Photosensitiser delivery for photodynamic therapy. Part 1: Topical carrier platforms

Photodynamic therapy (PDT) is a medical treatment in which a combination of a photosensitising drug and visible light causes destruction of selected cells. Due to the lack of true selectivity of preformed photosensitisers for neoplastic tissue and their high molecular weights, PDT of superficial skin lesions has traditionally been mediated by topical application of the porphyrin precursor 5-aminolevulinic acid (ALA). Objective: This article aims to review the traditional formulation-based approaches taken to topical delivery of ALA and discusses the more innovative strategies investigated for enhancement of PDT mediated by topical application of ALA and preformed photosensitisers. Methods: All of the available published print and online literature in this area was reviewed. As drug delivery of agents used in PDT is still something of an emerging field, it was not necessary to go beyond literature from the last 30 years. Results/conclusion: PDT of neoplastic skin lesions is currently based almost exclusively on topical application of simple semisolid dosage forms containing ALA or its methyl ester. Until expiry of patents on the current market-leading products, there is unlikely to be a great incentive to engage in design and evaluation of innovative formulations for topical PDT, especially those containing the more difficult-to-deliver preformed photosensitisers.

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.

Creative Activism: a pedagogical and research tool

Environmental activism has a long history in protest, addressing issues of degradation and segregation that threaten existing ecologies, social and built fabrics. Environmental activism is traditionally understood as a reaction, chiefly by groups of people, against a perceived external threat. In the 60’s and 70’s, an activist stance began to emerge in the work of some artists and architects, who used creative methods such as performances, happenings, temporary spatial interventions etc to convey their political/aesthetic messages. Some of this work engaged directly with communities but predominantly it was the production of one individual working ‘outside’ society. However such actions demonstrated not only the power of the visual in conveying a political message but also the potential of conceptual creative approaches to reveal alternative values and hidden potentials. This marked a shift from activism as protestation towards an activism of reconceptualisation. Recently, activist groups have developed a more politically informed process. Whilst their ‘tools’ may resemble work from the 60’s and 70’s , their methodologies are non-traditional, ’rhizomatic’, pedagogical and fluid; working alongside, rather than against, the established power and funding structures. Such creative processes build new, often unexpected, stakeholder networks; offer neutral spaces in which contentious issues can be faced; and create better understanding of values and identities. They can also lead to permanent improvements and development in the physical fabric. This paper will discuss a pedagogical example of activism in architectural education. The event (www.fourdaysontheoutside.com) is in its fifth year of existence and as such has revealed a value and impulse beyond its learning and teaching value. The paper will discuss how the event contributes to the university’s outreach programme and how its structure acts as a seedbed for potential research projects and partnerships. UK Universities talk extensively about applied research but have few actual strategies by which to generate it. Fourdaysontheoutside offers some potential ways forward.

Proofreading Using an Assistive Software Homophone Tool Compensatory and Remedial Effects on the Literacy Skills of Students With Reading Difficulties

The present study investigated the effects of using an assistive software homophone tool on the assisted proofreading performance and unassisted basic skills of secondary-level students with reading difficulties. Students aged 13 to 15 years proofread passages for homophonic errors under three conditions: with the homophone tool, with homophones highlighted only, or with no help. The group using the homophone tool significantly outperformed the other two groups on assisted proofreading and outperformed the others on unassisted spelling, although not significantly. Remedial (unassisted) improvements in automaticity of word recognition, homophone proofreading, and basic reading were found over all groups. Results elucidate the differential contributions of each function of the homophone tool and suggest that with the proper training, assistive software can help not only students with diagnosed disabilities but also those with generally weak reading skills.

Delivery of rSLPI in a liposomal carrier for inhalation provides protection against cathepsin L degradation

Secretory leukocyte protease inhibitor (SLPI) is an endogenous serine protease inhibitor that protects the lungs from excessive tissue damage caused by leukocyte proteases released during inflammation. Recombinant SLPI (rSLPI) has shown potential as a treatment for inflammatory lung conditions. To date, its clinical application has been limited by rapid enzymatic cleavage by cathepsins and rapid clearance from the lungs after inhalation. In this study, rSLPI was encapsulated in 1,2-Dioleoyl-sn-Glycero-3-[Phospho-L-Serine] : Cholesterol (DOPS : Chol) liposomes for inhalation. Incubation of rSLPI with cathepsin L leads to complete loss of activity while encapsulation of rSLPI in DOPS : Chol liposomes retained 92.6 of its activity after challenge with cathepsin L. rSLPI-loaded liposomes were aerosolized efficiently using a standard nebulizer with a minimal loss of activity and stability. This formulation was biocompatible and encapsulation did not appear to diminish access to intracellular sites of action in in vitro cell culture studies. Liposome encapsulation of rSLPI therefore improves stability and potentially reduces the level and frequency of dosing required for therapeutic effect after inhalation.