Drug-eluting beads loaded with antiangiogenic agents for chemoembolization: in vitro sunitinib loading and release and in vivo pharmacokinetics in an animal model.

PURPOSE: The combination of embolic beads with a multitargeted tyrosine kinase inhibitor that inhibits tumor vessel growth is suggested as an alternative and improvement to the current standard doxorubicin-eluting beads for use in transarterial chemoembolization. This study demonstrates the in vitro loading and release kinetics of sunitinib using commercially available embolization microspheres and evaluates the in vitro biologic efficacy on cell cultures and the resulting in vivo pharmacokinetics profiles in an animal model. MATERIALS AND METHODS: DC Bead microspheres, 70-150 µm and 100-300 µm (Biocompatibles Ltd., Farnham, United Kingdom), were loaded by immersion in sunitinib solution. Drug release was measured in saline in a USP-approved flow-through apparatus and quantified by spectrophotometry. Activity after release was confirmed in cell culture. For pharmacokinetics and in vivo toxicity evaluation, New Zealand white rabbits received sunitinib either by intraarterial injection of 100-300 µm sized beads or per os. Plasma and liver tissue drug concentrations were assessed by liquid chromatography-tandem mass spectroscopy. RESULTS: Sunitinib loading on beads was close to complete and homogeneous. A total release of 80% in saline was measured, with similar fast-release profiles for both sphere sizes. After embolization, drug plasma levels remained below the therapeutic threshold (< 50 ng/mL), but high concentrations at 6 hours (14.9 µg/g) and 24 hours (3.4 µg/g) were found in the liver tissue. CONCLUSIONS: DC Bead microspheres of two sizes were efficiently loaded with sunitinib and displayed a fast and almost complete release in saline. High liver drug concentrations and low systemic levels indicated the potential of sunitinib-eluting beads for use in embolization.

Effective mass and dielectric constant mismatch effects in spherical multishell quantum dots

The role of effective mass and dielectric mismatches on chemical potentials and addition energies of many-electron multishell quantum dots (QDs) is explored within the framework of a recent extension of the spin density functional theory. It is shown that although the gross electronic density is located in the wells of these multishell QDs, taking position-dependent effective mass and dielectric constant into account can lead to the appearance of relevant differences in chemical potential and addition energies as compared to standard calculations in which the effective mass and the dielectric constant of the well is assumed for the whole multishell structure.

Lateral instability in normal viscous fingers

We study a low-amplitude, long-wavelength lateral instability of the Saffman-Taylor finger by means of a phase-field model. We observe such an instability in two situations in which small dynamic perturbations are overimposed to a constant pressure drop. We first study the case in which the perturbation consists of a single oscillatory mode and then a case in which the perturbation consists of temporal noise. In both cases the instability undergoes a process of selection.

The "image" of the cave and the constant temptation to correct Plato: Benjamin Jowettt as an example

Translations of the first chapters of Book VII of Plato's Republic, in which he introduces the well-known image of the cave, eikón, reveals an astonishing and intriguing variety of interpretations of this image: "allegory", "myth", "fable", "parable", "simile" and "comparison", to cite but a few. Taking as an example the work by Benjamin Jowett, the Victorian translator of Plato, remarkable for its textual accuracy and by means of a close analysis of the terms related to the image, this paper insists on the need to neither interpret nor correct the great ideal philosopher, in this case revealing some evident contradictions that arise when this advice is not followed and pointing out the occasional use of terms extraneous to the Platonic lexicon such as "allegory".

Quantum black hole entropy and newton constant renormalization

ty that low-energy effective field theory could be sufficient to understand the microscopic degrees of freedom underlying black hole entropy. We propose a qualitative physical picture in which black hole entropy refers to a space of quasicoherent states of infalling matter, together with its gravitational field. We stress that this scenario might provide a low-energy explanation of both the black hole entropy and the information puzzle.