Expanding the therapeutic potential of Statins by means of nanotechnology enabled drug delivery systems

Statins are effective lipid lowering agents traditionally used for the primary and secondary prevention of cardiovascular disease. Statins also exert a range of pleiotropic effects that make them attractive candidates for use in a wide range of disorders, in particular inflammatory and immune mediated conditions. However, the exploitation of such pleiotropic effects has been greatly hindered by poor bioavailability and adverse effects on muscles and the liver at higher doses. Nanotechnology is often suggested as the solution to this problem, as it enables an increased bioavailability of statins. Moreover, colloidal carriers can offer targeted drug delivery approaches that enable localised biological effects of statins, further reducing their potential for unwanted toxicity and adverse effects. This article reviews the available evidences for the increased potential of statin therapy when administered in nano-formulations such as nanocrystals, nanoparticles, liposomes, micelles and various nano-enabled devices. © 2014 Bentham Science Publishers

On Black-Brane Instability In an Arbitrary Dimension

The black-hole black-string system is known to exhibit critical dimensions and therefore it is interesting to vary the spacetime dimension $D$, treating it as a parameter of the system. We derive the large $D$ asymptotics of the critical, i.e. marginally stable, string following an earlier numerical analysis. For a background with an arbitrary compactification manifold we give an expression for the critical mass of a corresponding black brane. This expression is completely explicit for ${\bf T}^n$, the $n$ dimensional torus of an arbitrary shape. An indication is given that by employing a higher dimensional torus, rather than a single compact dimension, the total critical dimension above which the nature of the black-brane black-hole phase transition changes from sudden to smooth could be as low as $D\leq 11$.Comment: 1+14 pages, 2 eps figures. Replaced with the published versio

Dynamic and Thermodynamic Stability and Negative Modes in Schwarzschild-Anti-de Sitter

The thermodynamic properties of Schwarzschild-anti-de Sitter black holes confined within finite isothermal cavities are examined. In contrast to the Schwarzschild case, the infinite cavity limit may be taken which, if suitably stated, remains double valued. This allows the correspondence between non-existence of negative modes for classical solutions and local thermodynamic stability of the equilibrium configuration of such solutions to be shown in a well defined manner. This is not possible in the asymptotically flat case. Furthermore, the non-existence of negative modes for the larger black hole solution in Schwarzschild-anti-de Sitter provides strong evidence in favour of the recent positive energy conjecture by Horowitz and Myers.Comment: 21 pages, 5 figures, LaTe

Casimir energy and black hole pair creation in Schwarzschild-de Sitter spacetime

Following the subtraction procedure for manifolds with boundaries, we calculate by variational methods, the Schwarzschild-de Sitter and the de Sitter space energy difference. By computing the one loop approximation for TT tensors we discover the existence of an unstable mode even for the non-degenerate case. This result seems to be in agreement with the sub-maximal black hole pair creation of Bousso-Hawking. The instability can be eliminated by the boundary reduction method. Implications on a foam-like space are discussed.Comment: 19 pages,RevTeX with package epsf and four eps figures. Added other references. Accepted for publication in Classical and Quantum Gravit

Casimir energy and variational methods in AdS spacetime

Following the subtraction procedure for manifolds with boundaries, we calculate by variational methods, the Schwarzschild-Anti-de Sitter and the Anti-de Sitter space energy difference. By computing the one loop approximation for TT tensors we discover the existence of an unstable mode at zero temperature, which can be stabilized by the boundary reduction method. Implications on a foam-like space are discussed.Comment: Submitted to Classical and Quantum Gravit

Classical and Thermodynamic Stability of Black Branes

It is argued that many non-extremal black branes exhibit a classical Gregory-Laflamme instability if, and only if, they are locally thermodynamically unstable. For some black branes, the Gregory-Laflamme instability must therefore disappear near extremality. For the black $p$-branes of the type II supergravity theories, the Gregory-Laflamme instability disappears near extremality for $p=1,2,4$ but persists all the way down to extremality for $p=5,6$ (the black D3-brane is not covered by the analysis of this paper). This implies that the instability also vanishes for the near-extremal black M2 and M5-brane solutions.Comment: 21 pages, LaTeX. v2: Various points clarified, typos corrected and reference adde

Some Aspects of Virtual Black Holes

In this paper we shall consistently third quantize modified gravity. Then we shall analyse certain aspects of virtual black holes in this third quantized modified gravity. We will see how a statistical mechanical origin for the Bekenstein-Hawking entropy naturally arises in this model. Furthermore, in this model the area and thus the entropy of a real macroscopic black hole is quantized. Virtual black holes cause loss of quantum coherence and this gives an intrinsic entropy to all physical systems which can be used to define a direction of time and hence provide a solution to the problem of time.Comment: 11 pages, 0 figures, accepted for publication in JET

Ultraspinning instability of anti-de Sitter black holes

Myers-Perry black holes with a single spin in d>5 have been shown to be unstable if rotating sufficiently rapidly. We extend the numerical analysis which allowed for that result to the asymptotically AdS case. We determine numerically the stationary perturbations that mark the onset of the instabilities for the modes that preserve the rotational symmetries of the background. The parameter space of solutions is thoroughly analysed, and the onset of the instabilities is obtained as a function of the cosmological constant. Each of these perturbations has been conjectured to represent a bifurcation point to a new phase of stationary AdS black holes, and this is consistent with our results.Comment: 22 pages, 7 figures. v2: Reference added. Matches published versio

The effect of drug ionization on lipid-based formulations for the oral delivery of anti-psychotics

Lipid-based formulations (LBFs) are well-known to improve the oral bioavailability of poorly water-soluble drugs (PWSDs) by presenting the drug to the gastrointestinal environment in a molecularly dispersed state, thus avoiding the rate-limiting dissolution step. Risperidone and lurasidone are antipsychotics drugs which experience erratic and variable absorption, leading to a low oral bioavailability. The aim of this research was to develop and investigate the performance of risperidone and lurasidone when formulated as an emulsion and silica-lipid hybrid (SLH). Lurasidone and risperidone were dissolved in Capmul® MCM at 100% and 80% their equilibrium solubility, respectively, prior to forming a sub-micron emulsion. SLH microparticles were fabricated by spray-drying a silica stabilised sub-micron emulsion to form a solid powder. The performances of the formulations were evaluated in simulated intestinal media under digesting conditions, where the emulsion and SLH provided a 17-fold and 23-fold increase in LUR solubilisation, respectively. However, the performance of RIS was reduced by 2.2-fold when encapsulated within SLH compared to pure drug. Owing to its pKa, RIS adsorbed to the silica and thus, dissolution was significantly hindered. The results reveal that LBFs may not overcome the challenges of all PWSDs and physiochemical properties must be carefully considered when predicting drug performance.</p