A p-value <0.05 was considered to indicate significance. MAP in the NaCl control group remained in the physiological range (90–120 mmHg) throughout the whole experiment (Fig. 1). MAP in the PVA group differed only slightly from control (91–100 mmHg). In sharp contrast, animals receiving PFD-filled PLGA microcapsules with a diameter of 1.5 µm experienced a significant, temporary descent of MAP to 57 mmHg shortly after start of infusion, regaining baseline conditions

after about 70 min. In all three groups heart rates stayed constant at about 300 bpm (Fig. S1A). In the PVA and microcapsule groups breathing rates increased from baseline level (about 50 breaths per min) to about 60 breaths per min from 0 to 80 min normalizing afterwards to baseline level (Fig. S1B). The body temperature of all animals was inconspicuous and persisted Trichostatin A cell line around 37 °C (Fig. S1C). The pH of all animals was slightly acidotic at about 7.3 (Fig. S2A). pCO2 was mildly elevated to about 55 mmHg ( Fig. S2B) while pO2 was inconspicuous and varied around MEK inhibitor clinical trial 500 mmHg in all three experimental groups ( Fig. S1D). Base excess diminished somewhat

in the NaCl and PVA treated animals, but did not move out of the physiological range (+3 to −3 mmol/l, Fig. S2C). However, the animals treated with microcapsules suffered from a significant decline from –0.9 mmol/l (0 min) to −5.9 mmol/l (120 min), compared to NaCl-infused animals. Blood lactate concentration in the NaCl and PVA groups increased only slightly to 1.2 and 1.0 mmol/l, respectively ( Fig. S2D). In contrast, in the animals treated with microcapsules, lactate concentration significantly increased. Values doubled from 0.8 mmol/l (0 min) to 1.7 mmol/l (120 min) finally descending to control level at the end of the experiment ( Fig. S2D). Assessment of cryosections revealed an excessive accumulation of PFD-filled PLGA microcapsules (1.5 µm) in spleen and liver (Fig. 2A–B) but displayed very few capsules in other organs, i.e.,

lung ( Fig. 2C), brain, kidney, heart and M. Gastrocnemius ( Fig. S3). Identical results were obtained after infusion of 1 µm-sized PFD-filled PLGA microcapsules (data not shown). Infusion of NaCl or PVA Methane monooxygenase did not affect plasma activities of the enzymes ALAT, ASAT, CK and LDH (Fig. 3). In contrast, after infusion of PFD-filled PLGA microcapsules plasma activities of ALAT (3.6-fold), ASAT (6-fold), CK (5-fold) and LDH (24-fold) were significantly elevated if compared to the NaCl group at the end of experiment (Fig. 3). Creatinine concentrations oscillated around 0.7 mg/dl in all three experimental groups (Fig. S4). Hematoxylin-eosin-staining revealed changes of spleen and liver architecture. Compared with NaCl- or PVA-infused animals (free of pathological indications), spleens of animals treated with PFD-filled PLGA microcapsules showed beginnings of dissolving tissue structures of white pulp and red pulp (Fig. 2D).