafts for controlled drug release by using box behnken response surface design

PubMed Central

Abbas, Ghulam; Hanif, Muhammad; Khan, Mahtab Ahmad

2017-01-01

Abstract Aim of the present work was to develop alginate raft forming tablets for controlled release pantoprazole sodium sesquihydrate (PSS). Box behnken design was used to optimize 15 formulations with three independent and three dependent variables. Physical tests of all formulations were within pharmacopoeial limits. Raft was characterized by their strength, thickness, resilience, acid neutralizing capacity, floating lag time and total floating time. Raft strength, thickness and resilience of optimized formulation AR9 were 7.43 ± 0.019 g, 5.8 ± 0.245 cm and greater than 480 min, respectively. Buffering and neutralizing capacity were 11.2 ± 1.01 and 6.5 ± 0.56 meq, respectively. Dissolution studies were performed by using simulated gastric fluid pH 1.2 and cumulative percentage release of optimized formulation AR9 was found 98%. First order release kinetics were followed and non-fickian diffusion was observed as value of n was greater than 0.45 in korsmeyer-peppas model. PSS, polymers, tablets and rafts were further characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffractometry (XRD) and differential scanning calorimetry (DSC). FTIR spectra of PSS, polymers and raft of optimized formulation AR9 showed peaks at 3223.09, 1688.17, 1586.67, 1302.64 and 1027.74 cm−1 due to –OH stretching, ester carbonyl group (C=O) stretching, existence of water and carboxylic group in raft, C–N stretching and –OH bending vibration showed no interaction between them. XRD showed diffraction lines indicates crystalline nature of PSS. DSC thermogram showed endothermic peaks at 250 °C for PSS. The developed raft was suitable for controlled release delivery of PSS. PMID:29491774

The development of injectable gelatin/silk fibroin microspheres for the dual delivery of curcumin and piperine.

PubMed

Ratanavaraporn, Juthamas; Kanokpanont, Sorada; Damrongsakkul, Siriporn

2014-02-01

The objective of this study was to develop the microspheres from gelatin (G) and silk fibroin (SF) aimed to be applied for the controlled release of curcumin and piperine. The glutaraldehyde-crosslinked G/SF microspheres at various weight blending ratios (100/0, 70/30, 50/50, and 30/70) were successfully fabricated by water in oil emulsion technique. The microspheres prepared from all compositions were in a round shape with homogeneous size distribution both in the dried (194-217 μm) and swollen states (297-367 μm). When subjected in collagenase solution at physiological condition, the G microspheres gradually degraded within 14 days while the blended G/SF microspheres, particularly at 50/50 and 30/70, were not degraded. For the release application, the microspheres were loaded with curcumin and/or piperine. It was found that the microspheres composed of SF tended to entrap curcumin and piperine with the high entrapment and loading efficiencies, possibly due to their hydrophobic interactions. The G/SF microspheres, particularly at the ratios of 50/50 and 30/70, released curcumin and piperine in a sustained manner both for the single and dual release systems. The controlled dual release of curcumin and piperine from the G/SF microspheres would prolong their half-life, provide the optimal concentrations for therapeutic effects at a target site, and improve the bioavailability of curcumin. These novel injectable microspheres dually releasing curcumin and piperine would be introduced for the treatment of diseases without the need of operation.

Osmotically regulated floating asymmetric membrane capsule for controlled site-specific delivery of ranitidine hydrochloride: optimization by central composite design.

PubMed

Chauhan, Manvendra S; Kumar, Anil; Pathak, Kamla

2012-12-01

A nondisintegrating, floating asymmetric membrane capsule (FAMC) was developed to achieve site-specific osmotic flow of a highly water-soluble drug, ranitidine hydrochloride (RHCl), in a controlled manner. Solubility suppression of RHCl was achieved by the common ion effect, using optimized coated sodium chloride as a formulation component. The capsular wall of FAMC was prepared by the phase inversion process wherein the polymeric membrane was precipitated on glass pins by dipping them in a solution of cellulose acetate followed by quenching. Central composite design was utilized to investigate the influence of independent variables, namely, level(s) of membrane former, pore former, and osmogen, on percent cumulative drug release (response). The release mechanism of RHCl through FAMC was confirmed as osmotic pumping. The asymmetry of the membrane was characterized by scanning electron microscopy that revealed a dense nonporous outer region of membrane supported by an inner porous region. Differential scanning calorimetry indicated no incompatibility between the drug and excipients. In vitro drug release in three biorelevant media, pH 2.5 (low fed), pH 4.5 (intermediate fed), and pH 6.5 (high fed), demonstrated pH-independent release of RHCl (P > 0.05). Floating ability for 12 h of the optimized FAMC9 was visually examined during the in vitro release studies that showed maximal drug release with zero-order kinetics (r (2) = 0.9991). Thus, a novel osmotically regulated floating capsular system was developed for site-specific delivery of RHCl.

Sustained release of methotrexate through liquid-crystalline folate nanoparticles.

PubMed

Misra, Rahul; Mohanty, Sanat

2014-09-01

To make chemotherapy more effective, sustained release of the drug is desirable. By controlling the release rates, constant therapeutic levels can be achieved which can avoid re-administration of drug. This helps to combat tumors more effectively with minimal side effects. The present study reports the control release of methotrexate through liquid-crystalline folate nanoparticles. These nanoparticles are composed of highly ordered folate self-assembly which encapsulate methotrexate molecules. These drug molecules can be released in a controlled manner by disrupting this assembly in the environment of monovalent cations. The ordered structure of folate nanoparticles offers low drug losses of about 4-5%, which is significant in itself. This study reports the size-control method of forming methotrexate encapsulated folate nanoparticles as well as the release of methotrexate through these nanoparticles. It has been demonstrated that methotrexate release rates can be controlled by controlling the size of the nanoparticles, cross-linking cation and cross-linking concentration. The effect of different factors like drug loading, release medium, and pH of the medium on methotrexate release rates was also studied.

Kinetics of drug release from ointments: Role of transient-boundary layer.

PubMed

Xu, Xiaoming; Al-Ghabeish, Manar; Krishnaiah, Yellela S R; Rahman, Ziyaur; Khan, Mansoor A

2015-10-15

In the current work, an in vitro release testing method suitable for ointment formulations was developed using acyclovir as a model drug. Release studies were carried out using enhancer cells on acyclovir ointments prepared with oleaginous, absorption, and water-soluble bases. Kinetics and mechanism of drug release was found to be highly dependent on the type of ointment bases. In oleaginous bases, drug release followed a unique logarithmic-time dependent profile; in both absorption and water-soluble bases, drug release exhibited linearity with respect to square root of time (Higuchi model) albeit differences in the overall release profile. To help understand the underlying cause of logarithmic-time dependency of drug release, a novel transient-boundary hypothesis was proposed, verified, and compared to Higuchi theory. Furthermore, impact of drug solubility (under various pH conditions) and temperature on drug release were assessed. Additionally, conditions under which deviations from logarithmic-time drug release kinetics occur were determined using in situ UV fiber-optics. Overall, the results suggest that for oleaginous ointments containing dispersed drug particles, kinetics and mechanism of drug release is controlled by expansion of transient boundary layer, and drug release increases linearly with respect to logarithmic time. Published by Elsevier B.V.

Coaxial electrospinning for encapsulation and controlled release of fragile water-soluble bioactive agents.

PubMed

Jiang, Hongliang; Wang, Liqun; Zhu, Kangjie

2014-11-10

Coaxial electrospinning is a robust technique for one-step encapsulation of fragile, water-soluble bioactive agents, including growth factors, DNA and even living organisms, into core-shell nanofibers. The coaxial electrospinning process eliminates the damaging effects due to direct contact of the agents with organic solvents or harsh conditions during emulsification. The shell layer serves as a barrier to prevent the premature release of the water-soluble core contents. By varying the structure and composition of the nanofibers, it is possible to precisely modulate the release of the encapsulated agents. Promising work has been done with coaxially electrospun non-woven mats integrated with bioactive agents for use in tissue engineering, in local delivery and in wound healing, etc. This paper reviews the origins of the coaxial electrospinning method, its updated status and potential future developments for controlled release of the class of fragile, water-soluble bioactive agents. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

A photoactivable multi-inhibitor nanoliposome for tumour control and simultaneous inhibition of treatment escape pathways

NASA Astrophysics Data System (ADS)

Spring, Bryan Q.; Bryan Sears, R.; Zheng, Lei Zak; Mai, Zhiming; Watanabe, Reika; Sherwood, Margaret E.; Schoenfeld, David A.; Pogue, Brian W.; Pereira, Stephen P.; Villa, Elizabeth; Hasan, Tayyaba

2016-04-01

Nanoscale drug delivery vehicles can facilitate multimodal therapies of cancer by promoting tumour-selective drug release. However, few are effective because cancer cells develop ways to resist and evade treatment. Here, we introduce a photoactivable multi-inhibitor nanoliposome (PMIL) that imparts light-induced cytotoxicity in synchrony with a photoinitiated and sustained release of inhibitors that suppress tumour regrowth and treatment escape signalling pathways. The PMIL consists of a nanoliposome doped with a photoactivable chromophore (benzoporphyrin derivative, BPD) in the lipid bilayer, and a nanoparticle containing cabozantinib (XL184)—a multikinase inhibitor—encapsulated inside. Near-infrared tumour irradiation, following intravenous PMIL administration, triggers photodynamic damage of tumour cells and microvessels, and simultaneously initiates release of XL184 inside the tumour. A single PMIL treatment achieves prolonged tumour reduction in two mouse models and suppresses metastatic escape in an orthotopic pancreatic tumour model. The PMIL offers new prospects for cancer therapy by enabling spatiotemporal control of drug release while reducing systemic drug exposure and associated toxicities.

Development of a single-dose recombinant CAMP factor entrapping poly(lactide-co-glycolide) microspheres-based vaccine against Streptococcus agalactiae.

PubMed

Liu, Gang; Yin, Jinhua; Barkema, Herman W; Chen, Liben; Shahid, Muhammad; Szenci, Otto; De Buck, Jeroen; Kastelic, John P; Han, Bo

2017-03-01

Streptococcus agalactiae is an important contagious bovine mastitis pathogen. Although it is well controlled and even eradicated in most Northern European and North American dairy herds, the prevalence of this pathogen remains very high in China. However, research on development of a vaccine against S. agalactiae mastitis is scarce. The aims of the present study were to: (1) develop a single-dose vaccine against S. agalactiae based on poly(lactic-co-glycolic acid) (PLGA) microspheres (MS) encapsulated CAMP factor, a conserved virulent protein encoded by S. agalactiae's cfb gene; and (2) evaluate its immunogenicity and protective efficacy in a mouse model. The cfb gene was cloned and expressed in a recombinant Escherichia coli strain Trans1-T1. The CAMP factor was tested to determine a safe dose range and then encapsulated in MS of PLGA (50:50) to assess its release pattern in vitro and immune reaction in vivo. Furthermore, a mouse model and a histopathological assay were developed to evaluate bacterial burden and vaccine efficacy. In the low dosage range (<100μg), CAMP factor had no obvious toxicity in mice. The release pattern in vitro was characterized by an initial burst release (44%), followed by a sustained and slower release over 7wk. In mice immunized with either pure CAMP factor protein or PLGA-CAMP, increased antibody titers were detected in the first 2wk, whereas only PLGA-CAMP immunization induced a sustained increase of antibody titers. In mice vaccinated with PLGA-CAMP, mortality and bacteria counts were lower (compared to a control group) after S. agalactiae challenge. Additionally, no pathological lesions were detected in the vaccinated group. Therefore, PLGA-CAMP conferred protective efficacy against S. agalactiae in our mouse model, indicating its potential as a vaccine against S. agalactiae mastitis. Furthermore, the slow-release kinetics of PLGA MS warranted optimism for development of a single-dose vaccine. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

SAD-B kinase regulates pre-synaptic vesicular dynamics at hippocampal Schaffer collateral synapses and affects contextual fear memory.

PubMed

Watabe, Ayako M; Nagase, Masashi; Hagiwara, Akari; Hida, Yamato; Tsuji, Megumi; Ochiai, Toshitaka; Kato, Fusao; Ohtsuka, Toshihisa

2016-01-01

Synapses of amphids defective (SAD)-A/B kinases control various steps in neuronal development and differentiation, such as axon specifications and maturation in central and peripheral nervous systems. At mature pre-synaptic terminals, SAD-B is associated with synaptic vesicles and the active zone cytomatrix; however, how SAD-B regulates neurotransmission and synaptic plasticity in vivo remains unclear. Thus, we used SAD-B knockout (KO) mice to study the function of this pre-synaptic kinase in the brain. We found that the paired-pulse ratio was significantly enhanced at Shaffer collateral synapses in the hippocampal CA1 region in SAD-B KO mice compared with wild-type littermates. We also found that the frequency of the miniature excitatory post-synaptic current was decreased in SAD-B KO mice. Moreover, synaptic depression following prolonged low-frequency synaptic stimulation was significantly enhanced in SAD-B KO mice. These results suggest that SAD-B kinase regulates vesicular release probability at pre-synaptic terminals and is involved in vesicular trafficking and/or regulation of the readily releasable pool size. Finally, we found that hippocampus-dependent contextual fear learning was significantly impaired in SAD-B KO mice. These observations suggest that SAD-B kinase plays pivotal roles in controlling vesicular release properties and regulating hippocampal function in the mature brain. Synapses of amphids defective (SAD)-A/B kinases control various steps in neuronal development and differentiation, but their roles in mature brains were only partially known. Here, we demonstrated, at mature pre-synaptic terminals, that SAD-B regulates vesicular release probability and synaptic plasticity. Moreover, hippocampus-dependent contextual fear learning was significantly impaired in SAD-B KO mice, suggesting that SAD-B kinase plays pivotal roles in controlling vesicular release properties and regulating hippocampal function in the mature brain. © 2015 International Society for Neurochemistry.

Rifaximin - Chitosan Nanoparticles for Inflammatory Bowel Disease (IBD).

PubMed

Kumar, Jatinder; Newton, Amaldoss M J

2017-01-01

Inflammatory Bowel Disease (IBD) cannot be controlled easily and the recurrence is the most challenging issue for the physicians. There are various controlled and colon targeted drug delivery systems available for the treatment with limited success rate. Nanoparticles prepared by using the colon targeted polymers such as chitosan may improve the IBD due to their smaller size, unique physico chemical properties and targeting potential. The aim of this investigation was designed to formulate and develop a colon targeted polysaccharide nanoparticles of rifaximin (RFX) by using linear polysaccharide chitosan, for the improvement of rifaximin solubility, overall therapeutic efficacy and colon targeting. The research was focused on developing RFX nanoparticles for the treatment of Inflammatory Bowel Disease (IBD) by ionic gelation method. Nanoparticles were subjected to various characterization techniques such as XRD, FTIR and mean particle size (MPS) by Master Sizer and Zeta Sizer. Transmission Electron Microscopy (TEM), drug entrapment efficiency and zeta potential are also determined for the developed formulations. The efficiency of drug release from prepared formulation was studied in vitro by using a dialysis bag diffusion technique in the buffer condition mimicking stomach, intestine and colonic pH conditions. The prepared nanoparticles demonstrated the size in the nano range. The drug release profile was controlled in the upper GI tract and the maximum amount of drug was released in the colonic conditions. The prepared nanoparticles significantly improved the solubility of rifaximin. The zeta potential of the best chitosan preparation was found to be 37.79, which confirms the stability of prepared nanosuspension. Nanoparticles with small particle size found to have high encapsulation efficiency and relatively high loading capacity and predetermined in vitro release profile. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Impacts of an Ammonia Leak on the Cabin Atmosphere of the International Space Station

NASA Technical Reports Server (NTRS)

Duchesne, Stephanie M.; Sweterlitsch, Jeff J.; Son, Chang H.; Perry, Jay L.

2011-01-01

Toxic chemical release into the cabin atmosphere is one of the three major emergency scenarios identified on the International Space Station (ISS). The release of anhydrous ammonia, the coolant used in the U.S. On-orbit Segment (USOS) External Active Thermal Control Subsystem (EATCS), into the ISS cabin atmosphere is one of the most serious toxic chemical release cases identified on board ISS. The USOS Thermal Control System (TCS) includes an Internal Thermal Control Subsystem (ITCS) water loop and an EATCS ammonia loop that transfer heat at the interface heat exchanger (IFHX). Failure modes exist that could cause a breach within the IFHX. This breach would result in high pressure ammonia from the EATCS flowing into the lower pressure ITCS water loop. As the pressure builds in the ITCS loop, it is likely that the gas trap, which has the lowest maximum design pressure within the ITCS, would burst and cause ammonia to enter the ISS atmosphere. It is crucial to first characterize the release of ammonia into the ISS atmosphere in order to develop methods to properly mitigate the environmental risk. This paper will document the methods used to characterize an ammonia leak into the ISS cabin atmosphere. A mathematical model of the leak was first developed in order to define the flow of ammonia into the ISS cabin atmosphere based on a series of IFHX rupture cases. Computational Fluid Dynamics (CFD) methods were then used to model the dispersion of the ammonia throughout the ISS cabin and determine localized effects and ventilation effects on the dispersion of ammonia. Lastly, the capabilities of the current on-orbit systems to remove ammonia were reviewed and scrubbing rates of the ISS systems were defined based on the ammonia release models. With this full characterization of the release of ammonia from the USOS TCS, an appropriate mitigation strategy that includes crew and system emergency response procedures, personal protection equipment use, and atmosphere monitoring and scrubbing hardware can be established.

Impacts of an Ammonia Leak on the Cabin Atmosphere of the International Space Station

NASA Technical Reports Server (NTRS)

Duchesne, Stephanie M.; Sweterlitsch, Jeffrey J.; Son, Chang H.; Perry Jay L.

2012-01-01

Toxic chemical release into the cabin atmosphere is one of the three major emergency scenarios identified on the International Space Station (ISS). The release of anhydrous ammonia, the coolant used in the U.S. On-orbit Segment (USOS) External Active Thermal Control Subsystem (EATCS), into the ISS cabin atmosphere is one of the most serious toxic chemical release cases identified on board ISS. The USOS Thermal Control System (TCS) includes an Internal Thermal Control Subsystem (ITCS) water loop and an EATCS ammonia loop that transfer heat at the interface heat exchanger (IFHX). Failure modes exist that could cause a breach within the IFHX. This breach would result in high pressure ammonia from the EATCS flowing into the lower pressure ITCS water loop. As the pressure builds in the ITCS loop, it is likely that the gas trap, which has the lowest maximum design pressure within the ITCS, would burst and cause ammonia to enter the ISS atmosphere. It is crucial to first characterize the release of ammonia into the ISS atmosphere in order to develop methods to properly mitigate the environmental risk. This paper will document the methods used to characterize an ammonia leak into the ISS cabin atmosphere. A mathematical model of the leak was first developed in order to define the flow of ammonia into the ISS cabin atmosphere based on a series of IFHX rupture cases. Computational Fluid Dynamics (CFD) methods were then used to model the dispersion of the ammonia throughout the ISS cabin and determine localized effects and ventilation effects on the dispersion of ammonia. Lastly, the capabilities of the current on-orbit systems to remove ammonia were reviewed and scrubbing rates of the ISS systems were defined based on the ammonia release models. With this full characterization of the release of ammonia from the USOS TCS, an appropriate mitigation strategy that includes crew and system emergency response procedures, personal protection equipment use, and atmosphere monitoring and scrubbing hardware can be established.

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.).

Continuous Microfluidic Self-Assembly of Hybrid Janus-Like Vesicular Motors: Autonomous Propulsion and Controlled Release.

PubMed

Wang, Lei; Liu, Yijing; He, Jie; Hourwitz, Matthew J; Yang, Yunlong; Fourkas, John T; Han, Xiaojun; Nie, Zhihong

2015-08-01

A microfluidic strategy is developed for the continuous fabrication of hybrid Janus vesicular motors that uniquely combine the capability of autonomous propulsion and externally controlled delivery of encapsulated payload. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Engineering dextran-based scaffolds for drug delivery and tissue repair

PubMed Central

Sun, Guoming; Mao, Jeremy J

2015-01-01

Owing to its chemically reactive hydroxyl groups, dextran can be modified with different functional groups to form spherical, tubular and 3D network structures. The development of novel functional scaffolds for efficient controlled release and tissue regeneration has been a major research interest, and offers promising therapeutics for many diseases. Dextran-based scaffolds are naturally biodegradable and can serve as bioactive carriers for many protein biomolecules. The reconstruction of the in vitro microenvironment with proper signaling cues for large-scale tissue regenerative scaffolds has yet to be fully developed, and remains a significant challenge in regenerative medicine. This paper will describe recent advances in dextran-based polymers and scaffolds for controlled release and tissue engineering. Special attention is given to the development of dextran-based hydrogels that are precisely manipulated with desired structural properties and encapsulated with defined angiogenic growth factors for therapeutic neovascularization, as well as their potential for wound repair. PMID:23210716

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.

Controlled release of cortisone drugs from block copolymers synthetized by ATRP

NASA Astrophysics Data System (ADS)

Valenti, G.; La Carta, S.; Mazzotti, G.; Rapisarda, M.; Perna, S.; Di Gesù, R.; Giorgini, L.; Carbone, D.; Recca, G.; Rizzarelli, P.

2016-05-01

Diseases affecting posterior eye segment, like macular edema, infection and neovascularization, may cause visual impairment. Traditional treatments, such as steroidal-drugs intravitreal injections, involve chronic course of therapy usually over a period of years. Moreover, they can require frequent administrations of drug in order to have an adequately disease control. This dramatically reduce patient's compliance. Efforts have been made to develop implantable devices that offer an alternative therapeutic approach to bypass many challenges of conventional type of therapy. Implantable drug delivery systems (DDS) have been developed to optimize therapeutic properties of drugs and ensure their slow release in the specific site. Polymeric materials can play an essential role in modulating drug delivery and their use in such field has become indispensable. During last decades, acrylic polymers have obtained growing interest. Biocompatibility and chemical properties make them extremely versatile, allowing their use in many field such as biomedical. In particular, block methacrylate copolymer with a balance of hydrophilic and hydrophobic properties can be suitable for prolonged DDS in biomedical devices. In this work, we focused on the realization of a system for controlled and long term release of betamethasone 17,21-dipropionate (BDP), a cortisone drug, from methacrylic block copolymers, to be tested in the treatment of the posterior eye's diseases. Different series of methyl methacrylate/hydroxyethyl methacrylate (MMA/HEMA) block and random copolymers, with different monomer compositions (10-60% HEMA), were synthetized by Atom Transfer Radical Polymerization (ATRP) to find the best hydrophilic/hydrophobic ratio, able to ensure optimal kinetic release. Copolymer samples were characterized by NMR spectroscopy (1H-NMR, 13C-NMR, CosY), SEC, TGA and DSC. Monitoring of drug release from films loaded with BDP was carried out by HPLC analysis. Evaluation of different kinetic models allowed to deduce that release of BDP is controlled over time from PMMA-b-PHEMA 53/47. In particular, PMMA-b-PHEMA 53/47 showed the best release profile to achieve the therapeutic reference dose of 3 µg/die, employed in treatment of posterior eye disease, up to four months. Accordingly, PMMA-b-PHEMA 53/47 has been tested to prepare ocular inserts. Ocular inserts with different shape and the same area of polymer films have been obtained using silicon moulds made by a 3D printer.

Controlled release of cortisone drugs from block copolymers synthetized by ATRP

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

Valenti, G.; La Carta, S.; Rapisarda, M.

Diseases affecting posterior eye segment, like macular edema, infection and neovascularization, may cause visual impairment. Traditional treatments, such as steroidal-drugs intravitreal injections, involve chronic course of therapy usually over a period of years. Moreover, they can require frequent administrations of drug in order to have an adequately disease control. This dramatically reduce patient’s compliance. Efforts have been made to develop implantable devices that offer an alternative therapeutic approach to bypass many challenges of conventional type of therapy. Implantable drug delivery systems (DDS) have been developed to optimize therapeutic properties of drugs and ensure their slow release in the specific site.more » Polymeric materials can play an essential role in modulating drug delivery and their use in such field has become indispensable. During last decades, acrylic polymers have obtained growing interest. Biocompatibility and chemical properties make them extremely versatile, allowing their use in many field such as biomedical. In particular, block methacrylate copolymer with a balance of hydrophilic and hydrophobic properties can be suitable for prolonged DDS in biomedical devices. In this work, we focused on the realization of a system for controlled and long term release of betamethasone 17,21-dipropionate (BDP), a cortisone drug, from methacrylic block copolymers, to be tested in the treatment of the posterior eye’s diseases. Different series of methyl methacrylate/hydroxyethyl methacrylate (MMA/HEMA) block and random copolymers, with different monomer compositions (10–60% HEMA), were synthetized by Atom Transfer Radical Polymerization (ATRP) to find the best hydrophilic/hydrophobic ratio, able to ensure optimal kinetic release. Copolymer samples were characterized by NMR spectroscopy ({sup 1}H-NMR, {sup 13}C-NMR, CosY), SEC, TGA and DSC. Monitoring of drug release from films loaded with BDP was carried out by HPLC analysis. Evaluation of different kinetic models allowed to deduce that release of BDP is controlled over time from PMMA-b-PHEMA 53/47. In particular, PMMA-b-PHEMA 53/47 showed the best release profile to achieve the therapeutic reference dose of 3 µg/die, employed in treatment of posterior eye disease, up to four months. Accordingly, PMMA-b-PHEMA 53/47 has been tested to prepare ocular inserts. Ocular inserts with different shape and the same area of polymer films have been obtained using silicon moulds made by a 3D printer.« less

Preparation, characterization, in vitro drug release, and cellular interactions of tailored paclitaxel releasing polyethylene oxide films for drug-coated balloons.

PubMed

Anderson, Jordan A; Lamichhane, Sujan; Remund, Tyler; Kelly, Patrick; Mani, Gopinath

2016-01-01

Drug-coated balloons (DCBs) are used to treat various cardiovascular diseases. Currently available DCBs carry drug on the balloon surface either solely or using different carriers. Several studies have shown that a significant amount of drug is lost in the blood stream during balloon tracking to deliver only a sub-therapeutic level of drug at the treatment site. This research is focused on developing paclitaxel (PAT) loaded polyethylene oxide (PEO) films (PAT-PEO) as a controlled drug delivery carrier for DCBs. An array of PAT-PEO films were developed in this study to provide tailored release of >90% of drug only at specific time intervals, which is the time frame required for carrying out balloon-based therapy. The characterizations of PAT-PEO films using SEM, FTIR, and DSC showed that the films developed were homogenous and the PAT was molecularly dispersed in the PEO matrix. Mechanical tests showed that most PAT-PEO films developed were flexible and ductile, with yield and tensile strengths not affected after PAT incorporation. The viability, proliferation, morphology, and phenotype of smooth muscle cells (SMCs) interacted with control-PEO and PAT-PEO films were investigated. All control-PEO and PAT-PEO films showed a significant inhibitory effect on the growth of SMCs, with the degree of inhibition strongly dependent on the w/v% of the polymer used. The PAT-PEO coating was produced on the balloons. The integrity of PAT-PEO coating was well maintained without any mechanical defects occurring during balloon inflation or deflation. The drug release studies showed that only 15% of the total PAT loaded was released from the balloons within the initial 1min (typical balloon tracking time), whereas 80% of the PAT was released between 1min and 4min (typical balloon treatment time). Thus, this study demonstrated the use of PEO as an alternate drug delivery system for the balloons. Atherosclerosis is primarily responsible for cardiovascular diseases (CVDs) in millions of patients every year. Drug-coated balloons (DCBs) are commonly used to treat various CVDs. However, in several currently used DCBs, a significant amount of drug is lost in the blood stream during balloon tracking to deliver only a sub-therapeutic level of drug at the treatment site. In this study, paclitaxel containing polyethylene oxide (PEO) films were developed to provide unique advantages including drug release profiles specifically tailored for balloon-based therapy, homogeneous films with molecularly dispersed drug, flexible and ductile films, and exhibits significant inhibitory effect on smooth muscle cell growth. Thus, this study demonstrated the use of PEO as an alternate drug delivery platform for DCBs to improve its efficacy. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Characteristics of taurine release in slices from adult and developing mouse brain stem.

PubMed

Saransaari, P; Oja, S S

2006-07-01

Taurine has been thought to function as a regulator of neuronal activity, neuromodulator and osmoregulator. Moreover, it is essential for the development and survival of neural cells and protects them under cell-damaging conditions. Taurine is also involved in many vital functions regulated by the brain stem, including cardiovascular control and arterial blood pressure. The release of taurine has been studied both in vivo and in vitro in higher brain areas, whereas the mechanisms of release have not been systematically characterized in the brain stem. The properties of release of preloaded [(3)H]taurine were now characterized in slices prepared from the mouse brain stem from developing (7-day-old) and young adult (3-month-old) mice, using a superfusion system. In general, taurine release was found to be similar to that in other brain areas, consisting of both Ca(2+)-dependent and Ca(2+)-independent components. Moreover, the release was mediated by Na(+)-, Cl(-)-dependent transporters operating outwards, as both Na(+)-free and Cl(-) -free conditions greatly enhanced it. Cl(-) channel antagonists and a Cl(-) transport inhibitor reduced the release at both ages, indicating that a part of the release occurs through ion channels. Protein kinases appeared not to be involved in taurine release in the brain stem, since substances affecting the activity of protein kinase C or tyrosine kinase had no significant effects. The release was modulated by cAMP second messenger systems and phospholipases at both ages. Furthermore, the metabotropic glutamate receptor agonists likewise suppressed the K(+)-stimulated release at both ages. In the immature brain stem, the ionotropic glutamate receptor agonists N-methyl-D-aspartate (NMDA) and 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) potentiated taurine release in a receptor-mediated manner. This could constitute an important mechanism against excitotoxicity, protecting the brain stem under cell-damaging conditions.

Polymer Coated Echogenic Lipid Nanoparticles with Dual Release Triggers

PubMed Central

Nahire, Rahul; Haldar, Manas K.; Paul, Shirshendu; Mergoum, Anaas; Ambre, Avinash H.; Katti, Kalpana S.; Gange, Kara N.; Srivastava, D. K.; Sarkar, Kausik; Mallik, Sanku

2013-01-01

Although lipid nanoparticles are promising drug delivery vehicles, passive release of encapsulated contents at the target site is often slow. Herein, we report contents release from targeted, polymer coated, echogenic lipid nanoparticles in the cell cytoplasm by redox trigger and simultaneously enhanced by diagnostic frequency ultrasound. The lipid nanoparticles were polymerized on the external leaflet using a disulfide cross-linker. In the presence of cytosolic concentrations of glutathione, the lipid nanoparticles released 76% of encapsulated contents. Plasma concentrations of glutathione failed to release the encapsulated contents. Application of 3 MHz ultrasound for 2 minutes simultaneously with the reducing agent enhanced the release to 96%. Folic acid conjugated, doxorubicin loaded nanoparticles showed enhanced uptake and higher cytotoxicity in cancer cells overexpressing the folate receptor (compared to the control). With further developments, these lipid nanoparticles have the potential to be used as multimodal nanocarriers for simultaneous targeted drug delivery and ultrasound imaging. PMID:23394107

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.

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.

GSH- and pH-responsive drug delivery system constructed by water-soluble pillar[5]arene and lysine derivative for controllable drug release.

PubMed

Wu, Xuan; Li, Yan; Lin, Chen; Hu, Xiao-Yu; Wang, Leyong

2015-04-21

Novel GSH- and pH-responsive supramolecular vesicles constructed by an amphiphilic inclusion complex formed from water-soluble pillar[5]arene and lysine derivative have been successfully developed, which can efficiently encapsulate anticancer drug MTZ and show rapid MTZ-release in a simulated acidic tumor environment with high GSH concentration, and exhibit potent antitumor activity.

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.

A Voltage-Responsive Free-Blockage Controlled-Release System Based on Hydrophobicity Switching.

PubMed

Jiao, Xiangyu; Sun, Ruijuan; Cheng, Yaya; Li, Fengyu; Du, Xin; Wen, Yongqiang; Song, Yanlin; Zhang, Xueji

2017-05-19

Controlled-release systems based on mesoporous silica nanomaterials (MSNs) have drawn great attention owing to their potential biomedical applications. Various switches have been designed to control the release of cargoes through the construction of physical blocking units on the surface of MSNs. However, such physical blockages are limited by poor sealing ability and low biocompatibility, and most of them lack closure ability. Herein, a voltage-responsive controlled-release system was constructed by functionalizing the nanopore of MSNs with ferrocene. The system realized free-blockage controlled release and achieved pulsatile release. The nanopores of the ferrocene-functionalized MSNs were hydrophobic enough to prevent invasion of the solution. Once a suitable voltage was applied, the nanopores became hydrophilic, which was followed by invasion of the solution and the release of the cargos. Moreover, pulsatile release was realized, which avoided unexpected release after the stimulus disappeared. Thus, we believe that our studies provide new insight into highly effective blockage for MSNs. Furthermore, the voltage-responsive release system is expected to find use in electrical stimulation combination therapy and bioelectricity-responsive release. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Glutathione- and pH-responsive nonporous silica prodrug nanoparticles for controlled release and cancer therapy

NASA Astrophysics Data System (ADS)

Xu, Zhigang; Liu, Shiying; Kang, Yuejun; Wang, Mingfeng

2015-03-01

A myriad of drug delivery systems such as liposomes, micelles, polymers and inorganic nanoparticles (NPs) have been developed for cancer therapy. Very few of them, however, have the ability to integrate multiple functionalities such as specific delivery, high circulation stability, controllable release and good biocompatibility and biodegradability in a single system to improve the therapeutic efficacy. Herein, we report two types of stimuli-responsive nonporous silica prodrug NPs towards this goal for controlled release of anticancer drugs and efficient combinatorial cancer therapy. As a proof of concept, anticancer drugs camptothecin (CPT) and doxorubicin (DOX) were covalently encapsulated into silica matrices through glutathione (GSH)-responsive disulfide and pH-responsive hydrazone bonds, respectively, resulting in NPs with sizes tunable in the range of 50-200 nm. Both silica prodrug NPs showed stimuli-responsive controlled release upon exposure to a GSH-rich or acidic environment, resulting in improved anticancer efficacy. Notably, two prodrug NPs simultaneously taken up by HeLa cells showed a remarkable combinatorial efficacy compared to free drug pairs. These results suggest that the stimuli-responsive silica prodrug NPs are promising anticancer drug carriers for efficient cancer therapy.A myriad of drug delivery systems such as liposomes, micelles, polymers and inorganic nanoparticles (NPs) have been developed for cancer therapy. Very few of them, however, have the ability to integrate multiple functionalities such as specific delivery, high circulation stability, controllable release and good biocompatibility and biodegradability in a single system to improve the therapeutic efficacy. Herein, we report two types of stimuli-responsive nonporous silica prodrug NPs towards this goal for controlled release of anticancer drugs and efficient combinatorial cancer therapy. As a proof of concept, anticancer drugs camptothecin (CPT) and doxorubicin (DOX) were covalently encapsulated into silica matrices through glutathione (GSH)-responsive disulfide and pH-responsive hydrazone bonds, respectively, resulting in NPs with sizes tunable in the range of 50-200 nm. Both silica prodrug NPs showed stimuli-responsive controlled release upon exposure to a GSH-rich or acidic environment, resulting in improved anticancer efficacy. Notably, two prodrug NPs simultaneously taken up by HeLa cells showed a remarkable combinatorial efficacy compared to free drug pairs. These results suggest that the stimuli-responsive silica prodrug NPs are promising anticancer drug carriers for efficient cancer therapy. Electronic supplementary information (ESI) available: Experimental details of SSP-CPT and SSP-DOX; 1H NMR and FT-IR spectra; DLS, TEM and SEM images of prodrug NPs; the TEM image, UV-vis absorption and photoluminescence spectra of CPT/DOX NPs; the TEM images of prodrug NPs incubated under physiological conditions; the reaction conditions and structure information of size-controlled prodrug NPs; the IC50 value of free drug and prodrug NPs at different times. See DOI: 10.1039/c5nr00297d

Application of a Smart Parachute Release Algorithm to the CPAS Test Architecture

NASA Technical Reports Server (NTRS)

Bledsoe, Kristin

2013-01-01

One of the primary test vehicles for the Capsule Parachute Assembly System (CPAS) is the Parachute Test Vehicle (PTV), a capsule shaped structure similar to the Orion design but truncated to fit in the cargo area of a C-17 aircraft. The PTV has a full Orion-like parachute compartment and similar aerodynamics; however, because of the single point attachment of the CPAS parachutes and the lack of Orion-like Reaction Control System (RCS), the PTV has the potential to reach significant body rates. High body rates at the time of the Drogue release may cause the PTV to flip while the parachutes deploy, which may result in the severing of the Pilot or Main risers. In order to prevent high rates at the time of Drogue release, a "smart release" algorithm was implemented in the PTV avionics system. This algorithm, which was developed for the Orion Flight system, triggers the Drogue parachute release when the body rates are near a minimum. This paper discusses the development and testing of the smart release algorithm; its implementation in the PTV avionics and the pretest simulation; and the results of its use on two CPAS tests.

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

PubMed

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

2002-01-01

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

Fluoride-Releasing Materials to Prevent White Spot Lesions around Orthodontic Brackets: A Systematic Review.

PubMed

Nascimento, Patrícia Layane de Menezes Macêdo; Fernandes, Micaelle Tenório Guedes; Figueiredo, Fabricio Eneas Diniz de; Faria-E-Silva, André Luis

2016-01-01

The relation between orthodontic fixed appliances use and enamel demineralization is well established. Different preventive approaches have been suggested to this problem, but controversy remains about which is the best. The aim of this study was to perform a systematic review of clinical trials that investigated the effectiveness of materials containing fluorides to lute brackets or cover the bonding interface in order to inhibit the development and progression of white spot lesions. The null hypothesis was that fluoride materials do not affect the incidence of white spot lesions around brackets. A MEDLINE search was conducted for randomized clinical trials evaluating the development of white spot lesions in patients using fixed orthodontic appliances, followed by meta-analysis comparing the results for patients for whom dental materials containing fluorides were used (experimental group) to those for whom these materials were not used (control group). The pooled relative risk of developing white spot lesions for the experimental group was 0.42 (95% confidence interval: 0.25 to 0.72); hence, when fluoride-releasing materials are used, the patient has 58% less risk of white spot lesion development. Regarding white spot lesion extent, the pooled mean difference between the experimental and control groups was not statistically significant (-0.12; 95% confidence interval: -0.29 to 0.04). In conclusion, the results of the present systematic review suggest that fluoride-releasing materials can reduce the risk of white spot lesions around brackets. However, when white spot lesions had already occurred, there is no evidence that fluoride-releasing materials reduce the extent of these lesions.

Development of PMMA membranes functionalized with hydroxypropyl-beta-cyclodextrins for controlled drug delivery using a supercritical CO(2)-assisted technology.

PubMed

Temtem, M; Pompeu, D; Jaraquemada, G; Cabrita, E J; Casimiro, T; Aguiar-Ricardo, A

2009-07-06

Cyclodextrin-containing polymers have proved themselves to be useful for controlled release. Herein we describe the preparation of membranes of poly(methylmethacrylate) (PMMA) containing hydroxypropyl-beta-cyclodextrins (HP-beta-CDs) using a supercritical CO(2)-assisted phase inversion method, for potential application as drug delivery devices. Results are reported on the membrane preparation, physical properties, and drug elution profile of a model drug. The polymeric membranes were obtained with HP-beta-CD contents ranging from 0 to 33.4 wt%, by changing the composition of the casting solution, and were further impregnated with ibuprofen using supercritical carbon dioxide (scCO(2)) in batch mode. The influence of the membrane functionalization in the controlled release of ibuprofen was studied by performing in vitro experiments in buffer solution pH at 7.4. The release of the anti-inflammatory drug could be tuned by varying the cyclodextrin content on the membranes.

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

Mehl, M; Kukkadapu, G; Kumar, K

The use of gasoline in homogeneous charge compression ignition engines (HCCI) and in duel fuel diesel - gasoline engines, has increased the need to understand its compression ignition processes under engine-like conditions. These processes need to be studied under well-controlled conditions in order to quantify low temperature heat release and to provide fundamental validation data for chemical kinetic models. With this in mind, an experimental campaign has been undertaken in a rapid compression machine (RCM) to measure the ignition of gasoline mixtures over a wide range of compression temperatures and for different compression pressures. By measuring the pressure history duringmore » ignition, information on the first stage ignition (when observed) and second stage ignition are captured along with information on the phasing of the heat release. Heat release processes during ignition are important because gasoline is known to exhibit low temperature heat release, intermediate temperature heat release and high temperature heat release. In an HCCI engine, the occurrence of low-temperature and intermediate-temperature heat release can be exploited to obtain higher load operation and has become a topic of much interest for engine researchers. Consequently, it is important to understand these processes under well-controlled conditions. A four-component gasoline surrogate model (including n-heptane, iso-octane, toluene, and 2-pentene) has been developed to simulate real gasolines. An appropriate surrogate mixture of the four components has been developed to simulate the specific gasoline used in the RCM experiments. This chemical kinetic surrogate model was then used to simulate the RCM experimental results for real gasoline. The experimental and modeling results covered ultra-lean to stoichiometric mixtures, compressed temperatures of 640-950 K, and compression pressures of 20 and 40 bar. The agreement between the experiments and model is encouraging in terms of first-stage (when observed) and second-stage ignition delay times and of heat release rate. The experimental and computational results are used to gain insight into low and intermediate temperature processes during gasoline ignition.« less

Risk Associated with the Release of Wolbachia-Infected Aedes aegypti Mosquitoes into the Environment in an Effort to Control Dengue.

PubMed

Murray, Justine V; Jansen, Cassie C; De Barro, Paul

2016-01-01

In an effort to eliminate dengue, a successful technology was developed with the stable introduction of the obligate intracellular bacteria Wolbachia pipientis into the mosquito Aedes aegypti to reduce its ability to transmit dengue fever due to life shortening and inhibition of viral replication effects. An analysis of risk was required before considering release of the modified mosquito into the environment. Expert knowledge and a risk assessment framework were used to identify risk associated with the release of the modified mosquito. Individual and group expert elicitation was performed to identify potential hazards. A Bayesian network (BN) was developed to capture the relationship between hazards and the likelihood of events occurring. Risk was calculated from the expert likelihood estimates populating the BN and the consequence estimates elicited from experts. The risk model for "Don't Achieve Release" provided an estimated 46% likelihood that the release would not occur by a nominated time but generated an overall risk rating of very low. The ability to obtain compliance had the greatest influence on the likelihood of release occurring. The risk model for "Cause More Harm" provided a 12.5% likelihood that more harm would result from the release, but the overall risk was considered negligible. The efficacy of mosquito management had the most influence, with the perception that the threat of dengue fever had been eliminated, resulting in less household mosquito control, and was scored as the highest ranked individual hazard (albeit low risk). The risk analysis was designed to incorporate the interacting complexity of hazards that may affect the release of the technology into the environment. The risk analysis was a small, but important, implementation phase in the success of this innovative research introducing a new technology to combat dengue transmission in the environment.

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.

The load and release characteristics on a strong cationic ion-exchange fiber: kinetics, thermodynamics, and influences.

PubMed

Yuan, Jing; Gao, Yanan; Wang, Xinyu; Liu, Hongzhuo; Che, Xin; Xu, Lu; Yang, Yang; Wang, Qifang; Wang, Yan; Li, Sanming

2014-01-01

Ion-exchange fibers were different from conventional ion-exchange resins in their non-cross-linked structure. The exchange was located on the surface of the framework, and the transport resistance reduced significantly, which might mean that the exchange is controlled by an ionic reaction instead of diffusion. Therefore, this work aimed to investigate the load and release characteristics of five model drugs with the strong cationic ion-exchange fiber ZB-1. Drugs were loaded using a batch process and released in United States Pharmacopoeia (USP) dissolution apparatus 2. Opposing exchange kinetics, suitable for the special structure of the fiber, were developed for describing the exchange process with the help of thermodynamics, which illustrated that the load was controlled by an ionic reaction. The molecular weight was the most important factor to influence the drug load and release rate. Strong alkalinity and rings in the molecular structures made the affinity between the drug and fiber strong, while logP did not cause any profound differences. The drug-fiber complexes exhibited sustained release. Different kinds and concentrations of counter ions or different amounts of drug-fiber complexes in the release medium affected the release behavior, while the pH value was independent of it. The groundwork for in-depth exploration and further application of ion-exchange fibers has been laid.

The load and release characteristics on a strong cationic ion-exchange fiber: kinetics, thermodynamics, and influences

PubMed Central

Yuan, Jing; Gao, Yanan; Wang, Xinyu; Liu, Hongzhuo; Che, Xin; Xu, Lu; Yang, Yang; Wang, Qifang; Wang, Yan; Li, Sanming

2014-01-01

Ion-exchange fibers were different from conventional ion-exchange resins in their non-cross-linked structure. The exchange was located on the surface of the framework, and the transport resistance reduced significantly, which might mean that the exchange is controlled by an ionic reaction instead of diffusion. Therefore, this work aimed to investigate the load and release characteristics of five model drugs with the strong cationic ion-exchange fiber ZB-1. Drugs were loaded using a batch process and released in United States Pharmacopoeia (USP) dissolution apparatus 2. Opposing exchange kinetics, suitable for the special structure of the fiber, were developed for describing the exchange process with the help of thermodynamics, which illustrated that the load was controlled by an ionic reaction. The molecular weight was the most important factor to influence the drug load and release rate. Strong alkalinity and rings in the molecular structures made the affinity between the drug and fiber strong, while logP did not cause any profound differences. The drug–fiber complexes exhibited sustained release. Different kinds and concentrations of counter ions or different amounts of drug–fiber complexes in the release medium affected the release behavior, while the pH value was independent of it. The groundwork for in-depth exploration and further application of ion-exchange fibers has been laid. PMID:25114504

Presidential Green Chemistry Challenge: 2010 Designing Greener Chemicals Award

EPA Pesticide Factsheets

Presidential Green Chemistry Challenge 2010 award winner, Clarke, developed Natular, a plaster matrix that encapsulates the pesticide spinosad, slowly releasing it into water and effectively controlling mosquito larvae.

A Tunable, Biodegradable, Thin-Film Polymer Device as a Long-Acting Implant Delivering Tenofovir Alafenamide Fumarate for HIV Pre-exposure Prophylaxis

PubMed Central

Schlesinger, Erica; Johengen, Daniel; Luecke, Ellen; Rothrock, Ginger; McGowan, Ian; van der Straten, Ariane; Desai, Tejal

2016-01-01

Purpose The effectiveness of Tenofovir based HIV pre-exposure prophylaxis (PrEP) is proven, but hinges on correct and consistent use. User compliance and therapeutic effectiveness can be improved by long acting drug delivery systems. Here we describe a thin-film polymer device (TFPD) as a biodegradable subcutaneous implant for PrEP. Methods A thin-film polycaprolactone (PCL) membrane controls drug release from a reservoir. To achieve membrane controlled release, TAF requires a formulation excipient such as PEG300 to increase the dissolution rate and reservoir solubility. Short-term In vitro release studies are used to develop an empirical design model, which is applied to the production of in vitro prototype devices demonstrating up to 90-days of linear release and TAF chemical stability. Results The size and shape of the TFPD are tunable, achieving release rates ranging from 0.5–4.4 mg/day in devices no larger than a contraceptive implant. Based on published data for oral TAF, subcutaneous constant-rate release for HIV PrEP is estimated at < 2.8mg/day. Prototype devices demonstrated linear release at 1.2mg/day for up to 90 days and at 2.2mg/day for up to 60 days. Conclusions We present a biodegradable TFPD for subcutaneous delivery of TAF for HIV PrEP. The size, shape and release rate of the device are tunable over a > 8-fold range. PMID:26975357

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

PubMed

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

2014-03-01

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

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.

Magnetic Active Agent Release System (MAARS): evaluation of a new way for a reproducible, externally controlled drug release into the small intestine.

PubMed

Dietzel, Christian T; Richert, Hendryk; Abert, Sandra; Merkel, Ute; Hippius, Marion; Stallmach, Andreas

2012-08-10

Human absorption studies are used to test new drug candidates for their bioavailability in different regions of the gastrointestinal tract. In order to replace invasive techniques (e.g. oral or rectal intubation) a variety of externally controlled capsule-based drug release systems has been developed. Most of these use ionizing radiation, internal batteries, heating elements or even chemicals for the localization and disintegration process of the capsule. This embodies potential harms for volunteers and patients. We report about a novel technique called "Magnetic Active Agent Release System" (MAARS), which uses purely magnetic effects for this purpose. In our trial thirteen healthy volunteers underwent a complete monitoring and release procedure of 250 mg acetylsalicylic acid (ASA) targeting the flexura duodenojejunalis and the mid-part of the jejunum. During all experiments MAARS initiated a sufficient drug release and was well tolerated. Beside this we also could show that the absorption of ASA is about two times faster in the more proximal region of the flexura duodenojejunalis with a tmax of 47±13 min compared to the more distal jejunum with tmax values of 100±10 min (p=0.031). Copyright © 2012 Elsevier B.V. All rights reserved.

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

Efficacy, pharmacokinetics, and biodistribution of thermosensitive chitosan/β-glycerophosphate hydrogel loaded with docetaxel.

PubMed

Li, Cuiyun; Ren, Shuangxia; Dai, Yu; Tian, Fengjie; Wang, Xin; Zhou, Sufeng; Deng, Shuhua; Liu, Qi; Zhao, Jie; Chen, Xijing

2014-04-01

Docetaxel (DTX) is a widely used anticancer drug for various solid tumors. However, its poor solubility in water and lack of specification are two limitations for clinical use. The aim of the study was to develop a thermosensitive chitosan/β-glycerophosphate (C/GP) hydrogel loaded with DTX for intratumoral delivery. The in vitro release profiles, in vivo antitumor efficacy, pharmacokinetics, and biodistribution of DTX-loaded C/GP hydrogel (DTX-C/GP) were evaluated. The results of in vitro release study demonstrated that DTX-C/GP had the property of controlled delivery for a reasonable time span of 3 weeks and the release period was substantially affected by initial DTX strength. The antitumor efficacy of DTX-C/GP was observed at 20 mg/kg in H22 tumor-bearing mice. It was found that the tumor volume was definitely minimized by intratumoral injection of DTX-C/GP. Compared with saline group, the tumor inhibition rate of blank gel, intravenous DTX solution, intratumoral DTX solution, and DTX-C/GP was 2.3%, 29.8%, 41.9%, and 58.1%, respectively. Further, the in vivo pharmacokinetic characteristics of DTX-C/GP correlated well with the in vitro release. DTX-C/GP significantly prolonged the DTX retention and maintained a high DTX concentration in tumor. The amount of DTX distributed to the normal tissues was minimized so that the toxicity was effectively reduced. In conclusion, DTX-C/GP demonstrated controlled release and significant efficacy and exhibited potential for further clinical development.

Host-guest interaction of ZnBDC-MOF + doxorubicin: A theoretical and experimental study

NASA Astrophysics Data System (ADS)

Vasconcelos, Iane B.; Wanderley, Kaline A.; Rodrigues, Nailton M.; da Costa, Nivan B.; Freire, Ricardo O.; Junior, Severino A.

2017-03-01

The incorporation of drugs in biodegradable polymeric particles is one of many processes that controllably and significantly increase their release and action. In this paper, we describe the synthesis and physicochemical characterization of ZnBDC-MOF + doxorubicin (DOXO@ZnBDC) and the system's effectiveness in the sustained release of the drug doxorubicin. An experimental and theoretical study is presented of the interaction between the [Zn(BDC)(H2O)2]n MOF and the drug doxorubicin (DOXO). The synthesis was characterized by elemental analysis and X-ray powder diffraction (XRPD). The experimental incorporation was accomplished and analyzed by Fourier transform infrared spectroscopy (FTIR), XRPD and UV-Vis (ultraviolet-visible) spectrophotometry. Based on an analysis of the doxorubicin release profile, our results suggest that the drug delivery system showed slower release than other systems under development. Studies of cytotoxicity by the MTT method showed good results for the system developed with antineoplastic doxorubicin, and together with the other results of this study, suggest the successful development of a MOF-based drug delivery system.

Digestion proteomics: tracking lactoferrin truncation and peptide release during simulated gastric digestion.

PubMed

Grosvenor, Anita J; Haigh, Brendan J; Dyer, Jolon M

2014-11-01

The extent to which nutritional and functional benefit is derived from proteins in food is related to its breakdown and digestion in the body after consumption. Further, detailed information about food protein truncation during digestion is critical to understanding and optimising the availability of bioactives, in controlling and limiting allergen release, and in minimising or monitoring the effects of processing and food preparation. However, tracking the complex array of products formed during the digestion of proteins is not easily accomplished using classical proteomics. We here present and develop a novel proteomic approach using isobaric labelling to mapping and tracking protein truncation and peptide release during simulated gastric digestion, using bovine lactoferrin as a model food protein. The relative abundance of related peptides was tracked throughout a digestion time course, and the effect of pasteurisation on peptide release assessed. The new approach to food digestion proteomics developed here therefore appears to be highly suitable not only for tracking the truncation and relative abundance of released peptides during gastric digestion, but also for determining the effects of protein modification on digestibility and potential bioavailability.

Development of an Automatic Ground Collision Avoidance System Using a Digital Terrain Database

DTIC Science & Technology

1989-12-01

release; distribution unlimited I I I I The purpose of this study was to develop a working control system that would perform automatic ground... control system analysis. I also wish to extend a hand of appreciation to my sponsor Mr. I Finley Barfield of the Flight Dynamics Laboratory for the use of...facilities, as- sistance in deciphering control law diagrams, and his expert knowledge of the F-16. Under the area of morale, I wish to thank all of my

Osmotic pellet system comprising osmotic core and in-process amorphized drug in polymer-surfactant layer for controlled delivery of poorly water-soluble drug.

PubMed

Saindane, Nilesh; Vavia, Pradeep

2012-09-01

The aim of the present investigation was to develop controlled porosity osmotic system for poorly water-soluble drug based on drug in polymer-surfactant layer technology. A poorly water-soluble drug, glipizide (GZ), was selected as the model drug. The technology involved core of the pellets containing osmotic agent coated with drug dispersed in polymer and surfactant layer, finally coated with release-retardant layer with pore former. The optimized drug-layer-coated pellets were evaluated for solubility of GZ at different pH conditions and characterized for amorphous nature of the drug by differential scanning calorimetry and X-ray powder diffractometry. The optimized release-retardant layer pellets were evaluated for in vitro drug release at different pH, hydrodynamic, and osmolality conditions. The optimized drug layer showed improvement in solubility (10 times in pH 1.2, 11 times in pH 4.5, and 21 times in pH 6.8), whereas pellets coated with cellulose acetate (15.0%, w/w, weight gain) with pore former triethyl citrate (10.0%, w/w, of polymer) demonstrated zero-order drug release for 24 h at different pH conditions; moreover, retardation of drug release was observed with increment of osmolality. This system could be a platform technology for controlled delivery of poorly water-soluble drugs. Copyright © 2012 Wiley Periodicals, Inc.

Polymer-Based Nanofibers Impregnated with Drug Infused Plant Virus Particles as a Responsive Fabric for Therapeutic Delivery

NASA Astrophysics Data System (ADS)

Honarbakhsh, Sara

A biodegradable and controlled drug delivery system has been developed herein composed of electrospun polymeric nanofibers impregnated with cargo loaded Red clover necrotic mosaic virus (RCNMV)---a robust plant virus---as the drug carrier nanoparticle. In this system, controlled drug release is achieved by altering the porosity of the biodegradable matrix as well as controlling the position and distribution of the cargo loaded nanocarriers in the matrix. Solution electrospinning as well as dipping method are used to create and to impregnate the matrix (the fibers of which possess uniformly distributed nano-size surface pores) with cargo loaded nanocarriers. Prior to the impregnation stage of cargo loaded nanocarriers into the matrix, compatibility of a group of candidate cargos (Ampicillin, Novanthrone, Doxorubicin and Ethidium Bromide) and RCNMV functionality with potential electrospinning solvents were investigated and a solvent with the least degradative effect was selected. In order to achieve both sustained and immediate drug release profiles, cargo loaded nanocarriers were embedded into the matrix---through co-spinning process---as well as on the surface of matrix fibers---through dipping method. SEM, TEM and Fluorescent Light Microscopy images of the medicated structures suggested that the nanocarriers were incorporated into/on the matrix. In vitro release assays were also carried out the results of which confirmed having obtained sustained release in the co-spun medicated structures where as dipped samples showed an immediate release profile.

Preformulation considerations for controlled release dosage forms. Part I. Selecting candidates.

PubMed

Chrzanowski, Frank

2008-01-01

The physical-chemical properties of interest for controlled release (CR) dosage form development presented are based on the author's experience. Part I addresses selection of the final form based on a logical progression of physical-chemical properties evaluation of candidate forms and elimination of forms with undesirable properties from further evaluation in order to simplify final form selection. Several candidate forms which could include salt, free base or acid, polymorphic and amorphic forms of a new chemical entity (NCE) or existing drug substance (DS) are prepared and evaluated for critical properties in a scheme relevant to manufacturing processes, predictive of problems, requiring small amounts of test materials and simple analytical tools. A stability indicating assay is not needed to initiate the evaluation. This process is applicable to CR and immediate release (IR) dosage form development. The critical properties evaluated are melting, crystallinity, solubilities in water, 0.1 N HCl, and SIF, hygrodymamics, i.e., moisture sorption and loss at extremes of RH, and LOD at typical wet granulation drying conditions, and processability, i.e., corrosivity, and filming and/or sticking upon compression.

Influence of hydroxypropyl methylcellulose on drug release pattern of a gastroretentive floating drug delivery system using a 3(2) full factorial design.

PubMed

Swain, Kalpana; Pattnaik, Satyanarayan; Mallick, Subrata; Chowdary, Korla Appana

2009-01-01

In the present investigation, controlled release gastroretentive floating drug delivery system of theophylline was developed employing response surface methodology. A 3(2) randomized full factorial design was developed to study the effect of formulation variables like various viscosity grades and contents of hydroxypropyl methylcellulose (HPMC) and their interactions on response variables. The floating lag time for all nine experimental trial batches were less than 2 min and floatation time of more than 12 h. Theophylline release from the polymeric matrix system followed non-Fickian anomalous transport. Multiple regression analysis revealed that both viscosity and content of HPMC had statistically significant influence on all dependent variables but the effect of these variables found to be nonlinear above certain threshold values.

Project W-211, initial tank retrieval systems, retrieval control system software configuration management plan

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

RIECK, C.A.

1999-02-23

This Software Configuration Management Plan (SCMP) provides the instructions for change control of the W-211 Project, Retrieval Control System (RCS) software after initial approval/release but prior to the transfer of custody to the waste tank operations contractor. This plan applies to the W-211 system software developed by the project, consisting of the computer human-machine interface (HMI) and programmable logic controller (PLC) software source and executable code, for production use by the waste tank operations contractor. The plan encompasses that portion of the W-211 RCS software represented on project-specific AUTOCAD drawings that are released as part of the C1 definitive designmore » package (these drawings are identified on the drawing list associated with each C-1 package), and the associated software code. Implementation of the plan is required for formal acceptance testing and production release. The software configuration management plan does not apply to reports and data generated by the software except where specifically identified. Control of information produced by the software once it has been transferred for operation is the responsibility of the receiving organization.« less

A physics-based model for the ionization of samarium by the MOSC chemical releases in the upper atmosphere

NASA Astrophysics Data System (ADS)

Bernhardt, Paul A.; Siefring, Carl L.; Briczinski, Stanley J.; Viggiano, Albert; Caton, Ronald G.; Pedersen, Todd R.; Holmes, Jeffrey M.; Ard, Shaun; Shuman, Nicholas; Groves, Keith M.

2017-05-01

Atomic samarium has been injected into the neutral atmosphere for production of electron clouds that modify the ionosphere. These electron clouds may be used as high-frequency radio wave reflectors or for control of the electrodynamics of the F region. A self-consistent model for the photochemical reactions of Samarium vapor cloud released into the upper atmosphere has been developed and compared with the Metal Oxide Space Cloud (MOSC) experimental observations. The release initially produces a dense plasma cloud that that is rapidly reduced by dissociative recombination and diffusive expansion. The spectral emissions from the release cover the ultraviolet to the near infrared band with contributions from solar fluorescence of the atomic, molecular, and ionized components of the artificial density cloud. Barium releases in sunlight are more efficient than Samarium releases in sunlight for production of dense ionization clouds. Samarium may be of interest for nighttime releases but the artificial electron cloud is limited by recombination with the samarium oxide ion.

Mechanisms of monoclonal antibody stabilization and release from silk biomaterials

PubMed Central

Guziewicz, Nicholas A.; Massetti, Andrew J.; Perez-Ramirez, Bernardo J.; Kaplan, David L.

2013-01-01

The availability of stabilization and sustained delivery systems for antibody therapeutics remains a major clinical challenge, despite the growing development of antibodies for a wide range of therapeutic applications due to their specificity and efficacy. A mechanistic understanding of protein-matrix interactions is critical for the development of such systems and is currently lacking as a mode to guide the field. We report mechanistic insight to address this need by using well-defined matrices based on silk gels, in combination with a monoclonal antibody. Variables including antibody loading, matrix density, charge interactions, hydrophobicity and water access were assessed to clarify mechanisms involved in the release of antibody from the biomaterial matrix. The results indicate that antibody release is primarily governed by hydrophobic interactions and hydration resistance, which are controlled by silk matrix chemistry, peptide domain distribution and protein density. Secondary ionic repulsions are also critical in antibody stabilization and release. Matrix modification by free methionine incorporation was found to be an effective strategy for mitigating encapsulation induced antibody oxidation. Additionally, these studies highlight a characterization approach to improve the understanding and development of other protein sustained delivery systems, with broad applicability to the rapidly developing monoclonal antibody field. PMID:23859659

The Core Flight System (cFS) Community: Providing Low Cost Solutions for Small Spacecraft

NASA Technical Reports Server (NTRS)

McComas, David; Wilmot, Jonathan; Cudmore, Alan

2016-01-01

In February 2015 the NASA Goddard Space Flight Center (GSFC) completed the open source release of the entire Core Flight Software (cFS) suite. After the open source release a multi-NASA center Configuration Control Board (CCB) was established that has managed multiple cFS product releases. The cFS was developed and is being maintained in compliance with the NASA Class B software development process requirements and the open source release includes all Class B artifacts. The cFS is currently running on three operational science spacecraft and is being used on multiple spacecraft and instrument development efforts. While the cFS itself is a viable flight software (FSW) solution, we have discovered that the cFS community is a continuous source of innovation and growth that provides products and tools that serve the entire FSW lifecycle and future mission needs. This paper summarizes the current state of the cFS community, the key FSW technologies being pursued, the development/verification tools and opportunities for the small satellite community to become engaged. The cFS is a proven high quality and cost-effective solution for small satellites with constrained budgets.

Topically Applied Epsilon-Aminocaproic Acid Reduces Blood Loss and Length of Hospital Stay After Total Knee Arthroplasty.

PubMed

Harper, Robert A; Sucher, Mark G; Giordani, Mauro; Nedopil, Alexander J

2017-11-01

Perioperative blood loss after total knee arthroplasty (TKA) affects postoperative recovery. Tranexamic acid is safe and efficient in reducing blood loss without increasing thromboembolic events. Epsilon-aminocaproic acid (ε-ACA) is less expensive than and as safe as tranexamic acid. Its efficiency when locally applied in TKA is unknown. The authors retrospectively followed 240 consecutive patients treated by 1 surgeon with TKA from January 2012 to August 2016. From January 2013 to May 2015, the authors topically applied 5 g of ε-ACA to the open wound after tourniquet release and before closure (ε-ACA-after-tourniquet-release group). From August 2015 to August 2016, the authors topically applied 5 g of ε-ACA intraoperatively to the open wound 3 minutes before tourniquet release (ε-ACA-before-tourniquet-release group). The last 80 patients not receiving ε-ACA (control group), the 80 patients in the ε-ACA-after-tourniquet-release group, and the 80 patients in the ε-ACA-before-tourniquet-release group were compared regarding blood loss, treatment costs, and thromboembolic complications. The mean±SD calculated blood loss was 1478.8±367.1 mL for the control group, 1424.0±249.3 mL for the ε-ACA-after-tourniquet-release group, and 1052.3±419.1 mL for the ε-ACA-before-tourniquet-release group (P<.05). Using ε-ACA before tourniquet release reduced the length of hospital stay by 0.7 days (P<.05) compared with not using ε-ACA, leading to cost savings of $1547.37 per patient. One patient in the ε-ACA-before-tourniquet-release group and 1 patient in the control group developed a venous thromboembolism in the postoperative period. Epsilon-aminocaproic acid significantly reduces blood loss after TKA when topically applied before tourniquet release. Its application reduced costs by decreasing the length of hospital stay and did not increase thromboembolic events. [Orthopedics. 2017; 40(6):e1044-e1049.]. Copyright 2017, SLACK Incorporated.

Controlled release of cyclosporine A self-nanoemulsifying systems from osmotic pump tablets: near zero-order release and pharmacokinetics in dogs.

PubMed

Zhang, Xi; Yi, Yueneng; Qi, Jianping; Lu, Yi; Tian, Zhiqiang; Xie, Yunchang; Yuan, Hailong; Wu, Wei

2013-08-16

It is very important to enhance the absorption simultaneously while designing controlled release delivery systems for poorly water-soluble and poorly permeable drugs (BCS IV). In this study, controlled release of cyclosporine (CyA) was achieved by the osmotic release strategy taking advantage of the absorption-enhancing capacity of self-nanoemulsifying drug delivery systems (SNEDDSs). The liquid SNEDDS consisting of Labrafil M 1944CS, Transcutol P and Cremophor EL was absorbed by the osmotic tablet core excipients (sucrose, lactose monohydrate, polyethylene oxide, and partly pregelatinized starch) and then transformed into osmotic tablets. Near zero-order release could be achieved for CyA-loaded nanoemulsions reconstituted from the SNEDDS. In general, the influencing factor study indicated that the release rate increased with increase of inner osmotic pressure, ratio of osmotic agent to suspending agent, content of pore-forming agent, and size of release orifice, whereas the thickness of the membrane impeded the release of CyA nanoemulsion. Pharmacokinetic study showed steady blood CyA profiles with prolonged Tmax and MRT, and significantly reduced Cmax for self-nanoemulsifying osmotic pump tablet (SNEOPT) in comparison with highly fluctuating profiles of the core tablet and Sandimmune Neoral(®). However, similar oral bioavailability was observed for either controlled release or non-controlled release formulations. It was concluded that simultaneous controlling on CyA release and absorption-enhancing had been achieved by a combination of osmotic tablet and SNEDDS. Copyright © 2013 Elsevier B.V. All rights reserved.

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...

Monitoring fugitive methane and natural gas emissions, validation of measurement techniques.

NASA Astrophysics Data System (ADS)

Robinson, Rod; Innocenti, Fabrizio; Gardiner, Tom; Helmore, Jon; Finlayson, Andrew; Connor, Andy

2017-04-01

The detection and quantification of fugitive and diffuse methane emissions has become an increasing priority in recent years. As the requirements for routine measurement to support industry initiatives increase there is a growing requirement to assess and validate the performance of fugitive emission measurement technologies. For reported emissions traceability and comparability of measurements is important. This talk will present recent work addressing these needs. Differential Absorption Lidar (DIAL) is a laser based remote sensing technology, able to map the concentration of gases in the atmosphere and determine emission fluxes for fugitive emissions. A description of the technique and its application for determining fugitive emissions of methane from oil and gas operations and waste management sites will be given. As DIAL has gained acceptance as a powerful tool for the measurement and quantification of fugitive emissions, and given the rich data it produces, it is being increasingly used to assess and validate other measurement approaches. In addition, to support the validation of technologies, we have developed a portable controlled release facility able to simulate the emissions from area sources. This has been used to assess and validate techniques which are used to monitor emissions. The development and capabilities of the controlled release facility will be described. This talk will report on recent studies using DIAL and the controlled release facility to validate fugitive emission measurement techniques. This includes side by side comparisons of two DIAL systems, the application of both the DIAL technique and the controlled release facility in a major study carried out in 2015 by South Coast Air Quality Management District (SCAQMD) in which a number of optical techniques were assessed and the development of a prototype method validation approach for techniques used to measure methane emissions from shale gas sites. In conclusion the talk will provide an update on the current status in the development of a European Standard for the measurement of fugitive emissions of VOCs and the use of validation data in the standardisation process and discuss the application of this to methane measurement.

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

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

A multiple functional connector for high-resolution optical satellites

NASA Astrophysics Data System (ADS)

She, Fengke; Zheng, Gangtie

2017-11-01

For earth observation satellites, perturbations from actuators, such as CMGs and momentum wheels, and thermal loadings from support structures often have significant impact on the image quality of an optical. Therefore, vibration isolators and thermal deformation releasing devices nowadays often become important parts of an image satellite. However, all these devices will weak the connection stiffness between the optical instrument and the satellite bus structure. This will cause concern of the attitude control system design for worrying about possible negative effect on the attitude control. Therefore, a connection design satisfying all three requirements is a challenge of advanced image satellites. Chinese scientists have proposed a large aperture high-resolution satellite for earth observation. To meet all these requirements and ensure image quality, specified multiple function connectors are designed to meet these challenging requirements, which are: isolating vibration, releasing thermal deformation and ensuring whole satellite dynamic properties [1]. In this paper, a parallel spring guide flexure is developed for both vibration isolation and thermal deformation releasing. The stiffness of the flexure is designed to meet the vibration isolation requirement. To attenuate vibration, and more importantly to satisfy the stability requirement of the attitude control system, metal damping, which has many merits for space applications, are applied in this connecter to provide a high damping ratio and nonlinear stiffness. The capability of the connecter for vibration isolation and attenuation is validated through numerical simulation and experiments. Connecter parameter optimization is also conducted to meet both requirements of thermal deformation releasing and attitude control. Analysis results show that the in-orbit attitude control requirement is satisfied while the thermal releasing performance is optimized. The design methods and analysis results are also provided in the present paper.

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

An overview of in vitro dissolution/release methods for novel mucosal drug delivery systems.

PubMed

Jug, Mario; Hafner, Anita; Lovrić, Jasmina; Kregar, Maja Lusina; Pepić, Ivan; Vanić, Željka; Cetina-Čižmek, Biserka; Filipović-Grčić, Jelena

2018-01-05

In vitro dissolution/release tests are an important tool in the drug product development phase as well as in its quality control and the regulatory approval process. Mucosal drug delivery systems are aimed to provide both local and systemic drug action via mucosal surfaces of the body and exhibit significant differences in formulation design, as well as in their physicochemical and release characteristics. Therefore it is not possible to devise a single test system which would be suitable for release testing of such complex dosage forms. This article is aimed to provide a comprehensive review of both compendial and noncompendial methods used for in vitro dissolution/release testing of novel mucosal drug delivery systems aimed for ocular, nasal, oromucosal, vaginal and rectal administration. Copyright © 2017 Elsevier B.V. All rights reserved.

Controlled Drug Release and Chemotherapy Response in a Novel Acoustofluidic 3D Tumor Platform.

PubMed

Zervantonakis, Ioannis K; Arvanitis, Costas D

2016-05-01

Overcoming transport barriers to delivery of therapeutic agents in tumors remains a major challenge. Focused ultrasound (FUS), in combination with modern nanomedicine drug formulations, offers the ability to maximize drug transport to tumor tissue while minimizing toxicity to normal tissue. This potential remains unfulfilled due to the limitations of current approaches in accurately assessing and quantifying how FUS modulates drug transport in solid tumors. A novel acoustofluidic platform is developed by integrating a physiologically relevant 3D microfluidic device and a FUS system with a closed-loop controller to study drug transport and assess the response of cancer cells to chemotherapy in real time using live cell microscopy. FUS-induced heating triggers local release of the chemotherapeutic agent doxorubicin from a liposomal carrier and results in higher cellular drug uptake in the FUS focal region. This differential drug uptake induces locally confined DNA damage and glioblastoma cell death in the 3D environment. The capabilities of acoustofluidics for accurate control of drug release and monitoring of localized cell response are demonstrated in a 3D in vitro tumor mode. This has important implications for developing novel strategies to deliver therapeutic agents directly to the tumor tissue while sparing healthy tissue. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Controlled release of GAG-binding enhanced transduction (GET) peptides for sustained and highly efficient intracellular delivery.

PubMed

Abu-Awwad, Hosam Al-Deen M; Thiagarajan, Lalitha; Dixon, James E

2017-07-15

Controlled release systems for therapeutic molecules are vital to allow the sustained local delivery of their activities which direct cell behaviour and enable novel regenerative strategies. Direct programming of cells using exogenously delivered transcription factors can by-pass growth factor signalling but there is still a requirement to deliver such activity spatio-temporally. We previously developed a technology termed GAG-binding enhanced transduction (GET) to efficiently deliver a variety of cargoes intracellularly, using GAG-binding domains which promote cell targeting, and cell penetrating peptides (CPPs) which allow cell entry. Herein we demonstrate that GET system can be used in controlled release systems to mediate sustained intracellular transduction over one week. We assessed the stability and activity of GET peptides in poly(dl-lactic acid-co-glycolic acid) (PLGA) microparticles (MPs) prepared using a S/O/W double emulsion method. Efficient encapsulation (∼65%) and tailored protein release profiles could be achieved, however intracellular transduction was significantly inhibited post-release. To retain GET peptide activity we optimized a strategy of co-encapsulation of l-Histidine, which may form a complex with the PLGA degradation products under acidic conditions. Simulations of the polymer microclimate showed that hydrolytic acidic PLGA degradation products directly inhibited GET peptide transduction activity, and use of l-Histidine significantly enhanced released protein delivery. The ability to control the intracellular transduction of functional proteins into cells will facilitate new localized delivery methods and allow approaches to direct cellular behaviour for many regenerative medicine applications. The goal for regenerative medicine is to restore functional biological tissue by controlling and augmenting cellular behaviour. Either Transcription (TFs) or growth factors (GFs) can be presented to cells in spatio-temporal gradients for programming cell fate and gene expression. Here, we have created a sustained and controlled release system for GET (Glycosaminoglycan-enhanced transducing)-tagged proteins using S/O/W PLGA microparticle fabrication. We demonstrated that PLGA and its acidic degradants inhibit GET-mediated transduction, which can be overcome by using pH-activated l-Histidine. l-Histidine inhibits the electrostatic interaction of GET/PLGA and allows enhanced intracellular transduction. GET could provide a powerful tool to program cell behaviour either in gradients or with sustained delivery. We believe that our controlled release systems will allow application of GET for tissue regeneration directly by TF cellular programming. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Extended release dosage form of glipizide: development and validation of a level A in vitro-in vivo correlation.

PubMed

Ghosh, Animesh; Bhaumik, Uttam Kumar; Bose, Anirbandeep; Mandal, Uttam; Gowda, Veeran; Chatterjee, Bappaditya; Chakrabarty, Uday Sankar; Pal, Tapan Kumar

2008-10-01

Defining a quantitative and reliable relationship between in vitro drug release and in vivo absorption is highly desired for rational development, optimization, and evaluation of controlled-release dosage forms and manufacturing process. During the development of once daily extended-release (ER) tablet of glipizide, a predictive in vitro drug release method was designed and statistically evaluated using three formulations with varying release rates. In order to establish internally and externally validated level A in vitro-in vivo correlation (IVIVC), a total of three different ER formulations of glipizide were used to evaluate a linear IVIVC model based on the in vitro test method. For internal validation, a single-dose four-way cross over study (n=6) was performed using fast-, moderate-, and slow-releasing ER formulations and an immediate-release (IR) of glipizide as reference. In vitro release rate data were obtained for each formulation using the United States Pharmacopeia (USP) apparatus II, paddle stirrer at 50 and 100 rev. min(-1) in 0.1 M hydrochloric acid (HCl) and pH 6.8 phosphate buffer. The f(2) metric (similarity factor) was used to analyze the dissolution data. The formulations were compared using area under the plasma concentration-time curve, AUC(0-infinity), time to reach peak plasma concentration, T(max), and peak plasma concentration, C(max), while correlation was determined between in vitro release and in vivo absorption. A linear correlation model was developed using percent absorbed data versus percent dissolved from the three formulations. Predicted glipizide concentrations were obtained by convolution of the in vivo absorption rates. Prediction errors were estimated for C(max) and AUC(0-infinity) to determine the validity of the correlation. Apparatus II, pH 6.8 at 100 rev. min(-1) was found to be the most discriminating dissolution method. Linear regression analysis of the mean percentage of dose absorbed versus the mean percentage of in vitro release resulted in a significant correlation (r(2)>or=0.9) for the three formulations.

Stabilized single-injection inactivated polio vaccine elicits a strong neutralizing immune response.

PubMed

Tzeng, Stephany Y; McHugh, Kevin J; Behrens, Adam M; Rose, Sviatlana; Sugarman, James L; Ferber, Shiran; Langer, Robert; Jaklenec, Ana

2018-05-21

Vaccination in the developing world is hampered by limited patient access, which prevents individuals from receiving the multiple injections necessary for protective immunity. Here, we developed an injectable microparticle formulation of the inactivated polio vaccine (IPV) that releases multiple pulses of stable antigen over time. To accomplish this, we established an IPV stabilization strategy using cationic polymers for pH modulation to enhance traditional small-molecule-based stabilization methods. We investigated the mechanism of this strategy and showed that it was broadly applicable to all three antigens in IPV. Our lead formulations released two bursts of IPV 1 month apart, mimicking a typical vaccination schedule in the developing world. One injection of the controlled-release formulations elicited a similar or better neutralizing response in rats, considered the correlate of protection in humans, than multiple injections of liquid vaccine. This single-administration vaccine strategy has the potential to improve vaccine coverage in the developing world. Copyright © 2018 the Author(s). Published by PNAS.

Application of the relative energy release criteria to enclosure fire testing. [aircraft compartments

NASA Technical Reports Server (NTRS)

Roschke, E. J.; Coulbert, C. D.

1979-01-01

The five relative energy release criteria (RERC) which are a first step towards formulating a unified concept that can be applied to the development of fires in enclosures, place upper bounds on the rate and amount of energy released during a fire. They are independent, calculated readily, and may be applied generally to any enclosure regardless of size. They are useful in pretest planning and for interpreting experimental data. Data from several specific fire test programs were examined to evaluate the potential use of RERC to provide test planning guidelines. The RERC were compared with experimental data obtained in full-scale enclosures. These results confirm that in general the RERC do identify the proper limiting constraints on enclosure fire development and determine the bounds of the fire development envelope. Plotting actual fire data against the RERC reveals new valid insights into fire behavior and reveals the controlling constraints in fire development. The RERC were calculated and plotted for several descrpitions of full-scale fires in various aircraft compartments.

Stabilized single-injection inactivated polio vaccine elicits a strong neutralizing immune response

PubMed Central

Tzeng, Stephany Y.; McHugh, Kevin J.; Behrens, Adam M.; Rose, Sviatlana; Sugarman, James L.; Ferber, Shiran; Jaklenec, Ana

2018-01-01

Vaccination in the developing world is hampered by limited patient access, which prevents individuals from receiving the multiple injections necessary for protective immunity. Here, we developed an injectable microparticle formulation of the inactivated polio vaccine (IPV) that releases multiple pulses of stable antigen over time. To accomplish this, we established an IPV stabilization strategy using cationic polymers for pH modulation to enhance traditional small-molecule–based stabilization methods. We investigated the mechanism of this strategy and showed that it was broadly applicable to all three antigens in IPV. Our lead formulations released two bursts of IPV 1 month apart, mimicking a typical vaccination schedule in the developing world. One injection of the controlled-release formulations elicited a similar or better neutralizing response in rats, considered the correlate of protection in humans, than multiple injections of liquid vaccine. This single-administration vaccine strategy has the potential to improve vaccine coverage in the developing world. PMID:29784798

Drug release from and hydrolytic degradation of a poly(ethylene glycol) grafted poly(3-hydroxyoctanoate).

PubMed

Kim, Hyung Woo; Chung, Chung Wook; Hwang, Sung Joo; Rhee, Young Ha

2005-07-01

Monoacrylate-poly(ethylene glycol)-grafted poly(3-hydroxyoctanoate) (PEGMA-g-PHO) copolymers were synthesized to develop a swelling-controlled release delivery system for ibuprofen as a model drug. The in vitro hydrolytic degradation of and the drug release from a film made of the PEGMA-g-PHO copolymer were carried out in a phosphate buffer saline (pH 7.4) medium. The hydrolytic degradation of the copolymer was strongly dependent on the degree of grafting (DG) of the PEGMA group. The degradation rate of the copolymer films in vitro increased with increasing DG of the PEGMA group on the PHO chain. The copolymer films showed a controlled delivery of ibuprofen to the medium in periods of time that depend on the composition, hydrophilic/hydrophobic characteristics, initial drug loading amount and film thickness of the graft copolymer support. The drug release rate from the grafted copolymer films was faster than the rate of weight loss of the films themselves. In particular, a combination of the low DG of the PEGMA group in the PHO chains with the low ibuprofen solubility in water led to long-term constant release from these matrices in vitro.

The application of halloysite tubule nanoclay in drug delivery.

PubMed

Lvov, Yuri M; DeVilliers, Melgardt M; Fakhrullin, Rawil F

2016-07-01

Natural and biocompatible clay nanotubes are among the best inorganic materials for drug nanoformulations. These halloysite tubes with SiO2 on the outermost surface have diameter of ca. 50 nm, length around 1 micrometer and may be loaded with drugs at 10-30 wt. %. Narrow tube openings allow for controllable sustained drug release for hours, days or even weeks. Physical-chemical properties of these nanotubes are described followed by examples of drug-loading capabilities, release characteristics, and control of duration of release through the end tube capping with polymers. Development of halloysite-polymer composites such as tissue scaffolds and bone cement/dentist resin formulations with enhanced mechanical properties and extension of the drug release to 2-3 weeks are described. Examples of the compression properties of halloysite in tablets and capsules are also shown. We expect that clay nanotubes will be used primarily for non-injectable drug formulations, such as topical and oral dosage forms, cosmetics, as well as for composite materials with enhanced therapeutic effects. These include tissue scaffolds, bone cement and dentist resins with sustained release of antimicrobial and cell growth-promoting medicines (including proteins and DNA) as well as other formulations such as compounds for antiseptic treatment of hospitals.

Human nitric oxide biomarker as potential NO donor in conjunction with superparamagnetic iron oxide @ gold core shell nanoparticles for cancer therapeutics.

PubMed

Singh, Nimisha; Patel, Khushbu; Sahoo, Suban K; Kumar, Rajender

2018-03-01

Nitric oxide releasing superparamagnetic (Fe 3 O 4 -Au@NTHP) nanoparticles were synthesized by conjugation of human biomarker of nitric oxide, N-nitrosothioproline with iron oxide-gold (Fe 3 O 4 -Au) core shell nanoparticles. The structure and morphology of the prepared nanoparticles were confirmed by ATR-FTIR, HR-TEM, EDAX, XPS, DLS and VSM measurements. N-nitrosothioproline is a natural molecule and nontoxic to humans. Thus, the core shell nanoparticles prepared were highly biocompatible. The prepared Fe 3 O 4 -Au@NTHP nanoparticles also provided an excellent release of nitric oxide in dark and upon light irradiation for cancer treatment. The amount of NO release was controllable with the wavelength of light and time of irradiation. The developed nanoparticles provided efficient cellular uptake and good cytotoxicity in picomolar range when tested on HeLa cancerous cells. These nanoparticles on account of their controllable NO release can also be used to release small amount of NO for killing cancerous cells without any toxic effect. Furthermore, the magnetic and photochemical properties of these nanoparticles provides dual platform for magneto therapy and phototherapy for cancer treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Release of DNA from polyelectrolyte multilayers fabricated using 'charge-shifting' cationic polymers: tunable temporal control and sequential, multi-agent release.

PubMed

Sun, Bin; Lynn, David M

2010-11-20

We report an approach to the design of multilayered polyelectrolyte thin films (or 'polyelectrolyte multilayers', PEMs) that can be used to provide tunable control over the release of plasmid DNA (or multiple different DNA constructs) from film-coated surfaces. Our approach is based upon methods for the layer-by-layer assembly of DNA-containing thin films, and exploits the properties of a new class of cationic 'charge-shifting' polymers (amine functionalized polymers that undergo gradual changes in net charge upon side chain ester hydrolysis) to provide control over the rates at which these films erode and release DNA. We synthesized two 'charge-shifting' polymers (polymers 1 and 2) containing different side chain structures by ring-opening reactions of poly(2-alkenyl azlactone)s with two different tertiary amine functionalized alcohols (3-dimethylamino-1-propanol and 2-dimethylaminoethanol, respectively). Subsequent characterization revealed large changes in the rates of side chain ester hydrolysis for these two polymers; whereas the half-life for the hydrolysis of the esters in polymer 1 was ~200 days, the half-life for polymer 2 was ~6 days. We demonstrate that these large differences in side chain hydrolysis make possible the design of PEMs that erode and promote the surface-mediated release of DNA either rapidly (e.g., over ~3 days for films fabricated using polymer 2) or slowly (e.g., over ~1 month for films fabricated using polymer 1). We demonstrate further that it is possible to design films with release profiles that are intermediate to these two extremes by fabricating films using solutions containing different mixtures of these two polymers. This approach can thus expand the usefulness of these two polymers and achieve a broader range of DNA release profiles without the need to synthesize polymers with new structures or properties. Finally, we demonstrate that polymers 1 and 2 can be used to fabricate multilayered films with hierarchical structures that promote the sequential release of two different DNA constructs with separate and distinct release profiles (e.g., the release of a first construct over a period of ~3 days, followed by the sustained release of a second for a period of ~70 days). With further development, this approach could contribute to the design of functional thin films and surface coatings that provide sophisticated control over the timing and the order of the release of two or more DNA constructs (or other agents) of interest in a range of biomedical contexts. Copyright © 2010 Elsevier B.V. All rights reserved.

Field Programmable Gate Array Control of Power Systems in Graduate Student Laboratories

DTIC Science & Technology

2008-03-01

NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS Approved for public release; distribution is unlimited FIELD PROGRAMMABLE...REPORT TYPE AND DATES COVERED Master’s Thesis 4. TITLE AND SUBTITLE Field Programmable Gate Array Control of Power Systems in Graduate Student...Electronics curriculum track is the development of a design center that explores Field Programmable Gate Array (FPGA) control of power electronics

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.

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)

Intravaginal ring delivery of the reverse transcriptase inhibitor TMC 120 as an HIV microbicide.

PubMed

Woolfson, A David; Malcolm, R Karl; Morrow, Ryan J; Toner, Clare F; McCullagh, Stephen D

2006-11-15

TMC 120 (Dapivirine) is a potent non-nucleoside reverse transcriptase inhibitor that is presently being developed as a vaginal HIV microbicide. To date, most vaginal microbicides under clinical investigation have been formulated as single-dose semi-solid gels, designed for application to the vagina before each act of intercourse. However, a clear rationale exists for providing long-term, controlled release of vaginal microbicides in order to afford continuous protection against heterosexually transmitted HIV infection and to improve user compliance. In this study we report on the incorporation of various pharmaceutical excipients into TMC 120 silicone, reservoir-type intravaginal rings (IVRs) in order to modify the controlled release characteristics of the microbicide. The results demonstrate that TMC 120 is released in zero-order fashion from the rings over a 28-day period and that release parameters could be modified by the inclusion of release-modifying excipients in the IVR. The hydrophobic liquid excipient isopropyl myristate had little effect on steady-state daily release rates, but did increase the magnitude and duration of burst release in proportion to excipient loading in the IVR. By comparison, the hydrophobic liquid poly(dimethylsiloxane) had little effect on TMC 120 release parameters. A hydrophilic excipient, lactose, had the surprising effect of decreasing TMC 120 burst release while increasing the apparent steady-state daily release in a concentration-dependent manner. Based on previous cell culture data and vaginal physiology, TMC120 is released from the various ring formulations in amounts potentially capable of maintaining a protective vaginal concentration. It is further predicted that the observed release rates may be maintained for at least a period of 1 year from a single ring device. TMC 120 release profiles and the mechanical properties of rings could be modified by the physicochemical nature of hydrophobic and hydrophilic excipients incorporated into the IVRs.

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...

Reflections on the Anopheles gambiae genome sequence, transgenic mosquitoes and the prospect for controlling malaria and other vector borne diseases.

PubMed

Tabachnick, Walter J

2003-09-01

The completion of the Anopheles gambiae Giles genome sequencing project is a milestone toward developing more effective strategies in reducing the impact of malaria and other vector borne diseases. The successes in developing transgenic approaches using mosquitoes have provided another essential new tool for further progress in basic vector genetics and the goal of disease control. The use of transgenic approaches to develop refractory mosquitoes is also possible. The ability to use genome sequence to identify genes, and transgenic approaches to construct refractory mosquitoes, has provided the opportunity that with the future development of an appropriate genetic drive system, refractory transgenes can be released into vector populations leading to nontransmitting mosquitoes. An. gambiae populations incapable of transmitting malaria. This compelling strategy will be very difficult to achieve and will require a broad substantial research program for success. The fundamental information that is required on genome structure, gene function and environmental effects on genetic expression are largely unknown. The ability to predict gene effects on phenotype is rudimentary, particularly in natural populations. As a result, the release of a refractory transgene into natural mosquito populations is imprecise and there is little ability to predict unintended consequences. The new genetic tools at hand provide opportunities to address an array of important issues, many of which can have immediate impact on the effectiveness of a host of strategies to control vector borne disease. Transgenic release approaches represent only one strategy that should be pursued. A balanced research program is required.

pH- and ion-sensitive polymers for drug delivery

PubMed Central

Yoshida, Takayuki; Lai, Tsz Chung; Kwon, Glen S; Sako, Kazuhiro

2013-01-01

Introduction Drug delivery systems (DDSs) are important for effective, safe, and convenient administration of drugs. pH- and ion-responsive polymers have been widely employed in DDS for site-specific drug release due to their abilities to exploit specific pH- or ion-gradients in the human body. Areas covered Having pH-sensitivity, cationic polymers can mask the taste of drugs and release drugs in the stomach by responding to gastric low pH. Anionic polymers responsive to intestinal high pH are used for preventing gastric degradation of drug, colon drug delivery and achieving high bioavailability of weak basic drugs. Tumor-targeted DDSs have been developed based on polymers with imidazole groups or poly(β-amino ester) responsive to tumoral low pH. Polymers with pH-sensitive chemical linkages, such as hydrazone, acetal, ortho ester and vinyl ester, pH-sensitive cell-penetrating peptides and cationic polymers undergoing pH-dependent protonation have been studied to utilize the pH gradient along the endocytic pathway for intracellular drug delivery. As ion-sensitive polymers, ion-exchange resins are frequently used for taste-masking, counterion-responsive drug release and sustained drug release. Polymers responding to ions in the saliva and gastrointestinal fluids are also used for controlled drug release in oral drug formulations. Expert opinion Stimuli-responsive DDSs are important for achieving site-specific and controlled drug release; however, intraindividual, interindividual and intercellular variations of pH should be considered when designing DDSs or drug products. Combination of polymers and other components, and deeper understanding of human physiology are important for development of pH- and ion-sensitive polymeric DDS products for patients. PMID:23930949

Novel poly(ε-caprolactone)/gelatin wound dressings prepared by emulsion electrospinning with controlled release capacity of Ketoprofen anti-inflammatory drug.

PubMed

Basar, A O; Castro, S; Torres-Giner, S; Lagaron, J M; Turkoglu Sasmazel, H

2017-12-01

In the present study, a single and binary Ketoprofen-loaded mats of ultrathin fibers were developed by electrospinning and their physical properties and drug release capacity was analyzed. The single mat was prepared by solution electrospinning of poly(ε-caprolactone) (PCL) with Ketoprofen at a weight ratio of 5wt%. This Ketoprofen-containing PCL solution was also used as the oil phase in a 7:3 (wt/wt) emulsion with gelatin dissolved in acidified water. The resultant stable oil-in-water (O/W) emulsion of PCL-in-gelatin, also containing Ketoprofen at 5wt%, was electrospun to produce the binary mat. Cross-linking process was performed by means of glutaraldehyde vapor on the electrospun binary mat to prevent dissolution of the hydrophilic gelatin phase. The performed characterization indicated that Ketoprofen was successfully embedded in the single and binary electrospun mats, i.e. PCL and PCL/gelatin, and both mats showed high hydrophobicity but poor thermal resistance. In vitro release studies interestingly revealed that, in comparison to the single PCL electrospun mat, the binary PCL/gelatin mat significantly hindered Ketoprofen burst release and exhibited a sustained release capacity of the drug for up to 4days. In addition, the electrospun Ketoprofen-loaded mats showed enhanced attachment and proliferation of L929 mouse fibroblast cells, presenting the binary mat the highest cell growth yield due to its improved porosity. The here-developed electrospun materials clearly show a great deal of potential as novel wound dressings with an outstanding controlled capacity to release drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

Recent advances in testing of microsphere drug delivery systems.

PubMed

Andhariya, Janki V; Burgess, Diane J

2016-01-01

This review discusses advances in the field of microsphere testing. In vitro release-testing methods such as sample and separate, dialysis membrane sacs and USP apparatus IV have been used for microspheres. Based on comparisons of these methods, USP apparatus IV is currently the method of choice. Accelerated in vitro release tests have been developed to shorten the testing time for quality control purposes. In vitro-in vivo correlations using real-time and accelerated release data have been developed, to minimize the need to conduct in vivo performance evaluation. Storage stability studies have been conducted to investigate the influence of various environmental factors on microsphere quality throughout the product shelf life. New tests such as the floating test and the in vitro wash-off test have been developed along with advancement in characterization techniques for other physico-chemical parameters such as particle size, drug content, and thermal properties. Although significant developments have been made in microsphere release testing, there is still a lack of guidance in this area. Microsphere storage stability studies should be extended to include microspheres containing large molecules. An agreement needs to be reached on the use of particle sizing techniques to avoid inconsistent data. An approach needs to be developed to determine total moisture content of microspheres.

Development of thermosensitive poly(n-isopropylacrylamide-co-((2-dimethylamino) ethyl methacrylate))-based nanoparticles for controlled drug release

NASA Astrophysics Data System (ADS)

Peng, Cheng-Liang; Tsai, Han-Min; Yang, Shu-Jyuan; Luo, Tsai-Yueh; Lin, Chia-Fu; Lin, Wuu-Jyh; Shieh, Ming-Jium

2011-07-01

Thermosensitive nanoparticles based on poly(N-isopropylacrylamide-co-((2-dimethylamino)ethylmethacrylate)) (poly(NIPA-co-DMAEMA)) copolymers were successfully fabricated by free radical polymerization. The lower critical solution temperature (LCST) of the synthesized nanoparticles was 41 °C and a temperature above which would cause the nanoparticles to undergo a volume phase transition from 140 to 100 nm, which could result in the expulsion of encapsulated drugs. Therefore, we used the poly(NIPA-co-DMAEMA) nanoparticles as a carrier for the controlled release of a hydrophobic anticancer agent, 7-ethyl-10-hydroxy-camptothecin (SN-38). The encapsulation efficiency and loading content of SN-38-loaded nanoparticles at an SN-38/poly(NIPA-co-DMAEMA) ratio of 1/10 (D/P = 1/10) were about 80% and 6.293%, respectively. Moreover, the release profile of SN-38-loaded nanoparticles revealed that the release rate at 42 °C (above LCST) was higher than that at 37 °C (below LCST), which demonstrated that the release of SN-38 could be controlled by increasing the temperature. The cytotoxicity of the SN-38-loaded poly(NIPA-co-DMAEMA) nanoparticles was investigated in human colon cancer cells (HT-29) to compare with the treatment of an anticancer drug, Irinotecan® (CPT-11). The antitumor efficacy evaluated in a C26 murine colon tumor model showed that the SN-38-loaded nanoparticles in combination with hyperthermia therapy efficiently suppressed tumor growth. The results indicate that these thermo-responsive nanoparticles are potential carriers for controlled drug delivery.

Metallic ions as therapeutic agents in tissue engineering scaffolds: an overview of their biological applications and strategies for new developments

PubMed Central

Mouriño, Viviana; Cattalini, Juan Pablo; Boccaccini, Aldo R.

2012-01-01

This article provides an overview on the application of metallic ions in the fields of regenerative medicine and tissue engineering, focusing on their therapeutic applications and the need to design strategies for controlling the release of loaded ions from biomaterial scaffolds. A detailed summary of relevant metallic ions with potential use in tissue engineering approaches is presented. Remaining challenges in the field and directions for future research efforts with focus on the key variables needed to be taken into account when considering the controlled release of metallic ions in tissue engineering therapeutics are also highlighted. PMID:22158843

Developmental increase of asynchronic glutamate release from hippocampal synapses in mutant taiep rat.

PubMed

Fuenzalida, Marco; Aliaga, Esteban; Olivares, Virginia; Roncagliolo, Manuel; Bonansco, Christian

2009-06-01

During development, regulation of the strength of synaptic transmission plays a central role in the formation of mammalian brain circuitries. In taiep rat, a neurological mutant with severe reactive astrogliosis and demyelination, we have described alterations in the synaptic transmission in central neurons, characterized by asynchronous excitatory postsynaptic currents ((ASYN)EPSCs), because of delayed neurotransmitter release. This hippocampal synaptic dysfunction has been described in juvenile mutants, concomitantly with the appearance of their main glial alterations. However, it is unknown whether this abnormal synaptic activity is correlated with some alterations of synaptic maturation during the postnatal development. Using intracellular electrophysiological recordings and immunohistochemistry assays, we studied the maturation of CA3-CA1 synapses in taiep rats. In taiep, the number of (ASYN)EPSCs evoked by conventional stimulation of Schaffer collaterals increases with age (P7-P30) and can be evoked by stimulation of single fiber. The amplitude and frequency of spontaneous EPSC (sEPSC) increased during the postnatal development in both control and taiep rats. However, in taiep, the increase of sEPSC frequency was significantly higher than in the control rats. The frequency of miniature EPSC (mEPSC) increased over the studied age range, without differences between taiep and control rats. In both control and taiep groups, the synaptophysin immunostaining (SYP-IR) in the stratum radiatum of CA1 region was significantly lower in the juvenile (P30) than in the neonatal (P10) rats, suggesting that synaptic pruning is normally occurring in taiep, even when SYP-IR was higher in taiep than control in both ages studied. These results suggest that, in taiep mutants, the asynchronic transmission is due to a dysfunction in the glutamate release mechanisms that progressively increases during development, which is not attributable to the existence of aberrant synaptic contacts. Synapse 63:502-509, 2009. (c) 2009 Wiley-Liss, Inc.

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

PubMed

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

2012-01-01

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

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

Suppression of a Field Population of Aedes aegypti in Brazil by Sustained Release of Transgenic Male Mosquitoes

PubMed Central

Garziera, Luiza; Lacroix, Renaud; Donnelly, Christl A.; Alphey, Luke; Malavasi, Aldo; Capurro, Margareth L.

2015-01-01

The increasing burden of dengue, and the relative failure of traditional vector control programs highlight the need to develop new control methods. SIT using self-limiting genetic technology is one such promising method. A self-limiting strain of Aedes aegypti, OX513A, has already reached the stage of field evaluation. Sustained releases of OX513A Ae. aegypti males led to 80% suppression of a target wild Ae. aegypti population in the Cayman Islands in 2010. Here we describe sustained series of field releases of OX513A Ae. aegypti males in a suburb of Juazeiro, Bahia, Brazil. This study spanned over a year and reduced the local Ae. aegypti population by 95% (95% CI: 92.2%-97.5%) based on adult trap data and 81% (95% CI: 74.9-85.2%) based on ovitrap indices compared to the adjacent no-release control area. The mating competitiveness of the released males (0.031; 95% CI: 0.025-0.036) was similar to that estimated in the Cayman trials (0.059; 95% CI: 0.011 – 0.210), indicating that environmental and target-strain differences had little impact on the mating success of the OX513A males. We conclude that sustained release of OX513A males may be an effective and widely useful method for suppression of the key dengue vector Ae. aegypti. The observed level of suppression would likely be sufficient to prevent dengue epidemics in the locality tested and other areas with similar or lower transmission. PMID:26135160

Controlled Bioactive Molecules Delivery Strategies for Tendon and Ligament Tissue Engineering using Polymeric Nanofibers.

PubMed

Hiong Teh, Thomas Kok; Hong Goh, James Cho; Toh, Siew Lok

2015-01-01

The interest in polymeric nanofibers has escalated over the past decade given its promise as tissue engineering scaffolds that can mimic the nanoscale structure of the native extracellular matrix. With functionalization of the polymeric nanofibers using bioactive molecules, localized signaling moieties can be established for the attached cells, to stimulate desired biological effects and direct cellular or tissue response. The inherently high surface area per unit mass of polymeric nanofibers can enhance cell adhesion, bioactive molecules loading and release efficiencies, and mass transfer properties. In this review article, the application of polymeric nanofibers for controlled bioactive molecules delivery will be discussed, with a focus on tendon and ligament tissue engineering. Various polymeric materials of different mechanical and degradation properties will be presented along with the nanofiber fabrication techniques explored. The bioactive molecules of interest for tendon and ligament tissue engineering, including growth factors and small molecules, will also be reviewed and compared in terms of their nanofiber incorporation strategies and release profiles. This article will also highlight and compare various innovative strategies to control the release of bioactive molecules spatiotemporally and explore an emerging tissue engineering strategy involving controlled multiple bioactive molecules sequential release. Finally, the review article concludes with challenges and future trends in the innovation and development of bioactive molecules delivery using polymeric nanofibers for tendon and ligament tissue engineering.

An integral projection model with YY-males and application to evaluating grass carp control

USGS Publications Warehouse

Erickson, Richard A.; Eager, Eric A.; Brey, Marybeth; Hansen, Michael J.; Kocovsky, Patrick

2017-01-01

Invasive fish species disrupt ecosystems and cause economic damage. Several methods have been discussed to control populations of invasive fish including the release of YY-males. YY-males are fish that have 2 male chromosomes compared to a XY-male. When YY-males mate, they only produce male (XY) offspring. This decreases the female proportion of the population and can, in theory, eradicate local populations by biasing the sex-ratio. YY-males have been used as a population control tool for brook trout in montane streams and lakes in Idaho, USA. The YY-male control method has been discussed for grass carp in Lake Erie, North America. We developed and presented an integral projection model for grass carp to model the use of YY-males as a control method for populations in this lake. Using only the YY-male control method, we found that high levels of YY-males would need to be release annually to control the species. Specifically, these levels were the same order of magnitude as the baseline adult population (e.g., 1000 YY-males needed to be released annual for 20 years to control a baseline adult population of 2500 grass carp). These levels may not be reasonable or obtainable for fisheries managers given the impacts of YY-males on aquatic vegetation and other constraints of natural resource management.

New insights into differential baroreflex control of heart rate in humans

NASA Technical Reports Server (NTRS)

Fadel, P. J.; Stromstad, M.; Wray, D. W.; Smith, S. A.; Raven, P. B.; Secher, N. H.

2003-01-01

Recent data indicate that bilateral carotid sinus denervation in patients results in a chronic impairment in the rapid reflex control of blood pressure during orthostasis. These findings are inconsistent with previous human experimental investigations indicating a minimal role for the carotid baroreceptor-cardiac reflex in blood pressure control. Therefore, we reexamined arterial baroreflex [carotid (CBR) and aortic baroreflex (ABR)] control of heart rate (HR) using newly developed methodologies. In 10 healthy men, 27 +/- 1 yr old, an abrupt decrease in mean arterial pressure (MAP) was induced nonpharmacologically by releasing a unilateral arterial thigh cuff (300 Torr) after 9 min of resting leg ischemia under two conditions: 1) ABR and CBR deactivation (control) and 2) ABR deactivation. Under control conditions, cuff release decreased MAP by 13 +/- 1 mmHg, whereas HR increased 11 +/- 2 beats/min. During ABR deactivation, neck suction was gradually applied to maintain carotid sinus transmural pressure during the initial 20 s after cuff release (suction). This attenuated the increase in HR (6 +/- 1 beats/min) and caused a greater decrease in MAP (18 +/- 2 mmHg, P < 0.05). Furthermore, estimated cardiac baroreflex responsiveness (DeltaHR/DeltaMAP) was significantly reduced during suction compared with control conditions. These findings suggest that the carotid baroreceptors contribute more importantly to the reflex control of HR than previously reported in healthy individuals.

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.

Pre-Demolition Planning

EPA Pesticide Factsheets

Developing a systematic approach to demolition can help manage liability, control, and costs. Careful planning can minimize the release of toxic chemicals and other harmful substances into the environment, and protect the health of workers and the public.

Design, Development, and Optimization of Dexibuprofen Microemulsion Based Transdermal Reservoir Patches for Controlled Drug Delivery

PubMed Central

Ali, Fatima Ramzan; Yousuf, Rabia Ismail; Ali, Syed Abid; Imtiaz, Muhammad Suleman; Bashir, Lubna; Naz, Shazia

2017-01-01

The aim of the study was to develop a reservoir-type transdermal patch for a controlled delivery of dexibuprofen and to evaluate its in vivo anti-inflammatory activity in Albino Wistar rats. In order to develop these patches, six formulations of dexibuprofen microemulsion comprising ethyl oleate, Tween 80: PG (2 : 1), and water were prepared by simplex lattice design and characterized. The reservoir compartment was filled with these microemulsions and in vitro release and skin permeation were assessed. The optimized patch was obtained on the basis of the responses: Q24 and flux. The impact of drug loading, surface area, membrane thickness, adhesive, and agitation speed on drug release and permeation was also studied. The skin sensitivity reaction and in vivo anti-inflammatory activity of optimized patch were evaluated. Stability study at three different temperatures for three months was carried out. The result suggests that a membrane based patch with zero-order release rate, Q24 of 79.13 ± 3.08%, and maximum flux of 331.17 µg/cm2h can be obtained exhibiting suitable anti-inflammatory activity with no visible skin sensitivity reaction. The outcomes of stability study recommend storage of patches at 4°C having shelf-life of 6.14 months. The study demonstrates that the reservoir-type transdermal patch of dexibuprofen microemulsion has a potential of delivering drug across skin in controlled manner with required anti-inflammatory activity. PMID:29090219

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.

Formulation and characterisation of magnetic resonance imageable thermally sensitive liposomes for use with magnetic resonance-guided high intensity focused ultrasound

PubMed Central

NEGUSSIE, AYELE H.; YARMOLENKO, PAVEL S.; PARTANEN, ARI; RANJAN, ASHISH; JACOBS, GENEVIEVE; WOODS, DAVID; BRYANT, HENRY; THOMASSON, DAVID; DEWHIRST, MARK W.; WOOD, BRADFORD J.; DREHER, MATTHEW R.

2012-01-01

Purpose Objectives of this study were to: 1) develop iLTSL, a low temperature sensitive liposome co-loaded with an MRI contrast agent (ProHance® Gd-HP-DO3A) and doxorubicin, 2) characterise doxorubicin and Gd-HP-DO3A release from iLTSL and 3) investigate the ability of magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) to induce and monitor iLTSL content release in phantoms and in vivo. Methods iLTSL was passively loaded with Gd-HP-DO3A and actively loaded with doxorubicin. Doxorubicin and Gd-HP-DO3A release was quantified by fluorescence and spectroscopic techniques, respectively. Release with MR-HIFU was examined in tissue-mimicking phantoms containing iLTSL and in a VX2 rabbit tumour model. Results iLTSL demonstrated consistent size and doxorubicin release kinetics after storage at 4°C for 7 days. Release of doxorubicin and Gd-HP-DO3A from iLTSL was minimal at 37°C but fast when heated to 41.3°C. The magnitude of release was not significantly different between doxorubicin and Gd-HP-DO3A over 10 min in HEPES buffer and plasma at 37°, 40° and 41.3°C (p>0.05). Relaxivity of iLTSL increased significantly (p <0.0001) from 1.95 ± 0.05 to 4.01 ± 0.1 mMs−1 when heated above the transition temperature. Signal increase corresponded spatially and temporally to MR-HIFU-heated locations in phantoms. Signal increase was also observed in vivo after iLTSL injection and after each 10-min heating (41°C), with greatest increase in the heated tumour region. Conclusion An MR imageable liposome formulation co-loaded with doxorubicin and an MR contrast agent was developed. Stability, imageability, and MR-HIFU monitoring and control of content release suggest that MR-HIFU combined with iLTSL may enable real-time monitoring and spatial control of content release. PMID:21314334

Controlled Release of 5-Fluorouracil from Alginate Beads Encapsulated in 3D Printed pH-Responsive Solid Dosage Forms.

PubMed

Gioumouxouzis, Christos I; Chatzitaki, Aikaterini-Theodora; Karavasili, Christina; Katsamenis, Orestis L; Tzetzis, Dimitrios; Mystiridou, Emmanouela; Bouropoulos, Nikolaos; Fatouros, Dimitrios G

2018-06-14

Three-dimensional printing is being steadily deployed as manufacturing technology for the development of personalized pharmaceutical dosage forms. In the present study, we developed a hollow pH-responsive 3D printed tablet encapsulating drug loaded non-coated and chitosan-coated alginate beads for the targeted colonic delivery of 5-fluorouracil (5-FU). A mixture of Eudragit® L100-55 and Eudragit® S100 was fabricated by means of hot-melt extrusion (HME) and the produced filaments were printed utilizing a fused deposition modeling (FDM) 3D printer to form the pH-responsive layer of the tablet with the rest comprising of a water-insoluble poly-lactic acid (PLA) layer. The filaments and alginate particles were characterized for their physicochemical properties (thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction), their surface topography was visualized by scanning electron microscopy and the filaments' mechanical properties were assessed by instrumented indentation testing and tensile testing. The optimized filament formulation was 3D printed and the structural integrity of the hollow tablet in increasing pH media (pH 1.2 to pH 7.4) was assessed by means of time-lapsed microfocus computed tomography (μCT). In vitro release studies demonstrated controlled release of 5-FU from the alginate beads encapsulated within the hollow pH-sensitive tablet matrix at pH values corresponding to the colonic environment (pH 7.4). The present study highlights the potential of additive manufacturing in fabricating controlled-release dosage forms rendering them pertinent formulations for further in vivo evaluation.

The 18th Aerospace Mechanisms Symposium

NASA Technical Reports Server (NTRS)

1984-01-01

Topics concerning aerospace mechanisms, their functional performance, and design specifications are presented. Discussed subjects include the design and development of release mechanisms, actuators, linear driver/rate controllers, antenna and appendage deployment systems, position control systems, and tracking mechanisms for antennas and solar arrays. Engine design, spaceborne experiments, and large space structure technology are also examined.

A review on oral liquid as an emerging technology in controlled drug delivery system.

PubMed

Torne, Sangmesh Raosaheb; Sheela, Angappan; Sarada, N C

2017-12-03

The oral liquid drug delivery system (OLDDS) remains as the primary choice of dosage form, though challenging, for the pharmaceutical scientists. In the last two decades, Oral Liquid Controlled Release (OLCR) formulation has gained a lot of attention because of its advantages over the conventional dosage forms. The world of nanotechnology has paved multiple ways to administer the drug through oral cavity in liquid dosage form with an additional advantage of control over the release. In the current study, the various approaches towards the same have been discussed comprehensively to understand the different mechanisms of OLCR. This review also emphasizes on the existing techniques and the developments that have been made to improve on its efficacy including various formulation related factors. It also provides valuable insights into the role of polymers in the development of OLCR formulation that can be used in the management of Gastroesophageal reflux disease (GERD). Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Evaluation of biodegradable polymers as encapsulating agents for the development of a urea controlled-release fertilizer using biochar as support material.

PubMed

González, M E; Cea, M; Medina, J; González, A; Diez, M C; Cartes, P; Monreal, C; Navia, R

2015-02-01

Biochar constitutes a promising support material for the formulation of controlled-release fertilizers (CRFs). In this study we evaluated the effect of different polymeric materials as encapsulating agents to control nitrogen (N) leaching from biochar based CRFs. Nitrogen impregnation onto biochar was performed in a batch reactor using urea as N source. The resulting product was encapsulated by using sodium alginate (SA), cellulose acetate (CA) and ethyl cellulose (EC). Leaching potential was studied in planted and unplanted soil columns, monitoring nitrate, nitrite, ammonium and urea concentrations. After 90 days, plants were removed from the soil columns and plant yield was evaluated. It was observed that the ammonium concentration in leachates presented a maximum concentration for all treatments at day 22. The highest concentration of N in the leachates was the nitrate form. The crop yield was negatively affected by all developed CRFs using biochar compared with the traditional fertilization. Copyright © 2014 Elsevier B.V. All rights reserved.

E-Control: First Public Release of Remote Control Software for VLBI Telescopes

NASA Technical Reports Server (NTRS)

Neidhardt, Alexander; Ettl, Martin; Rottmann, Helge; Ploetz, Christian; Muehlbauer, Matthias; Hase, Hayo; Alef, Walter; Sobarzo, Sergio; Herrera, Cristian; Himwich, Ed

2010-01-01

Automating and remotely controlling observations are important for future operations in a Global Geodetic Observing System (GGOS). At the Geodetic Observatory Wettzell, in cooperation with the Max-Planck-Institute for Radio Astronomy in Bonn, a software extension to the existing NASA Field System has been developed for remote control. It uses the principle of a remotely accessible, autonomous process cell as a server extension for the Field System. The communication is realized for low transfer rates using Remote Procedure Calls (RPC). It uses generative programming with the interface software generator idl2rpc.pl developed at Wettzell. The user interacts with this system over a modern graphical user interface created with wxWidgets. For security reasons the communication is automatically tunneled through a Secure Shell (SSH) session to the telescope. There are already successful test observations with the telescopes at O Higgins, Concepcion, and Wettzell. At Wettzell the software is already used routinely for weekend observations. Therefore the first public release of the software is now available, which will also be useful for other telescopes.

Trade-offs in experimental designs for estimating post-release mortality in containment studies

USGS Publications Warehouse

Rogers, Mark W.; Barbour, Andrew B; Wilson, Kyle L

2014-01-01

Estimates of post-release mortality (PRM) facilitate accounting for unintended deaths from fishery activities and contribute to development of fishery regulations and harvest quotas. The most popular method for estimating PRM employs containers for comparing control and treatment fish, yet guidance for experimental design of PRM studies with containers is lacking. We used simulations to evaluate trade-offs in the number of containers (replicates) employed versus the number of fish-per container when estimating tagging mortality. We also investigated effects of control fish survival and how among container variation in survival affects the ability to detect additive mortality. Simulations revealed that high experimental effort was required when: (1) additive treatment mortality was small, (2) control fish mortality was non-negligible, and (3) among container variability in control fish mortality exceeded 10% of the mean. We provided programming code to allow investigators to compare alternative designs for their individual scenarios and expose trade-offs among experimental design options. Results from our simulations and simulation code will help investigators develop efficient PRM experimental designs for precise mortality assessment.

The UAS control segment architecture: an overview

NASA Astrophysics Data System (ADS)

Gregory, Douglas A.; Batavia, Parag; Coats, Mark; Allport, Chris; Jennings, Ann; Ernst, Richard

2013-05-01

The Under Secretary of Defense (Acquisition, Technology and Logistics) directed the Services in 2009 to jointly develop and demonstrate a common architecture for command and control of Department of Defense (DoD) Unmanned Aircraft Systems (UAS) Groups 2 through 5. The UAS Control Segment (UCS) Architecture is an architecture framework for specifying and designing the softwareintensive capabilities of current and emerging UCS systems in the DoD inventory. The UCS Architecture is based on Service Oriented Architecture (SOA) principles that will be adopted by each of the Services as a common basis for acquiring, integrating, and extending the capabilities of the UAS Control Segment. The UAS Task Force established the UCS Working Group to develop and support the UCS Architecture. The Working Group currently has over three hundred members, and is open to qualified representatives from DoD-approved defense contractors, academia, and the Government. The UCS Architecture is currently at Release 2.2, with Release 3.0 planned for July 2013. This paper discusses the current and planned elements of the UCS Architecture, and related activities of the UCS Community of Interest.

Recent advances on smart TiO2 nanotube platforms for sustainable drug delivery applications.

PubMed

Wang, Qun; Huang, Jian-Ying; Li, Hua-Qiong; Zhao, Allan Zi-Jian; Wang, Yi; Zhang, Ke-Qin; Sun, Hong-Tao; Lai, Yue-Kun

To address the limitations of traditional drug delivery, TiO 2 nanotubes (TNTs) are recognized as a promising material for localized drug delivery systems. With regard to the excellent biocompatibility and physicochemical properties, TNTs prepared by a facile electrochemical anodizing process have been used to fabricate new drug-releasing implants for localized drug delivery. This review discusses the development of TNTs applied in localized drug delivery systems, focusing on several approaches to control drug release, including the regulation of the dimensions of TNTs, modification of internal chemical characteristics, adjusting pore openings by biopolymer coatings, and employing polymeric micelles as drug nanocarriers. Furthermore, rational strategies on external conditions-triggered stimuli-responsive drug release for localized drug delivery systems are highlighted. Finally, the review concludes with the recent advances on TNTs for controlled drug delivery and corresponding prospects in the future.

Recent advances on smart TiO2 nanotube platforms for sustainable drug delivery applications

PubMed Central

Wang, Qun; Huang, Jian-Ying; Li, Hua-Qiong; Zhao, Allan Zi-Jian; Wang, Yi; Zhang, Ke-Qin; Sun, Hong-Tao; Lai, Yue-Kun

2017-01-01

To address the limitations of traditional drug delivery, TiO2 nanotubes (TNTs) are recognized as a promising material for localized drug delivery systems. With regard to the excellent biocompatibility and physicochemical properties, TNTs prepared by a facile electrochemical anodizing process have been used to fabricate new drug-releasing implants for localized drug delivery. This review discusses the development of TNTs applied in localized drug delivery systems, focusing on several approaches to control drug release, including the regulation of the dimensions of TNTs, modification of internal chemical characteristics, adjusting pore openings by biopolymer coatings, and employing polymeric micelles as drug nanocarriers. Furthermore, rational strategies on external conditions-triggered stimuli-responsive drug release for localized drug delivery systems are highlighted. Finally, the review concludes with the recent advances on TNTs for controlled drug delivery and corresponding prospects in the future. PMID:28053530

Contributions of 5-HT neurons to respiratory control: neuromodulatory and trophic effects.

PubMed

Hodges, Matthew R; Richerson, George B

2008-12-10

Serotonin (5-hydroxytryptamine; 5-HT) is a neurotransmitter produced by a small number of neurons in the midbrain, pons and medulla. These neurons project widely throughout the neuraxis, where they release 5-HT and co-localized neuropeptides such as substance P (SP) and thyrotropin-releasing hormone (TRH). Each of these chemicals produce effects largely through G protein-coupled receptors, second messenger systems and subsequent neuromodulatory effects on target neurons. Emerging evidence suggests that 5-HT has additional modes of action during development and in adult mammals, including trophic effects (neurogenesis, cell differentiation, proliferation, migration and maturation) and influences on synaptic plasticity. Here, we discuss some of the neuromodulatory and trophic roles of 5-HT in general and in the context of respiratory control, as well as the regulation of release of modulatory neurotransmitters from 5-HT neurons. Future directions of study are also discussed.

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

Mussel-inspired catalytic selenocystamine-dopamine coatings for long-term generation of therapeutic gas on cardiovascular stents.

PubMed

Yang, Zhilu; Yang, Ying; Zhang, Li; Xiong, Kaiqin; Li, Xiangyang; Zhang, Feng; Wang, Jin; Zhao, Xin; Huang, Nan

2018-06-07

The development of a nitric oxide (NO)-generating surface with long-term, stable and controllable NO release improves the therapeutic efficacy of cardiovascular stents. In this work, we developed a "one-pot" method inspired by mussel adhesive proteins for copolymerization of selenocystamine (SeCA) and dopamine (Dopa) to form a NO-generating coating on a 316 L stainless steel (SS) stent. This "one-pot" method is environmentally friendly and easy to popularize, with many advantages including simple manufacturing procedure, high stability and no involvement of organic solvents. Such SeCA/Dopa coatings also enabled us to develop a catalytic surface for local NO-generation by reaction of endogenously existing S-nitrothiol species from fresh blood. We found that the developed SeCA/Dopa coatings could release NO in a controllable and stable manner for more than 60 days. Additionally, the released NO significantly inhibited smooth muscle cell (SMC) proliferation and migration, as well as platelet activation and aggregation through the up-regulation of cyclic guanosine monophosphate synthesis. Moreover, such NO generation enhanced the adhesion, proliferation and migration of endothelial cells (ECs), and achieved rapid in vivo re-endothelialization, effectively reducing in-stent restenosis and neointimal hyperplasia. We envision that the SeCA/Dopa-coated 316 L SS stent could be a promising platform for treatment of cardiovascular diseases. Copyright © 2018. Published by Elsevier Ltd.

Navigating sticky areas in transdermal product development.

PubMed

Strasinger, Caroline; Raney, Sam G; Tran, Doanh C; Ghosh, Priyanka; Newman, Bryan; Bashaw, Edward D; Ghosh, Tapash; Shukla, Chinmay G

2016-07-10

The benefits of transdermal delivery over the oral route to combat such issues of low bioavailability and limited controlled release opportunities are well known and have been previously discussed by many in the field (Prausnitz et al. (2004) [1]; Hadgraft and Lane (2006) [2]). However, significant challenges faced by developers as a product moves from the purely theoretical to commercial production have hampered full capitalization of the dosage forms vast benefits. While different technical aspects of transdermal system development have been discussed at various industry meetings and scientific workshops, uncertainties have persisted regarding the pharmaceutical industry's conventionally accepted approach for the development and manufacturing of transdermal systems. This review provides an overview of the challenges frequently faced and the industry's best practices for assuring the quality and performance of transdermal delivery systems and topical patches (collectively, TDS). The topics discussed are broadly divided into the evaluation of product quality and the evaluation of product performance; with the overall goal of the discussion to improve, advance and accelerate commercial development in the area of this complex controlled release dosage form. Published by Elsevier B.V.

DYNA3D Code Practices and Developments

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

Lin, L.; Zywicz, E.; Raboin, P.

2000-04-21

DYNA3D is an explicit, finite element code developed to solve high rate dynamic simulations for problems of interest to the engineering mechanics community. The DYNA3D code has been under continuous development since 1976[1] by the Methods Development Group in the Mechanical Engineering Department of Lawrence Livermore National Laboratory. The pace of code development activities has substantially increased in the past five years, growing from one to between four and six code developers. This has necessitated the use of software tools such as CVS (Concurrent Versions System) to help manage multiple version updates. While on-line documentation with an Adobe PDF manualmore » helps to communicate software developments, periodically a summary document describing recent changes and improvements in DYNA3D software is needed. The first part of this report describes issues surrounding software versions and source control. The remainder of this report details the major capability improvements since the last publicly released version of DYNA3D in 1996. Not included here are the many hundreds of bug corrections and minor enhancements, nor the development in DYNA3D between the manual release in 1993[2] and the public code release in 1996.« less

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

PubMed

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

2015-06-01

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

Fabrication of a microfluidic device for studying the in situ drug-loading/release behavior of graphene oxide-encapsulated hydrogel beads.

PubMed

Veerla, Sarath Chandra; Kim, Da Reum; Yang, Sung Yun

2018-01-01

Controlled drug delivery system is highly important for not only prolonged the efficacy of drug but also cellular development for tissue engineering. A number of biopolymer composites and nanostructured carriers behave been used for the controlled drug delivery of therapeutics. Recently, in vitro microfluidic devices that mimic the human body have been developed for drug-delivery applications. A microfluidic channel was fabricated via a two-step process: (i) polydimethyl siloxane (PDMS) and curing agent were poured with a 10:2 mass ratio onto an acrylic mold with two steel pipes, and (ii) calcium alginate beads were synthesized using sodium alginate and calcium chloride solutions. Different amounts (10, 25, 50 μg) of graphene oxide (GO) were then added by Hummers method, and studies on the encapsulation and release of the model drug, risedronate (Ris), were performed using control hydrogel beads (pH 6.3), GO-containing beads (10GO, 25GO and 50GO), and different pH conditions. MC3T3 osteoblastic cells were cultured in a microchannel with Ris-loaded GO-hydrogel beads, and their proliferation, viability, attachment and spreading were assessed for a week. The spongy and textured morphology of pristine hydrogel beads was converted to flowery and rod-shaped structures in drug-loaded hydrogel beads at reduced pH (6.3) and at a lower concentration (10 μg) of GO. These latter 10GO drug-loaded beads rapidly released their cargo owing to the calcium phosphate deposited on the surface. Notably, beads containing a higher amount of GO (50GO) exhibited an extended drug-release profile. We further found that MC3T3 cells proliferated continuously in vitro in the microfluidic channel containing the GO-hydrogel system. MTT and live/dead assays showed similar proliferative potential of MC3T3 cells. Therefore, a microfluidic device with microchannels containing hydrogel beads formulated with different amounts of GO and tested under various pH conditions could be a promising system for controlled drug release. The GO and drug (risedronate, Rig) were directed loaded into a hydrogel placed in a microchannel. Through interactions such as hydrogen bonding between Go and the Rig-loaded GO-hydrogel beads, the bead-loaded microfluidic device supported MC3T3 proliferation and development as osteoblast without additional osteogenic differentiation supplements.

Controlled release of folic acid through liquid-crystalline folate nanoparticles.

PubMed

Misra, Rahul; Katyal, Henna; Mohanty, Sanat

2014-11-01

The present study explores folate nanoparticles as nano-carriers for controlled drug delivery. Cross-linked nanoparticles of liquid crystalline folates are composed of ordered stacks. This paper shows that the folate nanoparticles can be made with less than 5% loss in folate ions. In addition, this study shows that folate nanoparticles can disintegrate in a controlled fashion resulting in controlled release of the folate ions. Release can be controlled by the size of nanoparticles, the extent of cross-linking and the choice of cross-linking cation. The effect of different factors like agitation, pH, and temperature on folate release was also studied. Studies were also carried out to show the effect of release medium and role of ions in the release medium on disruption of folate assembly. Copyright © 2014. Published by Elsevier B.V.

Undigested Pills in Stool Mimicking Parasitic Infection.

PubMed

Mir, Fazia; Achakzai, Ilyas; Ibdah, Jamal A; Tahan, Veysel

2017-01-01

Background . Orally ingested medications now come in both immediate release and controlled release preparations. Controlled release preparations were developed by pharmaceutical companies to improve compliance and decrease frequency of pill ingestion. Case Report . A 67-year-old obese male patient presented to our clinic with focal abdominal pain that had been present 3 inches below umbilicus for the last three years. This pain was not associated with any trauma or recent heavy lifting. Upon presentation, the patient reported that for the last two months he started to notice pearly oval structures in his stool accompanying his chronic abdominal pain. This had coincided with initiation of his nifedipine pills for his hypertension. He reported seeing these undigested pills daily in his stool. Conclusion . The undigested pills may pose a cause of concern for both patients and physicians alike, as demonstrated in this case report, because they can mimic a parasitic infection. This can result in unnecessary extensive work-up. It is important to review the medication list for extended release formulations and note that the outer shell can be excreted whole in the stool.

Temperature-Controlled Clamping and Releasing Mechanism

NASA Technical Reports Server (NTRS)

Rosing, David; Ford, Virginia

2005-01-01

A report describes the development of a mechanism that automatically clamps upon warming and releases upon cooling between temperature limits of approx. =180 K and approx. =293 K. The mechanism satisfied a need specific to a program that involved repeated excursions of a spectrometer between a room-temperature atmospheric environment and a cryogenic vacuum testing environment. The mechanism was also to be utilized in the intended application of the spectrometer, in which the spectrometer would be clamped for protection during launch of a spacecraft and released in the cold of outer space to allow it to assume its nominal configuration for scientific observations. The mechanism is passive in the sense that its operation does not depend on a control system and does not require any power other than that incidental to heating and cooling. The clamping and releasing action is effected by bolt-preloaded stacks of shape-memory-alloy (SMA) cylinders. In designing this mechanism, as in designing other, similar SMA mechanisms, it was necessary to account for the complex interplay among thermal expansion, elastic and inelastic deformation under load, and SMA thermomechanical properties.

Polypyrrole Film as a Drug Delivery System for the Controlled Release of Risperidone

NASA Astrophysics Data System (ADS)

Svirskis, Darren; Travas-Sejdic, Jadranka; Rodgers, Anthony; Garg, Sanjay

2009-07-01

Conducting polymers are finding applications in medicine including drug delivery systems, biosensors and templates for the regeneration of nervous pathways. We aim to develop a novel system where the drug release rate can be controlled by electrical stimulation. Polypyrrole (PPY) is being used as a drug delivery system due to its inherent electrical conductivity, ease of preparation and apparent biocompatibility. Risperidone is an atypical antipsychotic drug used in the treatment of psychosis and related disorders, including schizophrenia. PPY was synthesised using p-toluene sulfonic acid as a primary dopant, in the presence of risperidone. A validated high performance liquid chromatography (HPLC) analytical method was used to quantify risperidone release. It has been demonstrated that the release rate of risperidone can be altered through the application, or absence, of electrical stimulation. Technology such as this would find use in drug-delivering implants where the dose could be adjusted through application of external stimulus, optimising benefit to side effect ratio, while simultaneously ensuring patient adherence (which is a particular challenge in mental health conditions).

A nano-delivery system for bioactive ingredients using supercritical carbon dioxide and its release behaviors.

PubMed

Situ, Wenbei; Song, Xianliang; Luo, Shucan; Liang, Yan

2017-08-01

For the purpose of ensuring the bioavailability of bioactive ingredients, a nano-delivery system with low toxicity was developed using supercritical carbon dioxide (SC-CO 2 ). Compared to thin-film hydration (TFH), obtaining nano-scale liposomes is easier using SC-CO 2 . The characteristic of these liposomes was also demonstrated by the analysis of particle size and morphology. An in vitro release study showed that liposomes produced using SC-CO 2 were resistant to low pH in simulated gastric conditions. In a simulated intestinal environment, enteric solubility of these liposomes was enhanced, which are important properties for controlled releasing bioactive ingredient. Furthermore, SC-CO 2 -produced liposomes had a higher storage stability than those produced using TFH. Analysis of the organic solvent residue in the liposomes by gas chromatography-mass spectrometry (GC-MS) indicated that SC-CO 2 -produced liposomes had lower toxicity than those produced by TFH. A chemical free nano-delivery system using SC-CO 2 has been revealed for storage and controlled release of bioactive ingredients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dual-drug nanomedicine with hydrophilic F127-modified magnetic nanocarriers assembled in amphiphilic gelatin for enhanced penetration and drug delivery in deep tumor tissue.

PubMed

Lai, Yen-Ho; Chiang, Chih-Sheng; Kao, Tzu-Hsun; Chen, San-Yuan

2018-01-01

Deep penetration of large-sized drug nanocarriers into tumors is important to improve the efficacy of tumor therapy. In this study, we developed a size-changeable "Trojan Horse" nanocarrier (THNC) composed of paclitaxel (PTX)-loaded Greek soldiers (GSs; ~20 nm) assembled in an amphiphilic gelatin matrix with hydrophilic losartan (LST) added. With amphiphilic gelatin matrix cleavage by matrix metalloproteinase-2, LST showed fast release of up to 60% accumulated drug at 6 h, but a slow release kinetic (~20%) was detected in the PTX from the GSs, indicating that THNCs enable controllable release of LST and PTX drugs for penetration into the tumor tissue. The in vitro cell viability in a 3D tumor spheroid model indicated that the PTX-loaded GSs liberated from THNCs showed deeper penetration as well as higher cytotoxicity, reducing a tumor spheroid to half its original size and collapsing the structure of the tumor microenvironment. The results demonstrate that the THNCs with controlled drug release and deep penetration of magnetic GSs show great potential for cancer therapy.

Hypothalamic neural systems controlling the female reproductive life cycle: Gonadotropin-releasing hormone, glutamate, and GABA

PubMed Central

Maffucci, Jacqueline A.; Gore, Andrea C.

2009-01-01

The hypothalamic-pituitary-gonadal (HPG) axis undergoes a number of changes throughout the reproductive life cycle that are responsible for the development, puberty, adulthood, and senescence of reproductive systems. This natural progression is dictated by the neural network controlling the hypothalamus including the cells that synthesize and release gonadotropin-releasing hormone (GnRH) and their regulatory neurotransmitters. Glutamate and GABA are the primary excitatory and inhibitory neurotransmitters in the central nervous system, and as such contribute a great deal to modulating this axis throughout the lifetime via their actions on receptors in the hypothalamus, both directly on GnRH neurons as well as indirectly though other hypothalamic neural networks. Interactions among GnRH neurons, glutamate, and GABA, including the regulation of GnRH gene and protein expression, hormone release, and modulation by estrogen, are critical to age-appropriate changes in reproductive function. Here, we present evidence for the modulation of GnRH neurosecretory cells by the balance of glutamate and GABA in the hypothalamus, and the functional consequences of these interactions on reproductive physiology across the life cycle. PMID:19349036

Development and dissolution studies of bisphosphonate (clodronate)-containing hydroxyapatite-polylactic acid biocomposites for slow drug delivery.

PubMed

Macha, Innocent J; Cazalbou, Sophie; Shimmon, Ronald; Ben-Nissan, Besim; Milthorpe, Bruce

2017-06-01

An increase in clinical demand on the controlled release of bisphosphonates (BPs) due to complications associated with systemic administration, has been the current driving force on the development of BP drug-release systems. Bisphosphonates have the ability to bind to divalent metal ions, such as Ca 2+ , in bone mineral and prevent bone resorption by influencing the apoptosis of osteoclasts. Localized delivery using biodegradable materials, such as polylactic acid (PLA) and hydroxyapatite (HAp), which are ideal in this approach, have been used in this study to investigate the dissolution of clodronate (non-nitrogen-containing bisphosphonate) in a new release system. The effects of coral structure-derived HAp and the release kinetics of the composites were evaluated. The release kinetics of clodronate from PLA-BP and PLA-HAp-BP systems seemed to follow the power law model described by Korsmeyer-Peppas. Drug release was quantified by 31 P-NMR with detection and quantification limits of 9.2 and 30.7 mM, respectively. The results suggest that these biocomposite systems could be tuned to release clodronate for both relatively short and prolonged period of time. In addition to drug delivery, the degradation of HAp supplies both Ca 2+ and phosphate ions that can help in bone mineralization. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Pseudoephedrine hydrochloride sustained-release pellets prepared by a combination of hot-melt subcoating and polymer coating.

PubMed

Yang, Zi Yi; Lu, Yan; Tang, Xing

2008-12-01

Pseudoephedrine hydrochloride is an active very highly water soluble substance. In order to control release of a drug with this property, we developed the application of a combination of hot-melt subcoating and polymer coating was developed. The main objective was to investigate the influence of this combination on the release of highly water soluble drug and how it works. Hot-melt subcoating was achieved by using a coating pan. Subsequently, the outer polymer coating was prepared by fluidized bed, and the drug release was determined by high-performance liquid chromatograph (HPLC) method. Hot-melt subcoating can form a barrier between the drug-loaded pellets and the polymer coating layer, which prevents migration of the drug during film application. Consequently, the level of polymer coating can be reduced significantly, and the effectiveness of the polymer coating increased. In this study, the release profile of pellets with a 10% hot-melt subcoating and 5% polymer coating weight gain met the dissolution requirement of USP29 for pseudoephedrine hydrochloride extended-release capsules. Compared with pellets only polymer coated (10% level), the polymer coating level of pellets prepared by this technology was reduced by half due to hot-melt subcoating. By means of this hot-melt subcoating and polymer coating, sustained-release pellets containing pseudoephedrine hydrochloride were successfully prepared.

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.

Environmental pH-controlled loading and release of protein on mesoporous hydroxyapatite nanoparticles for bone tissue engineering.

PubMed

Zhang, Ning; Gao, Tianlin; Wang, Yu; Wang, Zongliang; Zhang, Peibiao; Liu, Jianguo

2015-01-01

To explore the controlled delivery of protein drugs in micro-environment established by osteoblasts or osteoclasts, the loading/release properties of bovine serum albumin (BSA) depending on pH environment were assessed. The adsorption amounts over mesoporous hydroxyapatite (MHA) or hydroxyapatite (HA) decreased as the pH increased, negatively correlating with zeta-potential values. The adsorption behavior over MHA fits well with the Freundlich and Langmuir models at different pHs. The results suggest that the adsorbed amount of protein on MHA or HA depended on the pH of protein solution. MHA adsorbed BSA at basic pH (MHApH 8.4) exhibited a different release kinetics compared with those in acid and neutral environments (MHApH 4.7 and MHApH 7.4), indicating that the release of protein could be regulated by environmental pH at which MHAs adsorb protein. MHApH 8.4 showed a sustained release for 6h before a gradual release when immersing in acidic environment, which is 2h longer than that in neutral environment. This suggests that MHApH 8.4 showed a more sustained release in acidic environment, which can be established by osteoclasts. The variation of adsorption strength between protein and MHA may be responsible for these behaviors. Our findings may be very useful for the development of MHA applications on both bone repair and protein delivery. Copyright © 2014. Published by Elsevier B.V.

Development of antimicrobial coating by later-by-layer dip coating of chlorhexidine-loaded micelles.

PubMed

Tambunlertchai, Supreeda; Srisang, Siriwan; Nasongkla, Norased

2017-06-01

Layer-by-layer (LbL) dip coating, accompanying with the use of micelle structure, allows hydrophobic molecules to be coated on medical devices' surface via hydrogen bonding interaction. In addition, micelle structure also allows control release of encapsulated compound. In this research, we investigated methods to coat and maximize the amount of chlorhexidine (CHX) on silicone surface through LbL dip coating method utilizing hydrogen bonding interaction between PEG on micelle corona and PAA. The number of coated cycles was varied in the process and 90 coating cycles provided the maximum amount of CHX loaded onto the surface. In addition, pre-coating the surface with PAA enhanced the amount of coated CHX by 20%. Scanning electron microscope (SEM) and Fourier Transform Infrared Spectroscopy (FTIR) were used to validate and characterize the coating. For control release aspect, the coated film tended to disrupt at physiological condition; hence chemical crosslinking was performed to minimize the disruption and maximize the release time. Chemical crosslinking at pH 2.5 and 4.5 were performed in the process. It was found that chemical crosslinking could help extend the release period up to 18 days. This was significantly longer when compared to the non-crosslinking silicone tube that could only prolong the release for 5 days. In addition, chemical crosslinking at pH 2.5 gave higher and better initial burst release, release period and antimicrobial properties than that of pH 4.5 or the normal used pH for chemical crosslinking process.

Are fluoride releasing dental materials clinically effective on caries control?

PubMed

Cury, Jaime Aparecido; de Oliveira, Branca Heloisa; dos Santos, Ana Paula Pires; Tenuta, Livia Maria Andaló

2016-03-01

(1) To describe caries lesions development and the role of fluoride in controlling disease progression; (2) to evaluate whether the use of fluoride-releasing pit and fissure sealants, bonding orthodontic agents and restorative materials, in comparison to a non-fluoride releasing material, reduces caries incidence in children or adults, and (3) to discuss how the anti-caries properties of these materials have been evaluated in vitro and in situ. The search was performed on the Cochrane Database of Systematic Reviews and on Medline via Pubmed. Caries is a biofilm-sugar dependent disease and as such it provokes progressive destruction of mineral structure of any dental surface - intact, sealed or restored - where biofilm remains accumulated and is regularly exposed to sugar. The mechanism of action of fluoride released from dental materials on caries is similar to that of fluoride found in dentifrices or other vehicles of fluoride delivery. Fluoride-releasing materials are unable to interfere with the formation of biofilm on dental surfaces adjacent to them or to inhibit acid production by dental biofilms. However, the fluoride released slows down the progression of caries lesions in tooth surfaces adjacent to dental materials. This effect has been clearly shown by in vitro and in situ studies but not in randomized clinical trials. The anti-caries effect of fluoride releasing materials is still not based on clinical evidence, and, in addition, it can be overwhelmed by fluoride delivered from dentifrices. Copyright © 2015 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

The effectiveness of the controlled release of simvastatin from β-TCP macrosphere in the treatment of OVX mice.

PubMed

Chou, Joshua; Ito, Tomoko; Otsuka, Makoto; Ben-Nissan, Besim; Milthorpe, Bruce

2016-03-01

Simvastatin, a cholesterol treatment drug, has been shown to stimulate bone regeneration. As such, there has been an increase interest in the development of suitable materials and systems for the delivery of simvastatin. Without the appropriate dosage of simvastatin, the therapeutic effects on bone growth will be significantly reduced. Furthermore, similar to many pharmaceutical compounds, at high concentration simvastatin can cause various adverse side-effects. Given the associated side-effects with the usage of simvastatin, the development of suitable controlled drug release system is pertinent. Calcium phosphate in particularly beta-tricalcium phosphate (β-TCP) has been extensively studied and used as a carrier material for drug delivery system. In this study, Foraminifera exoskeletons were used as calcium carbonate precursor materials, which were hydrothermally converted to β-TCP as a carrier material for simvastatin. Natural marine exoskeletons posses interconnected and uniformly porous network capable of improving drug loading and release rate. To prolong the release of simvastatin, an apatite coating was made around the β-TCP sample and in vitro release studies in simulated body fluid (SBF) showed a significant decrease in release rate. Osteoporotic mice were used to examine the compare therapeutic effectiveness of β-TCP, β-TCP with simvastatin, apatite-coated β-TCP with simvastatin and direct injection of simvastatin near the right femur of the mice. Localized and systemic effect were compared with the femur of the non-implanted side (left) and showed that β-TCP with or without simvastatin was able to induce significant bone formation over 6 weeks. Mechanical analysis showed that apatite-coated β-TCP with simvastatin produced significantly stronger bones compared with other experimental groups. This study shows that natural exoskeletons with the appropriate structure can be successfully used as a drug delivery system for simvastatin and can its release can be prolonged with an apatite coating to significantly promote relevant bone formation. Copyright © 2013 John Wiley & Sons, Ltd.

A space release/deployment system actuated by shape memory wires

NASA Astrophysics Data System (ADS)

Fragnito, Marino; Vetrella and, Sergio

2002-11-01

In this paper, the design of an innovative hold down/release and deployment device actuated by shape memory wires, to be used for the first time for the S MA RT microsatellite solar wings is shown. The release and deployment mechanisms are actuated by a Shape Memory wire (Nitinol), which allows a complete symmetrical and synchronous release, in a very short time, of the four wings in pairs. The hold down kinematic mechanism is preloaded to avoid vibration nonlinearities and unwanted deployment at launch. The deployment mechanism is a simple pulley system. The stiffness of the deployed panel-hinge system needs to be dimensioned in order to meet the on-orbit requirement for attitude control. One-way roller clutches are used to keep the panel at the desired angle during the mission. An ad hoc software has been developed to simulate both the release and deployment operations, coupling the SMA wire behavior with the system mechanics.

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.

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.

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.

[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.

Stability effect of cholesterol-poly(acrylic acid) in a stimuli-responsive polymer-liposome complex obtained from soybean lecithin for controlled drug delivery.

PubMed

Simões, M G; Alves, P; Carvalheiro, Manuela; Simões, P N

2017-04-01

The development of polymer-liposome complexes (PLCs), in particular for biomedical applications, has grown significantly in the last decades. The importance of these studies comes from the emerging need in finding intelligent controlled release systems, more predictable, effective and selective, for applications in several areas, such as treatment and/or diagnosis of cancer, neurological, dermatological, ophthalmic and orthopedic diseases, gene therapy, cosmetic treatments, and food engineering. This work reports the development and characterization of a pH sensitive system for controlled release based on PLCs. The selected hydrophilic polymer was poly(acrylic acid) (PAA) synthesized by atom transfer radical polymerization (ATRP) with a cholesterol (CHO) end-group to improve the anchoring of the polymer into the lipid bilayer. The polymer was incorporated into liposomes formulated from soybean lecithin and stearylamine, with different stearylamine/phospholipid and polymer/phospholipid ratios (5, 10 and 20%). The developed PLCs were characterized in terms of particle size, polydispersity, zeta potential, release profiles, and encapsulation efficiency. Cell viability studies were performed to assess the cytotoxic potential of PLCs. The results showed that the liposomal formulation with 5% of stearylamine and 10% of polymer positively contribute to the stabilization of the complexes. Afterwards, the carboxylic acid groups of the polymer present at the surface of the liposomes were crosslinked and the same parameters analyzed. The crosslinked complexes showed to be more stable at physiologic conditions. In addition, the release profiles at different pHs (2-12) revealed that the obtained complexes released all their content at acidic conditions. In summary, the main accomplishments of this work are: (i) innovative synthesis of cholesterol-poly(acrylic acid) (CHO-PAA) by ATRP; (ii) stabilization of the liposomal formulation by incorporation of stearylamine and CHO-PAA; (iii) new approach for CHO-PAA crosslinking, resulting in more stable PLCs at physiological conditions; (iv) destabilization of PLCs upon slight changes of pH, showing their pH sensitivity; and (v) the PLCs do not exhibit cellular toxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

Development and optimization of buspirone oral osmotic pump tablet

PubMed Central

Derakhshandeh, K.; berenji, M. Ghasemnejad

2014-01-01

The aim of the current study was to design a porous osmotic pump–based drug delivery system for controlling the release of buspirone from the delivery system. The osmotic pump was successfully developed using symmetric membrane coating. The core of the tablets was prepared by direct compression technique and coated using dip-coating technique. Drug release from the osmotic system was studied using USP paddle type apparatus. The effect of various processing variables such as the amount of osmotic agent, the amount of swellable polymer, concentration of the core former, concentration of the plasticizer, membrane thickness, quantum of orifice on drug release from osmotic pump were evaluated. Different kinetic models (zero order, first order and Higuchi model) were applied to drug release data in order to establish the kinetics of drug release. It was found that the drug release was mostly affected by the amount of NaCl as osmotic agent, the swellable polymer; hydroxy propyl methyl cellulose (HPMC), the amount of PEG-400 and cellulose acetate in the coating solution and thickness of the semipermeable membrane. The optimized formulation released buspirone independent of pH and orifice quantum at the osmogen amount of 42%, hydrophilic polymer of 13% and pore size of 0.8 mm on the tablet surface. The drug release of osmotic formulation during 24 h showed zero order kinetics and could be suggested that this formulation as a once-daily regimen improves pharmacokinetic parameters of the drug and enhances patient compliance. PMID:25657794

Development and optimization of buspirone oral osmotic pump tablet.

PubMed

Derakhshandeh, K; Berenji, M Ghasemnejad

2014-01-01

The aim of the current study was to design a porous osmotic pump-based drug delivery system for controlling the release of buspirone from the delivery system. The osmotic pump was successfully developed using symmetric membrane coating. The core of the tablets was prepared by direct compression technique and coated using dip-coating technique. Drug release from the osmotic system was studied using USP paddle type apparatus. The effect of various processing variables such as the amount of osmotic agent, the amount of swellable polymer, concentration of the core former, concentration of the plasticizer, membrane thickness, quantum of orifice on drug release from osmotic pump were evaluated. Different kinetic models (zero order, first order and Higuchi model) were applied to drug release data in order to establish the kinetics of drug release. It was found that the drug release was mostly affected by the amount of NaCl as osmotic agent, the swellable polymer; hydroxy propyl methyl cellulose (HPMC), the amount of PEG-400 and cellulose acetate in the coating solution and thickness of the semipermeable membrane. The optimized formulation released buspirone independent of pH and orifice quantum at the osmogen amount of 42%, hydrophilic polymer of 13% and pore size of 0.8 mm on the tablet surface. The drug release of osmotic formulation during 24 h showed zero order kinetics and could be suggested that this formulation as a once-daily regimen improves pharmacokinetic parameters of the drug and enhances patient compliance.

Zaleplon loaded bi-layered chronopatch: A novel buccal chronodelivery approach to overcome circadian rhythm related sleep disorder.

PubMed

Farag, Michael M; Abd El Malak, Nevine S; Yehia, Soad A

2018-05-05

The aim of this study was to develop a novel buccal bi-layered chronopatch capable of eliciting pulsatile release pattern of drugs treating diseases with circadian rhythm related manifestation. Zaleplon (ZLP) was used as a model drug intended to induce sleep and to treat middle of night insomnia. The chronopatch was prepared adopting double casting technique. The first layer was composed of a controlled release patch containing ZLP-Precirol melt granules intended to release ZLP in a sustained manner to maintain sleep and to prevent early morning awakening. The second layer was composed of a fast release lyophilized buccal disc containing ZLP loaded SNEDDS (Z-SNEDDS) intended for rapid sleep induction. Pharmacokinetic parameters of ZLP from the chronopatch were compared to those of the immediate release capsule, Siesta®, as reference in Mongrel dogs using a randomized crossover design. The appearance of two peaks having two C max and T max proved the pulsatile release pattern. The increase in relative bioavailability of ZLP from the chronopatch was 2.63 folds. The results revealed the ability of the developed ZLP loaded bi-layered chronopatch to be a candidate for overcoming early morning awakening without middle of night dose administration. Copyright © 2018 Elsevier B.V. All rights reserved.

PLGA-lecithin-PEG core-shell nanoparticles for controlled drug delivery.

PubMed

Chan, Juliana M; Zhang, Liangfang; Yuet, Kai P; Liao, Grace; Rhee, June-Wha; Langer, Robert; Farokhzad, Omid C

2009-03-01

Current approaches to encapsulate and deliver therapeutic compounds have focused on developing liposomal and biodegradable polymeric nanoparticles (NPs), resulting in clinically approved therapeutics such as Doxil/Caelyx and Genexol-PM, respectively. Our group recently reported the development of biodegradable core-shell NP systems that combined the beneficial properties of liposomal and polymeric NPs for controlled drug delivery. Herein we report the parameters that alter the biological and physicochemical characteristics, stability, drug release properties and cytotoxicity of these core-shell NPs. We further define scalable processes for the formulation of these NPs in a reproducible manner. These core-shell NPs consist of (i) a poly(D,L-lactide-co-glycolide) hydrophobic core, (ii) a soybean lecithin monolayer, and (iii) a poly(ethylene glycol) shell, and were synthesized by a modified nanoprecipitation method combined with self-assembly. Preparation of the NPs showed that various formulation parameters such as the lipid/polymer mass ratio and lipid/lipid-PEG molar ratio controlled NP physical stability and size. We encapsulated a model chemotherapy drug, docetaxel, in the NPs and showed that the amount of lipid coverage affected its drug release kinetics. Next, we demonstrated a potentially scalable process for the formulation, purification, and storage of NPs. Finally, we tested the cytotoxicity using MTT assays on two model human cell lines, HeLa and HepG2, and demonstrated the biocompatibility of these particles in vitro. Our data suggest that the PLGA-lecithin-PEG core-shell NPs may be a useful new controlled release drug delivery system.

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.

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.

Investigation of the effect of tablet surface area/volume on drug release from hydroxypropylmethylcellulose controlled-release matrix tablets.

PubMed

Reynolds, Thomas D; Mitchell, Shawn A; Balwinski, Karen M

2002-04-01

The purpose of this study was to investigate the influence of tablet surface area/volume (SA/Vol) on drug release from controlled-release matrix tablets containing hydroxypropylmethylcellulose (HPMC). Soluble drugs (promethazine HCl, diphenhydramine HCl, and propranolol HCl) were utilized in this study to give predominantly diffusion-controlled release. Drug release from HPMC matrix tablets with similar values of SA/Vol was comparable within the same tablet shape (i.e., flat-faced round tablets) and among different shapes (i.e., oval, round concave, flat-faced beveled-edge, and flat-faced round tablets). Tablets having the same surface area but different SA/Vol values did not result in similar drug release; tablets with larger SA/Vol values hadfaster release profiles. Utility of SA/Vol to affect drug release was demonstrated by changing drug doses, and altering tablet shape to adjust SA/Vol. When SA/Vol was held constant, similar release profiles were obtained with f2 metric values greater than 70. Thus, surface area/volume is one of the key variables in controlling drug release from HPMC matrix tablets. Proper use of this variable has practical application by formulators who may need to duplicate drug release profiles from tablets of different sizes and different shapes.

Doxycycline delivery from PLGA microspheres prepared by a modified solvent removal method.

PubMed

Patel, Roshni S; Cho, Daniel Y; Tian, Cheng; Chang, Amy; Estrellas, Kenneth M; Lavin, Danya; Furtado, Stacia; Mathiowitz, Edith

2012-01-01

We report on the development of a modified solvent removal method for the encapsulation of hydrophilic drugs within poly(lactic-co-glycolic acid) (PLGA). Using a water/oil/oil double emulsion, hydrophilic doxycycline was encapsulated within PLGA spheres with particle diameters ranging from approximately 600 nm to 19 µm. Encapsulation efficiencies of up to 74% were achieved for theoretical loadings from 1% to 10% (w/w), with biphasic release over 85 days with nearly complete release at the end of this time course. About 1% salt was added to the formulations to examine its effects on doxycycline release; salt modulated release only by increasing the magnitude of initial release without altering kinetics. Fourier transform infrared spectroscopy indicated no characteristic differences between doxycycline-loaded and control spheres. Differential scanning calorimetry and X-ray diffraction suggest that there may be a molecular dispersion of the doxycycline within the spheres and the doxycycline may be in an amorphous state, which could explain the slow, prolonged release of the drug.

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.

A Responsive Battery with Controlled Energy Release.

PubMed

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

2016-11-14

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

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

Two-Step Self-Assembly of Liposome-Multidomain Peptide Nanofiber Hydrogel for Time-Controlled Release

PubMed Central

2015-01-01

Progress in self-assembly and supramolecular chemistry has been directed toward obtaining macromolecular assemblies with higher degrees of complexity, simulating the highly structured environment in natural systems. One approach to this type of complexity are multistep, multicomponent, self-assembling systems that allow approaches comparable to traditional multistep synthetic organic chemistry; however, only a few examples of this approach have appeared in the literature. Our previous work demonstrated nanofibrous mimics of the extracellular matrix. Here we demonstrate the ability to create a unique hydrogel, developed by stepwise self-assembly of multidomain peptide fibers and liposomes. The two-component system allows for controlled release of bioactive factors at multiple time points. The individual components of the self-assembled gel and the composite hydrogel were characterized by TEM, SEM, and rheometry, demonstrating that peptide nanofibers and lipid vesicles both retain their structural integrity in the composite gel. The rheological robustness of the hydrogel is shown to be largely unaffected by the presence of liposomes. Release studies from the composite gels loaded with different growth factors EGF, MCP-1, and PlGF-1 showed delay and prolongation of release by liposomes entrapped in the hydrogel compared to more rapid release from the hydrogel alone. This bimodal release system may have utility in systems where timed cascades of biological signals may be valuable, such as in tissue regeneration. PMID:25308335

The effect of controlled release of PDGF-BB from heparin-conjugated electrospun PCL/gelatin scaffolds on cellular bioactivity and infiltration

PubMed Central

Lee, Jongman; Yoo, James J.; Atala, Anthony; Lee, Sang Jin

2013-01-01

Heparin-conjugated electrospun poly(ε-caprolactone) (PCL)/gelatin scaffolds were developed to provide controlled release of platelet-derived growth factor-BB (PDGF-BB) and allow prolonged bioactivity of this molecule. A mixture of PCL and gelatin was electrospun into three different morphologies. Next, heparin molecules were conjugated to the reactive surface of the scaffolds. This heparin-conjugated scaffold allowed the immobilization of PDGF-BB via electrostatic interaction. In vitro PDGF-BB release profiles indicated that passive physical adsorption of PDGF-BB to non-heparinized scaffolds resulted in an initial burst release of PDGF-BB within 5 days, which then leveled off. However, electrostatic interaction between PDGF-BB and the heparin-conjugated scaffolds gave rise to a sustained release of PDGF-BB over the course of 20 days without an initial burst. Moreover, PDGF-BB that was strongly bound to the heparin-conjugated scaffolds enhanced smooth muscle cell (SMC) proliferation. In addition, scaffolds composed of 3.0 µm diameter fibers that were immobilized with PDGF-BB accelerated SMC infiltration into the scaffold when compared to scaffolds composed of smaller diameter fibers or scaffolds that did not release PDGF-BB. We concluded that the combination of the large pore structure in the scaffolds and the heparin-mediated delivery of PDGF-BB provided the most effective cellular interactions through synergistic physical and chemical cues. PMID:22770570

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.

Development and characterization of different black raspberry confection matrices designed for delivery of phytochemicals.

PubMed

Gu, Junnan; Ahn-Jarvis, Jennifer H; Vodovotz, Yael

2015-03-01

Three forms of confections containing black raspberries (BRB) powder were developed to provide controlled release of phytochemicals for oral disease prevention. Our objective was to investigate the impact of varying confection matrices on the release rate of BRB phytochemicals. Confections were developed and prepared. Textural properties of confections were analyzed, compared and correlated with the release rate of phytochemicals from BRB confections with in vitro dissolution test. In the results, BRB content reached 22% in hard candy and pectin-based confections and 40% in starch-based confections, respectively. Pectin- and starch-based confections retained >93% of its original anthocyanins after processing while hard candy had 59%. Starch confections showed higher G' in rheological analysis and higher hardness but lower cohesiveness and springiness in textural profile analysis than pectin confections (P < 0.05). The confection types showed different microstructure with scanning electronic microscopy (SEM). Corresponding to their physicochemical properties, confections showed fast (hard candy), intermediate (pectin confections), and slow (starch confections) release rates with a final releasing time of 90, 150, and 540 min in dissolution studies. Three confections were rated between neither like nor dislike to like slightly (n = 60). Pectin confections had the highest overall acceptance (like slightly) and 62% of subjects rated this type of confection as the most liked ones. These results indicate that delivery matrix could modulate the phytochemical release rate from BRB confection and also influence sensory preference. © 2015 Institute of Food Technologists®

A pH and redox dual stimuli-responsive poly(amino acid) derivative for controlled drug release.

PubMed

Gong, Chu; Shan, Meng; Li, Bingqiang; Wu, Guolin

2016-10-01

A pH and redox dual stimuli-responsive poly(aspartic acid) derivative for controlled drug release was successfully developed through progressive ring-opening reactions of polysuccinimide (PSI). Polyethylene glycol (PEG) chains were grafted onto the polyaspartamide backbone via redox-responsive disulfide linkages, providing a sheddable shell for the polymeric micelles in a reductive environment. Phenyl groups were introduced into the polyaspartamide backbone via the aminolysis reaction of PSI to serve as the hydrophobic segment of micelles. The polyaspartamide scaffold was also functionalized with N-(3-aminopropyl)-imidazole to obtain the pH-responsiveness manifesting as a swelling of the core of micelles at a low pH. The polymeric micelles with a core-shell nanostructure forming in neutral media exhibited both pH and redox responsive characteristics. Doxorubicin (DOX) as a model drug was encapsulated into the core of micelles through both hydrophobic and π-π interactions between aromatic rings and the DOX-loaded polymeric micelles exhibited accelerated drug release behaviors in an acidic and reductive environment due to the swelling of hydrophobic cores and the shedding of PEG shells. Furthermore, the cytocompability of the polymer and the cytotoxicity of DOX-loaded micelles towards Hela cells under corresponding conditions were evaluated, and the endocytosis of DOX-loaded polymeric micelles and the intracellular drug release from micelles were observed. All obtained data indicated that the micelle was a promising candidate for controlled drug release. Copyright © 2016 Elsevier B.V. All rights reserved.

Orthodontic cement with protein-repellent and antibacterial properties and the release of calcium and phosphate ions.

PubMed

Zhang, Ning; Weir, Michael D; Chen, Chen; Melo, Mary A S; Bai, Yuxing; Xu, Hockin H K

2016-07-01

White spot lesions often occur in orthodontic treatments. The objective of this study was to develop a novel resin-modified glass ionomer cement (RMGI) as an orthodontic cement with protein-repellent, antibacterial and remineralization capabilities. Protein-repellent 2-methacryloyloxyethyl phosphorylcholine (MPC), antibacterial dimethylaminohexadecyl methacrylate (DMAHDM), nanoparticles of silver (NAg), and nanoparticles of amorphous calcium phosphate (NACP) were incorporated into a RMGI. Enamel shear bond strength (SBS) was determined. Calcium (Ca) and phosphate (P) ion releases were measured. Protein adsorption onto specimens was determined by a micro bicinchoninic acid method. A dental plaque microcosm biofilm model was tested. Increasing the NACP filler level increased the Ca and P ion release. Decreasing the solution pH increased the ion release. Incorporating MPC into RMGI reduced protein adsorption, which was an order of magnitude less than that of commercial controls. Adding DMAHDM and NAg into RMGI yielded a strong antibacterial function, greatly reducing biofilm viability and acid production. Biofilm CFU counts on the multifunctional orthodontic cement were 3 orders of magnitude less than that of commercial control (p<0.05). These benefits were achieved without compromising the enamel shear bond strength (p>0.1). A novel multifunctional orthodontic cement was developed with strong antibacterial and protein-repellent capabilities for preventing enamel demineralization. The new cement is promising to prevent white spot lesions in orthodontic treatments. The method of incorporating four bioactive agents may have wide applicability to the development of other bioactive dental materials to inhibit caries. Copyright © 2016 Elsevier Ltd. All rights reserved.

Web-based technical assistance and training to promote community tobacco control policy change.

PubMed

Young, Walter F; Montgomery, Debbie; Nycum, Colleen; Burns-Martin, Lavon; Buller, David B

2006-01-01

In 1998 the tobacco industry was released of claims that provided monetary relief for states. A significant expansion of tobacco control activity in many states created a need to develop local capacity. Technical assistance and training for new and experienced staff became a significant challenge for tobacco control leadership. In Colorado, this challenge was addressed in part through the development of a technical assistance and training Web site designed for local tobacco control staff and coalition members. Researchers, technical Web site development specialists, state health agency, and state tobacco control coalition staff collaborated to develop, promote, and test the efficacy of this Web site. The work group embodied a range of skills including tobacco control, Web site technical development, marketing, training, and project management. Persistent marketing, updating of Web site content, and institutionalizing it as a principal source of information and training were key to use by community coalition members.

The International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes--chapter 3: Pig islet product manufacturing and release testing.

PubMed

Korbutt, Gregory S

2009-01-01

This chapter provides recommendations on pig islet product manufacturing and release testing to scientific and corporate programs interested in future clinical studies using xenogeneic porcine pancreatic islet cell products for the treatment of type 1 diabetes.To facilitate control of manufacturing as well as reproducibility and consistency of product lots, the manufacturing process, and the manufacturing facility must be in compliance with current Good Manufacturing Practices regulations. Data must be provided to demonstrate that islet products can be consistently prepared that would meet basic lot release requirements. To facilitate product safety: (i) materials used in the manufacturing process, including the pig pancreas, must be free of adventitious agents; (ii) islets must be manufactured using aseptic processing; and (iii) final product must undergo tests for sterility, mycoplasma (if cultured) and endotoxin. Safety specifications for pig islet product release include a negative Gram stain and an endotoxin content of <5.0 EU/kg recipient body weight. Product post-release assessments must include sterility cultures on the final product. Because results for sterility are available only retrospectively, a plan of action must be in place for patient notification and treatment in case the sterility culture results are positive for contamination. Product characterization information must address important aspects of lot release testing such as identity/purity (cell composition), quantity [islet equivalents (IE), cell number] and potency (insulin secretory capacity, oxygen consumption rate corrected for DNA or transplant bioassay in immunoincompetent diabetic mice). This information is also critical to demonstrate manufacturing control and product consistency across multiple islet preparations (lots). Providing islet products containing an islet mass sufficient to restore euglycemia in trial participants (>or=10 000 IE/kg) requires pooling of islets from multiple donor pancreata (two to four from adult donors and seven to 10 from neonatal donors). Demonstration of product consistency across products from individual pancreata would warrant release testing to be performed on a sample of the pooled product. As product development and clinical trials advance, the increasingly more detailed specifications of potency assays on adult porcine islet products are expected to be predictive of post-transplant glycemic control. The immaturity of fetal and neonatal porcine islet tissue precludes the use of in vitro insulin secretion as a potency test as part of lot release testing; another measure of potency appropriate to fetal and neonatal cells will need to be developed for product release testing and evaluation of aliquots of these products in mouse transplant bioassays should be performed to provide meaningful post-release information.

Enhanced efficiency fertilisers: a review of formulation and nutrient release patterns.

PubMed

Timilsena, Yakindra Prasad; Adhikari, Raju; Casey, Phil; Muster, Tim; Gill, Harsharn; Adhikari, Benu

2015-04-01

Fertilisers are one of the most important elements of modern agriculture. The application of fertilisers in agricultural practices has markedly increased the production of food, feed, fuel, fibre and other plant products. However, a significant portion of nutrients applied in the field is not taken up by plants and is lost through leaching, volatilisation, nitrification, or other means. Such a loss increases the cost of fertiliser and severely pollutes the environment. To alleviate these problems, enhanced efficiency fertilisers (EEFs) are produced and used in the form of controlled release fertilisers and nitrification/urease inhibitors. The application of biopolymers for coating in EEFs, tailoring the release pattern of nutrients to closely match the growth requirement of plants and development of realistic models to predict the release pattern of common nutrients have been the foci of fertiliser research. In this context, this paper intends to review relevant aspects of new developments in fertiliser production and use, agronomic, economic and environmental drives for enhanced efficiency fertilisers and their formulation process and the nutrient release behaviour. Application of biopolymers and complex coacervation technique for nutrient encapsulation is also explored as a promising technology to produce EEFs. © 2014 Society of Chemical Industry.

Hybrid PCL/CaCO3 scaffolds with capabilities of carrying biologically active molecules: Synthesis, loading and in vivo applications.

PubMed

Saveleva, M S; Ivanov, A N; Kurtukova, M O; Atkin, V S; Ivanova, A G; Lyubun, G P; Martyukova, A V; Cherevko, E I; Sargsyan, A K; Fedonnikov, A S; Norkin, I A; Skirtach, A G; Gorin, D A; Parakhonskiy, B V

2018-04-01

Designing advanced biomaterials for tissue regeneration with drug delivery and release functionalities remains a challenge in regenerative medicine. In this research, we have developed novel composite scaffolds based on polymeric polycaprolactone fibers coated with porous calcium carbonate structures (PCL/CaCO 3 ) for tissue engineering and have shown their drug delivery and release in rats. In vivo biocompatibility tests of PCL/CaCO 3 scaffolds were complemented with in vivo drug release study, where tannic acid (TA) was used as a model drug. Release of TA from the scaffolds was realized by recrystallization of the porous vaterite phase of calcium carbonate into the crystalline calcite. Cell colonization and tissue vascularization as well as transplantability of developed PCL/CaCO 3 +TA scaffolds were observed. Detailed study of scaffold transformations during 21-day implantation period was followed by scanning electron microscopy and X-ray diffraction studies before and after in vivo implantation. The presented results demonstrate that PCL/CaCO 3 scaffolds are attractive candidates for implants in bone regeneration and tissue engineering with a possibility of loading biologically active molecules and controlled release. Copyright © 2017 Elsevier B.V. All rights reserved.

Mathematical Models for Controlled Drug Release Through pH-Responsive Polymeric Hydrogels.

PubMed

Manga, Ramya D; Jha, Prateek K

2017-02-01

Hydrogels consisting of weakly charged acidic/basic groups are ideal candidates for carriers in oral delivery, as they swell in response to pH changes in the gastrointestinal tract, resulting in drug entrapment at low pH conditions of the stomach and drug release at high pH conditions of the intestine. We have developed 1-dimensional mathematical models to study the drug release behavior through pH-responsive hydrogels. Models are developed for 3 different cases that vary in the level of rigor, which together can be applied to predict both in vitro (drug release from carrier) and in vivo (drug concentration in the plasma) behavior of hydrogel-drug formulations. A detailed study of the effect of hydrogel and drug characteristics and physiological conditions is performed to gain a fundamental insight into the drug release behavior, which may be useful in the design of pH-responsive drug carriers. Finally, we describe a successful application of these models to predict both in vitro and in vivo behavior of docetaxel-loaded micelle in a pH-responsive hydrogel, as reported in a recent experimental study. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Aptamer loaded MoS2 nanoplates as nanoprobes for detection of intracellular ATP and controllable photodynamic therapy

NASA Astrophysics Data System (ADS)

Jia, Li; Ding, Lin; Tian, Jiangwei; Bao, Lei; Hu, Yaoping; Ju, Huangxian; Yu, Jun-Sheng

2015-09-01

In this work we designed a MoS2 nanoplate-based nanoprobe for fluorescence imaging of intracellular ATP and photodynamic therapy (PDT) via ATP-mediated controllable release of 1O2. The nanoprobe was prepared by simply assembling a chlorine e6 (Ce6) labelled ATP aptamer on MoS2 nanoplates, which have favorable biocompatibility, unusual surface-area-to-mass ratio, strong affinity to single-stranded DNA, and can quench the fluorescence of Ce6. After the nanoprobe was internalized into the cells and entered ATP-abundant lysosomes, its recognition to ATP led to the release of the single-stranded aptamer from MoS2 nanoplates and thus recovered the fluorescence of Ce6 at an excitation wavelength of 633 nm, which produced a highly sensitive and selective method for imaging of intracellular ATP. Meanwhile, the ATP-mediated release led to the generation of 1O2 under 660 nm laser irradiation, which could induce tumor cell death with a lysosomal pathway. The controllable PDT provided a model approach for design of multifunctional theranostic nanoprobes. These results also promoted the development and application of MoS2 nanoplate-based platforms in biomedicine.In this work we designed a MoS2 nanoplate-based nanoprobe for fluorescence imaging of intracellular ATP and photodynamic therapy (PDT) via ATP-mediated controllable release of 1O2. The nanoprobe was prepared by simply assembling a chlorine e6 (Ce6) labelled ATP aptamer on MoS2 nanoplates, which have favorable biocompatibility, unusual surface-area-to-mass ratio, strong affinity to single-stranded DNA, and can quench the fluorescence of Ce6. After the nanoprobe was internalized into the cells and entered ATP-abundant lysosomes, its recognition to ATP led to the release of the single-stranded aptamer from MoS2 nanoplates and thus recovered the fluorescence of Ce6 at an excitation wavelength of 633 nm, which produced a highly sensitive and selective method for imaging of intracellular ATP. Meanwhile, the ATP-mediated release led to the generation of 1O2 under 660 nm laser irradiation, which could induce tumor cell death with a lysosomal pathway. The controllable PDT provided a model approach for design of multifunctional theranostic nanoprobes. These results also promoted the development and application of MoS2 nanoplate-based platforms in biomedicine. Electronic supplementary information (ESI) available: Supplementary figures. See DOI: 10.1039/c5nr02224j

Modeling Vascularized Bone Regeneration Within a Porous Biodegradable CaP Scaffold Loaded with Growth Factors

PubMed Central

Sun, X; Kang, Y; Bao, J; Zhang, Y; Yang, Y; Zhou, X

2013-01-01

Osteogenetic microenvironment is a complex constitution in which extracellular matrix (ECM) molecules, stem cells and growth factors each interact to direct the coordinate regulation of bone tissue development. Importantly, angiogenesis improvement and revascularization are critical for osteogenesis during bone tissue regeneration processes. In this study, we developed a three-dimensional (3D) multi-scale system model to study cell response to growth factors released from a 3D biodegradable porous calcium phosphate (CaP) scaffold. Our model reconstructed the 3D bone regeneration system and examined the effects of pore size and porosity on bone formation and angiogenesis. The results suggested that scaffold porosity played a more dominant role in affecting bone formation and angiogenesis compared with pore size, while the pore size could be controlled to tailor the growth factor release rate and release fraction. Furthermore, a combination of gradient VEGF with BMP2 and Wnt released from the multi-layer scaffold promoted angiogenesis and bone formation more readily than single growth factors. These results demonstrated that the developed model can be potentially applied to predict vascularized bone regeneration with specific scaffold and growth factors. PMID:23566802

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.

HPMA Copolymer-Drug Conjugates with Controlled Tumor-Specific Drug Release.

PubMed

Chytil, Petr; Koziolová, Eva; Etrych, Tomáš; Ulbrich, Karel

2018-01-01

Over the past few decades, numerous polymer drug carrier systems are designed and synthesized, and their properties are evaluated. Many of these systems are based on water-soluble polymer carriers of low-molecular-weight drugs and compounds, e.g., cytostatic agents, anti-inflammatory drugs, or multidrug resistance inhibitors, all covalently bound to a carrier by a biodegradable spacer that enables controlled release of the active molecule to achieve the desired pharmacological effect. Among others, the synthetic polymer carriers based on N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers are some of the most promising carriers for this purpose. This review focuses on advances in the development of HPMA copolymer carriers and their conjugates with anticancer drugs, with triggered drug activation in tumor tissue and especially in tumor cells. Specifically, this review highlights the improvements in polymer drug carrier design with respect to the structure of a spacer to influence controlled drug release and activation, and its impact on the drug pharmacokinetics, enhanced tumor uptake, cellular trafficking, and in vivo antitumor activity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Conceptual framework and rationale

PubMed Central

Robinson, Alan S; Knols, Bart GJ; Voigt, Gabriella; Hendrichs, Jorge

2009-01-01

The sterile insect technique (SIT) has been shown to be an effective and sustainable genetic approach to control populations of selected major pest insects, when part of area-wide integrated pest management (AW-IPM) programmes. The technique introduces genetic sterility in females of the target population in the field following their mating with released sterile males. This process results in population reduction or elimination via embryo lethality caused by dominant lethal mutations induced in sperm of the released males. In the past, several field trials have been carried out for mosquitoes with varying degrees of success. New technology and experience gained with other species of insect pests has encouraged a reassessment of the use of the sterility principle as part of integrated control of malaria vectors. Significant technical and logistic hurdles will need to be overcome to develop the technology and make it effective to suppress selected vector populations, and its application will probably be limited to specific ecological situations. Using sterile males to control mosquito vector populations can only be effective as part of an AW-IPM programme. The area-wide concept entails the targeting of the total mosquito population within a defined area. It requires, therefore, a thorough understanding of the target pest population biology especially as regards mating behaviour, population dynamics, dispersal and level of reproductive isolation. The key challenges for success are: 1) devising methods to monitor vector populations and measuring competitiveness of sterile males in the field, 2) designing mass rearing, sterilization and release strategies that maintain competitiveness of the sterile male mosquitoes, 3) developing methods to separate sexes in order to release only male mosquitoes and 4) adapting suppression measures and release rates to take into account the high reproductive rate of mosquitoes. Finally, success in area-wide implementation in the field can only be achieved if close attention is paid to political, socio-economic and environmental sensitivities and an efficient management organization is established taking into account the interests of all potential stakeholders of an AW-IPM programme. PMID:19917070

Evaluation of the effects of nitric oxide-releasing nanoparticles on plants

NASA Astrophysics Data System (ADS)

Pereira, A. E. S.; Narciso, A. M.; Seabra, A. B.; Fraceto, L. F.

2015-05-01

Nowadays, there are several commercially available products containing nanostructured materials. Meanwhile, despite the many benefits that can be obtained from nanotechnology, it is still necessary to understand the mechanisms in which nanomaterials interact with the environment, and to obtain information concerning their possible toxic effects. In agriculture, nanotechnology has been used in different applications, such as nanosensors to detect pathogens, nanoparticles as controlled release systems for pesticides, and biofilms to deliver nutrients to plants and to protect food products against degradation. Moreover, plants can be used as models to study the toxicity of nanoparticles. Indeed, phytotoxicity assays are required to identify possible negative effects of nanostructured systems, prior to their implementation in agriculture. Nitric oxide (NO) plays a key role in plant growth and defense, and recently, several papers described the beneficial effects due to application of exogenous NO donors in plants. The tripeptide glutathione (GSH) is an important anti-oxidant molecule and is the precursor of the NO donor, S-nitrosoglutathione (GSNO). In this context, the present work investigates the effects of different concentrations of alginate/chitosan nanoparticles, containing either GSH or GSNO, on the development of two test species (Zea mays and Glycine sp.). The results showed that the alginate/chitosan nanoparticles present a size average range from 300 to 550 nm with a polydispersity index of 0.35, and encapsulation efficiency of GSH between 45 - 56%. The NO release kinetics from the alginate/chitosan nanoparticles containing GSNO showed sustained and controlled NO release over several hours. Plant assays showed that at the concentrations tested (1, 5 and 10 mM of GSH or GSNO), polymeric nanoparticles showed no significant inhibitory effects on the development of the species Zea mays and Glycine sp., considering the variables shoot height, root length, and dry mass. Therefore, these nanoparticles seem to have promissing uses in agriculture, and might be potencially used as controlled release systems applied by the foliar route.

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.

Development of a novel osmotically driven drug delivery system for weakly basic drugs.

PubMed

Guthmann, C; Lipp, R; Wagner, T; Kranz, H

2008-06-01

The drug substance SAG/ZK has a short biological half-life and because of its weakly basic nature a strong pH-dependent solubility was observed. The aim of this study was to develop a controlled release (cr) multiple unit pellet formulation for SAG/ZK with pH-independent drug release. Pellets with a drug load of 60% were prepared by extrusion/spheronization followed by cr-film coating with an extended release polyvinyl acetate/polyvinyl pyrrolidone dispersion (Kollidon SR 30 D). To overcome the problem of pH-dependent drug release the pellets were then coated with a second layer of an enteric methacrylic acid and ethyl acrylate copolymer (Kollicoat MAE 30 DP). To increase the drug release rates from the double layered cr-pellets different osmotically active ionic (sodium and potassium chloride) and nonionic (sucrose) additives were incorporated into the pellet core. Drug release studies were performed in media of different osmotic pressure to clarify the main release mechanism. Extended release coated pellets of SAG/ZK demonstrated pH-dependent drug release. Applying a second enteric coat on top of the extended release film coat failed in order to achieve pH-independent drug release. Already low enteric polymer levels on top of the extended release coated pellets decreased drug release rates at pH 1 drastically, thus resulting in a reversal of the pH-dependency (faster release at pH 6.8 than in 0.1N HCl). The addition of osmotically active ingredients (sodium and potassium chloride, and sucrose) increased the imbibing of aqueous fluids into the pellet cores thus providing a saturated drug solution inside the beads and increasing drug concentration gradients. In addition, for these pellets increased formation of pores and cracks in the polymer coating was observed. Hence drug release rates from double layered beads increased significantly. Therefore, pH-independent osmotically driven SAG/ZK release was achieved from pellets containing osmotically active ingredients and coated with an extended and enteric polymer. In contrast, with increasing osmotic pressure of the dissolution medium the in vitro drug release rates decreased significantly.

After biocontrol: assessing indirect effects of insect releases

Treesearch

Julie S. Denslow; Carla M. D' Antonio

2005-01-01

Development of biological control agents for weeds has been motivated by the need to reduce the abundance and distribution of a pest plant where chemical and mechanical control were not cost effective. Primary objectives have been direct reduction in abundance of the target and, secondarily, the increase of desirable species. Recently, wildland weeds have become a...

Monitoring copper release in drinking water distribution systems.

PubMed

d'Antonio, L; Fabbricino, M; Panico, A

2008-01-01

A new procedure, recently proposed for on-line monitoring of copper released from metal pipes in household plumbing system for drinking water distribution during the development of corrosion processes, is tested experimentally. Experiments were carried out in laboratory controlled conditions, using synthetic water and varying the water alkalinity. The possibility of using the corrosion potential as a surrogate measure of copper concentration in stagnating water is shown, verifying, in the meantime, the effect of alkalinity on the development of passivation phenomena, which tend to protect the pipe from corrosion processes. Experimental data are discussed, highlighting the potentiality of the procedure, and recognizing its limitations. Copyright IWA Publishing 2008.

Top five industries resulting in injuries from acute chemical incidents—Hazardous Substance Emergency Events Surveillance, nine states, 1999-2008.

PubMed

Anderson, Ayana R; Wu, Jennifer

2015-04-10

Because industries using and/or producing chemicals are located in close proximity to populated areas, U.S. residents are at risk for unintentional chemical exposures. 1999-2008. The Hazardous Substances Emergency Events Surveillance (HSEES) system was operated by the Agency for Toxic Substances and Disease Registry during January 1991-September 2009 to collect data that would enable researchers to describe the public health consequences of chemical releases and to develop activities aimed at reducing the harm from such releases. This report summarizes data for the top five industries resulting in injuries from an acute chemical incident (lasting <72 hours) occurring in the nine states (Colorado, Iowa, Minnesota, New York, North Carolina, Oregon, Texas, Washington, and Wisconsin) that participated in HSEES during its last 10 full years of data collection (1999-2008). Five industries (truck transportation, educational services, chemical manufacturing, utilities, and food manufacturing) accounted for approximately one third of all incidents in which persons were injured as a result of unintentional release of chemicals; the same five industries were responsible for approximately one third of all persons injured as a result of such releases. Acute chemical incidents in these five industries resulted in serious public health implications including the need for evacuations, morbidity, and mortality. PUBLIC HEALTH IMPLICATIONS: Targeting chemical incident prevention and preparedness activities towards these five industries provides an efficient use of resources for reducing chemical exposures. A variety of methods can be used to minimize chemical releases in industries. One example is the Occupational Safety and Health Administration's hierarchy of controls model, which focuses on controlling exposures to occupational hazards. The hierarchy includes elimination, substitution, engineering controls, administrative controls, and use of personal protective equipment.

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.