New method for the characterization of domain morphology of polymer blends using ruthenium tetroxide staining and low voltage scanning electron microscopy (LVSEM)

Brown, G. M.; Butler, J. H.

doi:10.1016/s0032-3861(96)00962-7

Cited by 83 publications

(70 citation statements)

References 10 publications

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“…These PEG M-MSNs were monodisperse and stable at physiological pH with a size of 123 ± 3 nm. The polyethylene glycol grafted at the nanoparticles' surface was differentiated by heavy staining with OsO 4 (Brown and Butler 1997).…”

Section: Characterization Of Pristine and Coated M-msnsmentioning

confidence: 99%

Biocompatibility assessment of functionalized magnetic mesoporous silica nanoparticles in human HepaRG cells

et al. 2017

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Magnetic mesoporous silica nanoparticles (M-MSNs) are a promising class of nanoparticles for drug delivery. However, a deep understanding of the toxicological mechanisms of action of these nanocarriers is essential, especially in the liver. The potential toxicity on HepaRG cells of pristine, pegylated (PEG), and lipid (DMPC) M-MSNs were compared. Based on MTT assay and real-time cell impedance, none of these NPs presented an extensive toxicity on hepatic cells. However, we observed by transmission electron microscopy (TEM) that the DMPC and pristine M-MSNs were greatly internalized. In comparison, PEG M-MSNs showed a slower cellular uptake. Whole gene expression profiling revealed the M-MSNs molecular modes of action in a time-and dose-dependent manner. The lowest dose tested (1.6 mg/cm 2 ) induced no molecular effect and was defined as 'No Observed Transcriptional Effect level.' The dose 16 mg/cm 2 revealed nascent but transient effects. At the highest dose (80 mg/cm 2 ), adverse effects have clearly arisen and increased over time. The limit of biocompatibility for HepaRG cells could be set at 16 mg/cm 2 for these NPs. Thanks to a comparative pathway-driven analysis, we highlighted the sequence of events that leads to the disruption of hepatobiliary system, elicited by the three types of MMSNs, at the highest dose. The Adverse Outcome Pathway of hepatic cholestasis was implicated. Toxicogenomics applied to cell cultures is an effective tool to characterize and compare the modes of action of many substances. We propose this strategy as an asset for upstream selection of the safest nanocarriers in the framework of regulation for nanobiosafety. ARTICLE HISTORY

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Section: Characterization Of Pristine and Coated M-msnsmentioning

confidence: 99%

Biocompatibility assessment of functionalized magnetic mesoporous silica nanoparticles in human HepaRG cells

et al. 2017

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“…TEM images of quenched samples were recorded at 200 kV with either a JEOL (Tokyo, Japan) 2000FX or an FEI (Hillsboro, OR) Technai T-20 TEM. The contrast for the morphological characterization was achieved by a sample preparation technique that relies on different rates of diffusion of a RuO 4 stain into the amorphous and semicrystalline regions (21). First, the sample surface was cut at Ϫ170°C to make a smooth surface for the stain to penetrate into the sample.…”

Section: Synthesis Of Ipp-b-rpp-b-ipp-b-rpp-b-ipp (Isopb)mentioning

confidence: 99%

Semicrystalline thermoplastic elastomeric polyolefins: Advances through catalyst development and macromolecular design

Hotta

Cochran

Ruokolainen

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

125

116

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We report the design, synthesis, morphology, phase behavior, and mechanical properties of semicrystalline, polyolefin-based block copolymers. By using living, stereoselective insertion polymerization catalysts, syndiotactic polypropylene-blockpoly(ethylene-co-propylene)-block-syndiotactic polypropylene and isotactic polypropylene-block-regioirregular polypropyleneblock-isotactic polypropylene triblock copolymers were synthesized. The volume fraction and composition of the blocks, as well as the overall size of the macromolecules, were controlled by sequential synthesis of each block of the polymers. These triblock copolymers, with semicrystalline end-blocks and mid-segments with low glass-transition temperatures, show significant potential as thermoplastic elastomers. They have low Young's moduli, large strains at break, and better than 90% elastic recovery at strains of 100% or less. An isotactic polypropylene-block-regioirregular polypropylene-block-isotactic polypropylene-block-regioirregular polypropylene-block-isotactic polypropylene pentablock copolymer was synthesized that also shows exceptional elastomeric properties. Notably, microphase separation is not necessary in the semicrystalline isotactic polypropylenes to achieve good mechanical performance, unlike commercial styrenic thermoplastic elastomers.block copolymer ͉ polypropylene T he applications of a polymer are largely determined by its chemical, physical, and mechanical properties. These properties are in turn determined by polymer morphology, which is dictated by polymer structure and composition. Thermoplastic elastomers are a classic example where polymer architecture engenders unique properties. Block copolymers that contain at least two blocks that are hard at room temperature, separated by blocks with a glass transition temperature (T g ) below room temperature, typically exhibit elastomeric properties if the low T g block volume is large (1-5). The most well known elastomers of this type are the polystyrene (PS)-block (b)-polybutadiene-b-PS triblock copolymers, sold commercially by Kraton Polymers. Such materials normally possess a microphase-separated morphology in which 10-nm-scale domains of the hard blocks (e.g., PS) are embedded as spheres or cylinders within a continuous phase of the low T g soft blocks. The hard domains serve as thermally reversible crosslinks that at room temperature produce high levels of recoverable elasticity in the soft phase.Sequence control of a synthetic polymer is most easily accomplished by using a synthetic technique that allows the sequential addition of one or more monomers to the macromolecule in a chain growth process without spontaneous termination. These techniques are collectively called living polymerizations, and despite many successes over the last half century, their further development remains one of the most important frontiers in polymer science. In the case of the Kraton triblock copolymers, a living anionic polymerization process is used to synthesize the materials. Because approximately t...

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“…Ruthenium can be oxidized to ruthenium (IV) oxide (RuO 2 , oxidation state +4) which can in turn be oxidized by sodium metaperiodate to ruthenium tetroxide, RuO 4 (Brown and Butler, 1997). Ruthenium compounds should be regarded as highly toxic and as carcinogenic.…”

Section: Rutheniummentioning

confidence: 99%

Selected Genotoxic Impurities Profiling During WFI Qualification to Control Carcinogenesis in Large Volume Parenterals

Ullah¹

2015

American Journal of Pharmacology and Toxicology

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Water For Injections (WFI) which is the main vehicle of Large Volume Parenterals (LVPs) should be free from trace amount of genotoxic impurities. This review gives emphasis on quantification of genotoxic trace metals during qualification of WFI in LVPs manufacturing unit. According to ICH guidelines, impurities related to drug substances are classified into three main categories: Organic impurities, inorganic (elemental) impurities and residual solvents. Within these categories, genotoxic impurities form a special case that poses a significant safety risk, even at low concentrations, because they may be mutagenic and are therefore potentially damaging to DNA. As a result they can lead to mutations or cause cancer. Chemical carcinogens most often directly or after xenobiotic metabolism, act as genotoxic causes to induce DNA damage. The roles of trace metals (some of which are either genotoxic or non-genotoxic) in cancer development and inhibition have a complex character and have raised many questions because of their essential and toxic effects on people's health. Trace metals such as cadmium, nickel, arsenic, beryllium and chromium (VI) have been recognized as human or animal carcinogens by International Agency for Research on Cancer (IARC). There are several genotoxic chemicals like residual solvent, impurities and trace metals present in Pharmaceuticals to form carcinogens. Regulatory body like FDA and EMEA has fixed up specific limits for these elemental impurities. The toxicity of an elemental impurity is related to its extent of exposure (bioavailability). In that sense, parenteral dosage forms has its most possibility to be bioavailable than the other dosage forms, the limit of genotoxic impurities are 10 times lower than that of oral dosage forms by United States Pharmacopoeia (USP). The present article is for the importance of identification and quantification of the trace amount of the metal genotoxic impurities in Water For Injection (WFI) during qualification (IQ, OQ, PQ) as a preventive measure to control the production and distribution of WFI for Large Volume Parenteral (LVP) production.

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New method for the characterization of domain morphology of polymer blends using ruthenium tetroxide staining and low voltage scanning electron microscopy (LVSEM)

Cited by 83 publications

References 10 publications

Biocompatibility assessment of functionalized magnetic mesoporous silica nanoparticles in human HepaRG cells

Biocompatibility assessment of functionalized magnetic mesoporous silica nanoparticles in human HepaRG cells

Semicrystalline thermoplastic elastomeric polyolefins: Advances through catalyst development and macromolecular design

Selected Genotoxic Impurities Profiling During WFI Qualification to Control Carcinogenesis in Large Volume Parenterals

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