Preparation of two kinds of superparamagnetic iron oxide nanoparticles and their acute toxicity to rat lungs

Abstract:

Objective：To prepare superparamagnetic iron oxide nanoparticles（SPIONs） modified by chitosan and sodium oleate and to investigate their acute lung toxicity. Methods：The SPIONs were prepared by coprecipitation and their properties were measured. Fifty-four SD rats were divided into three groups randomly：control group（n=18），chitosan-SPIONs group（n=18） and sodi－um oleate-SPIONs group（n=18）. The rats were exposed to SPIONs by intratracheal instillation. General condition of the rats was observed. Six rats of each group were killed randomly at 24 h，72 h and 14 d after the exposure. The major blood biochemical indicators were analyzed with an automatic biochemical analyz－er. Bronchoalveolar lavage fluid（BALF） was taken and the total cells and neutrophil cells were counted. The pathological changes of lungs were observed with HE staining. Results：①Both of the SPIONs exhibited structure of spherical crystallization with a diameter of 30 nm. ②The normal situation of rats was good and no rat died；③Only two blood biochemical indicators including total protein（TP） of 24 h and alkaline phosphatase（ALP） of 14 d were different from those of control group（TP（g/L） 24 h group：chitosan-SPIONs group（n=6）：62.40±3.60，sodium oleate-SPIONs group（n=6）：69.95±5.16，control group（n=6）：63.22±2.55，F=6.344，P=0.010；ALP（u/L） 14 d group：chitosan-SPIONs group（n=6）：78.83±7.92，sodium oleate-SPIONs group（n=6）：106.83±26.95，control group（n=6）：99.85±9.63，F=4.336，P=0.033）. ④Total cells（×104） in BALF of experimental groups were higher than those in control group at 24 h and 72 h and total cells of sodium oleate-SPIONs group were obviously higher than those of chitosan-SPIONs group（chitosan-SPIONs 24 h group（n=6）：780.00±130.58，sodium oleate-SPIONs 24 h group（n=6）：1 000.00±166.85，control 24 h group（n=6）：498.33±114.75，F=19.605，P=0.000；chitosan-SPIONs 72 h group（n=6）：809.17±197.49，sodium oleate-SPIONs 72 h group（n=6）：920.00±125.54，control 72 h group（n=6）：580.00±123.29，F=7.735，P=0.005）. Both of them were decreased to normal on 14 d（chitosan-SPIONs group（n=6）：628.33±133.29，sodium oleate-SPIONs group（n=6）：654.17±99.27，control group（n=6）：570.83±94.15，F=0.898，P =0.428）. ⑤Neutrophil cells（×104） in BALF of experimental groups were higher than those of control group at 24 h and 72 h（chitosan-SPIONs 24 h group（n=6）：４５.00±1４.１２，sodium oleate-SPIONs 24 h group（n=6）：９0.00±２４.５０，control 24 h group（n=6）：１.０２±０.３３，F=44.565，P=0.000；chitosan-SPIONs 72 h group（n=6）：９.１５±8.82，sodium oleate-SPIONs 72 h group（n=6）：19.17±5.38，control 72 h group（n=6）：1.09±0.57，F=13.791，P=0.000）. Neutrophil cells in BALF were more in sodium oleate-SPIONs group than in chitosan-SPIONs group.⑥HE staining showed the fracture of pulmonary alveoli，thickening of alveolar walls，and inflammatory cell infiltration in the experimental groups which were more serious in sodium oleate-SPIONs group than in chitosan-SPIONs group. Conclusion：Chitosan modified SPIONs have less toxicity to the rats’ lungs than sodium oleate modified SPIONs and their lung toxicity reduces over time.