Exposure characteristics of ferric oxide nanoparticles released during activities for manufacturing ferric oxide nanomaterials

Abstract

The exposure characteristics of Fe₂O₃ nanoparticles (NPs) released in a factory were investigated, as exposure data on this type of NP is absent. The nature of the particles was identified in terms of their concentrations [i.e. number concentration (NC_20–1000?nm), mass concentration (MC_{100–1000?nm}), surface area concentration (SAC_10–1000?nm)], size distribution, morphology and elemental composition. The relationships between different exposure metrics were determined through analyses of exposure ranking (ER), concentration ratios (CR), correlation coefficients and shapes of the particle concentration curves. Work activities such as powder screening, material feeding and packaging generated higher levels of NPs as compared to those of background particles (p?<?0.01). The airborne Fe₂O₃ NPs exhibited a unimodal size distribution and a spindle-like morphology and consisted predominantly of the elements O and Fe. Periodic and activity-related characteristics were noticed in the temporal variations in NC_20–1000?nm and SAC_10–1000?nm. The modal size of the Fe₂O₃ NPs remained relatively constant (ranging from 10 to 15?nm) during the working periods. The ER, CR values and the shapes of NC_20–1000?nm and SAC_10–1000?nm curves were similar; however, these were significantly different from those for MC_{100–1000?nm}. There was a high correlation between NC_20–1000?nm and SAC_10–1000?nm, and relatively lower correlations between the two and MC_{100–1000?nm}. These findings suggest that the work activities during the manufacturing processes generated high levels of primary Fe₂O₃ NPs. The particle concentrations exhibited periodicity and were activity dependent. The number and SACs were found to be much more relevant metrics for characterizing NPs than was the mass concentration.     

Optimization and evaluation of pluronic lecithin organogels as a transdermal delivery vehicle for sinomenine

The purpose of the present study was to prepare and optimize sinomenine (SIN) pluronic lecithin organogels system (PLO), and to evaluate the permeability of the optimized PLO in vitro and in vivo. Box–Behnken design was used to optimize the PLO and the optimized formulation was pluronic F127 of 19.61%, lecithin of 3.60% and SIN of 1.27%. The formulation was evaluated its skin permeation and drug deposition both in vitro and in vivo compared with gel. Permeation and deposition studies of PLO were carried out with Franz diffusion cells in vitro and with microdialysis in vivo. In vitro studies, permeation rate (J_ss) of SIN from PLO was 146.55?±?2.93?μg/cm²/h, significantly higher than that of gel (120.39?μg/cm²/h) and the amount of SIN deposited in skin from the PLO was 10.08?±?0.86?μg/cm², significantly larger than that from gel (6.01?±?0.04?μg/cm²). In vivo skin microdialysis studies showed that the maximum concentration (C_max) of SIN from PLO in “permeation study” and “drug-deposition study” were 150.27?±?20.85?μg/ml and 67.95?μg/ml, respectively, both significantly higher than that of SIN from gel (29.66 and 6.73?μg/ml). The results recommend that PLO can be used as an advantageous transdermal delivery vehicle to enhance the permeation and skin deposition of SIN.     

Effects of Ambient Air Particulate Exposure on Blood–Gas Barrier Permeability and Lung Function

Particulate air pollution is associated with increased risk of pulmonary diseases and detrimental outcomes related to the cardiovascular system, including altered vessel functions. This study's objective was too evaluate the effects of ambient particle exposure on the blood–gas permeability, lung function and Clara cell 16 (CC16) protein release in healthy young subjects. Twenty-nine nonsmokers participated in a randomized, two-factor crossover study with or without biking exercise for 180 min and with 24-h exposure to particle-rich (6169–15,362 particles/cm³; 7.0–11.6?μg/m³ PM_2.5; 7.5–15.8?μg/m³ PM_10?2.5) or filtered (91–542 particles/cm³) air collected above a busy street. The clearance rate of aerosolized ^99mTc-labeled diethylenetriamine pentaacetic acid (^99mTc-DTPA) was measured as an index for the alveolar epithelial membrane integrity and permeability of the lung blood–gas barrier after rush-hour exposure. Lung function was assessed using body plethysmography, flow-volume curves, and measurements of the diffusion capacity of carbon monoxide. CC16 was measured in plasma and urine as another marker of alveolar integrity. Particulate matter exposure had no significant effect on the epithelial membrane integrity using the methods available in this study. Exercise increased the clearance rate of ^99mTc-DTPA indicated by a 6.8% (95% CI: 0.4–12.8%) shorter half-life and this was more pronounced in men than women. Neither particulate matter exposure nor exercise had an effect on the concentration of CC16 in plasma and urine or on the static and dynamic volumes or ventilation distribution of the lungs. The study thus demonstrates increased permeability of the alveolar blood–gas barrier following moderate exercise, whereas exposure to ambient levels of urban air particles has no detectable effects on the alveolar blood–gas barrier or lung function.     

Exposure assessment of workplaces manufacturing nanosized TiO2 and silver

With the increased production and widespread use of nanomaterials, human and environmental exposure to nanomaterials is inevitably increasing. Therefore, this study monitored the possible exposure to nanoparticles at workplaces that manufacture nano-TiO₂ and nano-silver. To estimate the potential exposure of workers, personal sampling, area monitoring, and real-time monitoring using a scanning mobility particle sizer (SMPS) and dust monitor were conducted at workplaces where the workers handle nanomaterials. The gravimetric concentrations of TiO₂ ranged from 0.10 to 4.99?mg/m³, which were lower than the occupational exposure limit 10?mg/m³ set by the Korean Ministry of Labor or American Conference of Governmental Industrial Hygienists (ACGIH). Meanwhile, the silver metal concentrations ranged from 0.00002 to 0.00118?mg/m³, which were also lower than the silver dust 0.1?mg/m³ and silver soluble compound 0.01?mg/m³ occupational exposure limits set by the ACGIH. The particle number concentrations at the nano-TiO₂ manufacturing workplaces ranged from 11,418 to 45,889 particles/cm³ with a size range of 15–710.5?nm during the reaction, although the concentration decreased to 14,000 particles/cm³ when the reaction was stopped. The particle concentrations at the TiO₂ manufacturing workplaces increased during the reactor and vacuum pump operations, and during the collection of the synthesized TiO₂ particles. Similarly, the particle concentrations at the silver nanoparticle manufacturing workplaces increased when the sodium citrates were weighed or reacted with the silver nitrates, and during the cleaning of the workplace. The number of silver nanoparticles in the samples obtained from the workplace manufacturing silver nanoparticles using induced coupled plasma ranged from 57,789 to 2,373,309 particles/cm³ inside the reactor with an average size of 20–30?nm and 535–25,022 particles/cm³ with a wide range of particle sizes due to agglomeration or aggregation after the release of nanoparticles into the workplace air. In contrast, the silver nanoparticles manufactured by the wet method ranged from 393 to 3526 particle/cm³ with an average size of 50?nm. Thus, when taken together, the TiO₂ and silver nanoparticle concentrations were relatively lower than existing occupational exposure limits.     

Mercury-induced motor and sensory neurotoxicity: systematic review of workers currently exposed to mercury vapor

The neurotoxicity of elemental mercury (Hg⁰) is well-recognized, but it is uncertain whether and for how long neurotoxicity persists; among studies that evaluated previously exposed workers, only one examined workers during and also years after exposure ceased. The aim of this review is to document the type, frequency, and dose-relatedness of objective neurological effects in currently exposed mercury workers and thereby provide first approximations of the effects one would have expected in previously exposed workers evaluated during exposure. We systematically reviewed studies of neurotoxicity in currently exposed mercury workers identified by searching MEDLINE (1950–2015), government reports, textbook chapters, and references cited therein; dental cohorts were not included. Outcomes on physical examination (PE), neurobehavioral (NB) tests, and electrophysiological studies were extracted and evaluated for consistency and dose-relatedness. Forty-five eligible studies were identified, comprising over 3000 workers chronically exposed to a range of Hg⁰ concentrations (0.002–1.7?mg/m³). Effects that demonstrated consistency across studies and increased frequency across urine mercury levels (<50; 50–99; 100–199; ≥200?μg/L) included tremor, impaired coordination, and abnormal reflexes on PE, and reduced performance on NB tests of tremor, manual dexterity and motor speed. The data suggest response thresholds of U_Hg ≈275?μg/L for PE findings and ≈20?μg/L for NB outcomes. These results indicate that PE is of particular value for assessing workers with U_Hg >200?μg/L, while NB testing is more appropriate for those with lower U_Hg levels. They also provide benchmarks to which findings in workers with historical exposure can be compared.     

Estimate of safe human exposure levels for lunar dust based on comparative benchmark dose modeling

Abstract

Brief exposures of Apollo astronauts to lunar dust occasionally elicited upper respiratory irritation; however, no limits were ever set for prolonged exposure to lunar dust. The United States and other space faring nations intend to return to the moon for extensive exploration within a few decades. In the meantime, habitats for that exploration, whether mobile or fixed, must be designed to limit human exposure to lunar dust to safe levels. Herein we estimate safe exposure limits for lunar dust collected during the Apollo 14 mission. We instilled three respirable-sized (～2 μ mass median diameter) lunar dusts (two ground and one unground) and two standard dusts of widely different toxicities (quartz and TiO₂) into the respiratory system of rats. Rats in groups of six were given 0, 1, 2.5 or 7.5?mg of the test dust in a saline-Survanta® vehicle, and biochemical and cellular biomarkers of toxicity in lung lavage fluid were assayed 1 week and one month after instillation. By comparing the dose--response curves of sensitive biomarkers, we estimated safe exposure levels for astronauts and concluded that unground lunar dust and dust ground by two different methods were not toxicologically distinguishable. The safe exposure estimates were 1.3?±?0.4?mg/m³ (jet-milled dust), 1.0?±?0.5?mg/m³ (ball-milled dust) and 0.9?±?0.3?mg/m³ (unground, natural dust). We estimate that 0.5–1?mg/m³ of lunar dust is safe for periodic human exposures during long stays in habitats on the lunar surface.     

FTIR microscopy reveals distinct biomolecular profile of crustacean digestive glands upon subtoxic exposure to ZnO nanoparticles

Biomolecular profiling with Fourier-Transform InfraRed Microscopy was performed to distinguish the Zn²⁺-mediated effects on the crustacean (Porcellio scaber) digestive glands from the ones elicited by the ZnO nanoparticles (NPs). The exposure to ZnO NPs or ZnCl₂ (1500 and 4000?µg Zn/g of dry food) activated different types of metabolic pathways: some were found in the case of both substances, some only in the case of ZnCl₂, and some only upon exposure to ZnO NPs. Both the ZnO NPs and the ZnCl₂ increased the protein (～1312?cm^?1; 1720–1485?cm^?1/3000–2830?cm^?1) and RNA concentration (～1115?cm^?1). At the highest exposure concentration of ZnCl₂, where the effects occurred also at the organismal level, some additional changes were found that were not detected upon the ZnO NP exposure. These included changed carbohydrate (most likely glycogen) concentrations (～1043?cm^?1) and the desaturation of cell membrane lipids (～3014?cm^?1). The activation of novel metabolic pathways, as evidenced by changed proteins’ structure (at 1274?cm^?1), was found only in the case of ZnO NPs. This proves that Zn²⁺ are not the only inducers of the response to ZnO NPs. Low bioavailable fraction of Zn²⁺ in the digestive glands exposed to ZnO NPs further supports the role of particles in the ZnO NP-generated effects. This study provides the evidence that ZnO NPs induce their own metabolic responses in the subtoxic range.     

Soy biodiesel emissions have reduced inflammatory effects compared to diesel emissions in healthy and allergic mice

Abstract

Toxicity of exhaust from combustion of petroleum diesel (B0), soy-based biodiesel (B100), or a 20% biodiesel/80% petrodiesel mix (B20) was compared in healthy and house dust mite (HDM)-allergic mice. Fuel emissions were diluted to target fine particulate matter (PM_2.5) concentrations of 50, 150, or 500?μg/m³. Studies in healthy mice showed greater levels of neutrophils and MIP-2 in bronchoalveolar lavage (BAL) fluid 2?h after a single 4-h exposure to B0 compared with mice exposed to B20 or B100. No consistent differences in BAL cells and biochemistry, or hematological parameters, were observed after 5?d or 4 weeks of exposure to any of the emissions. Air-exposed HDM-allergic mice had significantly increased responsiveness to methacholine aerosol challenge compared with non-allergic mice. Exposure to any of the emissions for 4 weeks did not further increase responsiveness in either non-allergic or HDM-allergic mice, and few parameters of allergic inflammation in BAL fluid were altered. Lung and nasal pathology were not significantly different among B0-, B20-, or B100-exposed groups. In HDM-allergic mice, exposure to B0, but not B20 or B100, significantly increased resting peribronchiolar lymph node cell proliferation and production of T_H2 cytokines (IL-4, IL-5, and IL-13) and IL-17 in comparison with air-exposed allergic mice. These results suggest that diesel exhaust at a relatively high concentration (500?μg/m³) can induce inflammation acutely in healthy mice and exacerbate some components of allergic responses, while comparable concentrations of B20 or B100 soy biodiesel fuels did not elicit responses different from those caused by air exposure alone.     

In vitro and in vivo genotoxic effects of straight versus tangled multi-walled carbon nanotubes

Some multi-walled carbon nanotubes (MWCNTs) induce mesothelioma in rodents, straight MWCNTs showing a more pronounced effect than tangled MWCNTs. As primary and secondary genotoxicity may play a role in MWCNT carcinogenesis, we used a battery of assays for DNA damage and micronuclei to compare the genotoxicity of straight (MWCNT-S) and tangled MWCNTs (MWCNT-T) in vitro (primary genotoxicity) and in vivo (primary or secondary genotoxicity). C57Bl/6 mice showed a dose-dependent increase in DNA strand breaks, as measured by the comet assay, in lung cells 24?h after a single pharyngeal aspiration of MWCNT-S (1–200?μg/mouse). An increase was also observed for DNA strand breaks in lung and bronchoalveolar lavage (BAL) cells and for micronucleated alveolar type II cells in mice exposed to aerosolized MWCNT-S (8.2–10.8?mg/m³) for 4 d, 4?h/d. No systemic genotoxic effects, assessed by the γ-H2AX assay in blood mononuclear leukocytes or by micronucleated polychromatic erythrocytes (MNPCEs) in bone marrow or blood, were observed for MWCNT-S by either exposure technique. MWCNT-T showed a dose-related decrease in DNA damage in BAL and lung cells of mice after a single pharyngeal aspiration (1–200?μg/mouse) and in MNPCEs after inhalation exposure (17.5?mg/m³). In vitro in human bronchial epithelial BEAS-2B cells, MWCNT-S induced DNA strand breaks at low doses (5 and 10?μg/cm²), while MWCNT-T increased strand breakage only at 200?μg/cm². Neither of the MWCNTs was able to induce micronuclei in vitro. Our findings suggest that both primary and secondary mechanisms may be involved in the genotoxicity of straight MWCNTs.     

A mechanistic review of particle overload by titanium dioxide

Chronic exposure to titanium dioxide (TiO₂) induces slight but significant pulmonary inflammation in experimental animals, and among potential mechanisms, particle overload is likely. Although mechanisms of particle overload are poorly understood, excess accumulation of dust particles in dust containing macrophages (dust cells) can impair their mobility, resulting in reduced clearance ability. Accordingly, retention half-times of inhaled TiO₂ increase linearly with lung burden in rodents, and mathematical (Michaelis–Menten-like) models for pulmonary clearance rates of TiO₂ as a function of lung burden have suggested an alternative mechanism for particle overload, involving excess accumulation of macrophages in the translocation pathway due to the narrow exit to the ciliated airway region, and leading to reduced pulmonary TiO₂ clearance rates. This mechanism is consistent with observations showing that TiO₂ retention half-times in the lungs of rats and mice show no change from the initial value until the lung burden exceeds around mass burden of 3?mg or surface area burden of 1000?cm². In addition, excess accumulation of macrophages is consistent with several particle overload-associated pathological changes, including accelerated neutrophilic inflammation, elevation of lymph node burden, and epithelial cell hyperplasia. Because excessive alveolar accumulation of macrophages may accelerate interstitialization of macrophages (including dust cells) and subsequent migration into lymph nodes, alveolar macrophages and dust cells likely migrate into interstitial spaces and escape to the luminal side of the ciliated airway region.     

Transdermal iontophoretic delivery of selegiline hydrochloride,in vitro

Transdermal iontophoretic delivery of selegiline hydrochloride (SH) across dermatomed human skin was studied. Electrochemical stability and various factors affecting the skin permeation were investigated. SH was stable under the influence of an electrical field. The permeation of SH was very low by passive delivery (2.29?±?0.05 μg/cm²/h) as compared to iontophoresis at 0.5 mA/cm² (65.10?±?5.04 μg/cm²/h). An increase in drug concentration from 1 to 20?mg/mL increased the iontophoretic flux by 13-fold. Optimal pH and salt (NaCl) concentration for iontophoretic delivery of SH were found to be pH 5 and 100?mM, respectively. Overall, with 20?mg/mL SH and a current density of 0.4 mA/cm², a maximum flux of 305.5?μg/cm²/h was obtained. Based on reported pharmacokinetic parameters, input target delivery rate to achieve effective plasma concentration of SH (2.2?ng/mL) was calculated. With a surface area of 40?cm², iontophoretic delivery can provide six to seven times higher levels of SH than the target delivery rate, which enables lowering of the dose and/or patch surface area. Further in vivo studies will be required to prove the efficacy of ionophoresis for enhanced delivery of SH.     

Toxicity evaluation of monodisperse PEGylated magnetic nanoparticles for nanomedicine

Abstract

Innovative nanotechnology aims to develop particles that are small, monodisperse, smart, and do not cause unintentional side effects. Uniform magnetic Fe₃O₄ nanoparticles (12?nm in size) were prepared by thermal decomposition of iron(III) oleate. To make them colloidally stable and dispersible in water and cell culture medium, they were modified with phosphonic acid- (PA) and hydroxamic acid (HA)-terminated poly(ethylene glycol) yielding PA-PEG@Fe₃O₄ and HA-PEG@Fe₃O₄ nanoparticles; conventional γ-Fe₂O₃ particles were prepared as a control. Advanced techniques were used to evaluate the properties and safety of the particles. Completeness of the nanoparticle coating was tested by real-time polymerase chain reaction. Interaction of the particles with primary human peripheral blood cells, cellular uptake, cytotoxicity, and immunotoxicity were also investigated. Amount of internalized iron in peripheral blood mononuclear cells was 72, 38, and 25?pg Fe/cell for HA-PEG@Fe₃O₄, γ-Fe₂O₃, and PA-PEG@Fe₃O₄, respectively. Nanoparticles were localized within the cytoplasm and in the extracellular space. No cytotoxic effect of both PEGylated nanoparticles was observed (0.12–75?μg/cm²) after 24 and 72-h incubation. Moreover, no suppressive effect was found on the proliferative activity of T-lymphocytes and T-dependent B-cell response, phagocytic activity of monocytes and granulocytes, and respiratory burst of phagocytes. Similarly, no cytotoxic effect of γ-Fe₂O₃ particles was observed. However, they suppressed the proliferative activity of T-lymphocytes (75?μg/cm², 72?h) and also decreased the phagocytic activity of monocytes (15?μg/cm², 24?h; 3–75?μg/cm², 72?h). We thus show that newly developed particles have great potential especially in cancer diagnostics and therapy.     

The beryllium bronchoalveolar lavage lymphocyte proliferation test: indicator of beryllium sensitization,inflammation or both?

Abstract

Context: We had available records on over 300 workers evaluated with the beryllium bronchoalveolar lavage lymphocyte proliferation test (BeBALLPT) at three expert chronic beryllium disease (CBD) diagnostic centers.

Objective: The objective was to describe the contribution of the BeBALLPT to classification of workers with respect to beryllium sensitization (BeS) and beryllium-induced lung inflammation.

Methods: Company records were used to identify beryllium workers who had undergone diagnostic bronchoscopy with BeBALLPT. Clinical, work and smoking information was abstracted from electronic and paper databases. We analyzed factors influencing BeBALLPT outcome, and its relation to blood-determined BeS and granulomatous inflammation.

Results: Positive BeBALLPTs contributed evidence of BeS in subjects without prior positive beryllium blood lymphocyte proliferation tests (BeBLPTs) and of pulmonary inflammation in persons without granulomata evident on lung biopsy. Positive BeBALLPTs were associated with positive BeBLPTs and more strongly with granulomata. The rate of both positive BeBALLPT and granulomata increased with time worked through 4 years and were lower in smoking subjects. The false negative rate of the BeBALLPT was 20%.

Conclusion: A positive BeBALLPT is closely linked to the presence of granulomata on lung biopsy and can be considered as an indicator of lung inflammation in addition to BeS. The ability to use BeBALLPT as a substitute for the more risky lung biopsy is limited by the BeBALLPT false negative rate and lack of information on the false positive rate. It is not recommended that a positive BeBALLPT be considered sufficient evidence for both lung inflammation and BeS.     

Role of Nanostructures for Anti-proliferation of Bacteria and Their Quantitative Study Validated by Statistical Analysis

The simple and sensitive UV–visible spectrophotometric analytical methods have been adopted for the determination and validation of ZnO nanostructures (nanorods (NRs), nanosphere (NSs), and nanonuts (NNTs)), concentration, which are used to control the bacterial growth of Escherichia coli. This method is based on processing conditions of nanostructures of ZnO using precursors zinc acetate dihydrate (Zn(AC₂)₂·2H₂O), zinc nitrate hexahydrate (Zn(NO₃)₂·6H₂O), sodium hydroxide, hexamethylenetetramine (HMT), methanol, etc. The optical density (OD) of the resulting solution of ZnO nanostructures with E. coli bacteria were measured at 600 nm against the reagent blank, prepared under the same conditions. The use of statistical analysis for evaluation of the resulting solution (ZnO-NRs, ZnO-NSs, and ZnO-NNTs with E. coli) was optimized and validated by various operational parameters. Beer’s law was followed (Concentration range from 0.25–2.0 μg ml^?1) with apparent molar absorptivity of 4.38?×?10² l mol^?1 cm^?1 for ZnO-NRs, 2.70?×?10² l mol^?1 cm^?1 for ZnO-NSs, and 3.10?×?10² l mol^?1 cm^?1 for ZnO-NNTs, respectively. The calibration curve shows linearity over the concentration range of 0.25–1.50 μg ml^?1 for ZnO-NRs and 0.25–2.0 μg ml^?1 for ZnO-NSs and ZnO-NNTs. Detection limit (LOD) and quantitation limit (LOQ) were found to be 0.022:0.068 μg ml^?1 for ZnO-NRs, 0.028:0.087 μg ml^?1 for ZnO-NSs, and 0.044:0.137 μg ml^?1 for ZnO-NNTs analyzed by spectrophotometric method, respectively.     

Relative systemic availability of budesonide in patients with asthma after inhalation from two dry powder inhalers

ABSTRACT

Background: To improve dosing consistency and product features, budesonide inhalation powder delivered via a dry powder inhaler (DPI) (DPI?A^* 200?μg) was redesigned to include lactose, a newly shaped mouthpiece, and a new dose indicator (DPI?B^*). Budesonide DPI?B is available in two strengths (90?μg, 180?μg).

Objective: To compare the relative rate and extent of the systemic availability of budesonide inhaled via DPI?A and DPI?B and test for systemic absorption bio­equivalence.

Methods: Adults (n?=37) with asthma as defined by the American Thoracic Society were randomized in an open-label, crossover, single-center, single-dose study to budesonide DPI?A 200?μg × 4 inhalations, budesonide DPI?B 180?μg × 4 inhalations, or budesonide DPI?B 90?μg × 8 inhalations, on 3 days, each separated by a washout period of?≥?5 days. Plasma samples were collected immediately before and up to 12?h after dosing. Primary pharmacokinetic variables were area under the drug plasma concentration–time curve from 0 to infinity (AUC_0–∞) and maximum plasma concentration (C_max); plasma concentration at 12?h (C_12h) and time to maximum plasma concentration (T_max) were secondary variables. Treatments were considered bioequivalent if the 90% confidence intervals (CIs) for their AUC_0–∞ and C_max ratios fell between 80 and 125%. Adverse events were collected.

Results: The 90% CIs for the ratios of AUC_0–∞ and C_max for budesonide DPI?A 200?μg and DPI?B 180?μg and for both budesonide DPI?B strengths fell between 80% and 125% (AUC_0–∞: budesonide DPI?B 180?μg × 4/DPI?A 200?μg × 4: 96.3% [90 % CI: 90.9, 102.1]; budesonide DPI?B 180?μg × 4/DPI?B 90?μg × 8: 92.2% [90 % CI: 87.0, 97.7]; C_max: (budesonide DPI?B 180?μg × 4/DPI?A 200?μg × 4: 100.4% [95 % CI: 92.1, 109.4]; budesonide DPI?B 180?μg × 4/DPI?B 90?μg × 8: 94.4% [90 % CI: 86.6, 102.9]). No differences in C_12h and T_max were found between treatments. All treatments were well tolerated.

Conclusions: Budesonide DPI?A 200?μg and DPI?B 180?μg have systemic absorption bioequivalence, and DPI?B 90?μg and 180?μg are dose-strength equivalent when administered at the same dose. These results may not be generalized to all patients with asthma, as this analysis included only patients with mild-to-moderate asthma aged?≥?19 years.     

Mucoadhesive buccal film containing ornidazole and dexamethasone for oral ulcers: in vitro and in vivo studies

A bilayered mucoadhesive buccal film containing a combination of ornidazole (OD) and dexamethasone sodium phosphate (DEX) was prepared using solvent casting to treat oral ulcers. Films were systematically evaluated in vitro to obtain the optimum formulation. The therapeutic effects of these films were investigated in the rabbit oral ulcer model and the in vivo release of OD and DEX in the human oral cavity was also evaluated. The backing layer contained ethyl cellulose and an optimal mucoadhesive layer containing both OD and DEX was produced. Films from the optimum formulation were 0.427?±?0.015?mm thick, weighed 55.89?±?0.79?mg, and had a surface pH of 6.34?±?0.01. The drug content of the optimum formulation approximated the theoretical value with good uniformity (2.959?±?0.106?mg/cm² for OD and 0.877?±?0.031?mg/cm² for DEX). The formulation showed favorable swelling characteristics and both drugs were released at >95% after 4?h. Moreover, the compound film had a statistically significant effect on mucosal repair and reduced ulcer inflammation without stimulating the human oral mucosa. C_max of OD in saliva was 37.04?μg/ml and that of DEX was 9.737?μg/ml. Given promising therapeutic effects, the compound film developed here could become a local drug delivery device for treating oral ulcers.     

Pt-MWCNT modified carbon electrode strip for rapid and quantitative detection of H2O2 in food

A single-use screen-printed carbon electrode strip was designed and fabricated. Nanohybrids, prepared by deposition of platinum (Pt) nanoparticles on multi-wall carbon nanotube (MWCNT), was modified on the surface of screen-printed carbon electrode for the development of a fast, sensitive and cost-effective hydrogen peroxide (H₂O₂) detection amperometric sensor strip. With Pt-MWCNT nanohybrids surface modification, current generated in response to H₂O₂ by the screen-printed carbon electrode strip was enhanced 100 fold with an applied potential of 300 mV. Quality of as-prepared electrode strip was assured by the low coefficient of variation (CV) (<5%) of currents measured at 5 s. Three linear detection ranges with sensitivity of 75.2, 120.7, and 142.8 μA mM^?1 cm^?2 were observed for H₂O₂ concentration in the range of 1–15 mM, 0.1–1 mM, and 10–100 μM, respectively. The lowest H₂O₂ concentration could be measured by the as-prepared strip was 10 μM. H₂O₂ levels in green tea infusion and pressed Tofu could be rapidly detected with results comparable to that measured by ferrous oxidation xylenol orange (FOX) assay and peroxidase colorimetric method.     

Effect of non–phospholipid-based cationic and phospholipid-based anionic nanosized emulsions on skin retention and anti-inflammatory activity of celecoxib

Context: Celecoxib (CXB, 0.2?g)-loaded anionic and cationic nanosized emulsions were prepared by a well-established combined emulsification method.

Objectives: To investigate the effect of non–phospholipid-based cationic and phospholipid-based anionic emulsions on skin retention and anti-inflammatory activity of CXB.

Methods: Using Keshary-Chien diffusion cells with cellulose acetate membrane or excised rat skin, in vitro release and skin retention of CXB from solution and emulsions were studied. The anti-inflammatory activity was evaluated by the carrageenan-induced hind paw edema method in Wistar rats.

Results: The amount of drug released through artificial membrane has decreased from 122.00?±?0.70?μg/cm² for the CXB solution to 55.80?±?0.70?μg/cm² for anionic emulsion, and then further decreased to 24.79?±?0.90?μg/cm² for cationic emulsion. The J_SS value obtained with solution, anionic, and cationic emulsions were 6825.79?±?920.86, 2513.15?±?382.71, and 1925.67?±?147.42, respectively. Cationic emulsion showed a significantly higher level (P?≤?0.05) of drug accumulation in full-thickness rat skin than anionic emulsion, and a substantially lesser percentage inhibition of edema values compared with both solution and anionic emulsion.

Discussion and conclusion: Sustained drug release together with increased skin accumulation and simultaneously decreased skin permeation as observed with cationic emulsion should substantiate its suitability as a topical delivery vehicle for CXB.     

Development of a buccal mucoadhesive film for fast dissolution: mathematical rationale,production and physicochemical characterization

Abstract

The validity of a mathematical rationale for preparation of a fast-dissolving buccal mucoadhesive was tested. A buccal mucoadhesive biopolymeric formulation has been developed having pullulan as the main component. The formulation was duly evaluated physicochemically, via assays for intrinsic viscosity (resulting in 71.61?cm³?g^?1), differential scanning calorimetry analysis (resulting in a Tg?=?63?°C), thermogravimetric analysis (244–341?°C), moisture content determinations (14%, w/w), dissolution timeframe (41.6?s), mucoadhesion force (40?kg/cm²), scanning electron microscopy analyses (critical ray under 1.0?μm), mechanic strength (tensile strength?=?58?N/mm², deformation?=?4.4%). The mucoadhesive formulation exhibited important characteristics for a drug carrier, that is, a 6?cm² area, a fast dissolution timeframe, an adequate mucoadhesivity, resistance to both oxygen and water vapor penetration, increased viscosity in solution (ranging from 33.2?cm³/g to 71.61?cm³/g), easy molding, suitable water solubility and transparency.     

Influence of sonophoresis and chemical penetration enhancers on percutaneous transport of penbutolol sulfate

The effect of ultrasound and chemical penetration enhancers on transcutaneous flux of penbutolol sulfate across split-thickness porcine skin was investigated. Penbutolol sulfate is a potent, noncardioselective beta-blocker, which is used for the management of hypertension. The drug is one of the most lipid soluble of the β-adrenoceptor antagonists used clinically. It has an n-octanol/pH 7.4 buffer partition coefficient of 179 compared to a value of 22 for propranolol. The amount of penbutolol sulfate transported across the skin is low. In this project, we studied the effect of sonophoresis and chemical penetration enhancers on transdermal delivery of penbutolol sulfate. Low-frequency sonophoresis at a frequency of 20?kHz increased transcutaneous flux of penbutolol sulfate by 3.5-fold (27.37?±?μg?cm^?2?h^?1) compared to passive delivery (7.82?±?1.72?μg?cm^?2?h^?1). We also investigated the effect of 50% ethanol, 1% limonene and 2% isopropyl myristate (IPM) on transcutaneous permeation of penbutolol sulfate. IPM, ethanol and limonene at the concentration of 1%, 50% and 2%, respectively, increased the steady-state flux values of penbutolol sulfate 2.2- (17.07?±?3.24?μg?cm^?2?h^?1), 2.6?- (19.40?±?6.40?μg?cm^?2?h^?1) and 3.4-times (26.38?±?5.01?μg?cm^?2?h^?1) compared to passive delivery (7.76?±?2.9?μg?cm^?2?h^?1). The results demonstrate that although there were slight increases in flux values, ultrasound, ethanol, limonene and IPM did not significantly enhance the transdermal delivery of penbutolol sulfate. Future studies will examine ways of optimizing sonophoretic and chemical enhancer parameters to achieve flux enhancement.