2E), while lung tissue was intact and did not display any sign of thickened alveoli walls (Fig. 2F). Microscopic investigations of the mucosa of the fourth segment of the small intestine did not reveal distinct pathological changes in any group (data not shown). In contrast, in the group of animals treated with PFD-filled PLGA microcapsules macroscopic assessment of the serosa revealed some petechiae scattered over the

entire jejunum. Plasma concentrations of IL-1α, IL-1β, IL-6, IL-10 and TNF-α displayed similar characteristics. After AZD5363 in vivo the infusion of PFD-filled PLGA microcapsules, pro-inflammatory cytokines (such as IL-1α, IL-1β, IL-6, TNF-α) were strongly elevated compared to NaCl controls, whereas infusion of PVA did not provoke any immune response (Fig. 4A–H). Notably, 90 min after begin of microcapsule infusion a clear increase of IL-10 took place and persisted until the end of the experiment (Fig. 4F). Irrespective of the treatment group, plasma levels of both IL-4 (<14.1 pg/ml) and IFN-γ (<35.0 pg/ml) were unaffected and only very small amounts of IL-5 (<113.0 pg/ml, not significantly different between

the treatment groups) were released (Fig. 4C/D/G). The application of NaCl did not alter the concentration of complement factor 3 (C3) in plasma. Only at 270 min, C3 level in the group treated with PFD-filled PLGA microcapsules was reduced significantly when compared to the NaCl group at 270 min (Fig. 4I). Infusion of NaCl or PVA did not affect the plasma amount of complement factor 4a (C4a) either. In both groups all values stayed below selleck the assay’s detection limit (Fig. 4J). In contrast, after infusion of PFD-filled PLGA microcapsules, the plasma concentration of C4a increased and differed significantly from the respective NaCl control at all time-points monitored (Fig. 4J). The diameters of sinusoids and postsinusoidal venules increased about 23% and 20% already 10 min after start of infusion of PFD-filled PLGA microcapsules (1.5 µm and 1 µm, respectively) whereas infusion of PLGA

microspheres caused a decrease of vessel Galeterone diameter of 15% compared to NaCl control group (Fig. S5). During the following 20 min of infusion, diameters of sinusoids and postsinusoidal venules of all microcapsule treated animals normalized, thereby reaching the baseline level at the end of the infusion (Fig. S5). After infusing 0.9% NaCl, the number of perfused vessels and MAP remained at baseline levels (100%, 100 mmHg, respectively, Fig. 5A). In contrast, at the very beginning of the infusion of PFD-filled PLGA microcapsules (1.5 µm) MAP (mmHg) and the number of perfused vessels (%) decreased to about 60 mmHg/50% from baseline. Only MAP regenerated during the following observation time, whereas the number of perfused vessels only reached 80% of baseline level (Fig. 5B). Infusion of PFD-filled PLGA microcapsules (diameter 1 µm) revealed identical results as obtained with 1.5 µm microcapsules (Fig. S6).