薄膜包衣对西罗莫司滴丸溶出度及稳定性的影响研究

目的：探讨薄膜包衣对西罗莫司（SRL）滴丸溶出度及稳定性的影响,以证实薄膜包衣的作用及合理性。方法：选用欧巴代为SRL滴丸的包衣材料进行包衣;对其体外释药及稳定性进行考察,并与未包衣的SRL滴丸进行比较。结果：与未包衣滴丸相比,在相同时间内,薄膜包衣SRL滴丸的体外释药量明显降低（P〈0.05）,而稳态释药速率并无显著影响（P〉0.05）;高湿条件下（75%±5%）包衣SRL滴丸的吸湿性显著下降,在强光环境中（4 500 lx±500 lx）,包衣SRL滴丸的稳定性也较好,而在高温条件下（40℃±2℃）,稳定性无显著提高。结论：欧巴代薄膜包衣可明显提高SRL滴丸的稳定性,而对其药物溶出无显著性影响。     

Oxidation of siloxanes during biogas combustion and nanotoxicity of Si-based particles released to the atmosphere

Siloxanes have been detected in the biogas produced at municipal solid waste landfills and wastewater treatment plants. When oxidized, siloxanes are converted to silicon oxides. The objectives of this study were to evaluate the transformation of siloxanes and potential nanotoxicity of Si-based particles released to the atmosphere from the gas engines which utilize biogas. Data available from nanotoxicity studies were used to assess the potential health risks associated with the inhalation exposure to Si-based nanoparticles. Silicon dioxide formed from siloxanes can range from 5 nm to about 100 nm in diameter depending on the combustion temperature and particle clustering characteristics. In general, silicon dioxide particles formed during from combustion process are typically 40–70 nm in diameter and can be described as fibrous dusts and as carcinogenic, mutagenic, astmagenic or reproductive toxic (CMAR) nanoparticles. Nanoparticles deposit in the upper respiratory system, conducting airways, and the alveoli. Size ranges between 5 and 50 nm show effective deposition in the alveoli where toxic effects are higher. In this study the quantities for the SiO₂ formed and release during combustion of biogas were estimated based on biogas utilization characteristics (gas compositions, temperature). The exposure to Si-based particles and potential effects in humans were analyzed in relation to their particle size, release rates and availability in the atmosphere. The analyses showed that about 54.5 and 73 kg/yr of SiO₂ can be released during combustion of biogas containing D4 and D5 at 14.1 mg/m³ (1 ppm) and 15.1 mg/m³ (1 ppm), respectively, per MW energy yield.     

In vivo monitoring of implant osseointegration in a rabbit model using acoustic sound analysis

Implant osseointegration can currently only be assessed reliably post mortem. A novel method that relies on the principle of acoustic sound analysis was developed to enable examination of the longitudinal progress of osseointegration. The method is based on a magnetic sphere inside a hollow cylinder of the implant. By excitation using an external magnetic field, collision of the sphere inside the implant produces a sound signal. Custom‐made titanium implants equipped thusly were inserted in each lateral femoral epicondyle of 20 New Zealand White Rabbits. Two groups were investigated: Uncoated, machined surface versus antiadhesive surface; and calcium phosphate‐coated surface versus antiadhesive surface. The sound analysis was performed postoperatively and weekly. After 4 weeks, the animals were euthanized, and the axial pull‐out strengths of the implants were determined. A significant increase in the central frequency was observed for the loose implants (mean pull‐out strength 21.1 ± 16.9 N), up to 6.4 kHz over 4 weeks. In comparison, the central frequency of the osseointegrated implants (105.2 ± 25.3 N) dropped to its initial value. The presented method shows potential for monitoring the osseointegration of different implant surfaces and could considerably reduce the number of animals needed for experiments. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:606–612, 2014.     

Ligand-conjugated mesoporous silica nanorattles based on enzyme targeted prodrug delivery system for effective lung cancer therapy

Epidermal growth factor receptor antibody (EGFRAb) conjugated silica nanorattles (SNs) were synthesized and used to develop receptor mediated endocytosis for targeted drug delivery strategies for cancer therapy. The present study determined that the rate of internalization of silica nanorattles was found to be high in lung cancer cells when compared with the normal lung cells. EGFRAb can specifically bind to EGFR, a receptor that is highly expressed in lung cancer cells, but is expressed at low levels in other normal cells. Furthermore, in vitro studies clearly substantiated that the cPLA₂α activity, arachidonic acid release and cell proliferation were considerably reduced by pyrrolidine-2 loaded EGFRAb-SN in H460 cells. The cytotoxicity, cell cycle arrest and apoptosis were significantly induced by the treatment of pyrrolidine-2 loaded EGFRAb-SN when compared with free pyrrolidine-2 and pyrrolidine-2 loaded SNs in human non-small cell lung cancer cells. An in vivo toxicity assessment showed that silica nanorattles and EGFRAb-SN-pyrrolidine-2 exhibited low systemic toxicity in healthy Balb/c mice. The EGFRAb-SN-pyrrolidine-2 showed a much better antitumor activity (38%) with enhanced tumor inhibition rate than the pyrrolidine-2 on the non-small cell lung carcinoma subcutaneous model. Thus, the present findings validated the low toxicity and high therapeutic potentials of EGFRAb-SN-pyrrolidine-2, which may provide a convincing evidence of the silica nanorattles as new potential carriers for targeted drug delivery systems.     

New silica nanostructure for the improved delivery of topical antibiotics used in the treatment of staphylococcal cutaneous infections

In this paper, we report the synthesis, characterization (FT-IR, XRD, BET, HR-TEM) and bioevaluation of a novel γ-aminobutiric acid/silica (noted GABA-SiO₂ or γ-SiO₂) hybrid nanostructure, for the improved release of topical antibiotics, used in the treatment of Staphylococcus aureus infections. GABA-SiO₂ showed IR bands which were assigned to Si–O–Si (stretch mode). The XRD pattern showed a broad peak in the range of 18–30° (2θ), indicating an amorphous structure. Based on the BET analysis, estimations about surface area (438.14 m²/g) and pore diameters (4.76 nm) were done. TEM observation reveals that the prepared structure presented homogeneity and an average size of particles not exceeding 10 nm. The prepared nanostructure has significantly improved the anti-staphylococcal activity of bacitracin and kanamycin sulfate, as demonstrated by the drastic decrease of the minimal inhibitory concentration of the respective antibiotics loaded in the GABA-SiO₂ nanostructure. These results, correlated with the high biocompatibility of this porous structure, are highlighting the possibility of using this carrier for the local delivery of the antimicrobial substances in lower active doses, thus reducing their cytotoxicity and side-effects.     

A novel multivariate approach using science-based calibration for direct coating thickness determination in real-time NIR process monitoring

This study demonstrates an approach, using science-based calibration (SBC), for direct coating thickness determination on heart-shaped tablets in real-time. Near-Infrared (NIR) spectra were collected during four full industrial pan coating operations. The tablets were coated with a thin hydroxypropyl methylcellulose (HPMC) film up to a film thickness of 28 μm. The application of SBC permits the calibration of the NIR spectral data without using costly determined reference values. This is due to the fact that SBC combines classical methods to estimate the coating signal and statistical methods for the noise estimation. The approach enabled the use of NIR for the measurement of the film thickness increase from around 8 to 28 μm of four independent batches in real-time. The developed model provided a spectroscopic limit of detection for the coating thickness of 0.64 ± 0.03 μm root-mean square (RMS). In the commonly used statistical methods for calibration, such as Partial Least Squares (PLS), sufficiently varying reference values are needed for calibration. For thin non-functional coatings this is a challenge because the quality of the model depends on the accuracy of the selected calibration standards. The obvious and simple approach of SBC eliminates many of the problems associated with the conventional statistical methods and offers an alternative for multivariate calibration.     

Characteristics of Cr-B Coatings Produced on Vanadis® 6 Tool Steel Using Laser Processing

The paper presents the results of a study of the microstructure, chemical composition, microhardness and corrosion resistance of Cr-B coatings produced on Vanadis 6 tool steel. In this study, chromium and boron were added to the steel surface using a laser alloying process. The main purpose of the study was to determine the impact of those chemical elements on surface properties. Chromium and boron as well as their mixtures were prepared in various proportions and then were applied on steel substrate in the form of precoat of 100 µm thickness. Depending on the type of precoat used and laser processing parameters, changes in microstructure and properties were observed. Coatings produced using precoat containing chromium and boron mixture were characterized by high microhardness (900 HV0.05–1300 HV0.005) while maintaining good corrosion resistance. It was also found that too low laser beam power contributed to the formation of cracks and porosity.     

Multilayer Diamond Coatings Applied to Micro-End-Milling of Cemented Carbide

Cobalt-cemented carbide micro-end mills were coated with diamond grown by chemical vapor deposition (CVD), with the purpose of micro-machining cemented carbides. The diamond coatings were designed with a multilayer architecture, alternating between sub-microcrystalline and nanocrystalline diamond layers. The structure of the coatings was studied by transmission electron microscopy. High adhesion to the chemically pre-treated WC-7Co tool substrates was observed by Rockwell C indentation, with the diamond coatings withstanding a critical load of 1250 N. The coated tools were tested for micro-end-milling of WC-15Co under air-cooling conditions, being able to cut more than 6500 m over a period of 120 min, after which a flank wear of 47.8 μm was attained. The machining performance and wear behavior of the micro-cutters was studied by scanning electron microscopy and energy-dispersive X-ray spectroscopy. Crystallographic analysis through cross-sectional selected area electron diffraction patterns, along with characterization in dark-field and HRTEM modes, provided a possible correlation between interfacial stress relaxation and wear properties of the coatings. Overall, this work demonstrates that high adhesion of diamond coatings can be achieved by proper combination of chemical attack and coating architecture. By preventing catastrophic delamination, multilayer CVD diamond coatings are central towards the enhancement of the wear properties and mechanical robustness of carbide tools used for micro-machining of ultra-hard materials.     

Weldability of Underwater Wet-Welded HSLA Steel: Effects of Electrode Hydrophobic Coatings

The paper presents the effects of waterproof coatings use to cover electrodes on the weldability of high-strength, low-alloy (HSLA) steel in water. With the aim of improving the weldability of S460N HSLA steel in water, modifications of welding filler material were chosen. The surfaces of electrodes were covered by different hydrophobic substances. The aim of the controlled thermal severity (CTS) test was to check the influence of these substances on the HSLA steel weldability in the wet welding conditions. The visual test, metallographic tests, and hardness Vickers HV10 measurements were performed during investigations. The results proved that hydrophobic coatings can reduce the hardness of welded joints in the heat-affected zone by 40–50 HV10. Additionally, the number of cold cracks can be significantly reduced by application of waterproof coatings on the filler material. The obtained results showed that electrode hydrophobic coatings can be used to improve the weldability of HSLA steel in underwater conditions.