The controlled release of tilmicosin from silica nanoparticles

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

Potassium sorbate controlled release from corn starch films

Active starch films with glycerol and potassium sorbate were obtained by casting. Native and acetylated corn starches, as well as the mixture of them in equal proportions were used and filmogenic suspensions with pH 4.5 were also prepared. Sorbate concentration decreased during film storage due to its oxidative degradation. Active films resulted more yellow and less transparent than films without sorbate. The minimum inhibitory concentration of sorbate resulted 0.3%, regardless of the starch type and the formulation pH. The use of antimicrobial package was more effective to prevent microbial growth on food surfaces than the use of conventional methods. Additive kinetic release was neither affected by the starch type nor by the formulation pH. Sorbate diffusion process was mathematically modeled satisfactorily. Active films were able to inhibit Candida spp., Penicillium spp., S. aureus and Salmonella spp. growth. Active films extended 21% the shelf life of refrigerated cheese, regardless of the formulation pH.     

The controlled release of tilmicosin from silica nanoparticles

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

Dexamethasone electrically controlled release from polypyrrole-coated nanostructured electrodes

One of the key challenges to engineering neural interfaces is to reduce their immune response toward implanted electrodes. One potential approach to minimize or eliminate this undesired early inflammatory tissue reaction and to maintain signal transmission quality over time is the delivery of anti-inflammatory biomolecules in the vicinity of the implant. Here, we report on a facile and reproducible method for the fabrication of high surface area nanostructured electrodes coated with an electroactive polymer, polypyrrole (PPy) that can be used to precisely release drug by applying an electrical stimuli. The method consists of the electropolymerization of PPy incorporated with drug, dexamethasone (DEX), onto a brush of metallic nanopillars, obtained by electrodeposition of the metal within the nanopores of gold-coated polycarbonate template. The study of the release of DEX triggered by electrochemical stimuli indicates that the system is a true electrically controlled release system. Moreover, it appears that the presence of metallic nanowires onto the electrode surface improves the adherence between the polymer and the electrode and increases the electroactivity of the PPy coating.     

Deposition of Al-doped ZnO thin-films with radio frequency magnetron sputtering for a source/drain electrode for pentacene thin-film transistor

Al-doped ZnO thin-films were deposited with the radio frequency magnetron sputtering technique at various temperatures and sputtering powers for a source/drain electrode in the pentacene thin-film transistor. With the increase in the deposition temperature and the decrease in the radio frequency sputtering power, the crystallinity was increased and the surface roughness was decreased, which lead to the decrease in the electrical resistivity of the film. Al-doped ZnO film deposited at 200 °C and sputtering power of 50 W showed a low resistivity (9.73 × 10⁴ μΩcm), high crystallinity, low roughness and uniform surface morphology. The pentacene thin-film transistor fabricated with Al-doped ZnO film as a source/drain electrode showed a device performance, (mobility: 7.89 × 10^− 3 cm²/Vs and on/off ratio: ~ 5 × 10⁴) which is comparable with an indium tin oxide electrode grown at room temperature.     

Chitosan-alginate multilayer beads for gastric passage and controlled intestinal release of protein

Chitosan-alginate beads loaded with a model protein, bovine serum albumin (BSA) were investigated to explore the temporary protection of protein against acidic and enzymatic degradation during gastric passage. Optimum conditions were established for preparation of homogenous, spherical, and smooth chitosan-alginate beads loaded with BSA. Multilayer beads were prepared by additional treatment with either chitosan or alginate or both. The presence of chitosan in the coagulation bath during bead preparation resulted in increased entrapment of BSA. During incubation in simulated gastric fluid (SGF pH 1.2), the beads showed swelling and started to float but did not show any sign of erosion. Inclusion of pepsin in the gastric fluid did not show a further effect on the properties of the beads. Release studies were done in simulated gastric fluid (SGF pH 1.2) and subsequently in simulated intestinal fluid (SIF pH 7.5) to mimic the physiological gastrointestinal conditions. After transfer to intestinal fluid, the beads were found to erode, burst, and release the protein. Microscopic and macroscopic observations confirmed that the release of protein was brought about by the burst of beads. Chitosan-reinforced calcium-alginate beads showed delay in the release of BSA. The multilayer beads disintegrated very slowly. The enzymes pepsin and pancreatin did not change the characteristics of BSA-loaded chitosan-alginate beads. Single layer chitosan-alginate beads released 80-90% of the model protein within 12 h while multilayer beads released only 40-50% in the same period of time. The release from chitosan-alginate beads and multilayer beads in SIF was further delayed without prior incubation in SGF. It is concluded that alginate beads reinforced with chitosan offer an excellent perspective for controlled gastrointestinal passage of protein drugs.     

Electrically controlled drug release from nanostructured polypyrrole coated on titanium

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

Electrochemically modulated separation, concentration, and detection of plutonium using an anodized glassy carbon electrode and inductively coupled plasma mass spectrometry

Plutonium is shown to be retained on anodized glassy carbon (GC) electrodes at potentials positive of +0.7 V (vs Ag/AgCl reference) and released upon potential shifts to values negative of +0.3 V. This phenomenon has been exploited for the separation, concentration, and detection of plutonium by the coupling an electrochemical flow cell on-line with an ICPMS system. The electrochemically controlled deposition and analysis of Pu improves detection limits by analyte preconcentration and by matrix and isobaric ion elimination. Information related to the parametric optimization of the technique and hypotheses regarding the mechanism of electrochemical accumulation of Pu are reported. The most likely accumulation scenario involves complexation of Pu(IV) species, produced under a controlled potential, with anions retained in the anodization film that develops during the activation of the GC electrode. The release mechanism is believed to result from the reduction of Pu(IV) in the anion complex to Pu(III), which has a lower tendency to form complexes.     

Dynamics of controlled release of heparin from swellable crosslinked starch microspheres

The microspheres of crosslinked starch have been prepared and characterized by IR spectral analysis and SEM technique. The prepared microspheres were loaded with an anticoagulant drug ‘heparin’ and the kinetics of in-vitro release of heparin was investigated spectrophotometrically at physiological pH (7.4) and body temperature (37 °C). The influence of percent loading of heparin, chemical architecture of the microspheres and pH of the release medium were examined on the release profiles of the drug. The chemical stability of heparin was tested in phosphate buffer saline (pH 7.4) and the release was also studied in various simulated biological fluids.     

Tricalcium phosphate and tricalcium phosphate/polycaprolactone particulate composite for controlled release of protein

β-Tricalcium phosphate (β-TCP) with three different particle size ranges was used to study the effects of particle size and surface area on protein adsorption and release. Polycaprolactone (PCL) coating was applied on the particle systems to investigate its effect on particulate system properties from both structural and application aspects. The maximum loading of 27 mg/g was achieved for 100 nm particles. Bovine serum albumin (BSA) loading amount was controlled by varying the BSA loading solution concentration, as well as the sample powder's surface area. Increasing the surface area of the delivery powder significantly increased loading and release yield. Unlike the samples with low surface area, the lowest particle size samples showed sigmoidal release profile. This indicated that release was governed by different mechanisms for particles with different sizes. While the majority of samples showed no more than 50% release, the 550 nm particles demonstrated 100% release. PCL coating showed no significant ability to attenuate burst release in PBS. However, it led to a steadier release profile as compared to the bare TCP particles. FTIR analysis also proved that the secondary structure of BSA did not change significantly during the adsorption; however, minor denaturation was found during the release. The same results were found when PCL coating was applied on the TCP particles. We envision potential use of TCP and TCP + PCL systems in bone growth factor or orthopedic drug delivery applications in future bone tissue engineering application.     

Hybrid nanostructured drug carrier with tunable and controlled drug release

We describe here a transformative approach to synthesize a hybrid nanostructured drug carrier that exhibits the characteristics of controlled drug release. The synthesis of the nanohybrid architecture involved two steps. The first step involved direct crystallization of biocompatible copolymer along the long axis of the carbon nanotubes (CNTs), followed by the second step of attachment of drug molecule to the polymer via hydrogen bonding. The extraordinary inorganic–organic hybrid architecture exhibited high drug loading ability and is physically stable even under extreme conditions of acidic media and ultrasonic irradiation. The temperature and pH sensitive characteristics of the hybrid drug carrier and high drug loading ability merit its consideration as a promising carrier and utilization of the fundamental aspects used for synthesis of other promising drug carriers. The higher drug release response during the application of ultrasonic frequency is ascribed to a cavitation-type process in which the acoustic bubbles nucleate and collapse releasing the drug. Furthermore, the study underscores the potential of uniquely combining CNTs and biopolymers for drug delivery.     

Electrochemically induced pH changes resulting in protein unfolding in the ion source of an electrospray mass spectrometer.

The operation of an electrospray ion source in the positive ion mode involves charge-balancing oxidation reactions at the liquid/metal interface of the sprayer capillary. One of these reactions is the electrolytic oxidation of water. The protons generated in this process acidify the analyte solution within the electrospray capillary. This work explores the effects of this acidification on the electrospray ionization (ESI) mass spectrum of the protein cytochrome c (cyt c). In aqueous solution containing 40% propanol, cyt c unfolds around pH 5.6. Mass spectra recorded under these conditions, using a simple ESI series circuit, display a bimodal charge-state distribution that reflects an equilibrium mixture of folded and unfolded protein in solution. These spectra are not strongly affected by electrochemical acidification. An "external loop" is added to the ESI circuit when the metal needle of the sample injection syringe is connected to ground. The resulting circuit represents two coupled electrolytic cells that share the ESI capillary as a common anode. Under these conditions, the rate of charge-balancing oxidation reactions is dramatically increased because the ion source has to supply electrons for both, the external circuit and the ESI circuit. The analytical implications of this effect are briefly discussed. Mass spectra of cyt c recorded with the syringe needle grounded are shifted to higher charge states, indicating that electrochemical acidification has caused the protein to unfold in the ion source. The acidification can be suppressed by increasing the flow rate and lowering the electrolyte concentration of the solution and by using an electrolyte that acts as redox buffer. The observed acidification is similar for sprayer capillaries made of platinum and stainless steel. Removal of the protective oxide layer on the stainless steel surface results in effective redox buffering for a few minutes.     

Drug sorption onto and release from soy protein fibers

Drug release in phosphate buffered saline (PBS pH 7.4) and artificial gastric juice (AGJ pH 1.2) and its relationship with kinetic and thermodynamic parameters of drug sorption onto soy protein (SP) fibers have been studied using Diclofenac, 5 Fluorouracil and Metformin as model drugs. Since SP is biodegradable, biocompatible, abundant and annually renewable, it has been widely used in medical applications. To understand drug release from SP fibers using sorption, kinetic and thermodynamic parameters have been investigated. Quantitative relationship between drug release and drug loading concentration, affinity, and activation energy for diffusion was established to predict initial bursts and later drug release. The study showed that Diclofenac had high initial bursts in PBS but more constant release in AGJ. It also has been found that drugs with lower diffusion coefficient and higher affinity (especially van der Waals force) on SP fiber are more suitable for sorption loading to achieve higher loading capacity and more constant releasing rate.     

Accelerating protein release from microparticles for regenerative medicine applications

There is a need to control the spatio-temporal release kinetics of growth factors in order to mitigate current usage of high doses. A novel delivery system, capable of providing both structural support and controlled release kinetics, has been developed from PLGA microparticles. The inclusion of a hydrophilic PLGA–PEG–PLGA triblock copolymer altered release kinetics such that they were decoupled from polymer degradation. A quasi zero order release profile over four weeks was produced using 10% w/w PLGA–PEG–PLGA with 50:50 PLGA whereas complete and sustained release was achieved over ten days using 30% w/w PLGA–PEG–PLGA with 85:15 PLGA and over four days using 30% w/w PLGA–PEG–PLGA with 50:50 PLGA. These three formulations are promising candidates for delivery of growth factors such as BMP-2, PDGF and VEGF. Release profiles were also modified by mixing microparticles of two different formulations providing another route, not previously reported, for controlling release kinetics. This system provides customisable, localised and controlled delivery with adjustable release profiles, which will improve the efficacy and safety of recombinant growth factor delivery.     

Ketotifen controlled release from cellulose acetate propionate and cellulose acetate butyrate membranes

Ketotifen was immobilised in cellulose acetate propionate (CAP) membranes and in cellulose acetate butyrate (CAB) membranes. The characteristics of each system were evaluated under a range of experimental conditions. The topography and uniformity of the membranes was assessed using scanning electron microscopy. The release characteristics associated with Ketotifen were monitored spectrophotometrically. The swelling capacity of the membranes was evaluated and attributed to the combined effects of diffusion and of complex dissociation, during swelling. The materials produced were able to provide controlled release of Ketotifen due to their controlled swelling behaviour and adequate release properties. The results showed that the release of Ketotifen from the CAB membranes is higher but the release from the CAP membranes is more uniform.     

A remotely triggered drug release system with dot array-like configuration for controlled release of multiple drugs

Near-infrared (NIR) light as noninvasive external stimuli to trigger on-demand drug release has attracted great attention in recent years. However, the current existing NIR-related drug delivery systems (DDSs) still have difficulty in controlling the release of the individual drug separately. In the present work, a dot array-like DDS was developed for accurately controlling the release of multiple drugs. Each dot had a drug core and an outer protective layer. The outer protective layer consisted of lauric acid (LA) and polylactic acid (PLA). LA is a kind of phase-change material (PCM) with melting point of 43.8 °C. When loaded with polypyrrole nanoparticles (PPy NPs) that acted as photothermal transducers, the outer protective layer became NIR light responsive and was able to convert light into heat to melt the LA. As a result, the drugs stored inside were released. By changing the PPy loading, NIR light power density, and mass ratio of LA to PLA, the drug release profile could be carefully controlled. Such a NIR-responsive DDS may find great potential applications in treating diseases that require long-term therapies using more than one drug.     

Encapsulation of nitrogen fertilizers in mixtures with organoclays for controlled release

Clean Technologies and Environmental Policy - To increase the effectiveness of fertilizers, new controlled release nitrogen fertilizers have been developed from a mixture of urea and natural...     

Heparin-functionalized collagen matrices with controlled release of basic fibroblast growth factor

Tissue engineering scaffolds with controlled long-term release of growth factors are constructed in an attempt to mimic the intelligent ability of the extracellular matrix (ECM) to release endogenous growth factors. In this study, collagen sponges (Collagen group) were modified by N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) crosslinking (EDC/NHS group) and heparin immobilization (EDC/NHS-H group), and subsequently seeded with human umbilical vein endothelial cells (HUVECs). Native and modified sponges were pre-adsorbed with basic fibroblast growth factor (bFGF) to evaluate the sustained release and bioactive maintenance of bFGF from the sponges. We found that modified collagen matrices permitted HUVECs to proliferate and migrate well and to distribute uniformly. The EDC/NHS-H group exhibited an excellent sustained-release profile and bioactive maintenance of the pre-adsorbed bFGF as compared with the Collagen and EDC/NHS groups. These results suggest that heparin-functionalized collagen matrices can support a controlled release of bFGF and thus, have potential as a tissue engineering scaffold.     

Order release in a workload controlled flow-shop with sequence-dependent set-up times

In this paper, we report a simulation study on the role of sequence-dependent set-up times in decision making at the order release level of a workload controlled make-to-order flow-shop. The study evaluates the potential for set-ups savings, dependent on the level of workload in the shop, for two alternative strategies, namely considering set-up times centrally, within the release decision or locally, within the dispatching decision. These strategies are compared and assessed on the basis of two main performance measures namely time in system and standard deviation of the job lateness. Results indicate that the local strategy, which has been traditionally adopted in practice and in most of the studies dealing with sequence-dependent set-up times, does not always give the best results. The release frequency and the shop workload appear critical to the selection of the strategy to adopt, strongly influencing system performance.