A laminated polymer film formulation for enteric delivery of live vaccine and probiotic bacteria

Live bacterial cells (LBC) are administered orally as attenuated vaccines, to deliver biopharmaceutical agents, and as probiotics to improve gastrointestinal health. However, LBC present unique formulation challenges and must survive gastrointestinal antimicrobial defenses including gastric acid after administration. We present a simple new formulation concept, termed Polymer Film Laminate (PFL). LBC are ambient dried onto cast acid-resistant enteric polymer films that are then laminated together to produce a solid oral dosage form. LBC of a model live bacterial vaccine and a probiotic were dried directly onto a cast film of enteric polymer. The effectiveness at protecting dried cells in a simulated gastric fluid (pH 2.0) depended on the composition of enteric polymer film used, with a blend of ethylcellulose plus Eudragit L100 55 providing greater protection from acid than Eudragit alone. However, although PFL made from blended polymers films completely released low molecular weight dye into intestinal conditions (pH 7.0), they failed to release LBC. In contrast, PFL made from Eudragit alone successfully protected dried probiotic or vaccine LBC from simulated gastric fluid for 2h, and subsequently released all viable cells within 60min of transfer into simulated intestinal fluid. Release kinetics could be controlled by modifying the lamination method.

Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults

Objective The colonic microbiota ferment dietary fibres, producing short chain fatty acids. Recent evidence suggests that the short chain fatty acid propionate may play an important role in appetite regulation. We hypothesised that colonic delivery of propionate would increase peptide YY (PYY) and glucagon like peptide-1 (GLP-1) secretion in humans, and reduce energy intake and weight gain in overweight adults. Design To investigate whether propionate promotes PYY and GLP-1 secretion, a primary cultured human colonic cell model was developed. To deliver propionate specifically to the colon, we developed a novel inulin-propionate ester. An acute randomised, controlled cross-over study was used to assess the effects of this inulin-propionate ester on energy intake and plasma PYY and GLP-1 concentrations. The long-term effects of inulin-propionate ester on weight gain were subsequently assessed in a randomised, controlled 24-week study involving 60 overweight adults. Results Propionate significantly stimulated the release of PYY and GLP-1 from human colonic cells. Acute ingestion of 10 g inulin-propionate ester significantly increased postprandial plasma PYY and GLP-1 and reduced energy intake. Over 24 weeks, 10 g/day inulin-propionate ester supplementation significantly reduced weight gain, intra-abdominal adipose tissue distribution, intrahepatocellular lipid content and prevented the deterioration in insulin sensitivity observed in the inulin-control group. Conclusions These data demonstrate for the first time that increasing colonic propionate prevents weight gain in overweight adult humans

Delivery of crop pollination services is an insufficient argument for wild pollinator conservation

There is compelling evidence that more diverse ecosystems deliver greater benefits to people, and these ecosystem services have become a key argument for biodiversity conservation. However, it is unclear how much biodiversity is needed to deliver ecosystem services in a cost-effective way. Here we show that, while the contribution of wild bees to crop production is significant, service delivery is restricted to a limited subset of all known bee species. Across crops, years and biogeographical regions, crop-visiting wild bee communities are dominated by a small number of common species, and threatened species are rarely observed on crops. Dominant crop pollinators persist under agricultural expansion and many are easily enhanced by simple conservation measures, suggesting that cost-effective management strategies to promote crop pollination should target a different set of species than management strategies to promote threatened bees. Conserving the biological diversity of bees therefore requires more than just ecosystem-service-based arguments.

An investigation of the required skills for the delivery of low and zero carbon buildings within a region

The United Kingdom is committed to a raft of requirements to create a low-carbon economy. Buildings consume approximately 40% of UK energy demand. Any improvement on the energy performance of buildings therefore can significantly contribute to the delivery of a low-carbon economy. The challenge for the construction sector and its clients is how to meet the policy requirements to deliver low and zero carbon (LZC) buildings, which spans broader than the individual building level, to requirements at the local and regional levels, and wider sustainability pressures. Further, the construction sector is reporting skills shortages coupled with the need for ‘new skills’ for the delivery of LZC buildings. The aim of this paper is to identify, and better understand, the skills required by the construction sector and its clients for the delivery of LZC buildings within a region. The theoretical framing for this research is regional innovation system (RIS) using a socio-technical network analysis (STNA) methodology. A case study of a local authority region is presented. Data is drawn from a review of relevant local authority documentation, observations and semi-structured interviews from one (project 1) of five school retrofit projects within the region. The initial findings highlight the complexity surrounding the form and operation of the LZC network for project 1. The skills required by the construction sector and its clients are connected to different actor roles surrounding the delivery of the project. The key actors involved and their required skills are: project management and energy management skills required by local authority; project management skills (in particular project planning), communication and research skills required by school end-users; and a ‘technical skill’ relating to knowledge of a particular energy efficient measure (EEM) and use of equipment to implement the EEM is required by the EEM contractors.

Targeting αvβ3 and α5β1 for gene delivery to proliferating VSMCs: synergistic effect of TGF-β1

TGF-beta1 levels increase after vascular injury and promote vascular smooth muscle cell (VSMC) proliferation. We define a nonviral gene delivery system that targets alphavbeta3 and alpha5beta1 integrins that are expressed on proliferating VSMCs and strongly induced by TGF-beta1. A 15-amino acid RGDNP-containing peptide from American Pit Viper venom was linked to a Lys(16) peptide as vector (molossin vector) and complexed with Lipofectamine or fusogenic peptide for delivery of luciferase or beta-galactosidase reporter genes to primary cultures of human, rabbit, and rat VSMCs. Preincubation of VSMCs with TGF-beta1 for 24 h, but not with PDGF-BB, interferon-gamma, TNF-alpha, nor PMA, increased alphavbeta3 and alpha5beta1 expressions on VSMCs and enhanced gene delivery of molossin vector. Thus beta-galactosidase activity increased from 35 +/- 5% (controls) to 75 +/- 5% after TGF-beta1 treatment, and luciferase activity increased fourfold over control values. Potential use of this system in vessel bypass surgery was examined in an ex vivo rat aortic organ culture model after endothelial damage. Molossin vector system delivered beta-galactosidase to VSMCs in the vessel wall that remained for up to 12 days posttransfection. The molossin vector system, when combined with TGF-beta1, enhances gene delivery to proliferating VSMCs and might have clinical applications for certain vasculoproliferative diseases.

Formulations of viable cells for oral delivery

This invention relates to solid formulations for the oral delivery of live microbial cells which comprise dried viable cells and small amounts of a bile acid binding agent, for example, an anion exchange resin such as cholestyramine. The presence of bile acid binding agents in the formulation significantly increases the survival of the cells in the intestinal tract and facilitates delivery of the viable cells to the intestine.

The perceived impact of the National Health Service on personalised nutrition service delivery among the UK public

Personalised nutrition (PN) has the potential to reduce disease risk and optimise health and performance. Although previous research has shown good acceptance of the concept of PN in the UK, preferences regarding the delivery of a PN service (e.g. online v. face-to-face) are not fully understood. It is anticipated that the presence of a free at point of delivery healthcare system, the National Health Service (NHS), in the UK may have an impact on end-user preferences for deliverances. To determine this, supplementary analysis of qualitative data obtained from focus group discussions on PN service delivery, collected as part of the Food4Me project in the UK and Ireland, was undertaken. Irish data provided comparative analysis of a healthcare system that is not provided free of charge at the point of delivery to the entire population. Analyses were conducted using the 'framework approach' described by Rabiee (Focus-group interview and data analysis. Proc Nutr Soc 63, 655-660). There was a preference for services to be led by the government and delivered face-to-face, which was perceived to increase trust and transparency, and add value. Both countries associated paying for nutritional advice with increased commitment and motivation to follow guidelines. Contrary to Ireland, however, and despite the perceived benefit of paying, UK discussants still expected PN services to be delivered free of charge by the NHS. Consideration of this unique challenge of free healthcare that is embedded in the NHS culture will be crucial when introducing PN to the UK.