6 research outputs found
Effect of calcium precursor on the bioactivity and biocompatibility of sol-gel-derived glasses
This study investigated the impact of different calcium reagents on the morphology, composition, bioactivity and biocompatibility of two-component (CaO-SiO2) glasses produced by the Stöber process with respect to their potential application in guided tissue regeneration (GTR) membranes for periodontal repair. The properties of the binary glasses were compared with those of pure silica Stöber particles. The direct addition of calcium chloride (CC), calcium nitrate (CN), calcium methoxide (CM) or calcium ethoxide (CE) at 5 mol % with respect to tetraethyl orthosilicate in the reagent mixture gave rise to textured, micron-sized aggregates rather than monodispersed ~500 nm spheres obtained from the pure silica Stöber synthesis. The broadening of the Si-O-Si band at ~1100 cm-1 in the infrared spectra of the calcium-doped glasses indicated that the silicate network was depolymerised by the incorporation of Ca2+ ions and energy dispersive X-ray analysis revealed that, in all cases, the Ca:Si ratios were significantly lower than the nominal value of 0.05. The distribution of Ca2+ ions was also found to be highly inhomogeneous in the methoxide-derived glass. All samples released soluble silica species on exposure to simulated body fluid, although only calcium-doped glasses exhibited in vitro bioactivity via the formation of hydroxyapatite. The biocompatibilities of model chitosan-glass GTR membranes were assessed using human MG63 osteosarcoma cells and were found to be of the order: CN < pure silica ~ CC << CM ~ CE. Calcium nitrate is the most commonly reported precursor for the sol-gel synthesis of bioactive glasses; however, the incomplete removal of nitrate ions during washing compromised the cytocompatibility of the resulting glass. The superior bioactivity and biocompatibility of the alkoxide-derived glasses is attributed to their ease of dissolution and lack of residual toxic anions. Overall, calcium ethoxide was found to be the preferred precursor with respect to extent of calcium-incorporation, homogeneity, bioactivity and biocompatibility
An in vitro evaluation of epigallocatechin gallate (eGCG) as a biocompatible inhibitor of ricin toxin
The catechin, epigallocatechin gallate (eGCG), found in green tea, has inhibitory activity against a number of protein toxins and was investigated in relation to its impact upon ricin toxin (RT) in vitro. The IC50 for RT was 0.08 ± 0.004 ng/mL whereas the IC50 for RT + 100 μM eGCG was 3.02 ± 0.572 ng/mL, indicating that eGCG mediated a significant (p < 0.0001) reduction in ricin toxicity. This experiment was repeated in the human macrophage cell line THP-1 and IC50 values were obtained for RT (0.54 ± 0.024 ng/mL) and RT + 100 μM eGCG (0.68 ± 0.235 ng/mL) again using 100 μM eGCG and was significant (p = 0.0013). The documented reduction in ricin toxicity mediated by eGCG was found to be eGCG concentration dependent, with 80 and 100 μg/mL (i.e. 178 and 223 μM respectively) of eGCG mediating a significant (p = 0.0472 and 0.0232) reduction in ricin toxicity at 20 and 4 ng/ml of RT in Vero and THP-1 cells (respectively). When viability was measured in THP-1 cells by propidium iodide exclusion (as opposed to the MTT assays used previously) 10 ng/mL and 5 ng/mL of RT was used. The addition of 1000 μM and 100 μM eGCG mediated a significant (p = 0.0015 and < 0.0001 respectively) reduction in ricin toxicity relative to an identical concentration of ricin with 1 μg eGCG. Further, eGCG (100 μM) was found to reduce the binding of RT B chain to lactose-conjugated Sepharose as well as significantly (p = 0.0039) reduce the uptake of RT B chain in Vero cells. This data suggests that eGCG may provide a starting point to refine biocompatible substances that can reduce the lethality of ricin
Biological Evaluation of Zinc Phosphate Cement for Potential Bone Contact Applications
Zinc phosphate cement is used in dentistry to lute crowns and bridges. So far, its biocompatibility for other applications has not been studied. This paper reports the biocompatibility of zinc phosphate towards MG63 cells, testing both the material (discs; 3 mm diameter × 1 mm thick) and leachate from the cement. Cell viability was determined using an MTT assay, and cytotoxicity from the effects of leachate, studied in triplicate. Microscopy (optical and scanning electron) determined the morphology and proliferation of cells attached to zinc phosphate. ICP-OES measured element release into leachate, and anti-microbial behaviour was determined against Streptococcus pyrogenes cultured on a Brain Heart Infusion agar using cement discs (3 mm diameter × 1 mm thick). Zones of inhibition were measured after 72 h. MG63 cells proliferated on zinc phosphate surfaces and retained their morphology. The cells were healthy and viable as shown by an MTT assay, both on cement and in leachate. High levels of phosphorus but low levels of zinc were released into leachate. The cement showed minimal antimicrobial activity against S. pyogenes, probably due to the long maturation times used. Zinc phosphate cement was found to be biocompatible towards MG63 cells, which indicates that it may be capable of use in bone contact applications
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Imaging select mammalian organelles using fluorescent microscopy: application to drug delivery
The microscopic imaging of specific organelles has become a staple of the single-cell assay and has helped define the molecular regulation of many physiological processes. This definition has been made possible by utilizing different criteria to identify specific subpopulations of organelles. These criteria can be biochemical, immunological, or physiological, and in many cases, markers regulate fusion to the organelle they define (e.g., Rab-GTPase proteins). Single-cell imaging technology allows, within the context of drug delivery, an evaluation of the intracellular trafficking of both biological and synthetic macromolecules. However, it should be remembered that there are many limitations associated with this type of study and quantitation is not easy. The temporal dissection of novel and default trafficking of both macromolecular “drugs” and macromolecular drug delivery systems is possible. These methodologies are detailed herein
Structural and biological investigation of ferrocene-substituted 3-methylidene-1,3-dihydro-2H-indol-2-ones
The Knoevenagel condensation of 1,3-dihydro-2H-indol-2-one with ferrocene carboxaldehyde afforded an approximate 2:1 mixture of the geometrical isomers (E)- and (Z)-3-ferrocenylmethylidene-1,3-dihydro-2H-indol-2-one respectively in an overall 67% yield; the air and solution-stable isomers were readily separated by preparative thin layer chromatography and their structures were unequivocally elucidated in solution, by (1)H NMR spectroscopy, and in the solid phase, by X-ray crystallography; both isomers of displayed in vitro toxicity against B16 melanoma and Vero cell lines in the micromolar range and inhibited the kinase VEGFR-2 with IC(50) values of ca. 200 nM
Synthesis of a 1,4-benzodiazepine containing palladacycle with in vitro anticancer and cathepsin B activity
The reaction of the five-membered C,N-palladacycle [(L)PdCl](2), where LH = 1-methyl-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one, with 1,2-ethanebis(diphenylphosphine), dppe, leads to the formation of the bridged palladacycle. [Pd(2)L(2)(mu-dppe)Cl(2)] 3, which was characterised in solution by (1)H and (31)P NMR spectroscopy and in the solid state by X-ray crystallography. Complex 3 was tested in vitro against a number of cell lines. For example, it inhibited K562 leukaemia cells with an IC(50) value of 4.3 microM (1 h exposure) and displayed cathepsin B inhibitory action with an IC(50) value of 3 microM