Liposomal vaccine delivery systems

INTRODUCTION: Liposomes remain at the forefront of drug and vaccine design owing to their well-documented abilities to act as delivery vehicles. Nevertheless, the concept of liposomes as delivery vehicles is not a new one, with most works focusing on their use for the delivery of genes and drugs. However, in the last 10 years a significant amount of research has focused on using liposomes as vaccine adjuvants, not only as an antigen delivery vehicle but also as a tool to increase the immunogenicity of peptide and protein antigens. AREAS COVERED: This paper reviews liposomal adjuvants now in vaccine development, with particular emphasis on their adjuvant mechanism and how specific physicochemical characteristics of liposomes affect the immune response. The inclusion of immunomodulators is also discussed, with prominence given to Toll-like receptor ligands. EXPERT OPINION: The use of liposomes as vaccine delivery systems is evolving rapidly owing to the combined increase in technological advances and understanding of the immune system. Liposomes that contain and deliver immunostimulators and antigens are now being developed to target diseases that require stimulation of both humoral and cell-mediated immune responses. The CAF liposomal system, described in detail in this review, is one liposomal model that shows such flexibility.

Semi-analytical Q parameter estimate in linear and nonlinear transmission systems

We compare the Q parameter obtained from the semi-analytical model with scalar and vector models for two realistic transmission systems. First a linear system with a compensated dispersion map and second a soliton transmission system.

Transmission of non-uniform OTDM channels in nonlinearly-guided dispersion-managed fibre system

The effects of channel inequality on nonlinear signal switching in a nonlinear optical fiber loop mirror (NOLM) were investigated. It was found that the channel-to-channel amplitude differences in optical time division multiplexing (OTDM) have strong impact on swiching behavior of individual channels in a 2R regenerator. The optical pulses in different channels face either suppression of the amplitude noise or increase in noise, depending on the inter-channel amplitude difference. It was stated that appropriate control of the channel uniformity in the OTDM transmitters is required to support stable long-haul transmission in 2R regenerated systems.

Development and formulation of wax-based transdermal drug delivery systems

Topical and transdermal formulations are promising platforms for the delivery of drugs. A unit dose topical or transdermal drug delivery system that optimises the solubility of drugs within the vehicle provides a novel dosage form for efficacious delivery that also offers a simple manufacture technique is desirable. This study used Witepsol® H15 wax as a abase for the delivery system. One aspect of this project involved determination of the solubility of ibuprofen, flurbiprofen and naproxen in the was using microscopy, Higuchi release kinetics, HyperDSC and mathematical modelling techniques. Correlations between the results obtained via these techniques were noted with additional merits such as provision of valuable information on drug release kinetics and possible interactions between the drug and excipients. A second aspect of this project involved the incorporation of additional excipients: Tween 20 (T), Carbopol®971 (C) and menthol (M) to the wax formulation. On in vitro permeation through porcine skin, the preferred formulations were: ibuprofen (5% w/w) within Witepsol®H15 + 1% w/w T; flurbiprofen (10% w/w) within Witepsol®H15 + 1% w/w T; naproxen (5% w/w) within Witepsol®H15 + 1% w/w T + 1% C and sodium diclofenac (10% w/w) within Witepsol®H15 + 1% w/w T + 1% w/w T + 1% w/w C + 5% w/w M. Unit dose transdermal tablets containing ibuprofen and diclofenac were produced with improved flux compared to marketed products; Voltarol Emugel® demonstrated flux of 1.68x10-3 cm/h compared to 123 x 10-3 cm/h for the optimised product as detailed above; Ibugel Forte® demonstrated a permeation coefficient value of 7.65 x 10-3 cm/h compared to 8.69 x 10-3 cm/h for the optimised product as described above.

Formulation and characterisation of an effective particulate delivery vehicle for the novel sub-unit vaccine antigen, Ag85B-ESAT-6

This research focused on the formation of particulate delivery systems for the sub-unit fusion protein, Ag85B-ESAT-6, a promising tuberculosis (TB) vaccine candidate. Initial work concentrated on formulating and characterising, both physico-chemically and immunologically, cationic liposomes based on the potent adjuvant dimethyl dioctadecyl ammonium (DDA). These studies demonstrated that addition of the immunomodulatory trehalose dibehenate (TDB) enhanced the physical stability of the system whilst also adding further adjuvanticity. Indeed, this formulation was effective in stimulating both a cell mediated and humoural immune response. In order to investigate an alternative to the DDA-TDB system, microspheres based on poly(DL-lactide-co-glycolide) (PLGA) incorporating the adjuvants DDA and TDB, either alone or in combination, were first optimised in terms of physico-chemical characteristics, followed by immunological analysis. The formulation incorporating PLGA and DDA emerged as the lead candidate, with promising protection data against TB. Subsequent optimisation of the lead microsphere formulation investigated the effect of several variables involved in the formulation process on physico-chemical and immunological characteristics of the particles produced. Further, freeze-drying studies were carried out with both sugar-based and amino acid-based cryoprotectants, in order to formulate a stable freexe-dried product. Finally, environmental scanning electron microscopy (ESEM) was investigated as a potential alternative to conventional SEM for the morphological investigation of microsphere formulations. Results revealed that the DDA-TDB liposome system proved to be the most immunologically efficient delivery vehicle studied, with high levels of antibody and cytokine production, particularly gamma-interferon (IFN-ϒ), considered the key cytokine marker for anti-mycobacterial immunity. Of the microsphere systems investigated, PLGA in combination with DDA showed the most promise, with an ability to initiate a broad spectrum of cytokine production, as well as antigen specific spleen cell proliferation comparable to that of the DDA-TDB formulation.

Voltage control on an uninhabited autonomous vehicle electrical distribution system

More-electric vehicle technology is becoming prevalent in a number of transportation systems because of its ability to improve efficiency and reduce costs. This paper examines the specific case of an Uninhabited Autonomous Vehicle (UAV), and the system topology and control elements required to achieve adequate dc distribution voltage bus regulation. Voltage control methods are investigated and a droop control scheme is implemented on the system. Simulation results are also presented.

Towards a theoretical framework for human performance modelling within manufacturing systems design

The performance of direct workers has a significant impact on the competitiveness of many manufacturing systems. Unfortunately, system designers are ill equipped to assess this impact during the design process. An opportunity exists to assist designers by expanding the capabilities of popular simulation modelling tools, and using them as a vehicle to better consider human factors during the process of system design manufacture. To support this requirement, this paper reports on an extensive review of literature that develops a theoretical framework, which summarizes the principal factors and relationships that such a modelling tool should incorporate.

On the theory of autosoliton propagation in optical fibers guided by in-line nonlinear devices

A theoretical model is developed to describe the propagation of ultra-short optical pulses in fiber transmission systems in the quasi-linear regime, with periodically inserted in-line lumped nonlinear optical devices. Stable autosoliton solutions are obtained for a particular application of the general theory.

Improving “last mile” delivery performance to retailers in hub and spoke distribution systems

Purpose – The purpose of this paper is to investigate the “last mile” delivery link between a hub and spoke distribution system and its customers. The proportion of retail, as opposed to non-retail (trade) customers using this type of distribution system has been growing in the UK. The paper shows the applicability of simulation to demonstrate changes in overall delivery policy to these customers. Design/methodology/approach – A case-based research method was chosen with the aim to provide an exemplar of practice and test the proposition that simulation can be used as a tool to investigate changes in delivery policy. Findings – The results indicate the potential improvement in delivery performance, specifically in meeting timed delivery performance, that could be made by having separate retail and non-retail delivery runs from the spoke terminal to the customer. Research limitations/implications – The simulation study does not attempt to generate a vehicle routing schedule but demonstrates the effects of a change on delivery performance when comparing delivery policies. Practical implications – Scheduling and spreadsheet software are widely used and provide useful assistance in the design of delivery runs and the allocation of staff to those delivery runs. This paper demonstrates to managers the usefulness of investigating the efficacy of current design rules and presents simulation as a suitable tool for this analysis. Originality/value – A simulation model is used in a novel application to test a change in delivery policy in response to a changing delivery profile of increased retail deliveries.

I am the very model of a special purpose vehicle

Purpose – This paper aims to provide a critical comment on complex funding systems. Design/methodology/approach – This is a critical comment written in the form of a poem. The poem is in the style of the English light opera composers Gilbert and Sullivan, and is a variation on their song “I Am the Very Model of a Modern Major General”, from The Pirates of Penzance. Findings - The poem spotlights financial failure. Originality/value - The poem spotlights the crazy names and poor transparency of special purpose vehicles.

Nonlinearity management in hybrid amplification systems

A theory of nonlinearity management in transmission lines with periodic dispersion compensation and hybrid Raman-EDFA amplification is developed. Different transmission/compensating fiber pairs performances are compared and the optimal amplification scheme determined for each case.

Estimation of transportation battery second life for use in electricity grid systems

This paper presents research from part of a larger project focusing on the potential development of commercial opportunities for the reuse of batteries on the electricity grid system, subsequent to their primary use in low and ultra-low carbon vehicles, and investigating the life cycle issues surrounding the batteries. The work has three main areas; examination of electric vehicle fleet data in detail to investigate usage in first life. Batteries that have passed through a battery recycler at the end of their first life have been tested within the laboratory to confirm the general assumption that remaining capacity of 80% after use in transportation is a reasonable assumption as a basis for second-life applications. The third aspect of the paper is an investigation of the equivalent usage for three different second-life applications based on connection to the electricity grid. Additionally, the paper estimates the time to cell failure of the batteries within their second-life application to estimate lifespan for use within commercial investigations. © 2014 IEEE.

On the theory of autosoliton propagation in optical fibers guided by in-line nonlinear devices

A theoretical model is developed to describe the propagation of ultra-short optical pulses in fiber transmission systems in the quasi-linear regime, with periodically inserted in-line lumped nonlinear optical devices. Stable autosoliton solutions are obtained for a particular application of the general theory.

Facilitating intuitive-guided learning in a serious game through integration with a learning content management system

Increased global uptake of entertainment gaming has the potential to lead to high expectations of engagement and interactivity from users of technology-enhanced learning environments. Blended approaches to implementing game-based learning as part of distance or technology-enhanced education have led to demonstrations of the benefits they might bring, allowing learners to interact with immersive technologies as part of a broader, structured learning experience. In this article, we explore how the integration of a serious game can be extended to a learning content management system (LCMS) to support a blended and holistic approach, described as an 'intuitive-guided' method. Through a case study within the EU-Funded Adaptive Learning via Intuitive/Interactive, Collaborative and Emotional Systems (ALICE) project, a technical integration of a gaming engine with a proprietary LCMS is demonstrated, building upon earlier work and demonstrating how this approach might be realized. In particular, how this method can support an intuitive-guided approach to learning is considered, whereby the learner is given the potential to explore a non-linear environment whilst scaffolding and blending provide guidance ensuring targeted learning objectives are met. Through an evaluation of the developed prototype with 32 students aged 14-16 across two Italian schools, a varied response from learners is observed, coupled with a positive reception from tutors. The study demonstrates that challenges remain in providing high-fidelity content in a classroom environment, particularly as an increasing gap in technology availability between leisure and school times emerges.