Persistence of antimicrobial activity through sustained release of triclosan from pegylated silicone elastomers

Microbial adhesion to silicone elastomer biomaterials is a major problem often resulting in infection and medical device failure. Several strategies have been employed to modulate eukaryotic cell adhesion and to hamper bacterial adherence to polymeric biomaterials. Chemical modification of the surface by grafting of polyethylene glycol (PEG) chains or the incorporation of non-antibiotic antimicrobial agents such as triclosan into the biomaterial matrix may reduce bacterial adhesion. Here, such strategies are simultaneously applied to the preparation of both condensation-cure and addition-cure silicone elastomer systems, seeking a sustained release antimicrobial device biomaterial. The influence of triclosan incorporation and degree of pegylation on antimicrobial release, surface microbial adherence and persistence (Escherichia coli and Staphylococcus epidermidis) were evaluated in vitro. Non-pegylated silicone elastomers provided an increased percentage release of triclosan extending over a relatively short duration (99% release by day 64) compared with their pegylated (4% w/w) counterparts (65% and 72% release by day 64, for condensation and addition-cure systems respectively). Viable E. coli adherence to a non-pegylated silicone elastomer containing 1% w/w triclosan was reduced by over 99% after 24 h compared to the non-pegylated silicone elastomer containing no triclosan. No viable S. epidermidis adhered to any of the triclosan-loaded (>0.1% w/w) formulations other than the control. Persistence of the antimicrobial activity of the triclosan-loaded pegylated silicone elastomers continued for at least 70 days compared to the triclosan-loaded non-pegylated elastomers (at least 49 days). Understanding how PEG affects the release of triclosan from silicone elastomers may prove useful in the development of a biomaterial providing prolonged, effective antimicrobial activity.

Gamma ray-induced bystander effect in tumour glioblastoma cells: a specific study on cell survival, cytokine release and cytokine receptors.

Recent experimental evidence has challenged the paradigm according to which radiation traversal through the nucleus of a cell is a prerequisite for producing genetic changes or biological responses. Thus, unexposed cells in the vicinity of directly irradiated cells or recipient cells of medium from irradiated cultures can also be affected. The aim of the present study was to evaluate, by means of the medium transfer technique, whether interleukin-8 and its receptor (CXCR1) may play a role in the bystander effect after gamma irradiation of T98G cells in vitro. In fact the cell specificity in inducing the bystander effect and in receiving the secreted signals that has been described suggests that not only the ability to release the cytokines but also the receptor profiles are likely to modulate the cell responses and the final outcome. The dose and time dependence of the cytokine release into the medium, quantified using an enzyme linked immunosorbent assay, showed that radiation causes alteration in the release of interleukin-8 from exposed cells in a dose-independent but time-dependent manner. The relative receptor expression was also affected in exposed and bystander cells.

Characterization of the Rheological, Mucoadhesive, and Drug Release Properties of Highly Structured Gel Platforms for Intravaginal Drug Delivery

This investigation describes the formulation and characterization of theologically structured vehicles (RSVs) designed for improved drug delivery to the vagina. Interactive, multicomponent, polymeric platforms were manufactured containing hydroxyethylcellulose (HEC, 5% w/w) polyvinylpyrrolidone (PVP, 4% w/w), Pluronic (PL, 0 or 10% w/w), and either polycarbophil (PC, 3% w/w) or poly(methylvinylether-co-maleic anhydride) (Gantrez S97, 3% w/w) as a mucoadhesive agent. The rheological (torsional and dynamic), mechanical (compressional), and mucoadhesive properties were characterized and shown to be dependent upon the mucoadhesive agent used and the inclusion/exclusion of PL. The dynamic theological properties of the gel platforms were also assessed following dilution with simulated vaginal fluid (to mimic in vivo dilution). RSVs containing PC were more rheologically structured than comparator formulations containing GAN. This trend was also reflected in formulation hardness, compressibility, consistency, and syringeability. Moreover, formulations containing PL (10% w/w) were more theologically structured than formulations devoid of PL. Dilution with simulated vaginal fluids significantly decreased rheological structure, although RSVs still retained a highly elastic stnicture (G' > G '' and tan delta <1). Furthermore, RSVs exhibited sustained drug release properties that were shown to be dependent upon their rheological structure. It is considered that these semisolid drug delivery systems may be useful as site-retentive platforms for the sustained delivery of therapeutic agents to the vagina.

‘Risk, Politics and the ‘Scientification’ of Political Judgement: Prisoner Release and Conflict Transformation in Northern Ireland’

Drawing on research in Northern Ireland into the process of release under the Belfast/Good Friday Agreement, this article explores the identification and classification of risk in relation to prisoners released early under the Sentences (NI) Act. The main argument is that conflict, post-conflict and transitional conditions expose more starkly the political underpinnings of risk-management strategy and the article demonstrates the particular variant of Politicized Risk Assessment (PRA) recently used in the release of prisoners in Northern Ireland

Effects of Constraint Errors on Parallel Manipulators with Decoupled Motion

From perspective of structure synthesis, certain special geometric constraints, such as joint axes intersecting at one point or perpendicular to each other, are necessary in realizing the end-effector motion of kinematically decoupled parallel manipulators (PMs) along individual motion axes. These requirements are difficult to achieve in the actual system due to assembly errors and manufacturing tolerances. Those errors that violate the geometric constraint requirements are termed “constraint errors”. The constraint errors usually are more troublesome than other manipulator errors because the decoupled motion characteristics of the manipulator may no longer exist and the decoupled kinematic models will be rendered useless due to these constraint errors. Therefore, identification and prevention of these constraint errors in initial design and manufacturing stage are of great significance. In this article, three basic types of constraint errors are identified, and an approach to evaluate the effects of constraint errors on decoupling characteristics of PMs is proposed. This approach is illustrated by a 6-DOF PM with decoupled translation and rotation. The results show that the proposed evaluation method is effective to guide design and assembly.