Photosensitiser delivery for photodynamic therapy. Part 2: systemic carrier platforms

Background: The treatment of solid tumours and angiogenic ocular diseases by photodynamic therapy (PDT) requires the injection of a photosensitiser (PS) to destroy target cells through a combination of visible light irradiation and molecular oxygen. There is currently great interest in the development of efficient and specific carrier delivery platforms for systemic PDT. Objective: This article aims to review recent developments in systemic carrier delivery platforms for PDT, with an emphasis on target specificity. Methods: Recent publications, spanning the last five years, concerning delivery carrier platforms for systemic PDT were reviewed, including PS conjugates, dendrimers, micelles, liposomes and nanoparticles. Results/conclusion: PS conjugates and supramolecular delivery platforms can improve PDT selectivity by exploiting cellular and physiological specificities of the targeted tissue. Overexpression of receptors in cancer and angiogenic endothelial cells allows their targeting by affinity-based moieties for the selective uptake of PS conjugates and encapsulating delivery carriers, while the abnormal tumour neovascularisation induces a specific accumulation of heavy weighted PS carriers by enhanced permeability and retention (EPR) effect. in addition, polymeric prodrug delivery platforms triggered by the acidic nature of the tumour environment or the expression of proteases can be designed. Promising results obtained with recent systemic carrier platforms will, in due course, be translated into the clinic for highly efficient and selective PDT protocols.

Processing difficulties and instability of carbohydrate microneedle arrays

A number of reports have suggested that many of the problems currently associated with the use of microneedle (MN) arrays for transdermal drug delivery could be addressed by using drug-loaded MN arrays prepared by moulding hot melts of carbohydrate materials.

Super-Resolution without Evanescent Waves

The past decade has seen numerous efforts to achieve imaging resolution beyond that of the Abbe-Rayleigh diffraction limit. The main direction of research alining to break this limit seeks to exploit the evanescent components containing fine detail of the electromagnetic field distribution at the Immediate proximity of the object. Here, we propose a solution that removes the need for evanescent fields. The object being imaged or stimulated with subwavelangth accuracy does not need to be In the immediate proximity of the superlens or field concentrator: an optical mask can be designed that creates constructive Interference of waves known as superoscillation, leading to a subwavelength focus of prescribed size and shape in a field of view beyond the evanescent fields, when illuminated by a monochromatic wave. Moreover, we demonstrate that such a mask may be used not only as a focusing device but also as a super-resolution imaging device.

Complex Interactions between Dioxin-Like and Non-Dioxin-Like Compounds for in Vitro Cellular Responses: Implications for the Identification of Dioxin Exposure Biomarkers

Despite considerable advances in reducing the production of dioxin-like toxicants in recent years, contamination of the food chain still occasionally occurs resulting in huge losses to the agri-food sector and risk to human health through exposure. Dioxin-like toxicity is exhibited by a range of stable and bioaccumulative compounds including polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), produced by certain types of combustion, and man-made coplanar polychlorinated biphenyls (PCBs), as found in electrical transformer oils. While dioxinergic compounds act by a common mode of action making exposure detection biomarker based techniques a potentially useful tool, the influence of co-contaminating toxicants on such approaches needs to be considered. To assess the impact of possible interactions, the biological responses of H4IIE cells to challenge by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in combination with PCB-52 and benzo-a-pyrene (BaP) were evaluated by a number of methods in this study. Ethoxyresorufin-O-deethylase (EROD) induction in TCDD exposed cells was suppressed by increasing concentrations of PCB-52, PCB-153, or BaP up to 10 mu M. BaP levels below 1 mu M suppressed TCDD stimulated EROD induction, but at higher concentrations, EROD induction was greater than the maximum observed when cells were treated with TCDD alone. A similar biphasic interaction of BaP with TCDD co-exposure was noted in the AlamarBlue assay and to a lesser extent with PCB-52. Surface enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF) profiling of peptidomic responses of cells exposed to compound combinations was compared. Cells co-exposed to TCDD in the presence of BaP or PCB-52 produced the most differentiated spectra with a substantial number of non-additive interactions observed. These findings suggest that interactions between dioxin and other toxicants create novel, additive, and non-additive effects, which may be more indicative of the types of responses seen in exposed animals than those of single exposures to the individual compounds.

Experiences of youth justice: Youth justice discourses and their multiple effects

Interventions within youth justice systems draw on a range of rationales and philosophies. Traditionally demarcated by a welfare/justice binary, the complex array of contemporary rationales meld different philosophies and practices, suggesting a mutability that gives this sphere a continued (re)productive and felt effect. While it may be increasingly difficult to ascertain which of these discourses is dominant in different jurisdictions in the UK, particular models of justice are perceived to be more prominent (Muncie, 2006). Traditionally it is assumed that Northern Ireland prioritises restoration, Wales prioritises rights, England priorities risk and Scotland welfare (McVie, 2011; Muncie, 2008, 2011). However, how these discourses are enacted in practice, how multiple and competing rationales circulate within them and most fundamentally how they are experienced by young people is less clear. This paper, based on research with young people who have experienced the full range of interventions in the youth justice system in Northern Ireland examines their narratives of ‘justice’. It considers how different discourses might influence the same intervention and how the deployment of multiple rationalities gives the experience of ‘justice’ its effect.