title: Biological evaluation of Fe₃O₄-poly(L-lactide)-poly(ethylene glycol)-poly(L-lactide) magnetic microspheres prepared in supercritical CO₂.
abstract: The biocompatibility of Fe₃O₄-poly(L-lactide)-poly(ethylene glycol)-poly(L-lactide) magnetic microspheres (Fe₃O₄-PLLA-PEG-PLLA MMPs) prepared in a process of suspension-enhanced dispersion by supercritical CO₂ (SpEDS) was evaluated at various levels: cellular, molecular, and integrated. At the cellular level, the investigations of cytotoxicity and intracellular reactive oxygen species (ROS) generation indicate that the polymer-coated MMPs (2.0 mg/mL) had a higher toxicity than uncoated Fe₃O₄ nanoparticles, which led to about 20% loss of cell viability and an increase (0.2 fold) in ROS generation; the differences were not statistically significant (p > 0.05). However, an opposite phenomenon was observed in tests of hemolysis, which showed that the MMPs displayed the weakest hemolytic activity, namely only about 6% at the highest concentration (20 mg/mL). This phenomenon reveals that polymer-coated MMPs created less toxicity in red blood cells than uncoated Fe₃O₄ nanoparticles. At the molecular level, the MMPs were shown to be less genotoxic than Fe₃O₄ nanoparticles by measuring the micronucleus (MN) frequency in CHO-K1 cells. Furthermore, the mRNA expression of pro-inflammatory cytokines demonstrates that polymer-coated MMPs elicited a less intense secretion of pro-inflammatory cytokines than uncoated Fe₃O₄ nanoparticles. Acute toxicity tests of MMPs show quite a low toxicity, with an LD₅₀ > 1575.00 mg/kg. The evidence of low toxicity presented in the results indicates that the Fe₃O₄-PLLA-PEG-PLLA MMPs from the SpEDS process have great potential for use in biomedical applications.
authors.affiliation: College of Chemical Engineering, Huaqiao University, Xiamen 361021, China. azchen@hqu.edu.cn
authors.forename: Ai-Zheng
authors.initials: AZ
authors.lastname: Chen
authors.forename: Xiao-Fen
authors.initials: XF
authors.lastname: Lin
authors.forename: Shi-Bin
authors.initials: SB
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Yuan-Gang
authors.initials: YG
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Ye
authors.forename: Guang-Ya
authors.initials: GY
authors.lastname: Wang
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000633:toxicity*; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004249:DNA Damage; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D005290:Ferric Compounds / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D007773:Lactates / Q000737:chemistry / Q000633:toxicity*; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D008863:Microspheres; D011092:Polyethylene Glycols / Q000737:chemistry / Q000633:toxicity*; D012313:RNA / Q000737:chemistry / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D001672:Biocompatible Materials; D016207:Cytokines; D005290:Ferric Compounds; D007773:Lactates; D017382:Reactive Oxygen Species; C088513:poly(lactic acid-ethylene glycol); C000499:ferric oxide; D011092:Polyethylene Glycols; D012313:RNA