Liposomes and skin: From drug delivery to model membranes

The early eighties saw the introduction of liposomes as skin drug delivery systems, initially promoted primarily for localised effects with minimal systemic delivery. Subsequently, a novel ultradeformable vesicular system (termed "Transfersomes" by the inventors) was reported for transdermal delivery with an efficiency similar to subcutaneous injection. Further research illustrated that the mechanisms of liposome action depended on the application regime and the vesicle composition and morphology. Ethical, health and supply problems with human skin have encouraged researchers to use skin models. 'IYaditional models involved polymer membranes and animal tissue, but whilst of value for release studies, such models are not always good mimics for the complex human skin barrier, particularly with respect to the stratum corneal intercellular lipid domains. These lipids have a multiply bilayered organization, a composition and organization somewhat similar to liposomes, Consequently researchers have used vesicles as skin model membranes. Early work first employed phospholipid liposomes and tested their interactions with skin penetration enhancers, typically using thermal analysis and spectroscopic analyses. Another approach probed how incorporation of compounds into liposomes led to the loss of entrapped markers, analogous to "fluidization" of stratum corneum lipids on treatment with a penetration enhancer. Subsequently scientists employed liposomes formulated with skin lipids in these types of studies. Following a brief description of the nature of the skin barrier to transdermal drug delivery and the use of liposomes in drug delivery through skin, this article critically reviews the relevance of using different types of vesicles as a model for human skin in permeation enhancement studies, concentrating primarily on liposomes after briefly surveying older models. The validity of different types of liposome is considered and traditional skin models are compared to vesicular model membranes for their precision and accuracy as skin membrane mimics. (c) 2008 Elsevier B.V. All rights reserved.

Can drug-bearing liposomes penetrate intact skin?

Using liposomes to deliver drugs to and through human skin is controversial, as their function varies with type and composition. Thus they may act as drug carriers controlling release of the medicinal agent. Alternatively, they may provide a localized depot in the skin so minimizing systemic effects or can be used for targeting delivery to skin appendages (hair follicles and sweat glands). Liposomes may also enhance transdermal drug delivery, increasing systemic drug concentrations. With such a multiplicity of functions, it is not surprising that mechanisms of liposomal delivery of therapeutic agents to and through the skin are unclear. Accordingly, this article provides an overview of the modes and mechanisms of action of different vesicles as drug delivery vectors in human skin. Our conclusion is that vesicles, depending on the composition and method of preparation, can vary with respect to size, lamellarity, charge, membrane fluidity or elasticity and drug entrapment. This variability allows for multiple functions ranging from local to transdermal effects. Application to dissimilar skins (animal or human) via diverse protocols may reveal different mechanisms of action with possible vesicle skin penetration reaching different depths, from surface assimilation to (rarely) the viable tissue and subsequent systemic absorption.

Spatial and temporal aspects of oculomotor inhibition as revealed by saccade trajectories

The spatial and temporal effect of distractor related inhibition on stimulus elicited (reflexive) and goal driven (voluntary) saccades, was examined using saccade trajectory deviations as a measure. Subjects made voluntary and reflexive saccades to a target location on the vertical midline, while the distance of a distractor from the target was systematically manipulated. The trajectory curvature of both voluntary and reflexive saccades was found to be subject to individual differences. Saccade curvature was found to decrease monotonically with increasing distractor distance from target for some subjects while for others no reduction in curvature or even an increase was found. These results could not be explained by latency differences or landing position effects. The different patterns of distractor effects on saccade trajectories suggest the additional influence of a non-spatial inhibitory mechanism. (c) 2005 Elsevier Ltd. All rights reserved.

The geometry of optimal control solutions on some six dimensional lie groups

This paper examines optimal solutions of control systems with drift defined on the orthonormal frame bundle of particular Riemannian manifolds of constant curvature. The manifolds considered here are the space forms Euclidean space E-3, the spheres S-3 and the hyperboloids H-3 with the corresponding frame bundles equal to the Euclidean group of motions SE(3), the rotation group SO(4) and the Lorentz group SO(1,3). The optimal controls of these systems are solved explicitly in terms of elliptic functions. In this paper, a geometric interpretation of the extremal solutions is given with particular emphasis to a singularity in the explicit solutions. Using a reduced form of the Casimir functions the geometry of these solutions are illustrated.

Integrating control systems defined on the frame bundles of the space forms

This paper considers left-invariant control systems defined on the orthonormal frame bundles of simply connected manifolds of constant sectional curvature, namely the space forms Euclidean space E-3, the sphere S-3 and Hyperboloid H-3 with the corresponding frame bundles equal to the Euclidean group of motions SE(3), the rotation group SO(4) and the Lorentz group SO(1, 3). Orthonormal frame bundles of space forms coincide with their isometry groups and therefore the focus shifts to left-invariant control systems defined on Lie groups. In this paper a method for integrating these systems is given where the controls are time-independent. In the Euclidean case the elements of the Lie algebra se(3) are often referred to as twists. For constant twist motions, the corresponding curves g(t) is an element of SE(3) are known as screw motions, given in closed form by using the well known Rodrigues' formula. However, this formula is only applicable to the Euclidean case. This paper gives a method for computing the non-Euclidean screw motions in closed form. This involves decoupling the system into two lower dimensional systems using the double cover properties of Lie groups, then the lower dimensional systems are solved explicitly in closed form.

Optimal 3D surface reconstruction from multiview photographic images

This paper describes a new method for reconstructing 3D surface using a small number, e.g. 10, of 2D photographic images. The images are taken at different viewing directions by a perspective camera with full prior knowledge of the camera configurations. The reconstructed object's surface is represented a set of triangular facets. We empirically demonstrate that if the viewing directions are uniformly distributed around the object's viewing sphere, then the reconstructed 3D points optimally cluster closely on a highly curved part of the surface and are widely, spread on smooth or fat parts. The advantage of this property is that the reconstructed points along a surface or a contour generator are not undersampled or underrepresented because surfaces or contours should be sampled or represented with more densely points where their curvatures are high. The more complex the contour's shape, the greater is the number of points required, but the greater the number of points is automatically generated by the proposed method Given that the viewing directions are uniformly distributed, the number and distribution of the reconstructed points depend on the shape or the curvature of the surface regardless of the size of the surface or the size of the object.

Integrating Hamiltonian systems defined on the Lie groups SO(4) and SO(1,3)

This paper examines optimal solutions of control systems with drift defined on the orthonormal frame bundle of particular Riemannian manifolds of constant curvature. The manifolds considered here are the space forms Euclidean space E³, the spheres S³ and the hyperboloids H³ with the corresponding frame bundles equal to the Euclidean group of motions SE(3), the rotation group SO(4) and the Lorentz group SO(1,3). The optimal controls of these systems are solved explicitly in terms of elliptic functions. In this paper, a geometric interpretation of the extremal solutions is given with particular emphasis to a singularity in the explicit solutions. Using a reduced form of the Casimir functions the geometry of these solutions is illustrated.

Planning rigid body motions using elastic curves

This paper tackles the problem of computing smooth, optimal trajectories on the Euclidean group of motions SE(3). The problem is formulated as an optimal control problem where the cost function to be minimized is equal to the integral of the classical curvature squared. This problem is analogous to the elastic problem from differential geometry and thus the resulting rigid body motions will trace elastic curves. An application of the Maximum Principle to this optimal control problem shifts the emphasis to the language of symplectic geometry and to the associated Hamiltonian formalism. This results in a system of first order differential equations that yield coordinate free necessary conditions for optimality for these curves. From these necessary conditions we identify an integrable case and these particular set of curves are solved analytically. These analytic solutions provide interpolating curves between an initial given position and orientation and a desired position and orientation that would be useful in motion planning for systems such as robotic manipulators and autonomous-oriented vehicles.

Singularities of optimal control problems on some 6-D lie groups

This paper considers the motion planning problem for oriented vehicles travelling at unit speed in a 3-D space. A Lie group formulation arises naturally and the vehicles are modeled as kinematic control systems with drift defined on the orthonormal frame bundles of particular Riemannian manifolds, specifically, the 3-D space forms Euclidean space E-3, the sphere S-3, and the hyperboloid H'. The corresponding frame bundles are equal to the Euclidean group of motions SE(3), the rotation group SO(4), and the Lorentz group SO (1, 3). The maximum principle of optimal control shifts the emphasis for these systems to the associated Hamiltonian formalism. For an integrable case, the extremal curves are explicitly expressed in terms of elliptic functions. In this paper, a study at the singularities of the extremal curves are given, which correspond to critical points of these elliptic functions. The extremal curves are characterized as the intersections of invariant surfaces and are illustrated graphically at the singular points. It. is then shown that the projections, of the extremals onto the base space, called elastica, at these singular points, are curves of constant curvature and torsion, which in turn implies that the oriented vehicles trace helices.

3D surface point and wireframe reconstruction from multiview photographic images

This paper describes a new method for reconstructing 3D surface points and a wireframe on the surface of a freeform object using a small number, e.g. 10, of 2D photographic images. The images are taken at different viewing directions by a perspective camera with full prior knowledge of the camera configurations. The reconstructed surface points are frontier points and the wireframe is a network of contour generators. Both of them are reconstructed by pairing apparent contours in the 2D images. Unlike previous works, we empirically demonstrate that if the viewing directions are uniformly distributed around the object's viewing sphere, then the reconstructed 3D points automatically cluster closely on a highly curved part of the surface and are widely spread on smooth or flat parts. The advantage of this property is that the reconstructed points along a surface or a contour generator are not under-sampled or under-represented because surfaces or contours should be sampled or represented with more densely points where their curvatures are high. The more complex the contour's shape, the greater is the number of points required, but the greater the number of points is automatically generated by the proposed method. Given that the viewing directions are uniformly distributed, the number and distribution of the reconstructed points depend on the shape or the curvature of the surface regardless of the size of the surface or the size of the object. The unique pattern of the reconstructed points and contours may be used in 31) object recognition and measurement without computationally intensive full surface reconstruction. The results are obtained from both computer-generated and real objects. (C) 2007 Elsevier B.V. All rights reserved.

Optimal 3D surface reconstruction from a small number of conventional 2D X-ray images

This paper describes a method for reconstructing 3D frontier points, contour generators and surfaces of anatomical objects or smooth surfaces from a small number, e. g. 10, of conventional 2D X-ray images. The X-ray images are taken at different viewing directions with full prior knowledge of the X-ray source and sensor configurations. Unlike previous works, we empirically demonstrate that if the viewing directions are uniformly distributed around the object's viewing sphere, then the reconstructed 3D points automatically cluster closely on a highly curved part of the surface and are widely spread on smooth or flat parts. The advantage of this property is that the reconstructed points along a surface or a contour generator are not under-sampled or under-represented because surfaces or contours should be sampled or represented with more densely points where their curvatures are high. The more complex the contour's shape, the greater is the number of points required, but the greater the number of points is automatically generated by the proposed method. Given that the number of viewing directions is fixed and the viewing directions are uniformly distributed, the number and distribution of the reconstructed points depend on the shape or the curvature of the surface regardless of the size of the surface or the size of the object. The technique may be used not only in medicine but also in industrial applications.

A structural analysis of M protein in coronavirus assembly and morphology

The M protein of coronavirus plays a central role in virus assembly, turning cellular membranes into workshops where virus and host factors come together to make new virus particles. We investigated how M structure and organization is related to virus shape and size using cryo-electron microscopy, tomography and statistical analysis. We present evidence that suggests M can adopt two conformations and that membrane curvature is regulated by one M conformer. Elongated M protein is associated with rigidity, clusters of spikes and a relatively narrow range of membrane curvature. In contrast, compact M protein is associated with flexibility and low spike density. Analysis of several types of virus-like particles and virions revealed that S protein, N protein and genomic RNA each help to regulate virion size and variation, presumably through interactions with M. These findings provide insight into how M protein functions to promote virus assembly.

Modified level set method with Canny operator for image noise removal

The level set method is commonly used to address image noise removal. Existing studies concentrate mainly on determining the speed function of the evolution equation. Based on the idea of a Canny operator, this letter introduces a new method of controlling the level set evolution, in which the edge strength is taken into account in choosing curvature flows for the speed function and the normal to edge direction is used to orient the diffusion of the moving interface. The addition of an energy term to penalize the irregularity allows for better preservation of local edge information. In contrast with previous Canny-based level set methods that usually adopt a two-stage framework, the proposed algorithm can execute all the above operations in one process during noise removal.

Effects of polydispersity on the order-disorder transition of diblock copolymer melts

The effect of polydispersity on an AB diblock copolymer melt is investigated using latticebased Monte Carlo simulations. We consider melts of symmetric composition, where the B blocks are monodisperse and the A blocks are polydisperse with a Schultz-Zimm distribution. In agreement with experiment and self-consistent field theory (SCFT), we find that polydispersity causes a significant increase in domain size. It also induces a transition from flat to curved interfaces, with the polydisperse blocks residing on the inside of the interfacial curvature. Most importantly, the simulations show a relatively small shift in the order-disorder transition (ODT) in agreement with experiment, whereas SCFT incorrectly predicts a sizable shift towards higher temperatures.

Aspects of the large scale tropical atmospheric circulation

An account is given of a number of recent studies with idealised models whose aim is to further understanding of the large-scale tropical atmospheric circulation. Initial-value integrations with a model with imposed heating are used to discuss aspects of the Asian summer monsoon, including constraints on cross-equatorial flow into the monsoon. The summer descent in the Mediterranean region and on the eastern sides of the summer subtropical anticyclones are seen to be associated with the monsoons to their east. An aqua-planet GCM is used to investigate the relationship between simple SST distributions and tropical convection and circulation. The existence of strong equatorial convection and Hadley cells is found to depend sensitively on the curvature of the meridional profile in SST. Zonally confined SST maxima produce convective maxima centred to the west and suppression of convection elsewhere. Strong equatorial zonal flow changes are found in some experiments and three mechanisms for producing these are investigated in a model with imposed heating. 1.