Increased in vivo glucose recovery via nitric oxide release

The in vivo glucose recovery of subcutaneously implanted nitric oxide (NO)-releasing microdialysis probes was evaluated in a rat model using saturated NO solutions to steadily release NO. Such methodology resulted in a constant NO flux of 162 pmol cm(-2) s(-1) from the probe membrane over 8 h of perfusion daily. The in vivo effects of enhanced localized NO were evaluated by monitoring glucose recovery over a 14 day period, with histological analysis thereafter. A difference in glucose recovery was observed starting at 7 days for probes releasing NO relative to controls. Histological analysis at 14 days revealed lessened inflammatory cell density at the probe surface and decreased capsule thickness. Collectively, the results suggest that intermittent sustained NO release from implant surfaces may improve glucose diffusion for subcutaneously implanted sensors by mitigating the foreign body reaction.     

Zinc oxide nanowire gas sensors: fabrication,functionalisation and devices

With the progress in the synthesis of high quality ZnO nanowires, their implementation as gas sensors has gained popularity. Relying on the surface ionosorption, these devices have demonstrated exquisite sensitivity with further improvement achieved through various functionalisation methods. Both resistive and transistor based methodologies are employed for gas sensing while integration of micro-heaters has also been attempted for portability of the devices. In order to achieve successful inclusion amongst semiconductor fabrication processes, top-down approaches are being explored along with conventional bottom-up synthesis routes. Major challenge of low selectivity can be overcome by Electronic Nose systems. This article reviews the progress in synthesis, functionalisation, and device implementation of ZnO nanowire gas sensors, concluding with remarks on associated challenges and future prospects.     

A review on fabrication, sensing mechanisms and performance of metal oxide gas sensors

Processes for developing layers onto a substrate as the active component of metal oxide gas sensors are presented and other promising alternatives as thermal spraying are also proposed. In order to understand the electrochemical mechanisms involved, the relationship between surface reactions and the electrical signal is presented as determined by the influence of three main factors: the receptor function, the transducer function and the approachability. Distinct aspects for each key-step are discussed with the aim of achieving a better comprehension of the overall system. Performances of the most operated metal oxides and target-gases in distinct application markets are also reviewed.     

In vivo electrochemical detection of nitric oxide in tumor-bearing mice

Interest in elucidating the mechanisms of action of various classes of anticancer agents and exploring the pathways of the induced-nitric oxide (NO) release provides an impetus to conceive a better designed approach to locally detect NO in tumors, in vivo. We report here on the first use of an electrochemical sensor that allows the in vivo detection of NO in tumor-bearing mice. In a first step, we performed the electrochemical characterization of a stable electroactive probe, K4Fe(CN)6, directly injected into the liquid microenvironment especially created around the electrode in the tumor. Second, the ability of the inserted electrode system to detect the presence of NO itself in the tumoral tissue was achieved by using the chemically modified Pt/Ir electrode as NO sensor and two NO donor molecules: diethylammonium (Z)-1-(N,N-diethylamino)diazen-1-ium 1,2-diolate (DEA-NONOate) and (Z)-1-[N-(2-aminopropyl)-N-(2-ammonio propyl)amino]diazen-1-ium 1,2-diolate (PAPA-NONOate). These two NO donor molecules allowed proving the electrochemical detection of (i) directly injected exogenous NO phosphate buffer solution into the tumor (decomposed DEA-NONOate) and (ii) biomimetically induced endogeneous release of NO in the tumoral tissue, upon injection of PAPA-NONOate into the tumor. This approach could be applied to the in vivo study of candidate anticancer drugs acting on the NO pathways.     

Quasi-one dimensional metal oxide semiconductors: Preparation, characterization and application as chemical sensors

The continuous evolution of nanotechnology in these years led to the production of quasi-one dimensional (Q1D) structures in a variety of morphologies such as nanowires, core-shell nanowires, nanotubes, nanobelts, hierarchical structures, nanorods, nanorings. In particular, metal oxides (MOX) are attracting an increasing interest for both fundamental and applied science. MOX Q1D are crystalline structures with well-defined chemical composition, surface terminations, free from dislocation and other extended defects. In addition, nanowires may exhibit physical properties which are significantly different from their coarse-grained polycrystalline counterpart because of their nanosized dimensions. Surface effects dominate due to the increase of their specific surface, which leads to the enhancement of the surface related properties, such as catalytic activity or surface adsorption: key properties for superior chemical sensors production.High degree of crystallinity and atomic sharp terminations make nanowires very promising for the development of a new generation of gas sensors reducing instabilities, typical in polycrystalline systems, associated with grain coalescence and drift in electrical properties. These sensitive nanocrystals may be used as resistors, and in FET based or optical based gas sensors.This article presents an up-to-date review of Q1D metal oxide materials research for gas sensors application, due to the great research effort in the field it could not cover all the interesting works reported, the ones that, according to the authors, are going to contribute to this field’s further development were selected and described.     

Sustained release optimized formulation of anastrozole-loaded chitosan microspheres: in vitro and in vivo evaluation

The purpose of this study was to develop sustained release formulation of anastrozole-loaded chitosan microspheres for treatment of breast cancer. Chitosan microspheres cross-linked with two different cross-linking agents viz, tripolyphosphate (TPP) and glutaraldehyde (GA) were prepared using single emulsion (w/o) method. A reverse phase HPLC method was developed and used for quantification of drug in microspheres and rat plasma. Influence of cross-linking agents on the properties of chitosan microspheres was extensively investigated. Formulations were characterized for encapsulation efficiency (EE), compatibility of drug with excipients, particle size, surface morphology, swelling capacity, erosion and drug release profile in phosphate buffer pH 7.4. EE varied from 30.4 ± 1.2 to 69.2 ± 3.2% and mean particle size distribution ranged from 72.5 ± 0.5 to 157.9 ± 1.5 μm. SEM analysis revealed smooth and spherical nature of microspheres. TPP microspheres exhibited higher swelling capacity, percentage erosion and drug release compared to GA microspheres. Release of anastrozole (ANS) was rapid up to 4 h followed by slow release status. FTIR analysis revealed no chemical interaction between drug and polymer. DSC analysis indicated ANS trapped in the microspheres existed in amorphous form in polymer matrix. The highest correlation coefficients (R ²) were obtained for Higuchi model, suggesting a diffusion controlled mechanism. There was significant difference in the pharmacokinetic parameters (AUC_0−∞, Kel and t_1/2) when ANS was formulated in the form of microspheres compared to pure drug. This may be attributed to slow release rate of ANS from chitosan microspheres and was detectable in rat plasma up to 48 h which correlates well with the in vitro release data.     

Detection of nitric oxide release from single neurons in the pond snail, Lymnaea stagnalis

Multiple film-coated nitric oxide sensors have been fabricated using Nafion and electropolymerized polyeugenol or o-phenylenediamine on 30-microm carbon fiber disk electrodes. This is a rare study that utilizes disk electrodes rather than the widely used protruding tip microelectrodes in order to measure from a biological environment. These electrodes have been used to evaluate the differences in nitric oxide release between two different identified neurons in the pond snail, Lymnaea stagnalis. These results show the first direct measurements of nitric oxide release from individual neurons. The electrodes are very sensitive to nitric oxide with a detection limit of 2.8 nM and a sensitivity of 9.46 nA microM-1. The sensor was very selective against a variety of neurochemical interferences such as ascorbic acid, uric acid, and catecholamines and secondary oxidation products such as nitrite. Nitric oxide release was measured from the cell bodies of two neurons, the cerebral giant cell (CGC) and the B2 buccal motor neuron, in the intact but isolated CNS. A high-Ca2+/high-K+ stimulus was capable of evoking reproducible release. For a given stimulus, the B2 neuron released more nitric oxide than the CGC neuron; however, both cells were equally suppressed by the NOS inhibitor l-NAME.     

Oxidation of nitric oxide in a two-stage chemical scrubber using dc corona discharge

The dc corona was studied as an alternative for NO oxidation in a two-stage chemical scrubber. The dc corona plasma reactor completely oxidized 150 ppm of NO to NO₂ in an air stream. The NO₂ was further oxidized at a higher voltage. For some cases, the NO₂ in the effluents of the plasma reactor was absorbed quantitatively by a caustic sodium sulfite aqueous solution in a 2 l bubble column gas absorber. The outlet concentrations of both NO and NO₂ from the plasma-scrubber combination system (corona-induced chemical scrubber) were below the detection limit of the chemiluminescent NO_x analyzer.     

Zinc oxide thin-film chemical sensors in conjunction with neural network pattern recognition for trimethylamine and dimethylamine gases

Transient response curves for exposure to several gases are observed using zinc oxide (ZnO) thin-film gas sensors. It is found that an aluminium-doped ZnO (ZnO:Al) sensor exhibits a high sensitivity and an excellent selectivity for amine gases. In order to discriminate between gas species such as trimethylamine (TMA), dimethylamine (DMA) and other gases pattern recognition analysis using a neural network is carried out using parameters which characterize the transient responses of the sensor for exposure to gases. The recognition probability of the neural network is 90% for TMA and DMA with constant concentration and is 100% for TMA and DMA with different concentrations, except for a concentration of 1 p.p.m.     

Preliminary evaluation of the in vitro release and in vivo absorption in rabbits of the modified-release dosage forms

Objective: The suitability of the rabbit as an animal model for the primary screening and selection of the pilot scale batches during the early stages of the formulation development was studied.

Materials and methods: Three modified-release formulations of aminophylline consisted of Carbopol® 971P/HPMC K4M (F-I), and HPMC K100M (F-II) or HPMC K4M (F-III) were used. Commercial products were Aminofilin retard 350?mg tablets, Srbolek, Serbia (R-I) and Phyllocontin^® 350, tablets Purdue Frederic, Canada (R-II).

Results: Calculated release rate constants and the ?2 values between R-I/F-I (84.1) and R-II/F-III (83.4) indicated similar in vitro release while the coefficient n showed presence of different mechanisms of release from Anomalous transport, Fickian diffusion to Case-II transport. Higher T_max, was found in the rabbits, dosed with F-II (12.00?h), F-III (10.50?h), and R-II (15.00?h) formulation. The highest C_max (9.22?mg/L) was obtained with F-II, similar lower values was seen for F-I and F-III, while commercial products showed the lowest values R-I (5.58?mg/L) and R-II (4.18?mg/L). Higher AUC values were detected for all three formulations (from 115.90 to 204.06 mgh/L) in relation to commercial products (105.33 and 113.25 mgh/L).

Discussion and conclusion: The results demonstrated a good correlation of Level A (r² = 0.97) for the two formulations (F-I, F-III) and commercial product (R-I) indicates that there is a reasonable assumption that the rabbit might be use as a model for the preliminary comparison of scale up formulations in the early stages of the product development.     

Performance evaluation of biofilters packed with carbon foam and lava for nitric oxide removal

Long-term (>8 months) results of nitric oxide (NO) removal in biofilters, respectively, packed with lava and two different pore sizes of carbon foam (24 pores/cm (PPC) and 18 PPC) were measured. During the operation, NO removal efficiency, pressure drops, pH dependence and removal profile were evaluated. NO removal efficiencies were above 93.8%, 79.4% and 58.6% in the biofilters, respectively, packed with 24 PPC carbon foam, 18 PPC carbon foam and lava. The lava-packed biofilter demonstrated higher buffer capacity for change of pH. However, with sufficient nutrient and buffer solution feeding, the biofilter packed with carbon foam showed a higher NO removal efficiency. The pressure drops of the biofilter packed with carbon foam did not exceed 11 mm H(2)O/m. The low-pressure drops made it possible by using carbon foam as packing to conveniently prevent the clogging and channeling problems associated with conventional biofilter operations.     

Incorporation of fiber-optic sensors in concrete specimens: testing and evaluation

As series of tests has been carried out on the performance of several fiber-optic temperature sensors, operating on the fluorescence lifetime principle using neodymium-doped fiber and configured into ruggedized temperature probes, mounted in a number of different concrete samples. The aim has been to evaluate the performance of probes fitted into concrete specimens to simulate the conditions experienced in structures used in civil applications, such as bridges and dams. A key feature of the investigation was observing the integrity of the sensors under investigation while obtaining temperature data from the device. The results show the sensors operated well from below room temperature to beyond 300/spl deg/C, preserving their integrity under adverse test conditions.     

In vivo biocompatibility and analytical performance of intravascular amperometric oxygen sensors prepared with improved nitric oxide-releasing silicone rubber coating

The in vivo biocompatibility and analytical performance of amperometric oxygen-sensing catheters prepared with a new type of nitric oxide (NO)-releasing silicone rubber polymer (DACA/N2O2 SR) is reported. The NO-release silicone rubber coating contains diazeniumdiolated secondary amine sites covalently anchored to a dimethylsiloxane matrix. Narrow diameter (0.9 mm, o.d.) silicone rubber tubing coated with this polymer can be employed to construct functional oxygen-sensing catheters that release NO continuously at levels > 1 x 10(-10) mol/cm2-min for more than 20 h. In vivo evaluation of such sensors within the carotid and femoral arteries of swine over a 16-h time period demonstrates that sensors prepared with the new NO-release coating exhibit no significant platelet adhesion or thrombus formation, but control sensors (non-NO release) implanted within the same animals do show a high propensity for cell adhesion and bulk clot formation. Furthermore, the in vivo analytical data provided by sensors fabricated with NO-release coatings (N = 9) are shown to be statistically equivalent to PO2 levels measured in vitro on discrete samples of blood. Control sensors (N = 9) placed within the same animals yield average PO2 values that are statistically different (p < or = 0.05) (lower) from both the levels measured on discrete samples and those provided by the NO-release sensors over a 16-h in vivo monitoring period.     

In vivo evaluation of titanium oxide and hydroxyapatite as an artificial cornea skirt

Keratoprosthetic devices are subject to chronic inflammatory, pathological processes and the external environment that affect their stability and biocompatibility with the ocular surface and adjacent ocular tissues. We compared the corrosion resistance property and tissue-implant reaction of titanium oxide (TiO₂) with hydroxyapatite (HA) in artificial tear fluid and a rabbit skin implantation model. The dissolution properties of the implant surfaces were evaluated with scanning electronic microscope (SEM) and atomic force microscope (AFM). Tissue inflammatory reactions were evaluated by Hematoxylin & Eosin staining, avidin biotin peroxidase complex (ABC) immunoassay and immunofluorescence. SEM and AFM images showed that there was less pitting corrosion on the surface of TiO₂ implants compared with HA. TiO₂ and HA exhibited a similar pattern of foreign body capsule formation and inflammatory cellular responses. The Collagen I/Collagen III ratio of the TiO₂ capsule was higher than that of the HA capsule. TiO₂ implants possess a high corrosion resistance property both in vitro and in vivo and the inflammatory cellular response to TiO₂ is similar to HA. With regards to corrosion resistance and inflammatory tissue responses, TiO₂ appears to be a promising material for keratoprosthetic skirt devices.     

Preparation of DHAQ-loaded mPEG-PLGA-mPEG nanoparticles and evaluation of drug release behaviors in vitro/in vivo

This study describes the preparation and the evaluation of biodegradation monomethoxy (polyethylene glycol)-poly (lactide-co-glycolide)-monomethoxy (polyethyleneglycol) (mPEG-PLGA-mPEG, PELGE) nanoparticles (PELGE-NP) containing mitoxantrone (DHAQ) as a model drug. PELGE copolymers with various molar ratios of lactic to glycolic acid and different molecular weights and various content mPEG were synthesized by ring-opening polymerization. mPEG with weight-average molecular weight (Mw) 2000 or 5000 was introduced as a hydrophilic segment into a hydrophobic PLGA. A double emulsion method with dextran70 as stabilizer in the external aqueous phase was used to prepare the nanoparticles. The drug entrapment efficiencies were more than 80% and the mean diameters of the nanoparticles were less than 200 nm. Various PELGE was studied as biodegradable drug carriers and there in vitro/in vivo release profiles were examined. It was found that drug loading, polymer molecular weight, copolymer composition and end group modifications were critical factors affecting the in vitro/in vivo release properties. The amount of drug released increased as the mPEG contents increased and the molar ratios of lactic acid decreased in vitro. The intravenous (i.v.) administration of mPEG-PLGA–mPEG nanoparticles of DHAQ in mice resulted in prolonged DHAQ residence in systemic blood circulation compared to the intravenous administration of PLGA nanoparticles.     

In vitro and in vivo evaluation of two extended release preparations of combination metformin and glipizide

A system that can deliver multi-drugs at a prolonged rate is very important to the treatment of various chronic diseases such as diabetes, asthma, and heart disease. Two controlled-release systems, which exhibited similar release profiles of metformin and glipizide, i.e., elementary osmotic pump tablets (EOP) and bilayer hydrophilic matrix tablet (BT), were designed. The effects of pH and hydrodynamic conditions on drug release from two formulations were investigated. It was found that both drug releases from EOP were not sensitive to dissolution media pH and hydrodynamics change, while the release of glipizide from BT was influenced by the stirring rate. Moreover, in vivo evaluation was performed, relative to the equivalent dose of conventional metformin tablet and glipizide tablet, by a three-crossover study in six Beagle dogs. Cumulative percent input in vivo was compared to in vitro release profiles. The linear correlations of metformin and glipizide between fraction absorbed in vivo and fraction dissolved in vitro were established for EOP—a true zero-order release formula, whereas only nonlinear correlations were obtained for BT. In conclusion, drug release from EOP was both independent of in vitro and in vivo conditions, where the best sustained release effect was achieved, whereas the in vitro dissolution test employed for BT needed to be further optimized to be biorelevant.     

Chitosan-TPP nanoparticles stabilized by poloxamer for controlling the release and enhancing the bioavailability of doxazosin mesylate: in vitro,and in vivo evaluation

Objective: Control the release and enhance the bioavailability of chitosan-doxazosin mesylate nanoparticles (DM-NPs).

Significance: Improve DM bioavailability for the treatment of benign prostatic hyperplasia and hypertension.

Methods: Plackett–Burman design was utilized to screen the variables affecting the quality of DM-NPs prepared by ionic gelation method. The investigated variables were initial drug load (X₁), chitosan percentage (X₂), tripolyphosphate sodium (TPP) percentage (X₃), poloxamer percentage (X₄), homogenization speed (X₅), homogenization time (X₆) and TPP addition rate (X₇). The prepared DM-loaded NPs have been fully evaluated for particle size (Y₁), Zeta potential (Y₂), production yield (Y₃), entrapment efficiency (Y₄), loading capacity (Y₅), initial burst (Y₆), and cumulative drug release (Y₇). Finally, DM pharmacokinetic has been investigated on healthy albino male rabbits by means of non-compartmental analysis.

Results: The combination of variables showed variability of Y₁, Y₂, and Y₃ equal to 122–710?nm, 3.49–23.63?mV, and 47.31–92.96%, respectively. While Y₄ and Y₅, reached 99.87%, and 8.53%, respectively. The prepared NPs revealed that X₂, X₃, and X₄ are the variables that play the important role in controlling the release behavior of DM from the NPs. The in vivo pharmacokinetic results indicated the enhancement in bioavailability of DM by 7 folds compared to drug suspension and the mean residence time prolonged to 23.72?h compared to 4.7?h of drug suspension.

Conclusion: The study proved that controlling the release of DM from NPs enhance its bioavailability and improve the compliance of patients with hypertension or benign prostatic hyperplasia.     

Improving the biocompatibility of NiTi alloy by chemical treatments: An in vitro evaluation in 3T3 human fibroblast cell

The nearly equi-atomic nickel titanium alloy was coated with calcium phosphates by socking the chemically treated alloy in simulated body fluid in order to prepare bioactive NiTi implants. The biocompatibility of the calcium phosphates coated NiTi alloy was investigated by in vitro 3T3 human embryonic fibroblast cell culture tests. The cells attachment and morphologies were studied using phase contrast light microscope and environmental scanning electron microscope. The mechanically polished and the calcium phosphates coated NiTi samples were well tolerated by the cells, whereas, the controlled pure Ni samples exhibited strong toxicity to the cells. Furthermore, the calcium phosphates coated NiTi samples showed good osteoconductivity.