Effects of excipients in nasal powder formulations for systemic drug delivery

The nose as a site of drug delivery offers therapeutic opportunities for a variety of indications, due to the presence of immunocompetent cells, direct contact with the central nervous system and easy access to a permeable and highly vascularised mucosa. However, nasal drug delivery is primarily associated with locally acting drugs, being applied as simple liquid sprays or drops. A new generation of nasal products that takes advantage of the opportunities offered, however, will likely require more sophisticated formulations, as it will need to address specific challenges of the nose, such as the short residence time of inhaled particles. The formulation of nasal powders and the targeted use of excipients are conceivable strategies in this regard. This work investigates influences of excipients in powder formulations that affect systemic absorption of nasally administered druds. The first part of the work characterises selected mucoadhesive excipients and fillers regarding their potential to extend the nasal residence time with methods that are suitable as screening tools in product development. Furthermore, the excipients were characterised regarding the occurrence of sensory and toxic effects on the nasal mucosa. Since the benefit of excipient properties depends on the drug to be formulated, in the second part of the work the effect of selected mucoadhesives and fillers was investigated in model formulations. The influences of the formulations on the rheological properties of the nasal fluid, and thus the nasal residence time, on the dissolution and release of the drug, as well as on the permeation of the drug through the epithelium were assessed separately, in order to detect additive and counteracting effects on drug absorption. The consideration of the characterised processes in product development can avoid failures and enable the development of successful nasal products

Precision and accuracy of fish length measurements obtained with two visual underwater methods

During the VITAL cruise in the Bay of Biscay in summer 2002, two devices for measuring the length of swimming fish were tested: 1) a mechanical crown that emitted a pair of parallel laser beams and that was mounted on the main camera and 2) an underwater auto-focus video camera. The precision and accuracy of these devices were compared and the various sources of measurement errors were estimated by repeatedly measuring fixed and mobile objects and live fish. It was found that fish mobility is the main source of error for these devices because they require that the objects to be measured are perpendicular to the field of vision. The best performance was obtained with the laser method where a video-replay of laser spots (projected on fish bodies) carrying real-time size information was used. The auto-focus system performed poorly because of a delay in obtaining focus and because of some technical problems

Nasal Powder Formulations: In-Vitro Characterisation of the Impact of Powders on Nasal Residence Time and Sensory Effects

Nasal drug delivery is still primarily associated with locally-effective drugs, but next-generation products utilising the benefits of nasal administration-such as easy access to a relatively permeable mucosa, the presence of immunocompetent cells, and a direct route to the brain-are under investigation. Nasal powders offer the potential to improve the drugs' effects by providing higher resistance against the mucociliary clearance, and thus prolonging the contact time of the drug with its target site. However, suitable and easy-to-use in-vitro setups tailored to the characterisation of this effect are missing. In this study, a selection of excipients for powder formulations were used to evaluate the applicability of different methods which investigate the influence on the contact time. The combination of the assessment of rheological properties, dynamic vapour sorption, and adhesiveness on agar-mucin plates was found to be a valuable predictive tool. For the additional assessment of the sensations associated with the close contact of powders and the mucosa, a slug mucosal irritation assay was conducted and adapted to powders. These methods are regarded as being especially useful for comparative screenings in early formulation development

An integrated assessment of the ecological and economical status of fisheries - application to the French fisheries in the Bay of Biscay

While indicators and assessment frameworks are being developed for ecosystems, and tools for determining the economic status of a fishery are readily available, integrated assessment tools are still mostly lacking. However, the development of an ecosystem approach to fisheries management requires the monitoring and assessment of exploited ecosystems in all their dimensions, including ecological, economical and social components. This presentation will bring together indicators of both ecological status, like abundance and average size of target and non-target stocks, or of the fish community, with economic indicators, like fish prices, fishermen wages and profitability. The interaction between the two components is quantified by the matrices of contributions (the share of each fleet in the production of each stock) and dependencies (the share of each stock in the production of each fleet). The analysis will focus on two questions: i) What is the influence of stocks and community status on the performance and dynamics of fleets, as compared to other factors (fish prices, costs including fuel)? ii) What is the influence of fleet status on the dynamics of fish stocks and of the fish community, as compared to other factors (recruitment, environment)? The Bay of Biscay provides an appropriate case-study with a diversity of stocks and fleets to be assessed and managed together. The approach is applied to the French fleets for which detailed economic data are available.Keywords: Bay of Biscay, Integrated assessment, Fisheries, Fisheries management, Ecological and economical status, Ecosystem approach, Fisheries EconomicsKeywords: Bay of Biscay, Integrated assessment, Fisheries, Fisheries management, Ecological and economical status, Ecosystem approach, Fisheries Economic

Statistical ecology comes of age

The desire to predict the consequences of global environmental change has been the driver towards more realistic models embracing the variability and uncertainties inherent in ecology. Statistical ecology has gelled over the past decade as a discipline that moves away from describing patterns towards modelling the ecological processes that generate these patterns. Following the fourth International Statistical Ecology Conference (1-4 July 2014) in Montpellier, France, we analyse current trends in statistical ecology. Important advances in the analysis of individual movement, and in the modelling of population dynamics and species distributions, are made possible by the increasing use of hierarchical and hidden process models. Exciting research perspectives include the development of methods to interpret citizen science data and of efficient, flexible computational algorithms for model fitting. Statistical ecology has come of age: it now provides a general and mathematically rigorous framework linking ecological theory and empirical data.Peer reviewe

Injectable Thermosensitive Chitosan-Collagen Hydrogel as A Delivery System for Marine Polysaccharide Fucoidan

Fucoidans, sulfated polysaccharides from brown algae, possess multiple bioactivities in regard to osteogenesis, angiogenesis, and inflammation, all representing key molecular processes for successful bone regeneration. To utilize fucoidans in regenerative medicine, a delivery system is needed which temporarily immobilizes the polysaccharide at the injured site. Hydrogels have become increasingly interesting biomaterials for the support of bone regeneration. Their structural resemblance with the extracellular matrix, their flexible shape, and capacity to deliver bioactive compounds or stem cells into the affected tissue make them promising materials for the support of healing processes. Especially injectable hydrogels stand out due to their minimal invasive application. In the current study, we developed an injectable thermosensitive hydrogel for the delivery of fucoidan based on chitosan, collagen, and β-glycerophosphate (β-GP). Physicochemical parameters such as gelation time, gelation temperature, swelling capacity, pH, and internal microstructure were studied. Further, human bone-derived mesenchymal stem cells (MSC) and human outgrowth endothelial cells (OEC) were cultured on top (2D) or inside the hydrogels (3D) to assess the biocompatibility. We found that the sol-gel transition occurred after approximately 1 min at 37 °C. Fucoidan integration into the hydrogel had no or only a minor impact on the mentioned physicochemical parameters compared to hydrogels which did not contain fucoidan. Release assays showed that 60% and 80% of the fucoidan was released from the hydrogel after two and six days, respectively. The hydrogel was biocompatible with MSC and OEC with a limitation for OEC encapsulation. This study demonstrates the potential of thermosensitive chitosan-collagen hydrogels as a delivery system for fucoidan and MSC for the use in regenerative medicine

A new class of predator prey models with interactions described by thresholds

There exists an urgent need in fisheries science for simple models for assessing the impact of fishing on the dynamics of fish communities. We present a new class of predator prey models that describe the relationship between predators and their prey by piecewise-linear differential equations. Interactions are governed by threshold values for population abundances. The simplest model has four distinct cases with different asymptotic stable states. The model allows for fishing mortality on both predator and prey. If fishing mortality on either the predator, the prey or both are varied, the system might move to new stable states. The threshold values act as reference points for fishing exploitation, as they indicate a structural change in the predator-prey relationship. The model is demonstrated for several predator-prey couples in the Celtic Sea

Capacity management, not stock status or economics, drives fleet dynamics in the Bay of Biscay ecosystem on a decadal time scale

International audienceThis paper introduces a semiqualitative approach to analyse the joint dynamics of fleets and stocks in a multispecies, multifleet fishery. We ask whether changes in fleets affect resource dynamics and whether trends in resource influence fleet dynamics more than external drivers do. External drivers include vessel buyback, fuel price, and fish prices, as well as environmental fluctuations. Resource status is measured by abundance and length metrics; fleet capacity is measured by total horse power, and economic metrics such as profitability and earnings are examined as well. A maximum likelihood approach is used to identify the combined metric trends with the largest support in the data. The approach is applied to the French Bay of Biscay fisheries in 2000-2007. Combined-metric time trends suggest that decreases in fleet capacity did not result in decreasing fishing impacts; trends in stocks and fish prices were not the major drivers of changes in fleets either. Rather, the vessel buyback program might have been the main factor determining fleet dynamics over that period.Notre étude présente une approche semi-qualitative pour analyser la dynamique conjointe des flottilles et des stocks dans une pêcherie multi-spécifique et multi-flottille. Nous examinons si les changements dans les flottilles affectent la dynamique des stocks, et si les tendances des stocks influencent la dynamique des flottilles davantage que des facteurs externes. Ces facteurs incluent un programme de sortie de flotte, les prix du gasoil et du poisson, ainsi que les fluctuations environnementales. L’état des stocks est évalué par des métriques d’abondance et de longueur; la capacité des flottilles est mesurée par la puissance totale; des indicateurs économiques comme la rentabilité et les salaires sont aussi examinés. Les tendances combinées de ces métriques les mieux appuyées par les données sont identifiées par une méthode de maximum de vraisemblance. L’approche est appliquée aux flottilles françaises dans le golfe de Gascogne de 2000 à 2007. Les tendances temporelles combinées suggèrent que la diminution de capacité de la flotte ne s’est pas traduite par une réduction de l’impact de la pêche sur les ressources; les changements dans l’état des stocks et le prix du poisson n’étaient pas non plus les principaux facteurs des changements dans les flottilles. C’est plutôt le programme de sortie de flotte qui semble avoir été le facteur majeur de l’évolution des flottilles pendant cette période

How Do Fishing and Environmental Effects Propagate Among and Within Functional Groups?

Competition and predation can play different roles in mediating the influence of external pressures, such as fishing or environmental variations, on marine communities. Pressure effects propagate through food webs along predation links. These predator-prey interactions may result in trophic cascades, but they can be buffered by competitive interactions. We investigated these mechanisms by taking a functional-group approach. Are functional groups affected by external pressures in a predictable way? Within functional groups, do all species respond in the same way, or does competitive release allow for compensation among species? We constructed a simple community model, with functional groups connected by predation links. Loop analysis was used to make qualitative predictions of the changes in functional groups that might result through either direct or indirect effects from changes in pressures. Actual changes in biomass and average weight in functional groups were then tracked from fish trawl-survey data; compensation within groups was examined with dynamic factor analysis. This approach was applied to the Georges Bank, Bay of Biscay, and North Sea fish communities, which have been subject to different fishing regimes and have undergone environmental changes over the last decades. All three communities changed substantially. Compensation did not prevent impacts from propagating through the three food webs; rather, antagonistic pressures did. Community responses to perturbation were mostly determined by community structure and by fisheries selectivity with respect to both functional groups and species