Analysis of particles from hamster lungs following pulmonary talc exposures: implications for pathogenicity.

BACKGROUND: Talc, a hydrous magnesium silicate, often used for genital hygiene purposes, is associated with ovarian carcinoma in case-control studies. Its potential to cause inflammation, injury, and functional changes in cells has been described. A complication of such studies is that talc preparations may be contaminated with other materials. A previous study by (Beck et al. Toxicol Appl Pharmacol 87:222-34, 1987) used a hamster model to study talc and granite dust exposure effects on various biochemical and cellular inflammatory markers. Our current study accessed key materials used in that 1987 study; we re-analyzed the original talc dust with contemporary scanning electron microscopy and energy dispersive x-ray analysis (SEM/EDX) for contaminants. We also examined the original bronchoalveolar lavage (BAL) cells with polarized light microscopy to quantify cell-associated birefringent particles to gain insight into the talc used. RESULTS: SEM/EDX analyses showed that asbestos fibers, quartz, and toxic metal particulates were below the limits of detection in the original talc powder. However, fibers with aspect ratios ≥3:1 accounted for 22% of instilled material, mostly as fibrous talc. Talc (based on Mg/Si atomic weight % ratio) was the most abundant chemical signature, and magnesium silicates with various other elements made up the remainder. BAL cell counts confirmed the presence of acute inflammation, which followed intratracheal instillation. Measurements of cell associated birefringent particles phagocytosis revealed significant differences among talc, granite, and control exposures with high initial uptake of talc compared to granite, but over the 14-day experiment, talc phagocytosis by lavaged cells was significantly less than that of granite. Phagocytosis of talc fibers by macrophages was observed, and birefringent particles were found in macrophages, neutrophils, and multinucleate giant cells in lavaged cells from talc-exposed animals. CONCLUSION: Our data support the contention that talc, even without asbestos and other known toxic contaminants, may elicit inflammation and contribute to lung disease. Our findings support the conclusions of (Beck et al. Toxicol Appl Pharmacol 87:222-34, 1987) study. By analyzing particulate exposures with polarized light microscopy and SEM/EDX, fibrous talc was identified and a distinctive pattern of impaired particulate ingestion was demonstrated.

Hierarchical porous Mg2SiO4-CoFe2O4 nanomagnetic scaffold for bone cancer therapy and regeneration: Surface modification and in vitro studies.

3D multifunctional bone scaffolds have recently attracted more attention in bone tissue engineering because of addressing critical issues like bone cancer and inflammation beside bone regeneration. In this study, a 3D bone scaffold is fabricated from Mg2SiO4-CoFe2O4 nanocomposite which is synthesized via a two-step synthesis strategy and then the scaffold's surface is modified with poly-3-hydroxybutyrate (P3HB)-ordered mesoporous magnesium silicate (OMMS) composite to improve its physicochemical and biological properties. The Mg2SiO4-CoFe2O4 scaffold is fabricated through polymer sponge technique and the scaffold exhibits an interconnected porous structure in the range of 100-600 µm. The scaffold is then coated with OMMS/P3HB composite via dip coating and the physical, chemical, and biological-related properties of OMMS/P3HB composite-coated scaffold are assessed and compared to the non-coated and P3HB-coated scaffolds in vitro. It is found that, on the one hand, P3HB increases the cell attachment, proliferation, and compressive strength of the scaffold, but on the other hand, it weakens the bioactivity kinetic. Addition of OMMS to the coating composition is accompanied with significant increase in bioactivity kinetic. Besides, OMMS/P3HB composite-coated scaffold exhibits higher drug loading capacity and more controlled release manner up to 240 h than the other samples because of OMMS which has a high surface area and ordered mesoporous structure suitable for controlled release applications. The overall results indicate that OMMS/P3HB coating on Mg2SiO4-CoFe2O4 scaffold leads to a great improvement in bioactivity, drug delivery potential, compressive strength, cell viability, and proliferation. Moreover, OMMS/P3HB composite-coated scaffold has heat generation capability for hyperthermia-based bone cancer therapy and so it is suggested as a multifunctional scaffold with great potentials for bone cancer therapy and regeneration.

Electrophoretically deposited mesoporous magnesium silicate with ordered nanopores as an antibiotic-loaded coating on surface-modified titanium.

Infection is quite usual for implants after surgery and a systemic administration of antibiotics causes problems before the eradication of bacteria. Localized drug delivery from implants is an effective way by which the mentioned target can be met. In the current work, ordered mesoporous magnesium silicate (OMMS) is coated on plasma electrolytic oxidation (PEO)-modified titanium (Ti) substrate through electrophoretic deposition (EPD) and rifampin as an antibiotic is loaded on OMMS coating to be applied as an antibacterial coating. The immersion test into simulated body fluid and also potentiodynamic polarization assay are adopted to assess the in vitro bioactivity up to 7 days and corrosion resistance of the specimens, respectively. The double surface coatings of PEO and EPD are achieved on Ti substrate and the thickness for each one is found to be 4 and 25 µm, respectively. Regarding to drug delivery capability of OMMS as the EPD coating, the loading capacity is 25% and release trend sustains up to 96 h. The antibacterial activity and also cell viability of OMMS coating are significantly increased with rifampin loading. The results of our study exhibit that OMMS as a multifunctional coating deposited on the PEO-modified Ti substrate improves corrosion resistance, in vitro bioactivity, alkaline phosphatase activity, and mineralization of the substrate. Moreover, rifampin-loaded OMMS coating is not only able to prevent infection, but it also increases the osteogenesis cells viability. Therefore, rifampin-loaded OMMS coating on Ti is potentially regarded appropriate for orthopedic applications.

Influences of doping mesoporous magnesium silicate on water absorption, drug release, degradability, apatite-mineralization and primary cells responses to calcium sulfate based bone cements.

In this study, composite cements containing mesoporous magnesium silicate (m-MS) and calcium sulfate (CS) were fabricated. The results revealed that the setting time of the m-MS/CS composite cements (m-MSC) slightly prolonged with the increase of m-MS content while the compressive strength suffered a little loss. The doping of m-MS improved the water absorption, drug release (vancomycin) and degradability of the m-MSC in Tris-HCl solution (pH=7.4). In addition, addition of m-MS facilitated the apatite-mineralization of m-MSC in simulated body fluid (SBF), indicating good bioactivity. For cell cultural experiments, the results revealed that the m-MSC promoted the cells adhesion and proliferation, and improved the alkaline phosphatase (ALP) activity of MC3T3-E1 cells, revealing good cytocompatibility. It could be suggested that the m-MSC might be promising cements biomaterials for bone tissue regeneration.

Molecular interaction in alginate beads reinforced with sodium starch glycolate or magnesium aluminum silicate, and their physical characteristics.

Diclofenac calcium-alginate (DCA) beads were reinforced with different amounts of sodium starch glycolate (SSG) or magnesium aluminum silicate (MAS) and were prepared using ionotropic gelation method. Complex formation of sodium alginate (SA) and SSG or MAS in calcium-alginate beads was revealed using FTIR spectroscopy. Differential scanning calorimetric study indicated that diclofenac sodium (DS) in amorphous form was dispersed in the matrix of DCA beads. The thermal behavior of SSG-DCA and MAS-DCA beads was similar to the control bead. Both additives can improve the entrapment efficiency of DCA beads. The swelling and water uptake of the beads depended on the properties of incorporated additives. The SSG-DCA beads showed a higher water uptake and swelling than MAS-DCA beads. Moreover, the swelling of the beads showed a good correlation with the square root of time. The release kinetic of the beads in pH 6.8 phosphate buffer was swelling controlled mechanism, while that in distilled water followed Higuchi's model. The slower release rate and the longer lag time in pH 6.8 phosphate buffer was obtained from the SSG-DCA and MAS-DCA beads because of complex formation between SA and SSG or MAS. However, SSG in the beads could increase the release of DS from the beads in distilled water because it acted as a channeling agent. In contrast, MAS retarded the release of DS from the beads in distilled water due to the stronger matrix formation.

3-aminopropyl functionalized magnesium phyllosilicate as an organoclay based drug carrier for improving the bioavailability of flurbiprofen.

This study aimed to develop an oral delivery system using clay-based organic-inorganic hybrid materials to improve the bioavailability of the drug, flurbiprofen, which is poorly soluble in water. 3-aminopropyl functionalized magnesium phyllosilicate (AMP clay) was synthesized by a one-pot direct sol-gel method, and then flurbiprofen (FB) was incorporated into AMP clay (FB-AMP) at different drug/clay ratios. The structural characteristics of AMP and FB-AMP formulation were confirmed by X-ray diffraction, Fourier transform infrared spectroscopy, and transmission electron microscopy. Among tested formulations, FB-AMP(3), dramatically increased the dissolution of FB and achieved rapid and complete drug release within 2 hours. More than 60% of FB was released from FB-AMP(3) after 30 minutes; the drug was completely dissolved in the water within 2 hours. Under the acidic condition (pH 1.2), FB-AMP(3) also increased the dissolution of FB by up to 47.1% within 1 hour, which was three-fold higher than that of untreated FB. Furthermore, following an oral administration of FB-AMP(3) to Sprague-Dawley rats, the peak plasma concentration and area under the plasma concentration-time curve of FB increased two-fold, and the time to reach the peak plasma concentration was shortened compared with that in the untreated FB. This result suggests that the oral drug delivery system using clay-based organic-inorganic hybrid material might be useful to improve the bioavailability of FB.

Pharmacokinetic study of zeolite A, sodium aluminosilicate, magnesium silicate, and aluminum hydroxide in dogs.

Zeolite A is a synthetic zeolite which may have therapeutic utility in osteoporotic individuals because of its ability to stimulate bone formation. A study of Zeolite A (30 mg/kg), sodium aluminosilicate (16 mg/kg), magnesium trisilicate (20 mg/kg), and aluminum hydroxide (675 mg) was designed in beagle dogs. The purpose of this study was to compare the oral bioavailability of silicon and aluminum from Zeolite A, sodium aluminosilicate, magnesium trisilicate, and aluminum hydroxide in dogs. Twelve female dogs received each compound as a single dose separated by one week in a randomized, 4-way, crossover design. Plasma samples were drawn at time 0 and for 24 hours after dosing. The concentrations of silicon and aluminum were determined by graphite furnace atomic absorption. The mean plasma silicon AUC values (+/- S.D.) were 9.5 +/- 4.5, 7.7 +/- 1.6, 8.8 +/- 3.0, 6.1 +/- 1.9 mg.hr/L and the mean plasma silicon Cmax values (+/- S.D.) were 1.07 +/- 1.06, 0.67 +/- 0.27, 0.75 +/- 0.31, 0.44 +/- 0.17 mg/L for Zeolite A, sodium aluminosilicate, magnesium trisilicate, and aluminum hydroxide respectively. Although mean silicon AUC and Cmax values were elevated when compared to baseline after administration of the silicon containing compounds, only the AUC from Zeolite A reached statistical significance (p = 0.041). The mean plasma silicon Tmax values (+/- S.D.) were 7.9 +/- 6.4, 5.8 +/- 4.6, 6.9 +/- 6.3 and 8.5 +/- 3.4 hrs for Zeolite A, sodium aluminosilicate, magnesium trisilicate and aluminum Hydroxide respectively.(ABSTRACT TRUNCATED AT 250 WORDS)