In-Vitro and in-vivo evaluation of carrageenan/methylcellulose polymeric systems for transscleral delivery of macromolecules

In this study, polymeric dispersions composed of methylcellulose (MC) and either kappa carrageenan (KC) or iota carrageenan (IC) were proposed as a platform for transscleral delivery of macromolecules. The additive effects of the two polymers were investigated using oscillatory rheometer and FT-IR spectroscopy. Mechanical spectra demonstrated a conformation dependent association of the two polymers at 37 °C in the presence of selected counter ions. The polymer association was also confirmed by the shifts in MC peaks at 1049.5, 1114 and 1132.9 cm(-1) in the presence of carrageenans, which corresponds to the stretching vibrations of C-O-C bonds of the polysaccharides. The MC-IC polymeric system displayed the highest bio-adhesion, owing to the relatively high negative charge. However, the MC-IC system did not affect the in-vitro scleral permeability of sodium fluorescein and 10 kDa FITC-dextran. Nonetheless, the formulation properties had a substantial impact on the results of the in-vivo studies. The efficacy of transscleral drug delivery was determined using rats with altered connexin 43 (Cx43) levels, a gap junction protein, in the choroid. Periocular injection of Cx43 antisense oligonucleotides (AsODN) incorporated in the MC-IC system lead to a significant reduction in the Cx43 levels in the choroid of rats at 24 h of treatment. AsODN incorporated in phosphate buffered saline (PBS) also demonstrated a trend towards reduced Cx43 levels; however this was not statistically significant owing to great variability between treated animals. Consequently the in-vivo data suggests the transscleral route to be of value in delivering therapeutics to the choroid. Moreover this study identified a new polymeric system based on MC and IC which provides aqueous loading of therapeutics and prolonged retention at the site of administration

Trade-off in ecosystem services of the Somerset Levels and Moors wetlands

It is widely recognised that healthy ecosystems can provide considerable benefits to people, including food, timber, freshwater, protection from floods and much of what we call quality of life. A global review of these ecosystem services carried out as part of the Millennium Ecosystem Assessment (MA) provided a framework for national and local studies. Using the MA approach, this paper reviews the ecosystem services provided by the Somerset Levels and Moors wetland system in south-west England. This wetland provides a series of important services that are beneficial locally, regional and globally, including grazing for cattle, potential carbon sequestration, flood water storage, recreation and archaeology. Some services are synergistic and reinforcing; for example, maintaining wet conditions supports wetland bird life that maintains biological diversity, attracts tourists, protects archaeological artefacts and reduces CO2 emissions. Other services are potentially conflicting, for example raising water levels may reduce potential flood water storage and increase methane emissions. Comparison of the services of the wetland with those of drier habitats reveals for example that carbon sequestration, bird habitat provision and hay production is greater in wetlands, whilst grazing quality and plant diversity may be reduced and distributions of disease vectors may be altered by wetland restoration through raising water levels. Management decisions affecting wetlands may necessitate a trade-off of ecosystem services