In spite of significant insolubility and toxicity, carbon nanotubes (CNTs) erupt into the biomedical research, and create an increasing interest in the field of nanomedicine. Single-walled CNTs ...(SWCNTs) are highly hydrophobic and have been shown to be toxic while systemically administrated. Thus, SWCNTs have to be functionalized to render water solubility and biocompatibility. Herein, we introduce a method for functionalizing SWCNT using phospholipids (PL) conjugated to hyaluronan (HA), a hydrophilic glycosaminoglycan, with known receptors on many types of cancer and immune cells. This functionalization allowed for CNT solubilization, endowed the particles with stealth properties evading the immune system, and reduced immune and mitochondrial toxicity both in vitro and in vivo. The CNTaPLaHA internalized into macrophages and showed low cytotoxicity. In addition, CNTaPLaHA did not induce an inflammatory response in macrophages as evidenced by the cytokine profiling and the use of image-based high-content analysis approach in contrast to non-modified CNTs. In addition, systemic administration of CNTaPLaHA into healthy C57BL/6 mice did not alter the total number of leukocytes nor increased liver enzyme release as opposed to CNTs. Taken together, these results suggest an immune protective mechanism by the PLaHA coating that could provide future therapeutic benefit.
The destabilisation of emulsions within the stomach alters their droplet size and surface area, which in turn influences the rate and extent of fat digestion. In this study, we sought to gain further ...understanding of the mechanisms of the colloidal destabilisation of emulsions during digestion by examining how the composition of the interface impacts on these destabilisation processes. Understanding of emulsion destabilisation within the stomach was then linked to the extent of fat digestion through in vitro lipolysis measurements and in vivo triglyceride absorption studies. Two factors were examined; 1) co-variance of protein and monoglyceride composition at the droplet surface and 2) fat phase composition. Of the two emulsifiers present, caseinate provided the colloidal stability to the emulsion via a combination of electrostatic and steric repulsion. The acidic pH of gastric fluid resulted in a loss of electrostatic charge and a collapse of the casein steric layer, ultimately causing the emulsion to flocculate. The presence of monoglyceride influenced the emulsions susceptibility to flocculation in gastric juice and the resistance of the interface to film rupture which impacted the degree of droplet coalescence. It appeared that there was an optimum ratio between monoglyceride and protein at the interface for emulsion destabilisation. An excessive decrease in protein at the interface as monoglyceride concentration increased limited initial droplet flocculation, because there were fewer junction points for protein bridging between droplets. These changes to emulsion droplet structure had an impact on the in vitro rate and the extent of lipolysis. However triglyceride absorption in vivo was only significantly impacted when the coalesced droplet structure (e.g. emulsion containing solid fat) was maintained until the intestine. The principle cause of the altered lipolysis profile was the destabilisation of the emulsion within the stomach. These results highlight that the complexity of real food systems (i.e. multiple/mixed ingredients) can have an important impact on the digestion of emulsions, and have implications for the creation of functional foods aimed at obesity and/or diabetes.
We describe a 1D and 2D electron spin echo envelope modulation investigation of VO super(2+) adsorbed on hydroxyapatite (HA) at different concentrations and compare with VO super(2+)-triphosphate ...(TPH) complexes studied previously in detail, in an effort to provide more insight into the structure of VO super(2+) coordination in bone. Structures of this interaction are important because of the role of bone in the long-term storage of administered vanadium, and the likely role of bone in the steady-state release of vanadium leading to the chronic insulin-enhancing anti-diabetic effects of vanadyl complexes. Three similar sets of cross-peaks from phosphorus nuclei observed in the super(31)P hyperfine sublevel correlation (HYSCORE) spectra of VO super(2+)-HA, VO super(2+)-TPH and VO super(2+)-bone suggest a common tridentate binding motif for triphosphate moieties to the vanadyl ion. The similarities between the systems present the possibility that in vivo vanadyl coordination in bone is relatively uniform. Experiments with HA samples containing different amounts of adsorbed VO super(2+) demonstrate additional peculiarities of the ion-adsorbent interaction which can be expected in vivo. The HYSCORE spectra of HA samples show varying relative intensities of super(31)P lines from phosphate ligands and super(1)H lines, especially lines from protons of coordinated water molecules. This result suggests that the number of equatorial phosphate ligands in HA could be different depending on the water content of the sample and the VO super(2+) concentration; complexes of different structures probably contribute to the spectra of VO super(2+)-HA. Similar behaviour can also be expected in vivo during VO super(2+) accumulation in bones.
It is well established that regular physiological stimulation by glucose plays a crucial role in the maintenance of the beta-cell differentiated phenotype. In contrast, prolonged or repeated exposure ...to elevated glucose concentrations both in vitro and in vivo exerts deleterious or toxic effects on the beta-cell phenotype, a concept termed as glucotoxicity.
The short half-life of super(212)Bi and super(213)Bi limits the application of these radionuclides in alpha radionuclide therapy. The labeling of biomolecules with super(212)Pb (mother nuclide of ...super(212)Bi) instead of super(212)Bi or super(213)Bi has the advantage of obtaining a conjugate with a half-life of 10.6 h, compared with of 60 min for super(212)Bi or 46 min for super(213)Bi. Previous attempts to prepare a potential in vivo generator with super(212)Pb complexed by the DOTA chelator failed, because about 36 % of Bi was reported to escape as a result of the radioactive decay super(212)Pb super( beta -) arrow right super(212)Bi. Herein, we report studies on the stability of the super(212)Pb complexes with eight selected polydentate ligands, which demonstrate high affinity for 3+ metal cations. From the ligand studied DOTP and BAPTA show a sufficient super(212)Pb labeling yields but only super(212)Pb-DOTP complex is stable in isotonic solution of sodium chloride making this way radioactivity level of released super(212)Bi is below the limit of detection. It should be emphasized that the DOTP complex is stable only in the case when the concentration of free DOTP exceeds 10 super(-4) M.
Biocompatible three-dimensional scaffolds for cell culturing may facilitate methods for the repair of damaged human tissues. A novel hybrid porous scaffold of poly(lactic-co-glycolic acid), ...hydroxyapatite and collagen was prepared using a supercritical CO sub(2 saturation technique. Expansion factors of scaffolds with different compositions were studied after supercritical CO) sub(2) treatment to choose the optimal composition for three-dimensional culture. The supercritical CO sub(2 process conditions, such as saturation temperature, saturation time and saturation pressure were varied to evaluate their influence on pore structure. The results showed that the pore size and porosity of the scaffold could be controlled by manipulating these process conditions. The porous samples were characterized by environmental scanning electron microscopy, energy-dispersive X-ray spectroscope, Fourier transform infrared spectroscopy and X-ray diffractometry. Finally, MG-63 cells were successfully cultured on the porous scaffold as assessed by electron and confocal microscopy, confirming the biocompatibility of this new hybrid porous scaffold.)
PDF
